FitSugar

Review: Secret Clinical Strength Sport Antiperspirant

FitSugar — Fri, 05 Sep 2008 08:00:00 -0700

Products marketed toward female athletes always pique my interest. Plus it is great to know that somebody out there knows we exist and like gear! When I saw a new antiperspirant by Secret with the word "sport" as well as the phrase "designed for athletes" on the front of the package, I was curious to try it. It was really the name of the sport fresh scent "marathon" that hooked me. Maybe if I wore this clinical strength formula I could run a marathon - only kidding.

I wore Clinical Strength Secret ($8) on a couple of runs and experienced absolutely no underarm sweating, and received no post-run comments about my stink factor from my 3-year-old. Then I read the fine print: this deodorant isn't really for female athletes. It was designed for women who suffer from excessive sweating, know as hyperhidrosis in medical speak. Secret recommends applying this clinical strength antiperspirant at bedtime, to allow for the active ingredient aluminum zirconium trichlorohydrex Gly to dissolve into your pores effectively plugging the sweat ducts for 24 hours. Honestly, the formation of "plugs" in my armpits while I sleep creeps me out a bit. I don't need 24-hour protection from sweating.

Although this product has a girly "sport fresh scent," its "prescription strength wetness protection" is overkill for me. However, it is truly effective and if you sweat regularly due to stress or physical exercise this could be the underarm protection you need. You can find it at DrugStore.com.

Have any of you tried Clinical Strength Secret? Tell me what you thought in the comments section below.

Omega-3 fatty acids

FitSugar — Wed, 08 Oct 2008 17:35:25 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Overview

Omega-3 fatty acids are considered essential fatty acids. They are essential to human health but cannot be manufactured by the body. For this reason, omega-3 fatty acids must be obtained from food. Omega-3 fatty acids can be found in fish, such as salmon, tuna, and halibut, other marine life such as algae and krill, certain plants (including purslane), and nut oils. Also known as polyunsaturated fatty acids (PUFAs), omega-3 fatty acids play a crucial role in brain function as well as normal growth and development. The American Heart Association recommends eating fish (particularly fatty fish such as mackerel, lake trout, herring, sardines, albacore tuna, and salmon) at least 2 times a week. It is advised that pregnant women and mothers, nursing mothers, young children, and women who might become pregnant not eat several types of fish, including swordfish, shark, and king mackerel. These individuals should also limit consumption of other fish, including albacore tuna, salmon, and herring. They can take omega-3 fatty acids in quality dietary supplements that are certified mercury-free by a reputable third-party lab.

There are three major types of omega 3 fatty acids that are ingested in foods and used by the body: alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Once eaten, the body converts ALA to EPA and DHA, the two types of omega-3 fatty acids more readily used by the body. Extensive research indicates that omega-3 fatty acids reduce inflammation and help prevent risk factors associated with chronic diseases such as heart disease, cancer, and arthritis. These essential fatty acids are highly concentrated in the brain and appear to be particularly important for cognitive (brain memory and performance) and behavioral function. In fact, infants who do not get enough omega-3 fatty acids from their mothers during pregnancy are at risk for developing vision and nerve problems. Symptoms of omega-3 fatty acid deficiency include extreme tiredness (fatigue), poor memory, dry skin, heart problems, mood swings or depression, and poor circulation.

It is important to maintain an appropriate balance of omega-3 and omega-6 (another essential fatty acid) in the diet, as these two substances work together to promote health. Omega-3 fatty acids help reduce inflammation, and most omega-6 fatty acids tend to promote inflammation. An inappropriate balance of these essential fatty acids contributes to the development of disease while a proper balance helps maintain and even improve health. A healthy diet should consist of roughly 2 - 4 times more omega-6 fatty acids than omega-3 fatty acids. The typical American diet tends to contain 14 - 25 times more omega-6 fatty acids than omega-3 fatty acids, and many researchers believe this imbalance is a significant factor in the rising rate of inflammatory disorders in the United States.

In contrast, however, the Mediterranean diet consists of a healthier balance between omega-3 and omega-6 fatty acids, and many studies have shown that people who follow this diet are less likely to develop heart disease. It also contains another fatty acid, omega-9 fatty acids, which have been reported to help lower risks associated with cancer and heart disease. The Mediterranean diet does not include much meat (which is high in omega-6 fatty acids) and emphasizes foods rich in omega-3 fatty acids, including whole grains, fresh fruits and vegetables, fish, olive oil, garlic, as well as moderate wine consumption.

Uses

Clinical studies suggest that omega-3 fatty acids may be helpful in treating a variety of health conditions. The evidence is strongest for heart disease and problems that contribute to heart disease, but the range of possible uses for omega-3 fatty acids include:

High cholesterol

Those who follow a Mediterranean-style diet tend to have higher high density lipoprotein (HDL or "good" )cholesterol levels. Similar to those who follow a Mediterranean diet, Inuit Eskimos, who consume high amounts of omega-3 fatty acids from fatty fish, also tend to have increased HDL cholesterol and decreased triglycerides (fatty material that circulates in the blood). In addition, fish oil supplements containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been reported in several large clinical studies to reduce low density lipoprotein (LDL or "bad") cholesterol and triglyceride levels. Finally, walnuts (which are rich in alpha linolenic acid or ALA) have been reported to lower total cholesterol and triglycerides in individuals with high cholesterol levels.

High blood pressure

Several clinical studies suggest that diets or supplements rich in omega-3 fatty acids lower blood pressure significantly in individuals with hypertension. An analysis of 17 clinical studies using fish oil supplements found that supplementation with 3 or more grams of fish oil daily can lead to significant reductions in blood pressure in individuals with untreated hypertension.

Heart disease

One of the best ways to help prevent and treat heart disease is to eat a low-fat diet and to replace foods rich in saturated and trans-fat with those that are rich in monounsaturated and polyunsaturated fats (including omega-3 fatty acids). Clinical evidence suggests that EPA and DHA found in fish oil help reduce risk factors for heart disease including high cholesterol and high blood pressure. There is also strong evidence that these substances can help prevent and treat atherosclerosis by inhibiting the development of plaque and blood clots, each of which tends to clog arteries. Clinical studies of heart attack survivors have found that daily omega-3 fatty acid supplements dramatically reduce the risk of death, subsequent heart attacks, and stroke. Similarly, people who eat an ALA-rich diet are less likely to suffer a fatal heart attack.

Strong evidence from population-based clinical studies suggests that omega-3 fatty acid intake (primarily from fish) helps protect against stroke caused by plaque buildup and blood clots in the arteries that lead to the brain. In fact, eating at least 2 servings of fish per week can reduce the risk of stroke by as much as 50%. However, people who eat more than 3 grams of omega-3 fatty acids per day (equivalent to 3 servings of fish per day) may be at an increased risk for hemorrhagic stroke, a potentially fatal type of stroke in which an artery in the brain leaks or ruptures.

Diabetes

Individuals with diabetes tend to have high triglyceride and low HDL levels. Omega-3 fatty acids from fish oil can help lower triglycerides and apoproteins (markers of diabetes), and raise HDL, so people with diabetes may benefit from eating foods or taking supplements that contain DHA and EPA. ALA (from flaxseed, for example) may not have the same benefit as DHA and EPA because some people with diabetes lack the ability to efficiently convert ALA to a form of omega-3 fatty acids that the body can use readily. There have been slight increases reported in fasting blood sugar levels in patients with type 2 diabetes while taking fish oil supplements.

Weight loss

Many individuals who are overweight suffer from poor blood sugar control, diabetes, and high cholesterol. Clinical studies suggest that overweight people who follow a weight loss program that includes exercise tend to achieve better control over their blood sugar and cholesterol levels when fish rich in omega-3 fatty acids (such as salmon, mackerel, and herring) is a staple in their low-fat diet.

Arthritis

Most clinical studies investigating the use of omega-3 fatty acid supplements for inflammatory joint conditions have focused almost entirely on rheumatoid arthritis. Several articles reviewing the research in this area conclude that omega-3 fatty acid supplements reduce tenderness in joints, decrease morning stiffness, and allow for a reduction in the amount of medication needed for people with rheumatoid arthritis.

In addition, laboratory studies suggest that diets rich in omega-3 fatty acids (and low in the inflammatory omega-6 fatty acids) may benefit people with other inflammatory disorders, such as osteoarthritis. In fact, several test tube studies of cartilage-containing cells have found that omega-3 fatty acids decrease inflammation and reduce the activity of enzymes that destroy cartilage. Similarly, New Zealand green lipped mussel (Perna canaliculus), another potential source of omega-3 fatty acids, has been reported to reduce joint stiffness and pain, increase grip strength, and enhance walking pace in a small group of people with osteoarthritis. In some participants, symptoms worsened before they improved.

An analysis was conducted of 17 randomized, controlled clinical trials assessing the pain relieving effects of omega-3 fatty acid supplementation in patients with rheumatoid arthritis or joint pain caused by inflammatory bowel disease (IBS) and painful menstruation (dysmenorrhea). The results suggest that omega-3 fatty acids are effective treatment, along with conventional therapies such as anti-inflammatory drugs, for joint pain associated with rheumatoid arthritis, inflammatory bowel disease, and dysmenorrhea.

Osteoporosis

Clinical studies suggest that omega-3 fatty acids such as EPA help increase levels of calcium in the body, deposit calcium in the bones, and improve bone strength. In addition, studies also suggest that people who are deficient in certain essential fatty acids (particularly EPA and gamma-linolenic acid [GLA], an omega-6 fatty acid) are more likely to suffer from bone loss than those with normal levels of these fatty acids. In a study of women over 65 with osteoporosis, those given EPA and GLA supplements experienced significantly less bone loss over 3 years than those who were given a placebo. Many of these women also experienced an increase in bone density.

Depression

People who do not get enough omega-3 fatty acids or do not maintain a healthy balance of omega-3 to omega-6 fatty acids in their diet may be at an increased risk for depression. The omega-3 fatty acids are important components of nerve cell membranes. They help nerve cells communicate with each other, which is an essential step in maintaining good mental health. In particular, DHA is involved in a variety of nerve cell processes.

Levels of omega-3 fatty acids were found to be measurably low and the ratio of omega-6 to omega-3 fatty acids were particularly high in a clinical study of patients hospitalized for depression. In a clinical study of individuals with depression, those who ate a healthy diet consisting of fatty fish 2 - 3 times per week for 5 years experienced a significant reduction in feelings of depression and hostility.

Bipolar disorder

In a clinical study of 30 people with bipolar disorder, those who were treated with EPA and DHA (in combination with their usual mood stabilizing medications) for 4 months experienced fewer mood swings and recurrence of either depression or mania than those who received placebo. Another 4-month long clinical study treating individuals with bipolar depression and rapid cycling bipolar disorder did not find evidence of efficacy for the use of in EPA in these patients.

Schizophrenia

Preliminary clinical evidence suggests that people with schizophrenia experience an improvement in symptoms when given omega-3 fatty acids. However, a recent well-designed study concluded that EPA supplements are no better than placebo in improving symptoms of this condition. The conflicting results suggest that more research is needed before conclusions can be drawn about the benefit of omega-3 fatty acids for schizophrenia. Similar to diabetes, individuals with schizophrenia may not be able to convert ALA to EPA or DHA efficiently.

Attention deficit/hyperactivity disorder (ADHD)

Children with attention deficit/hyperactivity disorder (ADHD) may have low levels of certain essential fatty acids (including EPA and DHA) in their bodies. In a clinical study of nearly 100 boys, those with lower levels of omega-3 fatty acids demonstrated more learning and behavioral problems (such as temper tantrums and sleep disturbances) than boys with normal omega-3 fatty acid levels. In animal studies, low levels of omega-3 fatty acids have been shown to lower the concentration of certain brain chemicals (such as dopamine and serotonin) related to attention and motivation. Clinical studies that examine the ability of omega-3 supplements to improve symptoms of ADHD are still needed. At this point in time, eating foods high in omega-3 fatty acids is a reasonable approach for someone with ADHD. A clinical study used omega-3 and omega-6 fatty acid supplementation in 117 children with ADHD. They study found significant improvements in reading, spelling, and behavior in the children over the 3 months of therapy. Another clinical study found that omega-3 fatty acid supplementation helped to decrease physical aggression in school children with ADHD. More studies, including comparisons with drug therapies (such as stimulants), should be performed.

Eating disorders

Clinical studies suggest that men and women with anorexia nervosa have lower than optimal levels of polyunsaturated fatty acids (including ALA and GLA). To prevent the complications associated with essential fatty acid deficiencies, some experts recommend that treatment programs for anorexia nervosa include PUFA-rich foods such as fish and organ meats (which include omega-6 fatty acids).

Burns

Essential fatty acids have been used to reduce inflammation and promote wound healing in burn victims. Animal research indicates that omega-3 fatty acids help promote a healthy balance of proteins in the body -- protein balance is important for recovery after sustaining a burn. Further research is necessary to determine whether omega-3s benefit people in the same way.

Skin disorders

In one clinical study, 13 people with a particular sensitivity to the sun known as photo dermatitis showed significantly less sensitivity to UV rays after taking fish oil supplements. Still, research indicates that topical sunscreens are much better at protecting the skin from damaging effects of the sun than omega-3 fatty acids. In another study of 40 people with psoriasis, those who were treated with medications and EPA supplements did better than those treated with the medications alone. In addition, many clinicians believe that flaxseed (which contains omega-3 fatty acids) is helpful for treating acne.

Inflammatory bowel disease (IBD)

When added to medication, such as sulfasalazine (a standard medication for IBD), omega-3 fatty acids may reduce symptoms of Crohn's disease and ulcerative colitis -- the 2 types of IBD. More studies to investigate this preliminary finding are under way. In animals, it appears that ALA works better at decreasing bowel inflammation than EPA and DHA. Plus, fish oil supplements can cause side effects that are similar to symptoms of IBD (such as flatulence, belching, bloating, and diarrhea).

Asthma

Clinical research suggests that omega-3 fatty acid supplements (in the form of perilla seed oil, which is rich in ALA) may decrease inflammation and improve lung function in adults with asthma. Omega-6 fatty acids have the opposite effect: they tend to increase inflammation and worsen respiratory function. In a small, well-designed clinical study of 29 children with asthma, those who took fish oil supplements rich in EPA and DHA for 10 months had improvement in their symptoms compared to children who took a placebo pill.

Macular Degeneration

A questionnaire administered to more than 3,000 people over the age of 49 found that those who consumed more fish in their diet were less likely to have macular degeneration (a serious age-related eye condition that can progress to blindness) than those who consumed less fish. Similarly, a clinical study comparing 350 people with macular degeneration to 500 without the eye disease found that those with a healthy dietary balance of omega-3 and omega-6 fatty acids and higher intake of fish in their diets were less likely to have this particular eye disorder. Another larger clinical study confirms that EPA and DHA from fish, 4 or more times per week, may reduce the risk of developing macular degeneration. Notably, however, this same study suggests that ALA may actually increase the risk of this eye condition.

Menstrual pain

In a clinical study of nearly 200 Danish women, those with the highest dietary intake of omega-3 fatty acids had the mildest symptoms, such as hot flashes and increased sweating, during menstruation.

Colon cancer

Consuming significant amounts of foods rich in omega-3 fatty acids appears to reduce the risk of colorectal cancer. For example, Eskimos, who tend to follow a high-fat diet but eat significant amounts of fish rich in omega-3 fatty acids, have a low rate of colorectal cancer. Animal studies and laboratory studies have found that omega-3 fatty acids prevent worsening of colon cancer while omega-6 fatty acids promote the growth of colon tumors. Daily consumption of EPA and DHA also appeared to slow or even reverse the progression of colon cancer in people with early stages of the disease.

Clinical studies have reported that low levels of omega-3 fatty acids in the body are a marker for an increased risk of colon cancer.

However, in an animal study of rats with metastatic colon cancer (in other words, cancer that has spread to other parts of the body such as the liver), omega-3 fatty acids actually promoted the growth of cancer cells in the liver. Until more information is available, it is best for people with advanced stages of colorectal cancer to avoid omega-3 fatty acid supplements and diets rich in this substance.

Breast cancer

Although not all experts agree, women who regularly consume foods rich in omega-3 fatty acids over many years may be less likely to develop breast cancer. In addition, the risk of dying from breast cancer may be significantly less for those who eat large quantities of omega-3 from fish and brown kelp seaweed (common in Japan). This is particularly true among women who substitute fish for meat. The balance between omega-3 and omega-6 fatty acids appears to play an important role in the development and growth of breast cancer. Further research is still needed to understand the effect that omega-3 fatty acids may have on the prevention or treatment of breast cancer. For example, researchers speculate that omega-3 fatty acids in combination with other nutrients (namely, vitamin C, vitamin E, beta-carotene, selenium, and coenzyme Q10) may prove to be of particular value for preventing and treating breast cancer.

Prostate cancer

Laboratory and animal studies indicate that omega-3 fatty acids (specifically, DHA and EPA) may inhibit the growth of prostate cancer. Similarly, population based clinical studies of groups of men suggest that a low-fat diet with the addition of omega-3 fatty acids from fish or fish oil help prevent the development of prostate cancer. Like breast cancer, the balance of omega-3 to omega-6 fatty acids appears to be particularly important for reducing the risk of this condition. ALA, however, may not offer the same benefits as EPA and DHA. In fact, one recent clinical study evaluating 67 men with prostate cancer found that they had higher levels of ALA compared to men without prostate cancer. More research in this area is needed.

Other

Although further research is needed, preliminary evidence suggests that omega-3 fatty acids may also prove helpful in protecting against certain infections and treating a variety of conditions, including autism, ulcers, migraine headaches, preterm labor, emphysema, psoriasis, glaucoma, Lyme disease, systemic lupus erythmatosus (lupus), irregular heart beats (arrhythmias), multiple sclerosis, and panic attacks. Omega-3 fatty acid supplementation may also help to reduce stress and the effects it has on the body.

Dietary Sources

Fish, plant, and nut oils are the primary dietary source of omega-3 fatty acids. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are found in cold-water fish such as salmon, mackerel, halibut, sardines, tuna, and herring. ALA is found in flaxseeds, flaxseed oil, canola (rapeseed) oil, soybeans, soybean oil, pumpkin seeds, pumpkin seed oil, purslane, perilla seed oil, walnuts, and walnut oil. Other sources of omega-3 fatty acids include sea life such as krill and algae.

Available Forms

In addition to the dietary sources described, EPA and DHA can be taken in the form of fish oil capsules. Flaxseed, flaxseed oil, fish and krill oils should be kept refrigerated. Whole flaxseeds must be ground within 24 hours of use, otherwise the ingredients lose their activity. Flaxseeds are also available in ground form in a special mylar package so that the components in the flaxseeds stay active.

Be sure to buy omega-3 fatty acid supplements made by established companies who certify that their products are free of heavy metals such as mercury, lead, and cadmium.

How to Take It

Dosing for fish oil supplements should be based on the amount of EPA and DHA in the product, not on the total amount of fish oil. Supplements vary in the amounts and ratios of EPA and DHA. A common amount of omega-3 fatty acids in fish oil capsules is 0.18 grams (180 mg) of EPA and 0.12 grams (120 mg) of DHA. Five grams of fish oil contains approximately 0.17 - 0.56 grams (170 -560 mg) of EPA and 0.072 - 0.31 grams (72 - 310 mg) of DHA. Different types of fish contain variable amounts of omega-3 fatty acids, and different types of nuts or oil contain variable amounts of a-linolenic acid. Fish oils contain approximately 9 calories per gram of oil.

Children (18 years and younger)

The precise safe and effective doses of all types of omega-3 fatty acid supplements in children have not been established. Omega-3 fatty acids are used in some infant formulas, although effective doses are not clearly established. Ingestion of fresh fish should be limited in young children due to the presence of potentially harmful environmental contaminants, including mercury. Fish oil capsules should not be used in children except under the direction of a health care provider.

Adults

Individuals taking more than 3 grams daily of omega-3 fatty acids from capsules should do so only under the supervision of a health care provider due to an increase risk of bleeding.

For healthy adults with no history of heart disease: The American Heart Association (AHA) recommends eating fish at least 2 times per week.

For adults with coronary heart disease: The American Heart Association (AHA) recommends an omega-3 fatty acid supplement (as fish oils), 1 gram daily of EPA and DHA. It may take 2 - 3 weeks for benefits of fish oil supplements to be seen.

For adults with high cholesterol levels: The American Heart Association (AHA) recommends an omega-3 fatty acid supplement (as fish oils), 2 - 4 grams daily of EPA and DHA. It may take 2 - 3 weeks for benefits of fish oil supplements to be seen.

Precautions

Because of the potential for side effects and interactions with medications, dietary supplements should be taken only under the supervision of a knowledgeable health care provider.

Omega-3 fatty acids should be used cautiously by people who bruise easily, have a bleeding disorder, or take blood-thinning medications, including warfarin (Coumadin) or clopidogrel (Plavix), because excessive amounts of omega-3 fatty acids may lead to bleeding. In fact, people who eat more than three grams of omega-3 fatty acids per day (equivalent to 3 servings of fish per day) may be at an increased risk for hemorrhagic stroke, a potentially fatal condition in which an artery in the brain leaks or ruptures.

Fish oil can cause flatulence, bloating, belching, and diarrhea. Time-release preparations may reduce these side effects, however.

People with either diabetes or schizophrenia may lack the ability to convert alpha-linolenic acid (ALA) to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the forms more readily used in the body. Therefore, people with these conditions should obtain their omega-3 fatty acids from dietary sources rich in EPA and DHA. Also, individuals with type 2 diabetes may experience increases in fasting blood sugar levels while taking fish oil supplements. If you have type 2 diabetes, only use fish oil supplements under the supervision of a health care provider.

Although studies have found that regular consumption of fish (which includes the omega-3 fatty acids EPA and DHA) may reduce the risk of macular degeneration, a recent study including 2 large groups of men and women found that diets rich in ALA may substantially increase the risk of this disease. More research is needed in this area. Until this information becomes available, it is best for people with macular degeneration to obtain omega-3 fatty acids from sources of EPA and DHA, rather than ALA.

Similar to macular degeneration, fish and fish oil may protect against prostate cancer, but ALA may be associated with increased risk of prostate cancer in men. More research in this area is needed.

Fish (and fish oil supplements) may contain potentially harmful contaminants, such as heavy metals (including mercury), dioxins, and polychlorinated biphenyls (PCBs). For sport-caught fish, the U.S. Environmental Protection Agency (EPA) recommends that intake be limited in pregnant or nursing women to a single 6-ounce meal per week, and in young children to less than 2 ounces per week. For farm-raised, imported, or marine fish, the U.S. Food and Drug Administration recommends that pregnant or nursing women and young children avoid eating types with higher levels of mercury (such as mackerel, shark, swordfish, or tilefish), and less than 12 ounces per week of other fish types. Unrefined fish oil preparations may contain pesticides.

Possible Interactions

If you are currently being treated with any of the following medications, you should not use omega-3 fatty acid supplements, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and alpha-linolenic acid (ALA), without first talking to your health care provider.

Blood-thinning medications -- Omega-3 fatty acids may increase the effects of blood thinning medications, including aspirin, warfarin (Coumadin), and clopedigrel (Plavix). While the combination of aspirin and omega-3 fatty acids may actually be helpful under certain circumstances (such as in heart disease), they should only be taken together under the guidance and supervision of a health care provider.

Blood sugar lowering medications -- Taking omega-3 fatty acid supplements may increase fasting blood sugar levels. Use with caution if taking blood sugar lowering medications, such as glipizide (Glucotrol and Glucotrol XL), glyburide (Micronase or Diabeta), glucophage (Metformin), or insulin, as omega-3 fatty acid supplements may increase your need for the medication(s).

Cyclosporine -- Taking omega-3 fatty acids during cyclosporine (Sandimmune) therapy may reduce toxic side effects, such as high blood pressure and kidney damage, associated with this medication in transplant patients.

Etretinate and topical steroids -- The addition of omega-3 fatty acids (specifically EPA) to the drug therapy etretinate (Tegison) and topical corticosteroids may improve symptoms of psoriasis.

Cholesterol-lowering medications -- Following certain nutritional guidelines, including increasing the amount of omega-3 fatty acids in your diet and reducing the omega-6 to omega-3 ratio, may allow a group of cholesterol lowering medications known as "statins", including atorvastatin (Liptor), lovastatin (Mevacor), and simvastatin (Zocor) to work more effectively.

Nonsteroidal anti-inflammatory drugs (NSAIDs) -- In an animal study, treatment with omega-3 fatty acids reduced the risk of ulcers from nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen (Motrin or Advil) and naproxen (Alleve or Naprosyn). More research is needed to evaluate whether omega-3 fatty acids would have the same effects in people.

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Review Date:
5/1/2007
Reviewed By:
Ernest B. Hawkins, MS, BSPharm, RPh, Health Education Resources; and Steven D. Ehrlich, N.M.D., private practice specializing in complementary and alternative medicine, Phoenix, AZ. Review provided by VeriMed Healthcare Network.

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Ovarian cancer

FitSugar — Wed, 08 Oct 2008 17:34:58 -0700

In This Report

Highlights
Introduction
Symptoms
Causes
Prevention
Diagnosis
Prognosis
Treatment
Surgery
Medications
Radiation Therapy
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Ovarian Cancer Symptoms

Even early-stage ovarian cancer can produce symptoms, according to a 2007 consensus statement issued by the American Cancer Society, the Gynecologic Cancer Foundation, and the Society of Gynecologic Oncologists. Because ovarian cancer can grow very rapidly, early detection is extremely important. Contact your doctor (preferably a gynecologist) if you experience these symptoms on a daily basis for more than a few weeks:

Bloating
Pelvic or abdominal pain
Difficulty eating or feeling full quickly
Urgent or frequent urination

Hormone Replacement Therapy (HRT) Increases Ovarian Cancer Risk

Post-menopausal women who use hormone replacement therapy (HRT) for more than 5 years are 20% more likely to develop ovarian cancer than women who do not use HRT, suggests a 2007 study in the Lancet. Researchers analyzed data from more than 1 million women.
A similar association between HRT use and ovarian cancer, especially for women who have not had a hysterectomy, was reported in a 2006 study in the Journal of the National Cancer Institute.

Surgery

About 1 in 3 women with ovarian cancer fail to receive recommended surgical treatment, according to a 2007 study in Cancer. The study found that women who are poor, African-American or Hispanic, or over age 70 are least likely to receive adequate care. Another Cancer study suggested that although experienced cancer centers may cost more than other facilities, they are more cost-effective over the long term than less experienced medical facilities.
For optimal ovarian cancer treatment, it is best to seek care from an experienced gynecologic oncologist and specialized cancer center.

Investigational Drugs

Aflibercept (VEGF-TRAP), an experimental anti-angiogenesis drug, may benefit patients with epithelial ovarian cancer who have not been helped by platinum-based chemotherapy, according to interim results of a Phase II study presented at the 2007 annual meeting of the American Society of Clinical Oncology. Anti-angiogenesis drugs prevent tumors from growing and spreading by starving them of their blood supply.

Introduction

The ovaries are two small, almond-shaped organs located on either side of the uterus. They are key components of a woman's reproductive system:

Ovaries store 200,000 - 400,000 follicles, tiny sacs that are present from birth, that nurture immature eggs (ova).
During each normal (usually monthly) reproductive cycle, a follicle in one ovary bursts and releases a mature or "ripened" egg. The egg travels down the fallopian tube into the uterus, where it either is fertilized by a man's sperm or, if unfertilized, breaks down and is excreted as part of the menstrual cycle.
Ovaries also secrete the important reproductive hormones estrogen and progesterone.

The uterus, commonly called the womb, is a hollow muscular organ located in the female pelvis between the bladder and rectum. The ovaries produce the eggs that travel through the fallopian tubes. Once the egg has left the ovary it can be fertilized and implant itself in the lining of the uterus. The main function of the uterus is to nourish the developing fetus prior to birth.

Ovarian cancers are potentially life-threatening malignancies that develop in one or both ovaries. Malignant ovarian tumors generally fall into three primary classes:

Epithelial tumors
Germ cell tumors
Stromal tumors

Epithelial Tumors. Epithelial tumors account for up to 90% of all ovarian cancers and therefore are the primary focus of this report. These cancers develop in a layer of cube-shaped cells known as the germinal epithelium, which surrounds the outside of the ovaries.

Germ Cell Tumors. Germ cell tumors, which account for about 3% of all ovarian cancers, are found in the egg-maturation cells of the ovary. They occur most often in teenagers and young women. Although they progress rapidly, they are very sensitive to treatments. About 90% of patients with germ cell malignancies can be cured, often preserving fertility.

Stromal Tumors. Stromal tumors, which account for 6% of all ovarian cancers, develop from connective tissue cells that hold the ovary together and that produce the female hormones, estrogen and progesterone. Stromal tumors do not usually spread, in which case the prognosis is good. If they spread, however, they can be more difficult to treat than others.

Click the icon to see an image of ovarian cancer.

Ovarian cancer is called the silent killer because it progress almost silently, with vague symptoms. By the time symptoms do appear, the ovarian tumor may have grown large enough to shed cancer cells throughout the abdomen. At such an advanced stage, the cancer is more difficult to cure.

Ovarian cancer cells that have spread outside the ovaries are referred to as metastatic ovarian cancers. Ovarian tumors tend to spread to the following locations:

Diaphragm
Intestine
Omentum (a fatty layer that covers and pads organs in the abdomen)

Cancer cells can also spread to other organs through lymph channels and the bloodstream.

Not all ovarian tumors are malignant. Benign cysts, dermoid tumors, and borderline malignant tumors all are distinct from ovarian cancer.

Benign Cysts. Benign cysts are common. They typically develop in one of two ways:

Follicular Cysts. During normal ovulation, follicles (the little sacs in the ovary) expel eggs. If the egg is not expelled, fluids and other substances can build up inside the follicle, forming a follicular cyst.
Corpus Luteum Cysts. Benign cysts may form when an egg has been released, but the emptied follicle (now called the corpus luteum) does not break down normally, instead filling with blood from nearby blood vessels.

Both follicular cysts and corpus luteum cysts are normal parts of the menstrual cycle and nearly always resolve within one or two cycles without treatment.

Dermoid Tumors. Dermoid tumors are benign growths that occur when an egg begins to develop without fertilization by a sperm; they can contain hair, teeth, and cartilage. They are easily removed by surgery.

Borderline Ovarian Tumors. About 15% of ovarian tumors are referred to as "borderline" because their appearance and behavior under the microscope is between benign and malignant. These tumors are often referred to as carcinomas of low malignant potential because they rarely metastasize or cause death. Even when borderline carcinomas do spread outside the ovary, only 10 - 20% are fatal.

Symptoms

Ovarian cancer used to be considered a “silent killer." Symptoms were thought to appear only when the cancer was in an advanced stage. Now, experts know this is not true -- even early-stage ovarian cancer can produce symptoms.

In June 2007, the Gynecologic Cancer Foundation, the Society of Gynecologic Oncologists, and the American Cancer Society released a consensus statement concerning ovarian cancer symptoms. If you have the following symptoms on a daily basis for more than a few weeks, you should see your doctor (preferably a gynecologist):

Bloating
Pelvic or abdominal pain
Difficulty eating or feeling full quickly

Ovarian cancer grows quickly and can progress from early to advanced stages within a year. Paying attention to symptoms can help improve a woman's chances of being diagnosed and treated promptly. Detecting cancer while it is still in its earliest stages can help improve prognosis. Even a few months delay in detection may affect survival.

Other symptoms are also sometimes associated with ovarian cancer. These symptoms include fatigue, indigestion, back pain, pain during intercourse, constipation, and menstrual irregularities. However, according to experts, these symptoms are not as useful in diagnosing ovarian cancer, because they are also commonly experienced by women who do not have cancer.

Based on the symptoms and physical examination, the doctor may order pelvic imaging tests or a CA-125 blood test. If these tests reveal signs of cancer, patients should be referred to a gynecologic oncologist or a surgeon who specializes in female reproductive system cancers.

Causes

About 22,430 new cases of ovarian cancer are expected in the United States in 2007. Evidence suggests that the incidence of ovarian cancer is declining. The average age for the onset of ovarian cancer is about 60, although ovarian cancer can develop in women from the ages of 20 - 90. The lifetime risk of ovarian cancer in women with no family history of the disease is approximately one in 70 (1.4%).

Women with a history of ovarian cancer in one first-degree relative (mother or sister) have an overall 5% risk of developing the disease, but it may be higher in women with specific genetic factors. The majority of women with ovarian cancer have no family history of the disease, however, meaning that genetic inheritance is not the only risk factor.

Genetic mutations causing abnormal cell growth and differentiation are the basis for all cancer. The great majority of genetic defects that cause cancer are due to unknown causes. Most likely overexposure to environmental assaults, or errors that occur during cell division, play a role in many cases.

Several circumstances that create hormonal changes may increase the risk of ovarian cancer.

Number of Ovulations. Risk of ovarian cancer is directly related to the number of times a woman ovulates, which is indicated by the total number of menstrual periods she has had. A lower number of ovulations occur when the menstrual periods are shut off (as in pregnancy), so the risk of developing ovarian cancer is reduced.

The following women have a lower risk for ovarian cancer:

Women with a history of multiple pregnancies.
Women who took birth control pills (these shut off the menstrual period).
Women who breast-fed. (The body usually does not release eggs while a woman is breast-feeding.)

Some researchers theorize that ovarian cancer develops in women with a higher number of ovulations because of persistent damage to the epithelial cells as the egg passes through during ovulation. Researchers postulate that the recurring cell division needed to heal these tiny wounds to the ovaries, month after month and year after year, creates opportunities for errors in cell reproduction that lead to the formation of cancerous cells. Therefore, the more ovulations, the more risk of ovarian cancer. Ovulation temporarily ceases during pregnancy, breast-feeding, and birth control pill use.

Gonadotropins and Fertility Drugs. Gonadotropins are hormones produced in the pituitary gland that stimulate the ovaries to secrete estrogen and cause the follicles to produce and release eggs.

The pituitary is a gland attached to the base of the brain which secretes hormones that govern the onset of puberty, sexual development and reproductive function.

In a few studies, elevated levels of gonadotropins have been associated with an increased risk for ovarian cancer. These hormones are the basis for many fertility drugs, including human menopausal gonadotropin (Pergonal, Repronal, Metrodin) and clomiphene (Clomid, Serophene). Although there has been concern about an increased risk for ovarian cancers in women, a growing body of evidence is finding no higher risk from the drugs themselves. Instead, evidence suggests that ovarian cancers are most likely caused by factors contributing to the infertility -- not the drugs used to treat it.

Hormone Replacement Therapy. Hormone replacement therapy (HRT) appears to increase the risk for ovarian cancer. A 2007 UK study of nearly 1 million women found that women who used HRT for more than 5 years were 20% more likely to develop and die from ovarian cancer than women who had never taken HRT. Another important study, from the U.S. National Cancer Institute, indicated that 5 or more years of combination HRT (estrogen and progestin) increases the risk of ovarian cancer for women who have not had a hysterectomy.

Family history plays a role in 5 - 10% of women who have ovarian cancer. Certain genes are being investigated and identified that are responsible for some of these cases. Depending on the particular genetic type, the lifetime risk for ovarian cancer in women who carry these genes ranges from 16 - 65%.

BRCA1 and 2 Genes. Inherited mutations in genes known as BRCA1 or BRCA2 are now believed to be responsible for 30 - 50% of breast cancers, ovarian cancers, or both in patients with a strong family history of these cancers.

According to some studies, the risks are as follows:

Studies indicate that about 25 - 40% of women who carry the abnormal BRCA1 gene may develop ovarian cancer.
The risk for women with the BRCA2 gene mutation is generally believed to be lower, about 9 - 15%.

The mutated genes are linked to an even higher risk for developing breast cancer. These mutations are present in only about 0.5% of the U.S. population overall but occur in about 2.5% of all Jewish women of Eastern European (Ashkenazi) descent. These mutations are not restricted to the Ashkenazi population and may occur in women of any ethnicity, including women of Asian and African descent.

Either a mother or father can pass down BRCA mutations to the daughter. These mutations may also occur in 5 - 10% of ovarian cancer patients who have no family history of breast or ovarian cancer. A number of studies have suggested that women with BRCA-mutated ovarian cancers tend to have better survival rates than other women.

A 2005 study in the Journal of the National Cancer Institute indicated that women who have a family history of breast cancer, but no history of BRCA genetic mutations, are not at increased risk for ovarian cancer.

Other Genetic Mutations. Women who carry the hereditary nonpolyposis colorectal cancer (HNPCC) gene have about a 9% chance of developing ovarian cancer.

Risk Factors for Inherited Ovarian Cancer. Women are considered at high risk for ovarian cancer if they have:

A first-degree relative (mother, sister, or daughter) with ovarian cancer at any age. The risk increases with the number of affected first-degree relatives.
A first-degree relative (or two second-degree relatives on the same side) with early onset breast cancer (occurring before age 50).
A family member with both breast and ovarian cancer.
A family history of male breast cancer (which might indicate a BRCA2 mutation).
A family history of hereditary nonpolyposis colorectal cancer.

When a woman describes her family history to her doctor, she should include the history of cancer in women on both the mother's and the father's side. Both are significant.

Screening High-Risk Women. It is now possible to test for genetic mutations in the BRCA1 and BRCA2 genes and for hereditary nonpolyposis colorectal cancer (HNPCC) and Peutz-Jeghers syndrome in high-risk women. Any positive result raises difficult issues:

The presence of a mutation in any of these genes does not predict with absolute certainty that either breast cancer or ovarian cancer will occur. The lifetime risk for BRCA1, for example, is significantly higher (up to 40%) than for BRCA2 (about 10 - 15%).
Surgical preventive strategies, which can involve both mastectomy and removal of the ovaries, do not completely eliminate the risk for cancer, since malignant cells may occur in nearby regions. Removal of the ovaries will reduce ovarian cancer risk, however, and may also reduce breast cancer risk in mutation carriers.

Screening Guidelines for BRCA Genes. In 2005, the U.S. Preventive Services Task Force (USPSTF) released updated guidelines for BRCA testing. While women at high risk should be tested, the USPSTF does not recommend routine genetic counseling or testing for BRCA genes in low-risk women (no family history of BRCA1 or BRCA2 genetic mutations).

Most ovarian cancers are the result of genetic mutations that are not inherited but occur from environmental or other factors that cause damage to genetic material over time. Such genetic changes are referred to as sporadic (as opposed to inherited). Genetic alterations that have been observed in ovarian cancers involve the p53 tumor suppressor gene, the HER2/neu gene, and the PIC3KA gene.

Some research indicates that ovarian cancer occurs more often in North America and Northern Europe and among middle-to-upper socioeconomic class women from highly industrialized countries. Ovarian cancer is also much more common in Caucasian women than in African-American women. Japan has a low, but rising, number of ovarian cancer cases. One study observed that when Japanese women immigrate to the United States, they and their daughters have an incidence of ovarian cancer that approaches that of Caucasian women, although another study did not support such findings.

Pregnancy. Women who have never had children are more likely to develop ovarian cancer than women who have had children. The more children a woman has had, the lower her risk for ovarian cancer.

Obesity. Obesity may increase the risk of developing more aggressive types of ovarian tumors. A 2006 study indicated that a higher body mass index was associated with poorer survival.

Endometriosis. Women with endometriosis may have some higher risk for ovarian cancer. However, endometriosis is very common and ovarian cancer is not, so the risk is still very low. Some research suggests that ovarian cancer associated with endometriosis may differ from most ovarian cancer cases and, in fact, have a better outlook.

Click the icon to see an image of endometriosis.

Fat Intake. Fats have been under scrutiny for some time for putting some women at higher risk for ovarian cancer. A review study reported an association between a high intake in animal fats and a greater risk. However, other studies on this subject have found no correlation between fat intake and ovarian cancer.

Prevention

No specific lifestyle factors are proven to protect against ovarian cancer, although the following study results suggest some lower or higher risk:

Some studies have suggested a lower rate of ovarian cancer in women who eat a diet rich in vegetables. The American Cancer Society recommends that women eat 5 servings of fruits and vegetables a day, and limit consumption of high-fat red meat.
A 2005 study of more than 61,000 women suggested that tea consumption may reduce the risk of ovarian cancer. Women in the study who drank at least 2 cups of tea a day (mainly black tea) had a lower risk of ovarian cancer than women who did not drink tea.
Exercise, which protects against many diseases and even some cancers, appears to have no effect on ovarian cancer. However, obesity is associated with poorer ovarian cancer survival. Women who are obese also have a higher risk for breast cancer. Regular exercise is a good idea in any case.
Smokers should quit. Although evidence of an association with ovarian cancer is weak, it is always wise to stop smoking.

In general, factors or behaviors that limit stimulation of the ovaries or inhibit ovulation appear to be protective.

Pregnancy. The more times a woman has been pregnant the less likely she is to develop ovarian cancer. One study indicated that ovarian cancer was reduced by 40% with one pregnancy and by an additional 14% with each subsequent pregnancy.

Breast-feeding. Breast-feeding, even for only 1 - 2 months, may also reduce the risk for ovarian cancer by as much as 40%. A longer duration of breast-feeding does not appear to increase its protective benefits.

Oral Contraceptives and Progestin. Studies have suggested that routine use of birth control pills that contain the female hormones estrogen and progestin, even low-dose forms, reduces a woman's risk of ovarian cancer by about 50% when compared to women who have never taken oral contraceptives. The longer a woman takes oral contraceptives the greater the protection and the longer protection lasts after stopping oral contraceptives.

Click the icon to see an illustrated series detailing the birth control pill.

Pregnant women or women with breast cancer should not take birth control pills. Other conditions that may preclude taking oral contraceptives include:

Liver disease
Migraines
Coronary artery disease and any risk factors for heart disease or stroke (particularly smoking, obesity, high blood pressure, blood clotting disorders, or diabetes)

Tubal Ligation. Tubal ligation, a method of sterilization that ties off the fallopian tubes, has been associated with a decreased risk for ovarian cancer in some -- but not all -- studies.

Click the icon to see an image of tubal ligation.

Surgical removal of the ovaries, called oophorectomy, significantly reduces the risk for ovarian cancer. When it is used to specifically prevent ovarian cancer in high-risk women, the procedure is called a prophylactic oophorectomy. Prophylactic oophorectomy is approximately 95% protective against ovarian cancer. It is sometimes recommended for women at high risk for ovarian cancer. These women generally have the BRCA1 or BRCA2 genetic mutation, or have two or more first-degree relatives who have had ovarian cancer.

Bilateral oophorectomy is the removal of both ovaries. Bilateral salpingo-oophorectomy is the removal of both fallopian tubes plus both ovaries. Several recent studies indicate that salpingo-oophorectomy is very effective in reducing risk for ovarian cancer in women who carry the BRCA1 or BRCA2 mutation.

A 2006 Journal of the American Medical Association study reported that bilateral salpingo-oophorectomy reduces ovarian cancer risk by 80% for women with certain mutations in the BRCA1 and BRCA2 genes. A study presented at the 2006 meeting of the American Society of Clinical Oncology (ASCO) indicated that this procedure is most effective for reducing ovarian cancer risk in women with the BRCA1 gene mutation. For women with BRCA2 gene mutation, the procedure was better at reducing the risk for breast cancer.

Even after oophorectomy, women in high-risk groups for ovarian cancer still have a risk for the development of cancer in the peritoneum (the sac inside the abdomen that holds the intestines, uterus, and ovaries).

Premenopausal women should realize that oophorectomy causes immediate menopause, which poses a risk for several health problems, including osteoporosis, heart disease, and reduction in muscle tone. Estrogen replacement can help offset these problems. Women who have a bilateral oophorectomy and do not receive hormone replacement therapy may experience more severe hot flashes than women who enter menopause naturally.

Diagnosis

Up to 95% of women diagnosed with ovarian cancer will survive longer than 5 years if their cancers are treated before they have spread beyond the ovaries. Unfortunately, there are no screening tests for ovarian cancer that are the equivalent to mammography for early detection of breast cancer. Therefore, only about 25% of ovarian cancer cases are diagnosed at such early stages. It is possible to perform genetic screening in high-risk women, but this raises some complex issues.

Every woman should have a regular annual examination with her doctor that includes:

Pelvic examination. Routine exams called bimanual pelvic examinations are a reasonable precaution, although they are not perfect screening methods due to their low sensitivity. This exam can be performed two ways. In the more common method, the doctor inserts two fingers into the vagina while palpating the abdomen with the other hand. The other method, called a bimanual rectovaginal exam, involves the insertion of one finger into the vagina and another into the rectum.

Either exam enables the doctor to assess the size of the ovaries as well as the contour and mobility of the uterus and to feel for masses and growths. The rectovaginal exam may reveal rectal lesions that may otherwise go unnoticed and is particularly important for women over 50. A mass felt on pelvic exam often requires further evaluation by ultrasound and sometimes requires surgery to make a definitive diagnosis.

Pap smear. This test is specifically designed to detect cervical cancer. In very rare instances, however, it may reveal abnormal ovarian cells, which might indicate the presence of an ovarian cancer.

Click the icon to see an image of a pap smear.

Unfortunately, ovarian cancer rarely produces changes that are detectable during a regular checkup.

An estimated 290,000 women are hospitalized each year in the United States because of ovarian growths or lesions. Many more women find out about some ovarian abnormality during their annual Ob/Gyn check up. The vast majority of conditions are noncancerous. They include:

Benign functional ovarian cysts
Abscesses and infection
Fibroids

Click the icon to see an image of a fibroid tumor.

Endometriosis
Polycystic ovaries

Click the icon to see an image of a polycystic ovary.

Ectopic pregnancies

Click the icon to see an image of an ectopic pregnancy.

Meig syndrome (which involves a benign ovarian growth associated with fluid buildup in the abdomen and around the lungs)
Ovarian hyperstimulation syndrome following fertility treatments.

Once a growth is detected, additional tests [below] may help the doctor gauge the risk for it being cancerous.

Ultrasound. Ultrasound is a noninvasive diagnostic tool that can evaluate tumors and masses discovered during the rectovaginal exam:

Typically, a probe is placed in the vagina and emits sound waves (ultrasound). The sound waves bounce off tissues, organs, and masses in the pelvic cavity. These echoes are collected and converted into a picture of the area called a sonogram.

Click the icon to see an image of transvaginal ultrasound.

The ultrasound probe may also be placed on abdominal walls above the ovaries (transabdominal ultrasound), but it does not provide as clear a picture of the ovaries. Healthy tissue, fluid-filled cysts, and solid tumors produce different sound waves.

Ultrasound is not helpful for identifying early-stage ovarian cancer in high-risk women. (Researchers hope that blood tests for protein markers may eventually provide a better method for diagnosing early-stage ovarian cancer.) In addition, ultrasound does not provide enough specific information to reliably determine which abnormal masses are cancerous or noncancerous.

Studies suggest that small so-called simple cysts (fluid-filled without an associated mass) are usually noncancerous, particularly when they appear in premenopausal women whose blood tests for the protein CA-125 are normal. Such women are sometimes given oral contraceptives and observed for a few months to see if the cyst goes away.
Postmenopausal women with small simple cysts and normal CA-125 levels may sometimes be observed for a time if they have no other risk factors or symptoms of ovarian cancer.
In contrast, a "complex" cyst (one that shows a mass or other abnormalities) is often surgically removed, since it has a higher chance of being malignant. Only a small percentage of these cysts turn out to be cancerous. (In one study 6% of complex cysts were actually cancerous.)

Click the icon to see an image of an ovarian cyst.

Other Imaging Techniques. Other imaging techniques are less common for the diagnosis or evaluation of suspected ovarian cancer but may help determine if cancer has spread to other parts of the body:

Computed tomography (CT). Computed tomography records x-ray absorption rates of tissue and bone. These data is converted into clear images on a screen. CT scans help determine if cancer has spread to the lymph nodes, abdominal organs, abdominal fluid, and the liver.

Click the icon to see an image of a CT scan.

Magnetic resonance imaging (MRI). MRI creates multiple cross-sectional images of the pelvis and abdominal organs, which are assembled into three-dimensional images. An MRI is not usually used to diagnose ovarian cancer, but may help determine if cancer has spread to the brain or spinal cord.

Click the icon to see an image of a MRI scan.

Chest x-rays. Find cancer that has spread to the lungs.

Click the icon to see an image of an x-ray machine.

CA-125 is a protein that is secreted by ovarian cancer cells and is elevated in over 80% of patients with ovarian cancer. The CA-125 blood test is not approved for screening in the general population. Oncologists will usually only obtain a blood test for this protein if ovarian cancer is strongly suspected or has been diagnosed. In general, a CA-125 level is considered to be normal if it is less than 35 U/mL (microns per milliliter). The test may also be useful for evaluating tumor growth and predicting survival in patients with recurrent cancer who have been treated with topotecan or paclitaxel-carboplatin chemotherapy regimens.

The test is not useful for diagnosis or early screening, however. In about half of women with very early ovarian cancer, CA-125 levels are not elevated above the normal standard at all. Furthermore, an elevated level can be caused by a number of other conditions including:

Endometriosis (which may be a risk factor for ovarian cancer)
Fibroids
Noncancerous ovarian cysts
Pregnancy
Pelvic inflammatory disease
Liver diseases
Other tumors, such as breast, colon, lung, and pancreatic cancers
Age and menstrual status can also affect the levels of CA-125

Research is under way to find better tests that will detect this cancer in early stages.

Proteomics. A promising new approach relies on a technique called proteomics. Proteomics is the analysis of certain proteins. In this approach, researchers are looking at a unique pattern of proteins produced by ovarian cancer cells. Studies suggest this set of proteins serves as an early biomarker for detecting ovarian cancer. Scientists at the National Cancer Institute (NCI) and Food and Drug Administration (FDA) have developed a blood test to check for the presence of these abnormal proteins. In one study, the proteomics tool identified 100% of patients with ovarian cancer and incorrectly diagnosed cancer in only 3 out of 66 of women who were actually cancer-free. A clinical trial is now under way comparing the proteomics test to the CA-125 test. OvaCheck, another investigational ovarian cancer blood test, is based on principles similar to the NCI and FDA platform, but is being developed independently by a private corporation.

Osteopontin. Scientists are also looking into the possibility that the protein osteopontin may be a biomarker for ovarian cancer. Studies have shown that osteopontin is overexpressed in tumors and serum of women with ovarian cancer.

Other Biomarkers. Researchers have also had preliminary success with a blood test that measures osteopontin along with three additional protein markers in blood: leptin, prolactin, and insulin-like growth factor-II. In early trials, prolactin and osteopontin levels were significantly elevated in women with early ovarian cancer. The other two proteins were greatly reduced. When measured collectively, these four proteins completely distinguished between healthy women and those with early ovarian cancer, according to the results published in the May 2005 journal of the Proceedings of the National Academy of Sciences.

An exploratory surgical procedure called laparotomy generally is required for the definitive diagnosis of ovarian cancer. Laparotomy involves the following steps:

It requires general anesthesia and employs standard surgical techniques to make a vertical, midline incision from the pubic bone to the navel.
Such an incision ensures careful evaluation of the entire abdominal area. After the incision is made, the surgeon assesses the fluid and cells in the abdominal cavity.
During this procedure, cysts or other suspicious areas will be removed and biopsied (tested for cancer).
If the lesion is cancerous, the surgeon continues with a process called surgical staging to find out how far the cancerous tumor has spread and to remove the ovaries and any cancerous tissue.

Investigators are also studying laparoscopy -- instead of more invasive surgery -- for initial surgical evaluation (staging).

Click the icon to see an image of pelvic laparoscopy.

Prognosis

Ovarian cancer ranks behind lung, breast, and colorectal cancer as the fourth most common cause of female cancer death in this country. About 15,280 American women are expected to die from ovarian cancer in 2007.

In general, overall 5-year survival rates (all stages combined) increased from 37% in 1974 to greater than 50% currently. Survival rates vary depending on different factors, including age and the stage at which it is detected.

The survival rate also varies according to the cancer stage:

Five-year survival rates are over 90% if the cancer is still confined to the ovary at diagnosis. However, only 19% of ovarian cancers are found at this stage.
If the cancer has spread to nearby regions in the pelvis, the survival rate drops to 60 - 80%.
If the cancer has spread to sites outside the pelvis, the 5-year survival rates are only 10 - 30%.

Unfortunately, most patients with ovarian cancer are not diagnosed until the disease is advanced. This usually means the cancer has spread to the upper abdomen. In order to establish a prognosis and determine treatment, the doctor needs to know the cell type, stage, and grade of the disease.

About 90% of ovarian epithelial cancers fall into one of four major subtypes based on their origin and shape as viewed under a microscope:

Serous. (This is the most common type.)
Endometrioid. (This is sometimes associated with endometriosis and tends to have a more favorable outlook.)
Mucinous. (The presence of malignant mucinous cells indicates a poorer outlook if the disease is advanced.)
Clear cell. (Clear cell carcinomas are the most difficult to treat even when the malignancy is still confined to the ovary.)

The remaining 10% of common epithelial cancers are referred to as undifferentiated, because their exact cell of origin cannot be determined microscopically. These epithelial ovarian carcinomas tend to grow and spread quickly.

Cancers are staged (I through IV) according to whether they are still localized (remaining in the ovary) or have spread beyond the original site.

Tumors are also graded according to how well or poorly organized they are (their differentiation). Ovarian tumors are graded on a scale of 1, 2, or 3. Grade 1 tends to closely resemble normal tissue and has a better prognosis than grade 3, which indicates very abnormal, poorly defined tissue.

Age. In general, younger women have a better prognosis than older women although stage and grade of tumor also are important to the prognosis.

BRCA Carriers. Some studies have reported that women who carry mutated BRCA genes may have better survival rates than non-carriers. The survival advantages may be due to having a slower course or being more responsive to therapies than sporadic ovarian cancers, although this is controversial.

Angiogenesis. Experimentally, the level of biochemicals stimulating the formation of new blood vessels that support tumor growth (angiogenesis) appears to correlate with prognosis. The more angiogenic factors present in a tumor population, the more new blood vessels will form, encouraging both tumor growth and metastasis.

Overexpression of p53 Mutations. High levels of a defective p53 gene (which regulates cell growth) are associated with a poorer outlook.

Women who survive ovarian cancer have a high risk for psychological stress. Support groups can be very helpful.

Treatment

In general, the course of treatment is determined by the stage of the cancer. Stages range from I to IV based on the cancer's specific characteristics, such as whether it has spread beyond the ovaries.

In stage I, the cancer has not spread. It is confined to one ovary (stage IA) or both ovaries (stage IB). In stages IA and IB, the ovarian capsules are intact, and there are no tumors on the surface. Stage IC can affect one or both ovaries, but the tumors are on the surface, or the capsule is ruptured, or there is evidence of tumor cells in abdominal fluid (ascites). The overall 5-year survival rate for stage IA or IB can be as high as 90%, but the presence of other factors may affect this rate. For example, non-clear-cell well-differentiated cancer cells or borderline tumors have a favorable prognosis. Clear cells or those that are more poorly differentiated have a worse outlook. Stage IC has a poorer outlook than the earlier stages. It is very important that women receive an accurate staging assessment, including a pathologic review conducted by a gynecologic pathologist.

Treatment Options: Treatment for most women with stage IA and IB includes surgical removal of the uterus and both ovaries and fallopian tubes (total hysterectomy and bilateral salpingo-oophorectomy), partial removal of the omentum (the fatty layer that covers and pads organs in the abdomen), and surgical staging of the lymph nodes and other tissues in the pelvis and abdomen. (Carefully selected premenopausal women in Stage I with the lowest-grade tumors in one ovary may sometimes be treated only with the removal of the diseased ovary and tube in order to preserve fertility.) Patients with stage IA or B disease, grade 1 (or sometimes grade 2), usually do not need further therapy after surgery. However, higher risk patients (stage IC, stage I/grade 3) are usually treated with platinum-based chemotherapy to reduce their risk of subsequent relapse.

A 2005 study suggested that adjuvant platinum-based chemotherapy (chemotherapy added to surgical treatment) can improve survival and reduce cancer recurrence. With the considerable adverse effects of chemotherapy, more research is needed to determine which stage 1 patients would benefit most from this adjuvant treatment.

Click the icon to see an illustrated series detailing hysterectomy.

In stage II, the cancer has spread to other areas in the pelvis. It may have advanced to the uterus or fallopian tubes (stage IIA), or other areas within the pelvis (stage IIB), but is still limited to the pelvic area. Stage IIC indicates capsular involvement, rupture, or positive washings (that is, they contain malignant cells). The 5-year survival rate for stage II is about 60 - 80%.

Treatment Options: Surgical management for most women in this stage is total hysterectomy, bilateral salpingo-oophorectomy, and removal of as much cancer in the pelvic area as possible (tumor debulking). Surgical staging should be performed.

After the operation, treatment with chemotherapy is usually necessary in an attempt to eradicate residual cancer and decrease the chance for relapse.

In stage III, one or both of the following are present: (1) The cancer has spread beyond the pelvis to the omentum (the fatty layer that covers and pads organs in the abdomen) and other areas within the abdomen, such as the surface of the liver or intestine. (2) The cancer has spread to the lymph nodes. The average 5-year survival rate for this stage is 20%.

Click the icon to see an image of the lymph system located near the ovaries.

Treatment Options: Surgical management for most women in this stage is total hysterectomy and bilateral salpingo-oophorectomy and removal of as much cancer as possible (tumor debulking).

Following surgery, chemotherapy is usually needed for any remaining cancer cells. Several approaches are under investigation for reducing high rates of recurrence (about 80%). These approaches include the following:

Experimental chemotherapy drugs
Anti-angiogenic therapies
Gene and biological therapies
Intraperitoneally administered high-dose chemotherapy
Neoadjuvant therapy (chemotherapy before surgery)
High-dose chemotherapy
Peripheral blood stem cell transplantation (to date this approach has proven to be very toxic with no convincing improvement in survival)

Stage IV is the most advanced cancer stage. The cancer may have spread to the inside of the liver or spleen. There may be distant spreading of the cancer, such as ovarian cancer cells in the fluid around the lungs. The average 5-year survival rate for this stage is less than 10%.

Treatment Options: Tumor debulking may be performed before chemotherapy.

Although not standard practice in the United States, a surgical procedure called retroperitoneal lymphadenectomy is sometimes performed. This procedure involves removal of aortic and pelvic lymph nodes from the rear of the abdomen. Results from a 2005 randomized controlled trial suggest that while retroperitoneal lymphadenectomy does help reduce cancer progression, it does not prolong survival.

Treatment Options: If ovarian cancer returns, chemotherapy is the mainstay of treatment, although it is not generally curative in the setting of relapsed disease.

If the interval between the last platinum-containing chemotherapy (carboplatin or cisplatin) and relapse is long (greater than 6 months), it is reasonable to attempt a repeat trial of platinum-based chemotherapy, with or without paclitaxel.

If the interval is short, or if these drugs fail to control the tumor, other second-line drugs may be useful in achieving a response. They include topotecan, liposomal doxorubicin, etoposide, docetaxel, gemcitabine, or tamoxifen. There is no evidence that second-line drug combinations are any more effective than single drugs, although they are generally more toxic.

Clinical trials using various investigative approaches are under way. It is not clear if there is a role of a second debulking surgical procedure. A 2004 study published in the New England Journal of Medicine found that additional debulking did not prevent cancer progression or prolong survival.

Surgery

Surgery for ovarian cancer uses laparotomy, a major abdominal operation. It is the primary diagnostic tool for ovarian cancer and also plays a role in treatment. Complete surgical intervention includes the following:

Surgical staging (examining all tissues and organs in the pelvic cavity for accurate assessment of the disease stage).
Debulking (removal of as much of the cancerous tissue as possible). This is an important component of ovarian cancer management and should be performed by a surgeon trained in cancer surgery techniques.

Patients with ovarian cancer should see a qualified gynecologic oncologist (a surgical specialist in female reproductive cancers) and a qualified medical oncologist with special expertise in the chemotherapeutic management of gynecologic cancer. Studies indicate that it is best for patients, especially those with advanced-stage ovarian cancer, to receive care at medical centers that specialize in cancer treatment and surgery.

According to a 2007 study, 1 in 3 patients with ovarian cancer fails to receive recommended surgical treatment. Women over age 70, poor patients, and African-American or Hispanic patients were least likely to receive proper treatment. Women who were not treated by gynecologic oncologists were also less likely to receive optimal surgical care.

Surgical staging includes biopsies of the following:

The undersurface of the diaphragm
The omentum (the fatty layer that covers and pads organs in the abdomen)
Sometimes lymph nodes along the abdominal aorta

An abdominal wash is performed by injecting a salt solution into the abdominal cavity to facilitate microscopic detection of cancerous cells not visible to the naked eye. The surgeon then evaluates the pelvis and abdomen and removes suspected cancer tissue. The entire affected ovary is usually removed (oophorectomy) during surgical staging if the surgeon believes it might be cancerous. The tissue is sent to a laboratory for an immediate evaluation called a frozen section diagnosis. The doctor will also examine the bowel and bladder for cancer invasion.

If the tumor is in an early stage on one ovary and a young woman wants to retain her ability to have children, the surgeon may be able to remove only the affected ovary and perform surgical staging. Chemotherapy follows in selected patients. Studies indicate that in carefully selected young patients, many can expect normal fertility afterward. However, most women with ovarian cancer are not candidates for this procedure.

The goal of surgery is to remove as much of the tumor as possible (called debulking or cytoreductive surgery) for improving symptoms and increasing the effectiveness of chemotherapy. The surgery itself is typically performed as follows:

In premenopausal women in later stages, and in all postmenopausal women, the surgeon usually removes the uterus (a hysterectomy) and both ovaries and fallopian tubes (a bilateral salpingo-oophorectomy).
In addition, the surgeon usually removes the omentum (omentectomy), any growths on the diaphragm and intestine, and possibly certain lymph nodes (lymphadenectomy).

If surgical staging reveals that the cancer has invaded the bowel, a portion of the intestine may have to be removed as well.

Postoperative Care. If possible, a patient should ask a family member or friend to help out for the first few days at home. The following are some of the precautions and tips for postoperative care:

For 1 - 2 days after surgery, the patient is given medications to prevent nausea and painkillers to relieve pain at the incision site.
As soon as the doctor recommends it, usually within a day of the operation, the patient should get up and walk in order to help prevent pneumonia, reduce the risk of blood-clot formation, and to hasten recovery.
Walking and slow, deep breathing exercises may help to relieve gas pains, which can cause major distress for the first few days.
Coughing can cause pain, which may be reduced by holding a pillow over a surgical abdominal wound or by crossing the legs after vaginal surgery.
Patients are advised not to lift heavy objects (including small children), not to douche or take baths, and not to climb stairs or drive for several weeks.
For the first few days after surgery, many women weep frequently and unexpectedly. These mood swings may be due to depression from the loss of reproductive capabilities and form abrupt changes in hormones, particularly if the ovaries have been removed.

The patient should talk to their doctor about when they can start exercise programs that are more intense than walking. The abdominal muscles are important for supporting the upper body, and recovering strength may take a long time. Even after the wound has healed, the patient may experience an on-going feeling of overall weakness, which can be demoralizing, particularly in women used to physical health. Some women do not feel completely well for as long as a year. Others may recover in only a few weeks.

Complications Following the Procedure. Minor complications after hysterectomy are very common:

Women may develop minor and treatable urinary tract infections.
There is usually light vaginal bleeding and pain after the operation, which can be well-controlled with pain medications.

More serious complications are uncommon but patients should be aware of their symptoms and call the doctor immediately if they occur:

Infection occurs in 10 - 15% of patients, with the risk being higher with abdominal than with vaginal surgery. Symptoms might include continuing or increasingly severe pain, fever, heavy discharge, or bleeding. Antibiotics given at the time of surgery help to reduce this risk. Other risk factors for infection include obesity, a longer than normal operative time, and low socioeconomic status.
There is a slight risk for small blood clots, usually in veins of the legs (thrombophlebitis). A sudden swelling or discoloration in the leg can indicate this condition and requires immediate medical attention.

This picture shows a red and swollen thigh and leg caused by a blood clot (thrombus) in the deep veins in the groin (iliofemoral veins), preventing normal return of blood from the leg to the heart.

Other serious and even life-threatening complications, though rare, include pulmonary embolism (blood clots that travel to the lung), abscesses, perforation of the bowel, fistulas (a passage that bores from an organ to the skin or to another organ), or dehiscence (the opening of the surgical wound).

Treating Menopausal Symptoms and Premature Menopause after Hysterectomy. After hysterectomy, premenopausal women usually have hot flashes, a symptom of menopause. Symptoms come on abruptly and may be more intense than those of natural menopause. Symptoms include hot flashes, vaginal dryness and irritation, and insomnia. A significant number of women gain weight.

The most important complications that occur in women who have had their ovaries removed are due to estrogen loss, which places women at risk for osteoporosis (loss of bone density) and a possible increase in risks for heart disease. Women have typically taken hormone replacement therapy (HRT) after surgery if their ovaries have been removed. There have been concerns however about health risks, including the risk for breast cancer and stroke, that have now limited its use. Risks in premenopausal women who have had a hysterectomy have not yet been clarified. Several nonhormonal drugs, however, can help protect both bones and heart.

After chemotherapy is completed, surgeons used to perform an exploratory procedure called second-look laparotomy. Although this procedure is the most sensitive way of detecting residual cancer that remains after chemotherapy, it has no proven impact on patient survival. Its use is restricted to patients being treated in clinical trials.

Bowel obstruction is common in ovarian cancer. Surgery can be very helpful for selected patients with this problem.

Medications

Following surgery, patients (other than those with early-stage, low-grade disease) usually have chemotherapy. Unlike surgery and radiation, which treat the cancerous tumor and the area surrounding it, drug therapy destroys rapidly dividing cells throughout the body, so it is as systemic therapy.

Ovarian cancers are very sensitive to chemotherapy and often respond well initially. Unfortunately, in most cases, ovarian cancer recurs. With treatment advances, however, more than half of women now survive 5 years or longer. Doctors are now approaching this disease as a chronic and potentially long-term illness that requires the following:

Identifying the disease recurrence as soon as possible
Administering treatments that are as effective as possible without causing suffering
Partnering with the patient in determining her own best course

Standard Chemotherapy. The standard initial chemotherapy uses a combination of:

A platinum-based drug, such as carboplatin (Paraplatin) or cisplatin (Platinol). Carboplatin is preferred over cisplatin in the combination. Carboplatin works as well as cisplatin but is less toxic and can be administered in a more convenient, outpatient regimen.
A taxane, such as paclitaxel (Taxol) or docetaxel (Taxotere). Currently paclitaxel is the drug most often used as initial therapy in combination with a platinum drug. Docetaxel, however, is less toxic to the nervous system (but has more adverse effects on blood cell production). Taxotere is now commonly substituted for Taxol.

Paclitaxel-carboplatin chemotherapy will reduce tumor size in about 70% of women. Older women (over age 60) may benefit as much as younger ones from this regimen.

Other drugs that may prove to be useful first-line treatments are gemcitabine (Gemzar) and doxorubicin (Doxil). A third drug, topotecan (Hycamtin), is not helpful for first-line treatment for advanced ovarian cancer, according to recent studies. In an important 2006 study, topotecan following paclitaxel-carboplatin therapy did not help prolong survival, and it caused many serious side effects, including anemia and infections.

Chemotherapy Drugs Studied for Relapsed or Refractory Cancer. Unfortunately, some ovarian tumors are resistant to platinum drugs. Even in patients who respond, the disease eventually becomes resistant to the first-line drugs, and the cancer returns. Various approaches for increasing responsiveness to these drugs are being investigated. Investigators are studying two approaches for preventing relapse after remission:

Developing more effective drug combination regimens to increase initial response rates and duration of the response.
Developing maintenance drugs to prevent or delay relapse.

Once cancer recurs or continues to progress, several second-line chemotherapies are available or under investigation. The following lists some drugs that are being used, usually as single drugs, for relapsed or refractory cancers:

Nucleoside analogs, including gemcitabine (Gemzar). In 2006, gemcitabine was approved as a treatment for recurrent ovarian cancer. It is used in combination with carboplatin for women with advanced ovarian cancer that has relapsed at least 6 months after initial therapy.
Paclitaxel or carboplatin alone or in combination. A landmark study published in the July 2003 Journal of Clinical Oncology, found that additional cycles of paclitaxel significantly delayed disease progression in women with advanced ovarian cancer.
Pegylated liposomal doxorubicin (Doxil) is a form of standard doxorubicin (Adriamycin) that remains in the bloodstream longer, tends to spare the bone marrow, and moves selectively through the tumor. It is showing promise in clinical trials and also may have fewer toxic effects than standard doxorubicin and other drugs used for ovarian cancer. Studies show that peglyated liposomal doxorubicin is very well tolerated, with a total response rate of about 20 - 30% in patients with recurrent cancer. This compares favorably with other drugs, such as topotecan, carboplatin, and taxol.
Topoisomerase I inhibitors, including topotecan (Hycamtin) and irinotecan (Campto).
Topoisomerase II alpha inhibitors, including etoposide (VePesid).
Alkaloids, including vinorelbine (Navelbine).
Hormonal drugs: tamoxifen (Nolvadex) or anastrozole (Arimidex).
Valspodar and capecitabine (Xeloda) are oral drugs that may help improve response to other drugs, although data are preliminary.

In addition to studying individual drugs in different combinations, investigators are looking for the optimal sequence, dosages and timing of administering them. In general, the typical regimen is as follows:

Paclitaxel and carboplatin are administered in an outpatient clinic within several weeks of the surgery.
Each treatment takes about 4 - 5 hours to complete.
It is repeated every 3 weeks for a total of six times. (Each 3-week interval is known as a cycle of chemotherapy.)

Such chemotherapy is usually administered intravenously (by vein). However, an important 2006 study in the New England Journal of Medicine found that patients with Stage III ovarian cancer who received intraperitoneal chemotherapy had a significant survival advantage compared with patients who received standard intravenous chemotherapy. (Intraperitoneal chemotherapy involves administering the drugs directly into the abdominal cavity.) Patients in the intraperitoneal group did have more severe side effects than those who had intravenous chemotherapy. Researchers are continuing to investigate ways to reduce these side effects. Another 2006 study noted that intraperitoneal chemotherapy requires careful catheter insertion and maintenance, and that doctors need to be well trained to perform this procedure.

Side effects occur with all chemotherapeutic drugs. They are more severe with higher doses and increase over the course of treatment. Some may be long-lasting. In one study of ovarian cancer survivors, 20% had long-term treatment side effects, such as gynecologic and abdominal problems. Even so, most enjoyed a high quality of life that was comparable to other cancer survivors and peers without a history of cancer.

Common side effects include:

Nausea and vomiting. Drugs known as serotonin antagonists, especially ondansetron (Zofran), can relieve these side effects in nearly all patients given moderate drugs and most patients who take more powerful drugs.
Diarrhea
Temporary hair loss
Weight loss
Fatigue
Depression

Serious short- and long-term complications can also occur and may vary depending on the specific drugs used. The following list includes some of these complications and a few of their treatments:

Anemia. Erythropoietin stimulates red blood cell production and can help reduce or prevent this side effect. It is available as epoetin alfa (Epogen, Procrit) and darbepoetin alfa (Aranesp). Aranesp stays in the blood longer than epoetin alfa, so fewer injections are needed.
Increased chance for infection from severe reduction in white blood cells (neutropenia). The addition of a drug called granulocyte colony-stimulating factor (filgrastim and lenograstim) is very helpful in reducing the risk for severe infection in selected patients.
Liver and kidney damage.
Abnormal bleeding (thrombocytopenia).
Allergic reaction, particularly to platinum-based drugs.
Rarely, secondary cancers such as leukemia.
Between a quarter and a third of women report problems in concentration, motor function, and memory. These problems may be long-term and may be due to reductions in estrogen levels after treatments.
Cumulative doses of anthracyclines can damage heart muscles over time and increase the risk for heart failure. An encapsulated form doxorubicin (Myocet, Doxil) may reduce the risk for toxic effects on the heart.
Taxanes can cause a drop in white blood cells and possible problems in the heart and central nervous system. Allergic reactions can occur. Talking a corticosteroid before taxane administration can help prevent such reactions. Taxane therapy may also cause severe joint and muscle pain in some patients, which is relievable with corticosteroids.

Physical Exam and CA-125 Blood Test. During treatment, the effectiveness of the chemotherapy is evaluated primarily with a physical examination and the CA-125 blood test. Falling CA-125 levels indicate effective treatment and persistently elevated levels indicate resistance to the chemotherapy.

Second Look Laparotomy. Second-look laparotomy is sometimes considered after completion of chemotherapy for patients who are participating in clinical trials.

Comparative Computed Tomography Scans. Another method for evaluating the success of chemotherapy is to compare computed tomography (CT) scans of the pelvis and abdomen before and after chemotherapy to check the size of any residual tumors that persisted after the original surgery. CT scanning is not always required, however.

Positron Emission Tomography ). Positron emission tomography (PET) scans have no proven role in the management of patients with ovarian cancer. More study is needed to determine their utility in diagnosing relapsed disease.

Any patient with ovarian cancer is a candidate for clinical trials. In addition to testing high-dose or combinations of chemotherapy, drugs with unique actions are being investigated.

Anti-angiogenesis drugs. Angiogenesis, the formation of new blood vessels that feed the growth of a cancerous tumor, is a critical process in the spread of ovarian cancer. Drugs that block this process are under investigation for ovarian cancer. Some of these drugs target vascular endothelial growth factor (VEGF), a protein involved in tumor cell growth. Results of a phase II study, presented at the 2007 meeting of the American Society of Clinical Oncology, indicated that the anti-angiogenesis drug aflibercept (VEGF-TRAP) may benefit patients with epithelial ovarian cancer who are resistant to platinum-based chemotherapy. Such drugs include thalidomide, gefinitib (Iressa), and carboxyamido-triazole (CAI).

Aromatase inhibitors. Aromatase inhibitors block aromatase, an enzyme that is a major source of estrogen in many body tissues. Aromatase inhibitors are used for treatment of estrogen-sensitive breast cancer. These drugs include anastrozole (Arimidex) and letrozole (Femara). Studies indicate that they may provide an alternative to chemotherapy for types of ovarian cancers that are responsive to anti-estrogen hormonal therapy.

Multiple signal transduction regulators. Phenoxodiol is an multiple signla transduction regulator that is being developed as a broad-spectrum anti-cancer drug. It is currently being evaluated in phase III clinical trials, in combination with other drugs, such as carboplatin, for its ability to shrink tumors or stop tumor growth in women with ovarian or fallopian cancer who have failed other forms of chemotherapy.

HER Dimerization Inihibitors. Pertuzumab (Omnitarg) is the first of a new class of drugs called HER dimerization inhibitors. It is designed to inhibit tumor growth for tumors that express the HER2 receptor protein. Pertuzumab is currently in phase II trials in combination with gemcitabine for women with platinum-resistant ovarian, peritoneal, or fallopian cancer.

Immunotherapy. Several therapies under investigation use the body's immune response to attack ovarian cancer cells. Experimental immunotherapies include vaccines designed to treat -- not prevent -- cancer. Some of these vaccines use specially designed antibodies (called monoclonal antibodies, or MAbs) to boost the immune responses against tumor-associated factors, such as CA125 or HER-2/neu. Vaccine therapy is still in early-stage clinical research and is being studied in combination with various chemotherapy drugs.

Epothilones. Epothilones are a new class of anti-cancer drugs that are similar to taxanes (paclitaxel) but are more potent. One of these drugs, ixabepilone (BMS-247550), is being studied for ovarian cancer.

Radiation Therapy

Radiation therapy is not typically used in ovarian cancer. This is because radiation would need to be given to the entire abdomen and pelvis, increasing its toxicity. Radiation is sometimes useful to treat isolated areas of tumor that are causing pain and are no longer responsive to chemotherapy.

Resources

www.cancer.gov -- National Cancer Institute
www.cancer.org -- American Cancer Society
www.aacr.org -- American Association for Cancer Research
www.asco.org -- American Society of Clinical Oncology
www.plwc.org -- People Living with Cancer
www.ovarian.org -- National Ovarian Cancer Coalition
www.ovariancancer.org -- Ovarian Cancer National Alliance
www.sgo.org -- Society of Gynecologic Oncologists
www.wcn.org -- Women's Cancer Network
www.ovariancancer.com -- The Gilda Radner Familial Ovarian Cancer Registry
www.cancer.gov/clinicaltrials -- Find clinical trials

References

Beral V; Million Women Study Collaborators; Bull D, Green J, Reeves G. Ovarian cancer and hormone replacement therapy in the Million Women Study. Lancet. 2007 May 19;369(9574):1703-10.

Bristow RE, Santillan A, Diaz-Montes TP, Gardner GJ, Giuntoli RL 2nd, Meisner BC, et al. Centralization of care for patients with advanced-stage ovarian cancer: a cost-effectiveness analysis. Cancer. 2007 Apr 15;109(:1513-22.

Goff BA, Mandel LS, Drescher CW, Urban N, Gough S, Schurman KM, et al. Development of an ovarian cancer symptom index: possibilities for earlier detection. Cancer. 2007 Jan 15;109(2):221-7.

Goff BA, Matthews BJ, Larson EH, Andrilla CH, Wynn M, Lishner DM, et al. Predictors of comprehensive surgical treatment in patients with ovarian cancer. Cancer. 2007 May 15;109(10):2031-42.

Lacey JV Jr, Brinton LA, Leitzmann MF, Mouw T, Hollenbeck A, Schatzkin A, et al. Menopausal hormone therapy and ovarian cancer risk in the National Institutes of Health-AARP Diet and Health Study Cohort. J Natl Cancer Inst. 2006 Oct 4;98(19):1397-405.

[No authors listed] An experiment in earlier detection of ovarian cancer. Lancet. 2007 Jun 23;369(9579):2051.

Smyth JF, Gourley C, Walker G, MacKean MJ, Stevenson A, Williams AR, et al. Antiestrogen therapy is active in selected ovarian cancer cases: the use of letrozole in estrogen receptor-positive patients. Clin Cancer Res. 2007 Jun 15;13(12):3617-22.

Review Date:
10/16/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Diabetes - type 2

FitSugar — Wed, 08 Oct 2008 17:34:58 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Symptoms
Screening Tests
Treatment
Lifestyle Changes
Medications
Long-Term Complications
Emergency Complications
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approvals

Sitagliptin (Januvia), the first in a new class of diabetes drugs called DPP-4 inhibitors, was approved in 2006.
Janumet, a 2-in-1 pill that contains both sitagliptin and metformin, was approved in 2007.
These drugs are taken by mouth and may be more convenient for patients than exenatide (Byetta), a similar drug. DPP-4 inhibitors do not cause weight gain and may pose a lower risk for hypoglycemia than some other diabetes drugs.

Drug Safety Alert

Rosiglitazone (Avandia) may significantly increase the risk for heart attack, indicates a review published in the Journal of the American Medical Association. In 2007, a panel of experts from the Food and Drug Administration (FDA) agreed the drug increases the risk of heart attacks -- but concluded it should remain on the market. The panel did, however, recommend the FDA require rosiglitazone's maker to add warnings to the drug's label. Rosiglitazone and a similar drug, pioglitazone (Actos), are known to significantly increase the risks for heart failure. There is also evidence that these drugs increase the risk for bone fracture.

Anemia Drugs Warning

Patients with anemia associated with end-stage kidney disease, especially those on dialysis, should be aware of new warnings concerning dosing target levels of erythpoiesis-stimulating drugs. In 2007, the FDA warned that darbepoetin alfa (Aranesp) and epoetin alfa (Epogen and Procrit) can increase the risk for blood clots, stroke, and heart attacks when excessive doses are given. The FDA has defined target hemoglobin levels and recommends that patients who receive these drugs have frequent blood tests. Patients should also report to their doctors any unusual symptoms.

Genetics Research Breakthroughs

Scientists have now identified 10 genes that are associated with increased risk for type 2 diabetes. Six of these genes were discovered in 2006 and 2007.

Diabetes and Pre-Diabetes

About 20 million Americans have type 2 diabetes, and an additional 54 million have pre-diabetes. According to a 2007 study by the U.S. Centers for Disease Control, the prevalence of type 2 diabetes has been increasing by 5% each year since 1990. Rising rates of obesity may be one factor.
For people with pre-diabetes, lifestyle changes, such as losing weight, appear to work as well as drug treatment in delaying the progression to diabetes, according to a 2007 British Medical Journal study.

Introduction

The two major forms of diabetes are type 1 (previously called insulin-dependent diabetes mellitus, IDDM, or juvenile-onset diabetes) and type 2 (previously called noninsulin-dependent diabetes mellitus, NIDDM, or maturity-onset diabetes).

Both type 1 and type 2 diabetes share one central feature: elevated blood sugar (glucose) levels due to insufficiencies of insulin, a hormone produced by the pancreas. Insulin is a key regulator of the body's metabolism. It works in the following way:

During and immediately after a meal the process of digestion breaks down carbohydrates into sugar molecules (including glucose) and proteins into amino acids.
Right after the meal, glucose and amino acids are absorbed directly into the bloodstream, and blood glucose levels rise sharply.
The rise in blood glucose levels signals important cells in the pancreas, called beta cells, to secrete insulin, which pours into the bloodstream. Within 10 minutes after a meal, insulin rises to its peak level.
Insulin enables glucose and amino acids to enter cells in the body, particularly muscle and liver cells. Here, insulin and other hormones direct whether these nutrients will be burned for energy or stored for future use. (The brain and nervous system are not dependent on insulin; they regulate their glucose needs through other mechanisms.)
When insulin levels are high, the liver stops producing glucose and stores it in other forms until the body needs it again.
As blood glucose levels reach their peak, the pancreas reduces the production of insulin.
About 2 - 4 hours after a meal, both blood glucose and insulin are at low levels, with insulin being slightly higher. The blood glucose levels are then referred to as fasting blood glucose concentrations.

The pancreas is located behind the liver and is where the hormone insulin is produced. Insulin is used by the body to store and utilize glucose.

Type 2 diabetes is the most common form of diabetes, accounting for 90 - 95% of cases. The disease mechanisms in type 2 diabetes are not wholly known, but some experts suggest that it may involve the following three stages in most patients:

The first stage in type 2 diabetes is the condition called insulin resistance. Although insulin can attach normally to receptors on liver and muscle cells, certain mechanisms prevent insulin from moving glucose (blood sugar) into these cells where it can be used. Most patients with type 2 diabetes produce variable, even normal or high, amounts of insulin. In the beginning, this amount is usually sufficient to overcome such resistance.
Over time, the pancreas becomes unable to produce enough insulin to overcome resistance. In type 2 diabetes, the initial effect of this stage is usually an abnormal rise in blood sugar right after a meal (called postprandial hyperglycemia). This effect is now believed to be particularly damaging to the body.
Eventually, the cycle of elevated glucose further impairs and possibly destroys beta cells, thereby stopping insulin production completely and causing full-blown diabetes. This is made evident by fasting hyperglycemia, in which elevated glucose levels are present most of the time.

In type 1 diabetes, the disease process is more severe and onset is usually in childhood:

Beta cells in the pancreas that produce insulin are gradually destroyed. Eventually insulin deficiency is absolute.
Without insulin to move glucose into cells, blood glucose levels become excessively high, a condition known as hyperglycemia.
Because the body cannot utilize the sugar, it spills over into the urine and is lost.
Weakness, weight loss, and excessive hunger and thirst are among the consequences of this "starvation in the midst of plenty."
Patients become dependent on administered insulin for survival. [See In-Depth Report #9: Diabetes - type 1.]

Click the icon to see an image of the pancreas.

Conditions that damage or destroy the pancreas, such as pancreatitis, pancreatic surgery, or certain industrial chemicals can cause diabetes. Polycystic ovaries are highly associated with diabetes. Certain drugs can also cause temporary diabetes, including corticosteroids, beta-blockers, and phenytoin. Rare genetic disorders (Klinefelter's syndrome, Huntington's chorea, Wolfram's syndrome, leprechaunism, Rabson-Mendenhall syndrome, lipoatrophic diabetes) and hormonal disorders (acromegaly, Cushing syndrome, pheochromocytoma, hyperthyroidism, somatostatinoma, aldosteronoma) are associated with or increase the risk for diabetes.

Causes

Type 2 diabetes is caused by a complicated interplay of genes, environment, insulin abnormalities, increased glucose production in the liver, increased fat breakdown, and possibly defective hormonal secretions in the intestine. The recent dramatic increase indicates that lifestyle factors (obesity and sedentary lifestyle) may be particularly important in triggering the genetic elements that cause this type of diabetes.

The characteristic features of most patients with type 2 diabetes are:

Insulin resistance in muscle cells
Normal or even excessive levels of insulin (to compensate for this resistance), eventually followed by a drop in insulin production

In addition, researchers are trying to determine the factors that might promote insulin resistance:

Both obesity and insulin resistance at different phases are marked by elevated levels of free fatty acids and the hormones resistin and leptin. It is not known yet if elevated levels are simply a product of obesity or play some causal role in diabetes.
Insulin resistance is associated with a chronic low inflammatory response, which involves a number of immune factors, such as TGH-beta 1 and C-reactive protein. Such factors can cause damage over time and may be responsible for the association between insulin resistance and heart disease.

Type 2 diabetes has a genetic component. In 2006 and 2007, major breakthroughs in genetic research identified six new genes associated with type 2 diabetes. Ten genes have now been positively confirmed as increasing the risk for type 2 diabetes: TCF7L2, SLC30A8, HHEX, PPARG, KCNJ11, IGF2B2, CDKAL1, CDKN2A, CDKN2B, and FTO.

Most of these genes play a role in regulating insulin action, including the processes that occur in the pancreas’ insulin-producing beta cells. The FTO gene increases the risk for obesity, which itself is a risk factor for type 2 diabetes. These genes appear to cluster around three genetic regions that include a number of chromosomes. Scientists hope that future research will help uncover how genes influence the progression from pre-diabetes to diabetes, and how lifestyle and medical intervention may help delay or prevent this process.

Risk Factors

Nearly 21 million Americans have diabetes; up to 95% of these cases are type 2. In addition, 26% of Americans age 20 and older (and 40% of Americans age 65 and older) have impaired fasting glucose, a pre-diabetes condition that increases the risk for diabetes. According to the American Diabetes Association, 54 million people have pre-diabetes, bringing a total of 75 million Americans who either have diabetes or are at risk of developing it.

Historically, type 2 diabetes usually developed after the age of 40, but it is now also increasing in children. The prevalence of diabetes in the U.S. has increased by 5% each year since 1990, and experts believe that obesity is the major factor behind this dramatic growth rate. Given the current epidemic of obesity, experts estimate that over a third of all people born in 2002 will eventually develop diabetes. Furthermore, the dramatic increase in diabetes is occurring worldwide as American lifestyles become global. Evidence strongly suggests that healthy lifestyles can prevent most cases of type 2 diabetes. People with pre-diabetes can substantially lower their risk by losing weight through diet and exercise.

Healthy adults age 45 and older should get tested for diabetes. Patients who are younger than age 45 and who are overweight or have other risk factors should also ask their doctors about testing. According to the National Institutes of Health, the following are major risk factors for diabetes and pre-diabetes:

Age 45 or older
Family history of diabetes
Overweight
Inactive lifestyle (exercise less than 3 times a week)
African-American, Hispanic/Latin American, American Indian and Alaska Native, Asian-American, or Pacific Islander ethnicity
High blood pressure (140/90 mm/Hg or higher)
HDL (“good”) cholesterol less than 35 mg/dL or triglyceride level 250 mg/dL or higher
Have had diabetes during pregnancy (gestational diabetes) or have given birth to a baby that weighed more than 9 pounds
Polycystic ovary syndrome (metabolic disorder that affects female reproductive system
Acanthosis nigricans (dark, thickened skin around neck or armpits)
History of disease of blood vessels to the heart, brain, or legs
Diabetes test history of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT)

Obesity is the number one risk factor for type 2 diabetes. It is estimated that 80 - 95% of the current dramatic increases in type 2 diabetes are due to obesity. Excess body fat appears to play a strong role in insulin resistance, but the way the fat is distributed is also significant. Weight concentrated around the abdomen and in the upper part of the body (apple-shaped) is associated with insulin resistance and diabetes, heart disease, high blood pressure, stroke, and unhealthy cholesterol levels. Waist circumferences greater than 35 inches in women and 40 inches in men have been specifically associated with a greater risk for heart disease and diabetes. (People with a "pear-shape" -- fat that settles around the hips and flank -- appear to have a lower risk for with these conditions.) However, obesity does not explain all cases of type 2 diabetes. It is also common among people in countries where weights tend to be low, such as Asia or India.

Metabolic Syndrome. A set of conditions referred to as metabolic syndrome (also called Syndrome X) is a pre-diabetic condition that is significantly associated with heart disease and higher mortality rates from all causes. The syndrome consists of obesity marked by abdominal fat, unhealthy cholesterol levels, high blood pressure, and insulin resistance. A 2002 study estimated that nearly a quarter of the U.S. population now has this condition. Even worse, according to a 2003 study, nearly a million American teenagers have this syndrome.

Between 25 - 33% of patients with type 2 diabetes have family members with diabetes. Having a first-degree relative with the disease poses a 40% risk of developing diabetes. One study reported that people with diabetic family histories have a higher risk for developing the disease at an earlier stage and with more severe features. Because families share many lifestyle features (eating and exercise habits) it is difficult to determine when genetics or environment play the major role. When clusters of type 1 and type 2 diabetes appear within families, genetic factors should be strongly suspected.

The risk for type 2 diabetes varies among population groups. Diabetes also seems to pose higher or lower risks for specific complications among ethnic groups. Genetic and socioeconomic factors, or both, seem to be involved in some ethnic differences, but in most cases the observed increase in ethnic groups in Americans is due to changes in traditional lifestyles.

African-Americans. African-American men have twice the risk of developing type 2 diabetes as Caucasian men. African-Americans with diabetes are also at higher risk for amputations than Caucasians. This is most likely due to a higher incidence of high blood pressure and smoking as well as poorer health care in African-Americans. Genetic factors may also play a role. For example, there is some evidence that African-Americans process insulin in the liver differently from Caucasians, which may make them more susceptible to diabetes when other risk factors are present.
Native Americans. The Pima tribe in Arizona has an incidence of type 2 diabetes that is 19 times higher than that of the white population. The risk for diabetic complications among young Pima adults is also very high. Other Native American tribes in North America are also at high risk for type 2 diabetes. The association between diet and diabetes among this population remains critical, however, in assessing the reason for their higher risk. For example, Pimas who live in Mexico exercise more and eat less fat (but consume more calories) than Pima tribes in Arizona. Mexican Pimas have a prevalence of diabetes of only 6%, while half of their Arizona Pima neighbors have diabetes.
Hispanic Americans. The rate of type 2 diabetes is also very high among Mexican-Americans, approximately double that for Caucasians. This group may also be at higher risk for heart problems than other ethnic groups with diabetes.
Asian-Americans. Overweight Asian-Americans and Pacific Islanders are at increased risk for developing type 2 diabetes. The risk for some Asian ethnic groups (such as Native Hawaiians and Filipinos) is twice that of Caucasians.

Smoking increases the risk for diabetes. According to a 2006 study, smokers are more than twice as likely to develop diabetes as people who have never smoked. Another 2006 study found that exposure to second-hand cigarette smoke also increases the risk for diabetes in non-smokers.

Low birth weight is now a recognized risk factor for type 2 diabetes and heart disease in adulthood. The reasons are unclear, although studies suggest it may represent a genetic factor. Studies have observed that babies of fathers with type 2 diabetes and of women who later developed type 2 diabetes tend to weigh less than babies of parents without diabetes. Such studies suggest that some parents may have some specific gene that affects insulin factors, putting both themselves and their children at risk for future diabetes. Theoretically, such a gene might also affect insulin factors in the developing fetus, causing low birth weight. (Of note, mothers of very high-weight babies are also at risk for diabetes -- although in these cases it is most often associated with gestational diabetes.)

Obesity-Related Type 2 Diabetes in Children. Until recent years, diabetes in children was almost always type 1 (an autoimmune disease). Between 1982 - 1994, however, the incidence of type 2 diabetes in children increased 10-fold. By 1996, a study reported that a third of all new diabetes cases in children were type 2. This increase parallels the rising epidemic in childhood obesity that has occurred both in the U.S. and worldwide, notably Europe and Japan. In some areas of Japan, type 2 diabetes has now become the dominant form of diabetes in children and adolescents. Obesity in children is also related to abnormalities in cholesterol, blood pressure, and insulin levels in adults. Administering glucose tolerance tests in overweight children may be helpful in identifying those at high risk for diabetes.

Maturity-Onset Diabetes in Caucasian Youth. Maturity-onset diabetes in youth (MODY) is a rare genetic form of type 2 diabetes that develops only in Caucasian teenagers. It accounts for 2 - 5% of type 2 cases. (This form of type 2 diabetes is not associated with obesity.)

An estimated 5% of pregnant women develop a form of type 2 diabetes, usually temporary, in their third trimester called gestational diabetes.

Gestational diabetes is diabetes that first appears during pregnancy. It usually develops during the third trimester of pregnancy. After delivery, blood sugar (glucose) levels generally return to normal, although 25% of these women develop type 2 diabetes within 15 years.

Who Gets Gestational Diabetes? Estimates for the prevalence of gestational diabetes are generally about 4%. Some studies, however, have suggested significantly higher rates. In one German study, 13% of pregnant women were diagnosed with this form of diabetes, including many who did not have any risk factors.

A pregnant woman's risk factors include:

Family history of diabetes
African-American, Hispanic, Asian, or Pacific Islander ethnicity
Overweight
Older than 25 years
Gestational diabetes with past pregnancy
Having given birth to a child weighing over 9 pounds
Diagnosis of pre-diabetes

Who Should Be Tested for Gestational Diabetes? A number of expert groups recommend that all pregnant women be tested for gestational diabetes between their 24th - 28th week. Pregnant women at high risk for diabetes should be tested earlier. The only women who do not need to be tested are those at very low risk. Generally they have the following characteristics:

Under 25 years old
Normal weight
No first-degree relatives with diabetes
Not belonging to high-risk ethnic groups

Effect of Diabetes on the Fetus. Because glucose crosses the placenta, a woman with diabetes can pass high levels of blood glucose to the fetus. In response, the fetus secretes high level of insulin. Studies indicate that such conditions may affect the developing fetus as soon as it is conceived, placing the unborn child at risk for:

Excessive fetal weight gain, which can lead to complications during delivery
Birth defects
Breathing problems and delayed lung development
Low blood sugar
Higher future risk for obesity and diabetes

Effect of Diabetes on the Pregnant Woman. In addition to endangering the fetus, diabetes also presents risks to the pregnant woman.

The most serious potential complications from gestational diabetes are high blood pressure during pregnancy, a condition called preeclampsia that is potentially dangerous. Because gestational diabetes increases the size of the fetus, it is also increases the likelihood that a woman will require a Cesarean delivery. Gestational diabetes also increases the risk that a woman will later develop type 2 diabetes.

How Is Gestational Diabetes Managed? Some suggestions for preventing complications include:

In most cases, increases in glucose levels can be managed with diet and exercise. Aerobic exercise before and during pregnancy may lower glucose levels and help protect women at risk or those who have gestational diabetes. (Any pregnant woman should check with her doctor before embarking on a vigorous exercise regimen.)
If a woman with gestational diabetes cannot control her glucose with lifestyle measures, she is usually given insulin.

The placenta provides the fetus with oxygen and nutrients and takes away waste, such as carbon dioxide, via the umbilical cord.

Polycystic Ovary Syndrome. Polycystic ovary syndrome (PCOS) is a condition that affects about 6% of women and results in the ovarian production of high amounts of androgens (male hormones), particularly testosterone. It appears to be an important cause of many menstrual disorders. Women with PCOS are at higher risk for insulin resistance, and about half of PCOS patients also have diabetes.

Click the icon to see an image of polycystic ovary syndrome.

Schizophrenia. While no definitive association has been established, research has suggested an increased background risk of diabetes among people with schizophrenia. In addition, many of the new generation of antipsychotic medications may elevate blood glucose levels. Patients taking antipsychotic medications (such as clozapine, olanzapine, risperidone, aripiprazole, quetiapine fumarate, ziprasidone) should receive a baseline blood glucose level test and be monitored for any increases during therapy.

Depression. According to a 2007 study, adults who have severe clinical depression may have a greater risk of developing type 2 diabetes than those who have never experienced depressive symptoms.

Hepatitis C. Patients with hepatitis C have a higher incidence of type 2 diabetes. The reasons for this are unclear.

Symptoms

Type 2 diabetes usually begins gradually and progresses slowly. Symptoms in adults include:

Excessive thirst
Increased urination
Fatigue
Blurred vision
Weight loss
In women, vaginal yeast infections or fungal infections under the breasts or in the groin
Severe gum problems
Itching
Erectile dysfunction in men
Unusual sensations, such as tingling or burning, in the extremities

Symptoms in children are often different:

Most children are obese or overweight
Increased urination is mild or even absent
Many children develop a skin problem called acanthosis, which is characterized by velvety, dark colored patches of skin

Screening Tests

There are no clear-cut guidelines for when to screen for diabetes. Some experts recommend that everyone over age 45 be tested regularly for diabetes, although others do not feel this necessary in people without symptoms or risk factors. In fact, early screening may identify some people with impaired glucose levels that would eventually normalize. Such people might be treated unnecessarily with medications that pose a risk for high blood sugar (hypoglycemia).

Still, given the risk for serious complications with diabetes and the potential value of early treatments, most experts recommend that all adults over 45 be screened and that younger adults be screened if they have one or more of the following conditions:

A weight that is 20% more than ideal body weight
Risk factors for heart disease (high blood pressure, unhealthy cholesterol levels -- especially for patients with low HDL cholesterol and high triglyceride levels
A close relative with diabetes
A high-risk ethnic group background
In women, having delivered a baby weighing over 9 pounds or having a history of gestational diabetes

Some experts recommend that children over age 10 should be tested for type 2 diabetes (even if they have no symptoms), if they are overweight and have at least two of the above mentioned risk factors.

Fasting Plasma Glucose. The fasting plasma glucose (FPG) test is the standard test for diabetes. It is a simple blood test taken after 8 hours of fasting. Results indicate:

FPG levels are considered normal up to 100 mg/dL (or 5.5 mmol/L).
Levels between 100 - 125 mg/dL (5.5 - 7.0 mmol/L) are referred to as impaired fasting glucose or pre-diabetes. These levels are considered to be risk factors for type 2 diabetes and its complications.
Diabetes is diagnosed when FPG levels are 126 mg/dL (7.0 mmol/L) or higher.

The FPG test is not always reliable, so a repeat test is recommended if the initial test suggests the presence of diabetes, or if the test is normal in people who have symptoms or risk factors for diabetes. For example, people who take the test in the afternoon and show normal results may actually have abnormal levels that would be revealed if they were tested in the morning.

A 2005 study suggested that even people with FPG levels in the high end of the normal range (high 90s) may be at increased risk for developing type 2 diabetes. Obesity further increases this risk. Patients with FPG levels in the upper 90s should strive to exercise and lose weight to help lower their FPG levels.

Glucose Tolerance Test. The oral glucose tolerance test (OGTT) is more complex than the FPG and may overdiagnose diabetes in people who do not have it. Some experts recommend it as a follow-up after FPG, if the latter test results are normal but the patient has symptoms or risk factors of diabetes. The test uses the following procedures:

It first uses an FPG test.
A blood test is then taken 2 hours later after drinking a special glucose solution.

The following results suggest different conditions:

OGTT levels are considered normal up to 140 mg/dL.
Levels between 140 - 199 mg/dL are referred to as impaired glucose tolerance or pre-diabetes.
Diabetes is diagnosed when OGTT levels are 200 mg/dL or higher.

Both the FPG and OGTT require that the patient not eat for at least 8 hours prior to the test.

Test for Glycated Hemoglobin. Tests for blood levels of glycated hemoglobin, also known as hemoglobin A1c (HbA1c), are not currently used for an initial diagnosis, but they are useful for determining the severity of diabetes. Some experts think this test can help predict complications in people who have FPG levels between 110 - 139, which are above normal but do not indicate full-blown diabetes.

The basis for its use as a diagnostic measurement in diabetes is as follows:

Hemoglobin is a protein molecule found in red blood cells. When glucose binds to it, the hemoglobin becomes modified, a process called glycosylation.
Glycosylation affects a number of proteins, and elevated levels of glycolated hemoglobin are strongly associated with complications of diabetes.
A glycated hemoglobin level of 1% above normal range identifies diabetes in 98% of patients. Normal HbA1c levels do not necessarily rule out diabetes, but if diabetes is present and levels are normal, the risk for complications is low.

The test is not affected by food intake so it can be taken at any time. A home test has been developed that might make it easier to measure HbA1c. In general, measurements suggest the following:

Normal HbA1c levels should be below 7%.
Levels of 11 - 12% glycolated hemoglobin indicate poor control of carbohydrates. High levels are also markers for kidney trouble.

Screening for Heart Disease. All patients with diabetes should be tested for hypertension and unhealthy cholesterol and lipid levels and given an electrocardiogram. For cholesterol, people with diabetes should aim for LDL levels below 100 mg/dL, HDL levels over 50 mg/dL, and triglyceride levels below 150 mg/dL. Blood pressure goals should be 130/80 mmHg or lower. Other tests may be needed in patients with signs of heart disease.

The electrocardiogram (ECG, EKG) is used extensively in the diagnosis of heart disease, from congenital heart disease in infants to myocardial infarction and myocarditis in adults. Several different types of electrocardiogram exist.

Screening for Kidney Damage. The earliest manifestation of kidney damage is microalbuminuria, in which tiny amounts (30 - 300 mg per day) of protein called albumin are found in the urine. About 20% of type 2 patients show evidence of microalbuminuria upon diagnosis of diabetes. (However, not all people with type 2 diabetes eventually develop kidney disease.) Microalbuminuria typically shows up in patients with type 2 diabetes who have high blood pressure.

The American Diabetes Association recommends that people with diabetes receive an annual microalbuminuria urine test. Patients should also have their blood creatinine tested at least once a year. Creatinine is a waste product that is removed from the blood by the kidneys. High levels of creatinine may indicate kidney damage. A doctor uses the results from a creatinine blood test to calculate the glomerular filtration rate (GFR). The GFR is an indicator of kidney function; it estimates how well the kidneys are cleansing the blood.

Screening for Retinopathy. The American Diabetes Association recommends that patients with type 2 diabetes get an initial comprehensive eye exam by an ophthalmologist or optometrist shortly after they are diagnosed with diabetes, and once a year thereafter. (People at low risk may need follow-up exams only every 2 - 3 years.) The eye exam should include dilation to check for signs of retinal disease (retinopathy).

Screening for Neuropathy. All patients should be screened for nerve damage (neuropathy), including a comprehensive foot exam. Patients who have loss of sensation in their feet should be sure to have a foot exam every 3 - 6 months to check for ulcers or infections.

Screening for Thyroid Abnormalities. Thyroid function tests should be administered.

Treatment

Pre-diabetes precedes the onset of type 2 diabetes. People who have pre-diabetes have fasting blood glucose levels that are 100 - 125 mg/dL -- higher than normal, but not yet high enough to be classified as diabetes. (Pre-diabetes used to be referred to as “impaired glucose tolerance.”) Pre-diabetes greatly increases the risk for diabetes.

Treatment of pre-diabetes is very important. Research shows that lifestyle and medical interventions can help prevent, or at least delay, the progression to diabetes. While insulin-regulating drugs such as metformin (Glucophage) and acarbose (Precose) are sometimes prescribed, evidence indicates that lifestyle changes can be at least as effective as drug therapy. The most important lifestyle treatment for people with pre-diabetes is to lose weight through diet and regular exercise. Even a modest weight loss of 10 - 15 pounds can significantly reduce the risk of progressing to diabetes.

Because people with pre-diabetes have a higher risk for heart disease and stroke, diet and exercise are also very important for heart health, as is quitting smoking. It is also important to have your doctor check your cholesterol and blood pressure levels on a regular basis. Your doctor should also check your fasting blood glucose levels every 1 - 2 years.

The major treatment goals for people with type 2 diabetes are:

Treat all conditions that place the patients at risk for heart disease and stroke, which are the major killers of people with type 2 diabetes.
Control blood glucose levels. The goal is to achieve fasting blood glucose levels of less than 110 mg/dL and glycolated hemoglobin (HbA1c) levels of less than 7%. The objective is to reduce complications in small blood vessels and the nerve damage associated with diabetes.

An intensive multi-pronged approach is critical for reducing complications and improving survival rates in patients with diabetes. Intensive therapy includes:

Healthy lifestyle changes: Regular exercise; heart-healthy diet; quitting smoking.
Controlling blood sugar levels. Monitor blood sugar and hemoglobin HbA1C levels. Oral anti-hyperglycemic drugs such as metformin are first-line drug treatments. Insulin may eventually be needed.
Heart-protective drugs. These medications include various drugs to control high blood pressure (ACE inhibitors, diuretics, others) and cholesterol (statins, fibrates). Controlling high blood pressure is a proven factor in reducing mortality rates. Aspirin may help prevent blood clots and heart attack.

Different goals may be required for specific individuals, including pregnant women, very old and very young people, and those with accompanying serious medical conditions. Treating children with type 2 diabetes depends on the severity of the condition at diagnosis. Metformin is approved for children. Formerly, only insulin was approved for treating children with diabetes.

Lifestyle Changes

A simple heart-healthy diet with weight control and exercise is important for people with pre-diabetes and may be sufficient for some people with type 2 diabetes. Some patients may be able to control their blood sugar with lifestyle measures and not need medication. Even for patients who do need to take drugs, lifestyle plays an essential role in controlling diabetes. Lifestyle changes can be difficult to initiate and sustain, however. Patients should surround themselves with a solid network of doctors, dietitians, family, and friends who understand both their condition and their needs.

Although there are many major dietary approaches for protecting health, experts generally agree on the following recommendations for heart protection:

Choose fiber-rich food (whole grains, legumes, nuts) as the main source of carbohydrates, along with a high intake of fresh fruits and vegetables. High fiber foods help improve blood glucose levels. Whole grain cereals, which are rich in both fiber and magnesium, may also help reduce the risk for diabetes.
Limit saturated fats (found mostly in animal products) to less than 7% of total daily calories and avoid trans fatty acids (found in hydrogenated fats and many commercial products and fast foods). Choose unsaturated fats (particularly omega-3 fatty acids found in vegetable and fish oils).
In selecting proteins, choose soy protein, poultry, and fish over meat. A 2006 study found that soy does not help improve cholesterol. However, experts still recommend it as a heart-healthy food choice.
Weight control, quitting smoking, and exercise are essential components of any diet program.

[See In-Depth Report #43: Heart-healthy diet.]

There is no such thing as a single diabetes diet. Patients should meet with a professional dietitian to plan an individualized diet within the general guidelines that takes into consideration their own health needs.

Healthy eating habits along with good control of blood glucose are the basic goals, and several good dietary methods are available to meet them. General dietary guidelines for diabetes recommend:

Carbohydrates should provide 45 - 65% of total daily calories. The type and amount of carbohydrate are both important. Best choices are vegetables, fruits, beans, and whole grains. These foods are also high in fiber. Patients with diabetes should monitor their carbohydrate intake either through carbohydrate counting or meal planning exchange lists.
Fats should provide 25 - 35% of daily calories. Monounsaturated (olive, peanut, canola oils; avocados; nuts) and omega-3 polyunsaturated (fish, flaxseed oil, walnuts) fats are the best types. Limit saturated fat (red meat, butter) to less than 7% of daily calories. Choose nonfat or low-fat dairy instead of whole milk products. Limit trans-fats (hydrogenated fat found in snack foods, fried foods, commercially baked goods) to less than 1% of total calories.
Protein should provide 12 - 20% of daily calories, although this may vary depending on a patient’s individual health requirements. Patients with kidney disease should limit protein intake to less than 10% of calories. Fish, soy, and poultry are better protein choices than red meat.

[For detailed information, including diabetic exchange lists and carbohydrate counting, see In-Depth Report #42: Diabetes diet.]

Being overweight is the number one risk factor for type 2 diabetes. Even modest weight loss can help prevent type 2 diabetes from developing. It can also help control or even stop progression of type 2 diabetes in people with the condition and reduce risk factors for heart disease. Patients should aim to lose weight if their body mass index (BMI) is 25 - 29 (overweight) or higher (obese).

The American Diabetes Association recommends that patients aim for a small but consistent weight loss of ½ - 1 pound per week. Most patients should follow a diet that supplies at least 1,000 - 1,200 kcal/day for women and 1,200 - 1,600 kcal/day for men.

Unfortunately, not only is weight loss difficult to sustain, but many of the oral medications used in type 2 diabetes cause weight gain as a side effect. For obese patients who cannot control weight using dietary measures alone, weight-loss drugs, such as orlistat (Xenical) or sibutramine (Meridia), may be helpful. Orlistat may have specific benefits for people with diabetes. It may not only help achieve weight but also improve glucose, cholesterol, and lipid levels. In 2007, the FDA approved a non-prescription form of orlistat (alli). [See In-Depth Report #53: Obesity.]

Sedentary habits, especially TV watching, are associated with significantly higher risks for obesity and type 2 diabetes. Regular exercise, even of moderate intensity (such as brisk walking), improves insulin sensitivity and may play a significant role in preventing type 2 diabetes -- regardless of weight loss. An important study reported a 58% lower risk for type 2 diabetes in adults who performed moderate exercise for as little as 2.5 hours a week.

Aerobic Exercise. Aerobic exercise has significant and particular benefits for people with diabetes. Regular aerobic exercise, even of moderate intensity, improves insulin sensitivity. People with diabetes are at particular risk for heart disease, so the heart-protective effects of aerobic exercise are especially important. Moderate exercise protects the heart in people with type 2 diabetes, even if they have no risk factors for heart disease other than diabetes itself.

For improving glycemic control, the American Diabetes Association recommends at least 150 minutes per week of moderate-intensity physical activity (50 - 70% of maximum heart rate) or at least 90 minutes per week of vigorous aerobic exercise (more than 70% of maximum heart rate). Exercise at least 3 days a week, and do not go more than 2 consecutive days without physical activity.

Strength Training. Strength training, which increases muscle and reduces fat, is also helpful for people with diabetes who are able to do this type of exercise. The American Diabetes Association recommends performing resistance exercise three times a week. Build up to three sets of 8 - 10 repetitions using weight that you cannot lift more than 8 - 10 times without developing fatigue. Be sure that your strength training targets all of the major muscle groups.

Exercise Precautions. The following are precautions for all people with diabetes, both type 1 and type 2:

Because people with diabetes are at higher than average risk for heart disease, they should always check with their doctors before undertaking vigorous exercise. For fastest results, frequent high-intensity (not high-impact) exercises are best for people who are cleared by their doctors. For people who have been sedentary or have other medical problems, lower-intensity exercises are recommended.
Strenuous strength training or high-impact exercise is not recommended for people with uncontrolled diabetes. Such exercises can strain weakened blood vessels in the eyes of patients with retinopathy. High-impact exercise may also injure blood vessels in the feet.

Patients who are taking medications that lower blood glucose, particularly insulin, should take special precautions before embarking on a workout program:

Monitor glucose levels before, during, and after workouts (glucose levels swing dramatically during exercise).
Avoid exercise if glucose levels are above 300 mg/dL or under 100 mg/dL.
Inject insulin in sites away from the muscles used during exercise; this can help avoid hypoglycemia.
Drink plenty of fluids before and during exercise; avoid alcohol, which increases the risk of hypoglycemia.
Insulin-dependent athletes may need to decrease insulin doses or take in more carbohydrates prior to exercise, but may need to take an extra dose of insulin after exercise (stress hormones released during exercise may increase blood glucose levels).
Wear good, protective footwear to help avoid injuries and wounds to the feet.
Some blood pressure drugs can interfere with exercise capacity. Patients who use blood pressure medication should consult their doctors on how to balance medications and exercise. Patients with high blood pressure should also aim to breathe as normally as possible during exercise. Holding the breath can increase blood pressure.

[See In-Depth Report #29: Exercise.]

According to the American Diabetes Association, people with diabetes should aim for preprandial (before eating) plasma glucose levels of 90 - 130 mg/dL and postprandial (after eating) plasma glucose levels less than 180 mg/dL. Hemoglobin A1C levels should be less than 7%.

Measuring Blood Glucose. In patients being treated with insulin or insulin-producing or sensitizing drugs, it is important to monitor blood glucose levels carefully to avoid hypoglycemia. Different goals may be required for specific individuals, including pregnant women, very old and very young people, and those with accompanying serious medical conditions.

Blood glucose levels are generally more stable in type 2 diabetes than in type 1, so experts usually recommend measuring blood levels only once or twice a day. For patients who have become insulin-dependent, more intensive monitoring is necessary. Usually, a drop of blood obtained by pricking the finger is applied to a chemically treated strip. The glucose level is read on a standard meter or a small, portable digital display device. For patients who have trouble controlling hypoglycemia (low blood sugar) or fluctuating blood sugar levels, continuous glucose sensor monitors are also available. In 2007, the FDA approved the STS-7 System, which continuously measures glucose levels for up to 7 days through a sensor inserted beneath the skin of the abdomen. Continuous glucose sensor monitors do not replace fingerstick glucose meters and test strips, but are used in combination with them. [See In-Depth Report #9: Diabetes - type 1.]

Measuring Hemoglobin A1C. Hemoglobin A1c (also called HbA1c , HA1c, or A1C) is measured periodically every 2 - 3 months to determine the average blood-sugar level over the lifespan of the red blood cell. Normal A1C levels should be below 7%. Home tests are also available for measuring A1C.

To monitor the amount of glucose within the blood a person with diabetes should test their blood regularly. The procedure is quite simple and can often be done at home.

Some research suggests that not getting enough sleep may impair insulin use and increase the risk for obesity. More research is needed, but it is always wise to improve sleep habits.

Medications

The American Heart Association now recommends that patients should aim for the following test results for intensive control of glucose levels:

Fasting plasma glucose concentrations below 110 mg/dL.
Glycolated hemoglobin (HbA1c) levels of less than 7%. Controlling HbA1c is the most important factor for reducing the risk of complications in patients with diabetes. According to one 2000 study, a 1% reduction in people with elevated glycolated hemoglobin levels lowers the risk for complications by 21%.

Evidence clearly supports strict glycemic control for reducing complications in the nervous system and blood vessels that occur in both type 1 and type 2 diabetes. Research shows that tight glucose control can help prevent heart disease and complications.

Managing risk factors for heart disease and stroke, particularly strict control of blood pressure, may be more important for improving survival than strict control of blood glucose levels for some patients. Such goals also seem to be more attainable for many patients with type 2 diabetes.

Oral Anti-Hyperglycemic Drugs. Many oral anti-hyperglycemic drugs are available to help patients with type 2 diabetes control their blood sugar levels. Most of these drugs are aimed at using or increasing sensitivity to the patient's own natural stores of insulin. Metformin is the only drug to date that achieves lower mortality rates. Oral type 2 diabetes drugs include:

Biguanides (metformin). Metformin increases tissue sensitivity to available insulin. Metformin also has beneficial effects on cholesterol, blood pressure, and clotting factors. It does not cause weight gain or hypoglycemia. Diarrhea and digestive problems are the most common side effects. Metformin produces lower mortality rates than other drugs, including insulin, and should be considered as first-line therapy for most patients with type 2 diabetes.
Sulfonylureas (glyburide, glipizide, glimepiride, repaglinide). Stimulate insulin secretion but can cause hypoglycemia more than other drugs.
DPP-4 inhibitors (sitagliptin). Also called gliptins, DPP-4 inhibitors were first approved in 2006 and are the newest class of oral diabetes drugs. Like metformin, they do not cause weight gain and have low risks for hypoglycemia.
Meglitinides (repaglinide, nateglinide). Stimulate insulin secretion. These newer drugs are better than sulfonylureas in controlling glucose spikes after meals.
Thiazolidinediones (pioglitazone and rosiglitazone). Reduce insulin resistance. These drugs improve cholesterol levels and may reduce the risk for blood clots. However, they can cause swelling from fluid build-up, which can worsen heart failure or even precipitate it. They may also injure the liver.
Alpha-glucosidase inhibitors (acarbose and miglitol). Slow intestinal absorption of carbohydrates. Have only modest effects on diabetes and have gastrointestinal side effects. Can slightly raise HDL (“good”) cholesterol levels.
Combinations of these drugs, particularly with metformin, are often used to increase effectiveness.

A 2007 review in the Annals of Internal Medicine compared these various classes of medications. The review found that older drugs -- such as metformin and sulfonylureas -- are less expensive than and work as well as newer diabetes drugs. In particular, the review cited metformin as a safe and effective drug because it does not cause weight gain or too-low blood sugar. Metformin can also help lower LDL (“bad”) cholesterol.

Injectable Anti-Hyperglycemic Drugs. In 2005, the FDA approved two new injectable drugs to help patients improve blood sugar control:

Exenatide (Byetta). Exenatide is the first drug in a new class of drugs called incretin mimetics. It lowers blood glucose levels by increasing insulin secretion. Exenatide is used in combination with oral antihyperglycemics, such as metformin or a sulfonylurea drug.
Pramlintide (Symlin). Pramlintide is a first-in-class drug that is a synthetic form of the hormone amylin. The drug is meant for patients who take insulin but still have difficulty controlling their glucose levels.

Insulin Replacement. Insulin replacement may be required when natural insulin reserves are depleted. It is typically started in combination with an oral drug. Eventually, some patients may need to go on full insulin replacement. In addition to injectable forms of insulin, an inhaled insulin product (Exubera) is now available.

Metformin (Glucophage) is a biguanide, which works by reducing glucose production in the liver and by making tissues more sensitive to insulin. Many experts recommend it as a first choice for most patients with type 2 diabetes who are insulin resistant, particularly if they are overweight. Metformin achieves lower mortality rates from diabetes and all causes than other drugs. In one comparison study, it achieved the lowest mortality rates (8%) compared to insulin (28%), a sulfonylurea (16%), and a thiazolidinedione (14%). Combinations with insulin-secreting drugs, other insulin-sensitizing drugs, or insulin itself are particularly effective.

Metformin does not cause hypoglycemia or add weight, so it is particularly well-suited for obese patients with type 2 diabetes. (In some studies, in fact, patients lost weight.) Metformin also appears to have beneficial effects on cholesterol and lipid levels and may help protect the heart. Some research has suggested that it significantly reduces the risk for heart attack. It is also the first choice for children who need oral drugs and is proving to be very effective for women with polycystic ovary syndrome and insulin resistance.

Side Effects. Side effects include:

A metallic taste
Gastrointestinal problems, including nausea, and diarrhea
Interference with absorption of vitamin B12 and folic acid, (which are important for protection against heart disease)
Rare reports of lactic acidosis, a potentially life-threatening condition, particularly in people with risk factors for it. Major studies, however, found no greater risk with metformin than with any of the other drugs used for type 2 diabetes.

Certain people should not use this drug, including anyone with heart failure or kidney or liver disease. It is rarely suitable for adults over age 80.

Sulfonylureas are oral drugs that stimulate the pancreas to release insulin. They are also first-line oral drugs. For adequate control of blood glucose levels, the drugs should be taken only 20 - 30 minutes before a meal. A number of brands are available, including chlorpropamide (Diabinese), tolazamide (Tolinase), acetohexamide (Dymelor), glipizide (Glucotrol), tolbutamide (Orinase), glyburide (Micronase), glimepiride (Amaryl), and repaglinide (Prandin).

Most patients can take sulfonylureas for 7 - 10 years before they lose effectiveness. Combinations with small amounts of insulin or with other oral anti-hyperglycemic drugs (such as metformin or a thiazolidinedione) may extend their benefits. A combination of glyburide and metformin in one pill (Glucovance) is available. Glucovance may be particularly beneficial for patients with unhealthy cholesterol levels and poor control of their blood sugar levels. Some doctors recommend the combination as first-line treatment.

An encouraging 2000 study of patients with severe type 2 diabetes reporting that combinations of insulin with either chlorpropamide or glipizide achieved better glucose control over the long term than insulin alone.

Side Effects and Complications. In general, sulfonylureas should not be used by women who are pregnant or nursing or by individuals who are allergic to sulfa drugs. Side effects may include:

Weight gain (some sulfonylureas, such as glimepiride, may produce less weight gain than others)
Water retention
Although sulfonylureas pose a lower risk for hypoglycemia than insulin does, the hypoglycemia produced by sulfonylureas may be especially prolonged and dangerous. The newer sulfonylureas, such as glimipiride, have much less risk of hypoglycemia than older sulfonylureas.
Some sulfonylureas may pose a slight risk for cardiac events.

Sulfonylureas interact with many other drugs, and patients should be sure to inform their doctor of any medications they are taking, including alternative or over-the-counter drugs.

Meglitinides stimulate beta cells to produce insulin. They include repaglinide (Prandin), nateglinide (Starlix), and mitiglinide. These drugs are rapidly metabolized and short-acting. If taken before every meal, they actually mimic the normal effects of insulin after eating. Patients, then, can vary their meal times with this drug. (Nateglinide appears to work more quickly and is shorter-acting than repaglinide). These drugs may be particularly helpful in combination with metformin or other drugs. They may also be a good choice for people with potential kidney problems.

Side Effects. Side effects include diarrhea and headache. As with the sulfonylureas, repaglinide poses a slightly increased risk for cardiac events. (Newer drugs, such as nateglinide, may pose less of a risk.) People with heart failure or liver disease should use them with caution and be monitored.

Thiazolidinediones, also known as peroxisome proliferator-activated receptor (PPAR) agonists, include rosiglitazone (Avandia) and pioglitazone (Actos). They improve insulin sensitivity by activating certain genes involved in fat synthesis and carbohydrate metabolism. These drugs are usually taken once or twice per day; however, it may take several days before the patient notices any results from them and several weeks before they take full effect. Thiazolidinediones are usually taken in combination with other oral drugs or insulin.

Side Effects. Thiazolidinediones can have serious side effects. They tend to increase fluid-build up, which can cause or worsen heart failure in some patients. Combinations with insulin increase the risk. They should not be used by patients with existing heart failure and should be used cautiously in those with risk factors for heart failure.

In 2007, a study published in the New England Journal of Medicine (NEJM) raised serious concerns that rosiglitazone may increase the risk of heart attack. The study reviewed 42 clinical trials of rosiglitazone. Results suggested that patients who took rosiglitazone were 43% more likely to have a heart attack, and 64% more likely to die from overall heart causes, than patients with diabetes who did not take the drug. A subsequent interim analysis in the NEJM found that while rosiglitazone was definitely associated with increased risk of heart failure, the data were insufficient to determine if the drug increases heart attack risk. The FDA has concluded that rosiglitazone may increase the risk of heart attack and will likely restrict its use. In 2007, a panel of experts from the Food and Drug Administration (FDA) agreed the drug increases the risk of heart attacks -- but concluded it should remain on the market. The panel did, however, recommend the FDA require rosiglitazone's maker to add warnings to the drug's label. Patients who take rosiglitazone, especially those who have heart disease or who are at high risk for heart attack, should discuss their treatment options with their doctors.

Thiazolidinediones may cause more weight gain than other diabetes medications or insulin. Any patient who experiences sudden weight gain, water retention, or shortness of breath should immediately call their doctor. These drugs have also been linked to increased risks for bone fracture.

There have been rare reports of rosiglitazone causing or worsening diabetic macular edema. This is an eye condition associated with diabetic retinopathy that causes swelling in the macular area of the retina. Symptoms include blurred vision and decreased color sensitivity. Most patients who had this side effect also had swelling in the feet and legs (peripheral edema). The condition resolved or improved when patients stopped taking the drug.

Thiazolidinediones can also cause liver damage. Patients who take these drugs should have their liver enzymes checked regularly.

Alpha-glucosidase inhibitors, including acarbose (Precose, Glucobay) and miglitol (Glyset), reduce glucose levels by interfering with the absorption of starch in the small intestine. Acarbose tends to lower insulin levels after meals, a particular advantage, since higher levels of insulin after meals are associated with an increased risk for heart disease. Some evidence suggests that early use of these drugs may reduce heart risk factors, including high blood pressure. A 2002 study of acarbose suggested that these drugs may possibly delay the development of type 2 diabetes in high-risk individuals. Alpha-glucosidase inhibitors are not as effective alone as other single oral drugs, but combinations, such as with metformin, insulin, or a sulfonylurea, increase their effectiveness.

Side Effects. These medications need to be taken with meals. Unfortunately, about a third of patients stop taking the drug because of flatulence and diarrhea, particularly after high-carbohydrate meals. The drug may also interfere with iron absorption.

Alpha-glucosidase inhibitors do not cause hypoglycemia when used alone, but combinations with other drugs do. In such cases, it is important that the patient receive a solution that contains glucose or lactose, not table sugar. This is because acarbose inhibits the breakdown of complex sugar and starches, which includes table sugar.

Incretin mimetics belong to a new class of drugs that help improve blood sugar control. Incretins include glucagon-like peptide-1 (GLP-1) inhibitors and DDP-4 inhibitors.

In 2005, the FDA approved exenatide (Byetta), the first GLP-1 inhibitor drug. Exenatide is an injectable drug that is a synthetic version of the hormone found in the saliva of the Gila monster, a venomous desert lizard. Exenatide is injected twice a day, 1 hour before morning and evening meals. It is prescribed for patients with type 2 diabetes who have not been able to control their glucose with metformin or a sulfonylurea drug. It can be taken in combination with these drugs or alone.

Side Effects. Exenatide stimulates insulin secretion only when blood sugar levels are high and so has less risk for causing low blood sugar (hypoglycemia) when it is taken alone. However, the risk for hypoglycemia increases when exenatide is taken along with a sulfonylurea drug. There does not appear to be a risk for hypoglycemia when exenatide is used along with metformin. Other side effects may include nausea, vomiting, and diarrhea.

A 2005 study compared exenatide to insulin for improving glucose control in patients taking metformin and a sulfonylurea. Both insulin and exenatide worked well for glucose control. Patients lost weight with exenatide and gained weight with insulin. However, patients who received exenatide had significantly more problems with nausea, vomiting, and diarrhea than those who received insulin.

Dipeptidyl peptidase-4 (DPP-4) inhibitors, also called gliptins, are the second class of incretin drugs. In October 2006, the FDA approved the first DPP-4 inhibitor -- sitagliptin (Januvia). It can be used alone or in combination with metformin or a thiazolidinedione drug. In April 2007, the FDA approved Janumet, which combines sitagliptin with metformin in one pill. Other DPP-4 drugs being studied include vildagliptin (Galvus) and saxagliptin.

DPP-4 inhibitors work in a similar way to GLP-1 inhibitors. However, unlike exenatide, which is given by injection, DPP-4 inhibitor drugs are taken as pills by mouth.

Like exenatide, DPP-4 inhibitors do not cause weight gain, have low risks for hypoglycemia, and have few severe side effects. The most common side effects include upper respiratory tract infection, sore throat, and diarrhea.

Insulin replacement is the best treatment for strict control of blood glucose and is required once natural insulin reserves are depleted. Because type 2 diabetes is progressive, most patients eventually require insulin, typically starting it in combination with an oral anti-hyperglycemic drug. However, when a single oral drug fails to control blood sugar it is not clear whether it is better to add insulin replacement or to add a second or third oral drug.

Some experts advocate using insulin as early as possible for optimal control. However, in patients who still have insulin reserves, there is concern that extra natural insulin will have adverse effects. Low blood sugar (hypoglycemia) and weight gain are the main side effects of insulin therapy. Some research suggests that insulin may also cause heart complications. A 2006 study reported that insulin therapy increases the risk of developing high blood pressure (hypertension). It is still not clear if insulin replacement improves survival rates compared to oral drugs, notably metformin.

One approach is to combine insulin with metformin, which achieves blood glucose control without added weight gain. Newer forms of insulin analogues, such as glargine, may be especially helpful for people with type 2 diabetes and reduce the risk for hypoglycemia.

Fortunately, studies to date have not reported any adverse cardiac effects in patients with type 2 diabetes who take insulin. In fact, insulin has been associated, in some cases, with improvement in heart risk factors. More research is needed to clarify these important issues.

Forms of Insulin. Experts are working toward administering insulin so that it closely mimics the daily pattern of insulin, which responds to blood sugar levels by surging after meals and then falling to a steady base level afterward. To achieve this, doctors may use two insulin types:

Fast-Acting Insulins for Surges. Insulin lispro and aspart are fast-acting insulins. They mimic insulin's response to food intake. They are taken before meals, and their short action reduces the risk for hypoglycemia afterward.
Slower Insulins for Base Levels. Intermediate forms (including NPH and lente) and long-acting forms (glargine, ultralente) were developed to provide a steady level of insulin throughout the day. To date, glargine (Lantus) seems to be the most successful in achieving this goal in type 2 diabetes.

In 2006, the FDA approved the first non-injected form of insulin. Exubera is an inhaled form of insulin. It is approved for adults but should not be used by patients who smoke or have quit smoking within the past 6 months. Patients with asthma, bronchitis, or emphysema should also not use inhaled insulin. Clinical trials indicate that Exubera can provide sustained blood sugar control over a 2-year period. Patients in the trials who took Exubera experienced half as much weight gain as those who took injected insulin. Scientists are also developing other types of non-injected insulin, including spray formulas.

In a 2005 trial, Exubera improved blood sugar control when it was added to or substituted for combination oral drug therapy (sulphonylurea and thiazolidenedione). However, as with other forms of insulin, Exubera caused more hypoglycemia and weight gain than the oral anti-hyperglycemic drugs.

Pramlintide (Symlin) is a new type of injectable drug that may help patients who take insulin but still need better blood sugar control. The FDA approved this drug in 2005. Pramlintide is a synthetic form of amylin, a hormone that is related to insulin. Pramlintide is used in combination with insulin to lower blood sugar levels in the 3 hours after meals.

[See In-Depth Report #9: Diabetes - type 1.]

Sodium Glucose Uptake Transporter 2 (SGLT-2) Inhibitors. SGLT-2 inhibitors are a new class of drug being investigated for treatment of type 2 diabetes. Preliminary trials for two of these drugs, dapagliflozin and serglifozin, have shown promising results in helping improve blood glucose control. The drugs are being tested in combination with metformin.

Various fraudulent products are often sold on the Internet as “cures” or treatments for diabetes. These dietary supplements have not been studied or approved. In 2006, the FDA and Federal Trade Commission (FTC) launched a crackdown on these scams. The FDA and FTC warn patients with diabetes not to be duped by bogus and unproven remedies.

Long-Term Complications

Patients with diabetes have higher mortality rates than people who do not have diabetes regardless of sex, age, or other factors. Heart disease and stroke are the leading causes of death in these patients. All lifestyle and medical efforts should be made to reduce the risk for these conditions.

People with type 2 diabetes are also at risk for nerve damage (neuropathy) and abnormalities in both small and large blood vessels (vascular injuries) that occur as part of the diabetic disease process. Such abnormalities produce complications over time in many organs and structures in the body. Although these complications tend to be more serious in type 1 diabetes, they still are of concern in type 2 diabetes. All people with diabetes should aim for fasting blood glucose levels of less than 110 mg/dL and hemoglobin HbA1C of less than 7%.

There are two important approaches to preventing complications from diabetes:

Intensive control of blood glucose and keeping glycosylated hemoglobin (HbA1c) levels below 7%. Tight blood glucose and HbA1c control can prevent complications due to vascular (blood vessel) abnormalities and nerve damage (neuropathy) that can cause major damage to organs, including the eyes, kidneys, and heart.
Managing risk factors for heart disease. Control of blood glucose also helps the heart, but its benefits occur over time. It is very important that people with diabetes control blood pressure, cholesterol levels, and other factors associated with heart disease.

Heart attacks account for 60% and strokes for 25% of deaths in patients with diabetes. Diabetes affects the heart in many ways:

Both type 1 and 2 diabetes speed the progression of atherosclerosis (hardening of the arteries). Diabetes can adversely affect blood lipid levels by lowering HDL ("good cholesterol") and increasing triglycerides. This can lead to coronary artery disease, heart attack, or stroke. According to a 2007 study, the risk of stroke doubles within 5 years of type 2 diabetes diagnosis.
Impaired nerve function (neuropathy) associated with diabetes also causes heart abnormalities. Some experts estimate that the mortality rates from neuropathy-related heart conditions range between 15 - 53%.
Women with diabetes are at particularly high risk for heart problems. A 2007 study indicated that while progress has been made in reducing mortality rates among men with diabetes, women with diabetes continue to face a high risk of death from heart disease and overall causes.

Tight blood sugar control may help protect blood vessels and reduce the risk for blood clotting. It is still not known whether intensive control will have a major protective effect on the heart, however. People with diabetes must be sure to use other measures as well to protect the heart.

Aspirin for Reducing the Risk for Blood Clots. Taking a daily aspirin (75 - 162 mg/day) reduces the risk for blood clotting and may help protect against heart attacks and heart disease. In a 2000 study, low-dose aspirin was associated with a 30% lower risk for death from heart disease in adults with type 2 diabetes.

Controlling Blood Pressure. Strict control of blood pressure is critical for preventing complications of diabetes and has proven to improve survival rates. Patients should strive for blood pressure levels of less than 130/80 mm Hg (systolic/diastolic). (Controlling systolic pressure may be especially important for reducing the risk for kidney complications.)

Dozens of anti-hypertensive drugs are available. Most fall into the following categories:

Diuretics rid the body of extra sodium (salt) and water. There are three main types of diuretics: Potassium-sparing, thiazide, and loop.
Angiotensin-converting enzyme (ACE) inhibitors reduce the production of angiotensin, a chemical that causes arteries to narrow.
Angiotensin-receptor blockers (ARBs) block angiotensin.
Beta-blockers block the effects of adrenaline and ease the heart’s pumping action.
Calcium-channel blockers (CCBs) decrease the contractions of the heart and widen blood vessels.

The American Diabetes Association (ADA) recommends any of these classes of drugs as first-line treatment for hypertension. New research suggests, however, that beta-blockers are less effective at preventing strokes and heart attacks than other types of blood pressure medications. Many patients require more than one type of drug to control blood pressure. For patients with diabetes who have microalbuminuria, the ADA strongly recommends ACE inhibitors or ARBs. Microalbuminuria is an accumulation of protein in the blood, which can signal the onset of kidney disease (nephropathy).

Anti-hypertensive drugs that block or reduce angiotensin are the first option for many people with diabetes. Angiotensin is a natural chemical that influences all aspects of blood pressure control and also interferes with insulin's normal metabolic signaling. In fact, angiotensin may be the common factor linking diabetes and high blood pressure.

The 2005 landmark Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) indicated that a thiazide-type diuretic works as well as an ACE inhibitor or CCB for patients with diabetes and high blood pressure. Compared with ACE inhibitors or CCBs, diuretics appeared to be better at lowering systolic blood pressure and preventing heart failure. In addition, the trial suggested that diuretics are especially helpful for African-Americans, by offering greater protection than ACE inhibitors or CCBS in preventing strokes.

Several 2006 studies suggested that anti-hypertensive drugs may increase the risk of developing diabetes. One study found more risk for thiazide diuretics and beta-blockers than ACE inhibitors and CCBs. Another study indicated that the ACE inhibitor ramipril had a lower risk of causing diabetes in African-Americans than a CCB or beta-blocker. A 2007 review in the Lancet also found a higher risk for new-onset diabetes with beta-blockers and diuretics, a medium risk with CCBs, and the lowest risk with ARBs and ACE inhibitors.

Research in this subject is important for patients with pre-diabetes who have high blood pressure. Results of future research may help doctors decide which treatment is most appropriate for patients with high blood pressure who are at high risk for diabetes. [See In-Depth Report #14: High blood pressure.]

Improving Cholesterol and Lipid Levels. Abnormal cholesterol and lipid levels are common in diabetes. High LDL (“bad”) cholesterol should always be lowered, but people with diabetes also often have additional harmful imbalances including low HDL (“good”) cholesterol and high triglycerides. Patients should aim for LDL levels below 100 mg/dL, HDL levels over 50 mg/dL and triglyceride levels below 150 mg/dL. Patients with diabetes and existing heart disease should strive for even lower LDL levels; the American Diabetes Association recommends LDL levels below 70 mg/dL for these patients.

Statins are the best cholesterol-lowering drugs. They include atorvastatin (Lipitor), lovastatin (Mevacor, generics), pravastatin (Pravachol), simvastatin (Zocor, generics), fluvastatin (Lescol), and rosuvastatin (Crestor). These drugs are very effective for lowering LDL cholesterol levels. Recent studies indicate that aggressive high-dose statin therapy may be an important treatment approach for high-risk patients who need to substantially lower their LDL levels. A 2006 study found that patients with diabetes and heart disease who were treated with 80 mg daily of atorvastatin had a 25% lower risk of heart attack and stroke than patients who received the standard 10 mg daily dose.

The primary safety concern with statins has involved myopathy, an uncommon condition that can cause muscle damage and, in some cases, muscle and joint pain. A specific myopathy called rhabdomyolysis can lead to kidney failure. People with diabetes and risk factors for myopathy should be monitored for muscle symptoms

Although lowering LDL is beneficial, statins are not as effective as other medications -- such as fibrates, niacin, ezetimbe, or bile acid sequesters -- in addressing HDL and triglyceride imbalances. This is a common problem in type 2 diabetes. Combinations of statins with one of these drugs may be helpful for people with diabetes who have heart disease, low HDL, and near-normal LDL levels. Although combinations of statins and fibrates or niacin increase the risk of myopathy, both combinations are considered safe if used with extra care. Research presented at the 2007 annual meeting of the American Diabetes Association suggested that statins and fibrates may also help reduce the risk of developing peripheral neuropathy, the diabetes-associated nerve damage that can lead to loss of sensation in the feet.

Gemfibrozil (Lopid) and fenofibrate (Tricor) are usually the first choice for fibrate drugs. Niacin has the most favorable effect on raising HDL and lowering triglycerides of all the cholesterol drugs. However, about 30% of patients who take high-dose niacin experience increased blood glucose levels. Moderate doses of niacin can achieve lipid control without causing serious blood glucose problems. [See In-Depth Report #23: Cholesterol.]

Kidney disease (nephropathy) is a very serious complication of diabetes. With this condition, the tiny filters in the kidney (called glomeruli) become damaged and leak protein into the urine. Over time this can lead to kidney failure. Urine tests showing microalbuminuria (small amounts of protein in the urine) are important markers for kidney damage.

Prevention and Treatment of Nephropathy. Tight control of blood sugar and blood pressure is essential for preventing the onset of kidney disease. Long-term studies report that strict control of these two conditions produces a 60% reduction in new cases of nephropathy and a delay in progression of the disease. ACE inhibitors and ARBs, two classes of blood pressure medications, are very helpful for preventing or slowing the progression of diabetic kidney disease.

A doctor may recommend a low-protein diet for patients whose kidney disease is progressing despite tight blood sugar and blood pressure control. Protein-restricted diets can help slow disease progression and delay the onset of end-stage renal disease (kidney failure). However, patients with end-stage renal disease who are on dialysis generally require higher amounts of protein. [See In-Depth Report #42: Diabetes diet.]

Diabetic nephropathy occurs in about 20 - 40% of patients with diabetes and is the leading cause of end-stage renal disease. If the kidneys fail, dialysis is required. Symptoms of kidney failure may include swelling in the feet and ankles, itching, fatigue, and pale skin color.

Anemia is a common complication of end-stage kidney disease. Patients on dialysis usually require injections of erythropoiesis-stimulating drugs to increase red blood cell counts and control anemia. Dosing target levels of erythropoiesis-stimulating drugs are controversial, especially for patients with chronic kidney disease. In 2006, two important New England Journal of Medicine studies indicated that aggressive dosing to completely normalize hemoglobin levels does not work better than standard dosing that only partially corrects anemia.

In 2007, the FDA issued new warnings on darbepoetin alfa (Aranesp) and epoetin alfa (Epogen and Procrit). The warnings describe an increased risk with blood clots, strokes, and heart attacks in patients with end-stage kidney disease when these drugs were given at higher than recommended doses. The FDA has set new dosing and hemoglobin target levels for these drugs.

Another controversy surrounding erythropoiesis-stimulating drugs concerns their overuse at dialysis centers. A 2007 study in the Journal of the American Medical Association suggested that large, for-profit dialysis centers tend to administer higher-than-appropriate doses of these drugs compared to nonprofit facilities. The study suggested that for-profit centers are giving higher doses for financial, not medical, reasons.

The FDA recommends that patients with end-stage kidney disease who receive erythropoiesis-stimulating drugs should:

Maintain hemoglobin levels that do not exceed 12 g/dL
Receive frequent blood tests to monitor hemoglobin levels
Contact their doctors if they experience such symptoms as shortness of breath, pain, swelling in the legs, or increases in blood pressure

[See In-Depth Report #57: Anemia.]

Click the icon to see an image of the pancreas and kidneys.

Diabetes reduces or distorts nerve function, causing a condition called neuropathy. Neuropathy refers to a group of disorders that affect nerves. The two main types of neuropathy are:

Peripheral (affects nerves in the toes, feet, legs, hand, and arms)
Autonomic (affects nerves that help regulate digestive, bowel, bladder, heart, and sexual function)

Peripheral neuropathy particularly affects sensation. It is a common complication that affects nearly half of people with type 1 or type 2 diabetes after 25 years. The most serious consequences of neuropathy occur in the legs and feet and pose a risk for ulcers and, in very severe cases, amputation. Peripheral neuropathy usually starts in the fingers and toes and moves up to the arms and legs (called a stocking-glove distribution). Symptoms include:

Tingling
Weakness
Burning sensations
Loss of the sense of warm or cold
Numbness (if the nerves are severely damaged, the patient may be unaware that a blister or minor wound has become infected)
Deep pain

Autonomic neuropathy can cause digestive problems (constipation, diarrhea, nausea, vomiting), bladder infections, and erectile dysfunction. In some cases, neuropathy may mask angina, the chest pain warning for heart disease and heart attack. Patients with diabetes should be aware of other warning signs of a heart attack, including sudden fatigue, sweating, shortness of breath, nausea, and vomiting.

Blood sugar control is the only treatment for neuropathy. Studies show that tight control of blood glucose levels delays the onset and slows progression of neuropathy. A 2005 study also suggested that heart disease risk factors can increase the likelihood of developing neuropathy. Lowering triglycerides, losing weight, reducing blood pressure, and quitting smoking may help prevent the onset of neuropathy.

Prevention of Neuropathy. Patients with type 2 diabetes should receive regular screenings for loss of sensation in feet and other signs of neuropathy. A 2007 study suggested that statin and fibrate drugs, which are used to control cholesterol, may help protect against diabetic peripheral neuropathy.

Pain Relief for Peripheral Neuropathy. A number of different drugs are used for peripheral neuropathy pain relief. They include:

Nonprescription analgesics such as aspirin, acetaminophen, and non-steroidal anti-inflammatory drugs (NSAIDs). (Patients with stomach or kidney problems should check with their doctors before using these drugs.)
Prescription painkillers, such as tramadol (Ultram). Tramadol is a drug that is similar to opioids. It can help relieve pain but has significant side effects, including nausea, constipation, and headache.
Topical medications, particularly capsaicin (the active ingredient in hot peppers), are applied to the skin to relieve minor local pain. A 5% lidocaine patch has also shown good results in clinical trials.
Tricyclic antidepressants, such as amitriptyline (Elavil) or doxepin (Sinequan), are effective in reducing pain from neuropathy in up to 75% of patients. A combination of doxepin and capsaicin (applied to the skin) may be particularly beneficial. Unfortunately, tricyclics may cause heart rhythm problems.
Duloxetine (Cymbalta) is a serotonin and norepinephrine reuptake inhibitor, a newer type of antidepressant, which was approved in 2004 for treatment of pain associated with diabetic peripheral neuropathy.
The anti-convulsant drug pregabalin (Lyrica) was approved in 2004 for neuropathic pain management. It is classified as a controlled substance (like narcotics), which indicates a potential risk for abuse. Other anti-seizure drugs used for peripheral neuropathy pain relief include gabapentin (Neurontin) and valproate (Depakote).

Treatments under investigation include acetyl-l-carnitine and intravenous alpha-lipoic acid. Patients may also benefit from transcutaneous electrostimulation (TENS), a treatment that involves administering mild electrical pulses to painful areas. Alternative treatments such as hypnosis, biofeedback, relaxation techniques, and acupuncture have helped some patients manage pain. Doctors also recommend lifestyle measures such as walking and wearing elastic stockings.

Treatments for Other Complications of Neuropathy. Neuropathy also impacts other functions, and treatments are needed to reduce their effects. If diabetes affects the nerves in the autonomic nervous system, then abnormalities of blood pressure control and bowel and bladder function may occur. Erythromycin, domperidone (Motilium), or metoclopramide (Reglan) may be used to relieve delayed stomach emptying caused by neuropathy.

Erectile dysfunction is also associated with neuropathy. Evidence shows that phosphodiesterase type 5 (PDE-5) drugs, such as sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis), are safe and effective, at least in the short term, for patients with diabetes. Typical side effects are minimal but may include headache, flushing, and upper respiratory tract and flu-like symptoms.

Perhaps the most serious consequences of diabetic neuropathy occur in the lower limbs. An estimated 15% of patients with diabetes experience serious foot problems. They are the leading cause of hospitalizations for these patients.

Diabetes is responsible for more than half of all lower limb amputations performed in the U.S. Each year there are about 88,000 non-injury amputations, 50 - 75% of them due to diabetes. The number is increasing as the prevalence in diabetes type 2 rises. According to a 2005 study in the Lancet, every 30 seconds someone in the world receives a lower limb amputation due to diabetes. About 85% of amputations start with foot ulcers, which develop in about 12% of people with diabetes.

In general, foot ulcers develop from infections, such as those resulting from blood vessel injury. A 2006 study reported that people with diabetes who develop foot infections are 155 times more likely to have an amputation than people who did not develop infections. Foot infections often develop from injuries. Even minor infections can develop into severe complications. Numbness from nerve damage, which is common in diabetes, compounds the danger since the patient may not be aware of injuries. About one-third of foot ulcers occur on the big toe.

A 2003 government survey found that those at higher risk for foot ulcers tend to be people with diabetes who are overweight, smokers, and those with a long history of diabetes. People who have the disease for more than 20 years and are insulin-dependent are at the highest risk. Related conditions that put people at risk include peripheral neuropathy, peripheral artery disease, foot deformities, and a history of ulcers. [See In-Depth Report #102: Peripheral artery disease and intermittent claudication.]

Charcot Foot. Charcot foot or Charcot joint (medically referred to as neuropathic arthropathy) occurs in about 2.5% of people with diabetes. Early changes appear like an infection, with the foot becoming swollen, red, and warm. A seriously affected foot can become deformed. The bones may crack, splinter, and erode, and the joints may shift, change shape, and become unstable. It typically develops in people who have neuropathy to the extent that they cannot feel sensation in the foot and are not aware of an existing injury. Instead of resting an injured foot or seeking medical help, the patient often continues normal activity, causing further damage.

Charcot foot is initially treated with strict immobilization of the foot and ankle; some centers use a cast that allows the patient to move and still protects the foot. A 2001 study in the U.K. concluded that a single dose of pamidronate, a bisphosphonate, reduces bone turnover, symptoms, and disease activity. When the acute phase has passed, patients usually need lifelong protection of the foot using a brace initially and custom footwear.

Measures to Prevent Foot Ulcers. Preventive foot care can significantly reduce the risk of ulcers and amputation. Some tips for preventing problems include:

Patients should inspect their feet daily and watch for changes in color or texture, odor, and firm or hardened areas, which may indicate infection and potential ulcers.
When washing the feet, the water should be warm (not hot), and the feet and areas between the toes should be thoroughly dried afterward. Check water temperature with the hand or a thermometer before stepping in.
Moisturizers should be applied, but not between the toes.
Corns and calluses should be gently pumiced and toenails trimmed short and the edges filed to avoid cutting adjacent toes.
Patients should not use medicated pads or try to shave the corns or calluses themselves.
Well-fitting footwear is very important. People should be sure the shoe is wide enough; according to a 2001 study, 30% of patients with diabetes wear shoes that are too narrow. Patients should also avoid high heels, sandals, thongs, and going barefoot. Shoes with a rocker sole reduce pressure under the heel and front of the foot by 35 - 65% and may be particularly helpful. Custom-molded boots increase the surface area over which foot pressure is distributed. This reduces stress on the ulcers and allows them to heal.
Shoes should be changed often during the day.
Wear socks, particularly with extra padding (which can be specially purchased).
Patients should avoid tight stockings or any clothing that constricts the legs and feet.
Foot pain, numbness, or tingling is worse at night; diphenhydramine (Benadryl) may help.
A specialist in foot care should be consulted for any problems.

People with diabetes are prone to foot problems because the disease can cause damage to the blood vessels and nerves, which may result in decreased ability to sense trauma to the foot. The immune system is also altered, so that the patient cannot efficiently fight infection.

Treating Foot Ulcers in Diabetes. About one-third of foot ulcers will heal within 20 weeks with good wound care treatments. Treatments include:

Antibiotics are generally given. In some cases, hospitalization and intravenous antibiotics for up to 28 days may be needed for severe foot ulcers.
In virtually all cases, wound care requires debridement, which is the removal of injured tissue until only healthy tissue remains. Debridement may be accomplished using chemical (enzymes), surgical, or mechanical (irrigation) means.
Hydrogels (Nu-Gel, Intrasite Gel, Scherisorb, Clearsite, Duoderm, Geliperm) are helpful in healing ulcers and are noninvasive and soothing.
Felted foam may be helpful in healing ulcers on the sole of the foot. Felted foam uses a multi-layered foam pad over the bottom of the foot with an opening over the ulcer.

Other Treatments for Foot Ulcers. Doctors are also using or investigating other treatments to heal ulcers. These include:

Administering hyperbaric oxygen (oxygen given at high pressure) is showing promise in promoting healing. In one study, patients who had had ulcers that had not responded to treatment for over 3 months received daily treatments that lasted 90 minutes for 2 weeks. About 15 days after completion, patients who received oxygen had significant reduction in ulcers, sometimes with complete healing. Other studies are also demonstrating good results.
Monochromatic near-infrared photo energy (MIRE) uses light therapy to improve sensation in the feet of patients with peripheral neuropathy.
Total-contact casting (TCC) uses a cast that is designed to match the exact contour of the foot and to distribute weight along the entire length of the foot. It is usually changed weekly. It may be helpful for ulcer healing and for Charcot foot. Although it is very effective in healing ulcers, recurrence is common.

Diabetes accounts for 12,000 - 24,000 of new cases of blindness annually and is the leading cause of new cases of blindness in adults age 20 - 74. The most common eye disorder in diabetes is retinopathy. People with diabetes are also at higher risk for developing cataracts and certain types of glaucoma, such as primary-open angle glaucoma (POAG). The risk for POAG is especially high for women with type 2 diabetes. [See In-Depth Report #26: Cataracts and In-Depth Report #25: Glaucoma.]

Description of Retinopathy. Retinopathy is a condition in which the retina in the eye becomes damaged. The two primary abnormalities that occur are a weakening of the blood vessels in the retina and the obstruction in the capillaries -- probably from very tiny blood clots. Retinopathy generally occurs in one or two phases:

Click the icon to see an image of diabetic retinopathy.

The early and more common type of this disorder is called nonproliferative or background retinopathy. The blood vessels in the retina are abnormally weakened. They rupture and leak, and waxy areas may form. If these processes affect the central portion of the retina, swelling may occur, causing reduced or blurred vision.
If the capillaries become blocked and blood flow is cut off, soft, "woolly" areas may develop in the retina's nerve layer. These woolly areas may signal the development of proliferative retinopathy. Often there are no symptoms of progressing retinopathy. In this more severe condition, new abnormal blood vessels form and grow on the surface of the retina. They may spread into the cavity of the eye or bleed into the back of the eye. Major hemorrhage or retinal detachment can result, causing severe visual loss or blindness. The sensation of seeing flashing lights may indicate retinal detachment.

Click the icon to see an animation on diabetic retinopathy.

According to a 2003 study, about 40% of young adults with type 1 diabetes had developed retinopathy within 10 years of diagnosis. (Although this rate is high, it is significantly lower than in previous years when blood glucose control was not as strict.) The risk is lower in patients with type 2 diabetes, although in one study over 20% had signs of retinopathy 6 years after diagnosis. Patients who are newly diagnosed with type 2 diabetes should get a comprehensive eye examination, including dilation. In general, all patients with diabetes should have a yearly eye examination. Patients with no signs of retinal damage or low risk factors for retinopathy may only require screening every 2 - 3 years.

Prevention of Retinopathy. Fortunately, severe and even moderate vision loss is largely preventable with tight control of blood glucose levels. (Intense glucose control can cause early worsening of retinopathy, although this is nearly always counterbalanced by long-term benefits.) Tight control of blood pressure can also help protect against retinopathy. Aspirin therapy does not help prevent retinopathy.

Treatment of Retinopathy. Patients with severe diabetic retinopathy or macular edema (swelling of the retina) should be sure to see an eye specialist who is experienced in the management and treatment of diabetic retinopathy. Once damage to the eye develops, laser eye surgery may be needed. Laser surgery can help reduce vision loss in high-risk patients.

Studies indicate that patients with type 2 diabetes face a higher than average risk of developing dementia caused either by Alzheimer's disease or problems in blood vessels in the brain. Problems in attention and memory can occur even in people under age 55 who have had diabetes for a number of years. In one study of people with type 1 diabetes, high glucose levels (hyperglycemia) were associated with slower brain function, including less verbal fluency and slower ability to do mental arithmetic.

Respiratory Infections. People with diabetes face a higher risk for influenza and its complications, including pneumonia, possibly because the disorder neutralizes the effects of protective proteins on the surface of the lungs. In fact, deaths among people with diabetes increase by 5 - 15% during flu epidemics, and they are six times more likely to be hospitalized with complications from flu than nondiabetic patients who have flu. Everyone with diabetes should have annual influenza vaccinations and a vaccination against pneumococcal pneumonia.

Urinary Tract Infections. Women with diabetes face a significantly higher risk for urinary tract infections, which are likely to be more complicated and difficult to treat than in the general population.

Diabetes doubles the risk for depression. Furthermore, according to one study, depression, in turn, increases the risk for hyperglycemia and complications of diabetes. Restoring mental health, both through medication and psychotherapy, not only improves quality of life but may help patients control their blood sugar levels.

Diabetes changes bone quality and density, but the effects differ, depending on type:

Type 1 diabetes is associated with a slightly reduced bone density, putting patients at risk for osteoporosis and possibly fractures. The best medications for bone loss in patients with diabetes are bisphosphonates, such as alendronate (Fosamax) and risedronate (Actonel). They not only help prevent bone loss but may even reduce daily insulin requirements in patients taking insulin. [See In-Depth Report #18: Osteoporosis.]
Type 2 diabetes, on the other hand, is associated with an increased bone density but is also associated with fractures. In such cases, the bone quality itself may be impaired.

Older patients with either type of diabetes are at risk for falling, which compounds the risk for fracture.

Diabetes increases the risk for other conditions, including:

Hearing loss
Periodontal disease
Carpal tunnel syndrome
Nonalcoholic fatty liver disease, also called nonalcoholic steatohepatitis (NASH), a particular danger for people who are obese
Colorectal cancer
Uterine cancer

Emergency Complications

People with diabetes who need to intensively control glucose levels are at risk for low blood sugar (hypoglycemia). Hypoglycemia, also called insulin shock, develops if blood sugar levels fall below normal. It may also be caused by insufficient intake of food, excess exercise, or alcohol intake. The condition is usually manageable, but occasionally it can be severe or even life threatening, particularly if the patient fails to recognize the symptoms. Mild hypoglycemia is common among people with type 2 diabetes, but severe episodes are rare, even among those who are taking insulin. Still, all patients who intensively control blood sugar (glucose) levels should be aware of warning symptoms.

Risk Factors for Severe Hypoglycemia. People at highest risk for severe hypoglycemia are those who intensively control blood glucose and also have one or more of the following conditions:

Long-term diabetes
Less education on their condition
A previous history of severe hypoglycemia
Hypoglycemia unawareness

Hypoglycemia unawareness is a condition in which people become insensitive to hypoglycemic symptoms. It affects about 25% of patients who use insulin, nearly always people with type 1 diabetes. In such cases, hypoglycemia appears suddenly, without warning, and can escalate to a severe level. Even a single recent episode of hypoglycemia may make it more difficult to detect the next episode. With vigilant monitoring and by rigorously avoiding low blood glucose levels, patients can often regain the ability to sense the symptoms. However, even very careful testing may fail to detect a problem, particularly one that occurs during sleep.

Symptoms. Mild hypoglycemia symptoms usually occur at moderately low and easily correctable levels of blood glucose. They include:

Sweating
Trembling
Hunger
Rapid heartbeat

Severely low blood glucose levels can cause neurologic symptoms, such as:

Confusion
Weakness
Disorientation
Combativeness
In rare and worst cases, coma, seizure, and death

Preventive Measures. The following tips may help avoid hypoglycemia or prepare for attacks:

Patients are at highest risk for hypoglycemia at night. Bedtime snacks may be helpful.
Patients who intensively control their blood sugar should monitor blood levels as often as possible, four times or more per day. This is particularly important for patients with hypoglycemia unawareness.
In adults, it is also particularly critical to monitor blood glucose levels before driving, when hypoglycemia can be very hazardous.
Patients who use medications that put them at risk for hypoglycemia should always carry hard candy, juice, sugar packets, or commercially available glucose substitutes designed for individuals with diabetes.

Family and friends should be aware of the symptoms and be prepared:

If the patient is helpless (but not unconscious), family or friends should administer three to five pieces of hard candy, two to three packets of sugar, half a cup (four ounces) of fruit juice, or a commercially available glucose solution.
If there is inadequate response within 15 minutes, additional oral sugar should be provided or the patient should receive emergency medical treatment, including intravenous administration of glucose.
Family members and friends can learn to inject glucagon, a hormone, which, in contrast to insulin, raises blood glucose.

Click the icon to see a glucagon kit.

Diabetic ketoacidosis (DKA) is a life-threatening complication caused by insulin depletion. Until recently, it was a complication almost exclusively of type 1 diabetes. In such cases, it is nearly always due to noncompliance with insulin treatments. However, DKA is being reported increasingly in type 2 diabetes, especially among Hispanic- and African-Americans. It is not clear what causes total insulin depletion in these patients. Researchers are trying to learn which individuals are at particular risk.

Diabetic ketoacidosis often develop as follows:

The process is usually triggered in insulin-deficient patients by a stressful event, most often pneumonia or urinary tract infections. Other triggers include alcohol abuse, physical injury, pulmonary embolism, heart attacks, or other illnesses.
Severely low insulin levels cause excessive amounts of glucose in the bloodstream (hyperglycemia).
Fat breakdown then accelerates and increases the production of fatty acids.
These fatty acids are converted into chemicals called ketone bodies, which are toxic at high levels.

Symptoms and complications may include:

Nausea and vomiting
Abnormally deep and rapid breathing with frequent sighing
Rapid heartbeat
If the condition persists, coma and, eventually, death, may occur; however, over the past 20 years, death from DKA has decreased to about 2% of all cases.
Other serious complications from DKA include aspiration pneumonia and adult respiratory distress syndrome.

Life-saving treatment uses rapid rehydration with a saline solution followed by low-dose insulin and potassium replacement.

Resources

www.diabetes.org -- American Diabetes Association
www.niddk.nih.gov -- National Institute of Diabetes and Digestive and Kidney Diseases
www.americanheart.org -- American Heart Association
www.kidney.org -- National Kidney Foundation
www.nei.nih.gov -- National Eye Institute
www.medicalert.org -- Medic Alert
www.eatright.org -- American Dietetic Association
http://limaye.ecri.org -- Limaye Center

References

American Diabetes Association (ADA). Standards of medical care in diabetes. IV. Prevention/delay of type 2 diabetes. Diabetes Care. 2007 Jan;30(Suppl 1):S7-8.

American Diabetes Association (ADA). Standards of medical care in diabetes. V. Diabetes care. Diabetes Care. 2007 Jan;30(Suppl 1):S8-15.

American Diabetes Association (ADA). Standards of medical care in diabetes. VI. Prevention and management of diabetes complications. Diabetes Care. 2007 Jan;30(Suppl 1):S15-24.

Amori RE, Lau J, Pittas AG. Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta-analysis. JAMA. 2007 July 11;298:194-206.

Aschner P, Kipnes MS, Lunceford JK, Sanchez M, Mickel C, Williams-Herman DE, et al. Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care. 2006 Dec;29(12):2632-7.

Bolen S, Feldman L, Vassy J, Wilson L, Yeh H-C, Marinopoulos S, et al. Systematic review: comparative effectiveness and safety of oral medications for type 2 diabetes mellitus. Ann Intern Med. 2007 Jul 17; 147(6). [Epub ahead of print]

Carnethon MR, Biggs ML, Barzilay JI, Smith NL, Vaccarino V, Bertoni AG, et al. Longitudinal association between depressive symptoms and incident type 2 diabetes mellitus in older adults: the cardiovascular health study. Arch Intern Med. 2007 Apr 23;167(:802-7.

Charbonnel B, Karasik A, Liu J, Wu M, Meininger G; Sitagliptin Study 020 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone. Diabetes Care. 2006 Dec;29(12):2638-43.

Drueke TB, Locatelli F, Clyne N, Eckardt KU, Macdougall IC, Tsakiris D, et al. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med. 2006 Nov 16;355(20):2071-84.

Elliott WJ, Meyer PM. Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis. Lancet. 2007 Jan 20;369(9557):201-7.

Florez JC, Jablonski KA, Bayley N, Pollin TI, de Bakker PI, Shuldiner AR, et al. TCF7L2 polymorphisms and progression to diabetes in the Diabetes Prevention Program. N Engl J Med. 2006 Jul 20;355(3):241-50.

Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science. 2007 May 11;316(5826):889-94. Epub 2007 Apr 12.

Gillies CL, Abrams KR, Lambert PC, Cooper NJ, Sutton AJ, Hsu RT, et al. Pharmacological and lifestyle interventions to prevent or delay type 2 diabetes in people with impaired glucose tolerance: systematic review and meta-analysis. BMJ. 2007 Feb 10;334(7588):299. Epub 2007 Jan 19.

Grant SF, Thorleifsson G, Reynisdottir I, Benediktsson R, Manolescu A, Sainz J, et al. Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat Genet. 2006 Mar;38(3):320-3. Epub 2006 Jan 15.

Gregg EW, Gu Q, Cheng YJ, Narayan KM, Cowie CC. Mortality trends in men and women with diabetes, 1971-2000. Ann Intern Med. 2007 Jun 18; [Epub ahead of print]

Home PD, Pocock SJ, Beck-Nielsen H, Gomis R, Hanefeld M, Jones NP, et al. Rosiglitazone evaluated for cardiovascular outcomes--an interim analysis. N Engl J Med. 2007 Jul 5;357(1):28-38. Epub 2007 Jun 5.

Jeerakathil T, Johnson JA, Simpson SH, Majumdar SR. Short-term risk for stroke is doubled in persons with newly treated type 2 diabetes compared with persons without diabetes: a population-based cohort study. Stroke. 2007 Jun;38(6):1739-43. Epub 2007 May 3.

Lee AJ, Hiscock RJ, Wein P, Walker SP, Permezel M. Gestational diabetes mellitus: clinical predictors and long-term risk of developing type 2 diabetes: a retrospective cohort study using survival analysis. Diabetes Care. 2007 Apr;30(4):878-83.

Pasquale LR, Kang JH, Manson JE, Willett WC, Rosner BA, Hankinson SE. Prospective study of type 2 diabetes mellitus and risk of primary open-angle glaucoma in women. Ophthalmology. 2006 Jul;113(7):1081-6. Epub 2006 Jun 6.

Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007 Jun 14;356(24):2457-71. Epub 2007 May 21.

Psaty BM, Furberg CD. Rosiglitazone and cardiovascular risk. N Engl J Med. 2007 Jun 14;356(24):2522-4. Epub 2007 May 21.

Schulze MB, Schulz M, Heidemann C, Schienkiewitz A, Hoffmann K, Boeing H. Fiber and magnesium intake and incidence of type 2 diabetes: a prospective study and meta-analysis. Arch Intern Med. 2007 May 14;167(9):956-65.

Scott LJ, Mohlke KL, Bonnycastle LL, Willer CJ, Li Y, Duren WL, et al. A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science. 2007 Jun 1;316(5829):1341-5. Epub 2007 Apr 26.

Singh AK, Szczech L, Tang KL, Barnhart H, Sapp S, Wolfson M, et al. Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med. 2006 Nov 16;355(20):2085-98.

Thamer M, Zhang Y, Kaufman J, Cotter D, Dong F, Hernen MA. Dialysis facility ownership and epoetin dosing in patients receiving hemodialysis. JAMA. 2007 Apr 18;297(15):1667-74.

Vardi M, Nini A. Phosphodiesterase inhibitors for erectile dysfunction in patients with diabetes mellitus. Cochrane Database Syst Rev. 2007 Jan 24(1):CD002187.

Zeggini E, Weedon MN, Lindgren CM, Frayling TM, Elliott KS, Lango H, et al. Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science. 2007 Jun 1;316(5829):1336-41. Epub 2007 Apr 26.

Review Date:
7/31/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

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Osteoarthritis

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In This Report

Highlights
Introduction
Causes
Symptoms
Conditions with Similar Sym...
Risk Factors
Diagnosis
Prognosis
Lifestyle Changes
Medications
Alternative and Complementa...
Surgery
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Pain Medications

Nonsteroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors work equally well for pain management, but both types of drugs increase the risk for heart attacks, according to an important report from the U.S. Agency for Healthcare Quality and Research.
The prescription NSAID diclofenac (Voltaren, Cataflam) may present a higher risk for heart attack than other NSAIDs, suggests a 2006 Journal of the American Medical Association study.
Standard osteoarthritis medications provide moderate pain relief for only 2 - 3 weeks, suggests a 2007 review in the European Journal of Pain.

Acupuncture

Acupuncture may be helpful for people with knee and hip osteoarthritis, according to several 2006 studies:

An Annals of Internal Medicine study of 1,007 people with chronic osteoarthritis knee pain indicated that patients who received acupuncture plus standard care had greater improvement than those who received only physical therapy and anti-inflammatory drugs.
An Arthritis and Rheumatism study of 3,663 patients with chronic osteoarthritis knee or hip pain suggested that acupuncture plus routine care can provide significant improvements in pain relief and quality of life. In both studies, the benefits of acupuncture were sustained for up to 6 months after treatment completion.

Exercise and Knee Osteoarthritis

Weight-bearing exercise (walking, jogging) neither prevents nor increases the risk of knee osteoarthritis in healthy middle-aged and elderly people, suggests a 2007 study in Arthritis and Rheumatism.

Risk of Hip Osteoarthritis

About 1 in 4 Americans can expect to develop osteoarthritis of the hip at some point in life, according to research presented at the 2006 American College of Rheumatology annual meeting. Body weight is a factor. People who are normal weight have a 20% risk, compared to those who are overweight (25%) or obese (39%).

Introduction

Osteoarthritis, also known as degenerative joint disease, is the most common form of arthritis. Scientists now believe osteoarthritis results from a combination of genetic abnormalities and joint injuries. In this disorder, an affected joint experiences a progressive loss of cartilage, the slippery material that cushions the ends of bones.

Osteoarthritis is a chronic disease of the joint cartilage and bone, often thought to result from "wear and tear" on a joint, although there are other causes such as congenital defects, trauma, and metabolic disorders. Joints appear larger, are stiff and painful, and usually feel worse with increased use throughout the day.

As a result, the bone beneath the cartilage undergoes changes that lead to bony overgrowth. The tissue that lines the joint can become inflamed, the ligaments can loosen, and the associated muscles can weaken. The patient experiences pain when using the joint. In addition to humans, nearly all vertebrates suffer from osteoarthritis, including porpoises and whales, as did long-extinct terrestrial travelers such as dinosaurs.

Click the icon to see an animation about osteoarthritis.

Joints are designed to provide flexibility, support, stability, and protection. These functions, essential for normal and painless movement, are primarily supplied by specific parts of the joint: the synovium and cartilage.

Synovium. The synovium is a membrane that surrounds the entire joint. It is filled with synovial fluid, a lubricating liquid that supplies nutrients and oxygen to cartilage.

Cartilage. The cartilage is a slippery tissue that coats the ends of the bones. Cartilage is one of the few tissues in the body that does not have its own blood supply. It has a number of essential components:

Click the icon to see an image of the synovial membrane and cartilage in the knee joint.

Chondrocytes. Chondrocytes, the basic cartilage cells, are critical for balance and function.
Water. Cartilage contains a high percentage of water, although it decreases with age. About 85% of cartilage is water in young people, and about 70% is water in older individuals.
Proteoglycans. These are large molecules that help make up cartilage. Their important value is their capacity to bond to water, which ensures the high-fluid content in cartilage.
Collagen. This is the critical protein in cartilage. It forms a mesh to give support and flexibility to the joint. Collagen is the main protein found in all the connective tissues of the body, including the muscles, ligaments, and tendons.

The combination of the collagen meshwork and the high water content, tightly bound by proteoglycans, creates a resilient and slippery pad in the joint, which resists the compression between bones during muscle movement. The synovial fluid lubricates and provides oxygen and nutrients to the bloodless cartilage.

Deterioration of Cartilage. Osteoarthritis develops when cartilage in a joint deteriorates. The process is usually slow.

In the early stages of the disease the surface of the cartilage, or even the synovium in some people, becomes inflamed and swollen. There is a loss of proteoglycan molecules and other tissue components that cause water loss. Fissures and pits appear in the cartilage.
As the disease progresses and more tissue is lost, the cartilage loses elasticity and fluid. It becomes increasingly prone to damage due to repetitive use and injury.
Eventually large amounts of cartilage are destroyed, leaving the ends of the bone within the joint unprotected.

To compound the process, bone around arthritic joints is not structurally normal. As the body tries to repair damage to the cartilage, problems can develop:

Clusters of damaged cells or fluid-filled cysts may form around the bony areas or near the fissures.
Fluid pockets may also form within the bone marrow itself, causing swelling. The marrow, which runs up through the center of bone, is rich in nerve fibers, and such injuries may be an important source of pain in many patients with osteoarthritis.
Bone cells may respond to damage by multiplying, growing, and forming dense, misshapen plates around exposed areas.
At the margins of the joint, the bone may produce outcroppings, on which new cartilage cells (chondrocytes) proliferate and grow abnormally.

Unlike some other types of arthritis, such as rheumatoid arthritis, osteoarthritis does not spread through the entire body. (In other words, it is not systemic.) Rather, it affects one or several joints. Osteoarthritis affects joints differently depending on their location in the body.

Osteoarthritis is commonly found in joints of the fingers, feet, knees, hips, and spine.
It sometimes occurs in the wrist, elbows, shoulders, and jaw, but is not common in these locations.

Causes

The biologic factors leading to the deterioration of cartilage in osteoarthritis are not entirely understood. Many experts believe that osteoarthritis results from a genetic susceptibility that causes some biologic response to injuries to the joint, which in turn leads to progressive deterioration of cartilage. In addition, the ability to make repairs becomes progressively limited as cartilage cells age.

Although osteoarthritis generally accompanies aging, osteoarthritic cartilage is chemically different from normal aged cartilage. As chondrocytes (the cells that make up cartilage) age, they lose their ability to make repairs and produce more cartilage. This process may play an important role in the development and progression of osteoarthritis.

Researchers report a high correlation of osteoarthritis between parents and children or between siblings. Genetic factors are thought to be involved in about half of osteoarthritis cases in the hands and hips and a somewhat lower percentage of cases in the knee. A number of genes are under investigation that might contribute to an inherited risk.

For example, mutations in the ank gene may be important in some cases. The ank gene regulates pyrophosphate, a chemical that inhibits the formation of mineral deposits, and may protect the cartilage in joints. Mutations in the ank gene then may result in lower pyrophosphate levels in the joint, leading to accumulation of mineral deposits and arthritis. (About 60% of people with osteoarthritis have mineral deposits in their cartilage.)

Another gene, called the osteoprotegerin gene, is important in regulating bone and cartilage formation. Mutations in this gene may play a role in osteoarthritis.

The inflammatory response is an overreaction of the immune system to an injury or other assault in the body, such as an infection. This response causes specific immune factors, called cytokines, to gather in injured areas and cause inflammation and damage to body tissue and cells. The inflammatory response plays an important role in rheumatoid arthritis and other muscle and joint problems associated with autoimmune diseases. It has generally been believed that inflammation plays at most a minor role in osteoarthritis and is more likely to be a result -- not a cause -- of the disease.

However, recent studies suggest that inflammation may play an important role in the progression of osteoarthritis and its chronic nature. For example, a 2003 study found evidence of severe inflammation in the lining of the joints in 30% of patients with osteoarthritis. Still, the effects of the inflammatory response in osteoarthritis are likely to be different from those in rheumatoid arthritis and less severe.

Some theories on how this response may contribute to osteoarthritis involve overproduction of enzymes called matrix metalloproteinases or MMPs (also called collagenases). In large amounts they break down collagen, the building blocks of cartilage. Some studies suggest that immune factors called vascular endothelial growth factor (VEGF) are overproduced during the inflammatory response and in turn increase production of MMPs.

Another theory suggests that the inflammatory response is triggered by the changes and injuries in the bone that occur during osteoarthritis. According to this theory, immune factors released in this process diffuse into the cartilage, where they suppress cartilage cell growth and activate MMPs.

Joint injuries are the starting point in the disease process. Osteoarthritis sometimes develops years after a single traumatic injury to or near a joint. One large study found that by age 65, osteoarthritis developed in almost 14% of those who had joint injuries as young adults, compared to just 6% in those without earlier injuries. Patients with knee injuries were five times more likely to have osteoarthritis in the injured knee than those without injuries, and patients with hip injuries were more than three times more likely to develop arthritis in the injured hip. Proper treatment of injuries, such as surgical repair of ligament tears in the knee with a strong rehabilitation approach, may help to prevent the development of osteoarthritis.

Other causes of osteoarthritis include:

Bleeding disorders such as hemophilia that cause bleeding to occur in the joint
Disorders such as avascular necrosis that block the blood supply near the joint
Complications of persistent, inflammatory arthritic conditions, particularly chronic gout, pseudogout, or rheumatoid arthritis
Conditions that cause iron build-up in the joints such as hemochromatosis

Symptoms

The pain of osteoarthritis typically begins gradually and progresses slowly over many years. People under age 40 may have the condition with no symptoms at all. Osteoarthritis is commonly identified by the following symptoms:

The most common symptom of osteoarthritis in any joint is pain that worsens during activity and gets better during rest. As the disease advances, the pain may occur even when the joint is at rest.
Pain is generally described as aching, stiffness, and loss of mobility.
The pain may behave like a roller coaster, with bad spells followed by periods of relative relief.
Pain seems to increase in humid weather.
Some people experience muscle spasm and contractions in the tendons.
Osteoarthritis in the knee may cause a crackling-like noise (called crepitus) when moved.

Hand. Osteoarthritis of the hand occurs most often in older women and may be inherited within families. The following joints are most frequently affected:

Distal interphalangeal (DIP) joint. The first joint below the fingertips is the most common location of osteoarthritis of the hand. These joints can develop bony growths known as Heberden's nodes.
Carpometacarpal (CMC) joint. The joint at the base of the thumb, where the thumb joint connects with the wrist, is the second most common location.
Proximal interphalangeal (PIP) joint. The middle joints of the fingers can also develop osteoarthritis. These joints may develop small, solid lumps (nodules) known as Bouchard's nodes.

Click the icon to see an image of osteoarthritis.

Recent studies suggest that osteoarthritis of the hand may predict the later development of osteoarthritis in the hip or knee. A 2005 study found that patients with hand osteoarthritis were three times more likely to develop hip arthritis. Osteoarthritis of the hand also slightly increased the risk for knee osteoarthritis.

Knee. Osteoarthritis is particularly debilitating in the weight-bearing joints of the knees. The joint is usually stable until the disease reaches an advanced stage when the knee becomes enlarged and swollen. Although painful, the arthritic knee usually retains reasonable flexibility.

Osteoarthritis can cause loss of cartilage in the knee. The meniscus, the cartilage pad between the joint formed by the thighbone and the shinbone, plays an important role in protecting the joint. It acts as a shock absorber. In knee surgery called meniscectomy, the doctor removes the damaged cartilage. However, a 2006 study suggested that preserving the meniscus, even if it is damaged, is better than removing it. Researchers showed that even a small amount of meniscus helps protect the joint and prevent osteoarthritis from worsening. Experts recommend that patients try lifestyle changes (exercise and weight loss), braces, and medication before undergoing knee surgery.

Click the icon to see an image of the knee joint.

Hips. About 1 in 4 people will develop hip arthritis over the course of their lifetime. Being obese increases the risk. Osteoarthritis frequently strikes the weight-bearing joints in one or both hips. Pain develops slowly, usually in the groin and on the outside of the hips, or sometimes in the buttocks. The pain also may radiate to the knee, confusing the diagnosis. Those with osteoarthritis of the hip often have a restricted range of motion (particularly when trying to rotate the hip) and walk with a limp, because they slightly turn the affected leg to avoid pain.

Click the icon to see an image of the hip joint.

Spine. Osteoarthritis may affect the cartilage in the disks that form cushions between the bones of the spine, the moving joints of the spine itself, or both. Osteoarthritis in any of these locations can cause pain, muscle spasms, and diminished mobility. In some cases, the nerves may become pinched, which also produces pain. Advanced disease may result in numbness and muscle weakness. Osteoarthritis of the spine is most troublesome when it occurs in the lower back or in the neck, where it can cause difficulty in swallowing.

Click the icon to see an image of the spine.

Shoulder. Osteoarthritis is less common in the shoulder area than in other joints, but it may develop in the shoulder joint (the glenohumeral joint). In such cases, it is most often associated with a previous injury, and patients gradually develop pain and stiffness in the back of the shoulder. Osteoarthritis also can develop in the acromioclavicular (AC) joint, which is between the shoulder blade and the collarbone. However, it rarely causes symptoms in this location.

Conditions with Similar Symptoms

Numerous conditions have symptoms of joint aches and pains. Something as benign as sleeping on a bad mattress to the serious afflictions associated with cancer can mirror symptoms of osteoarthritis. Other problems that can cause aches and pains in the joints include physical injuries, infections, tendinitis, and poor circulation. A number of rare genetic diseases attack the joints.

Osteoarthritis can generally be distinguished from other joint diseases by considering several factors together:

Osteoarthritis usually occurs in older people and is located in only one or a few joints
The joints are less inflamed than in other arthritic conditions
Progression of pain is usually gradual.

A few of the most common disorders that can be confused with, or may even accompany, osteoarthritis are discussed below.

Osteoarthritis may be confused with rheumatoid arthritis, particularly when osteoarthritis affects multiple joints in the body. Rheumatoid arthritis begins in the synovial membrane rather than the cartilage. It normally occurs earlier in life than osteoarthritis, often striking people in their 30s and 40s. Rheumatoid arthritis affects many joints, and often occurs symmetrically on both sides of the body. People generally have morning stiffness that lasts for at least an hour. (Stiffness from osteoarthritis usually clears up within half an hour.)

X-rays show changes in the bones that differ from those occurring in osteoarthritis. In rheumatoid arthritis, blood tests often show a specific antibody, known as rheumatoid factor, which is not present with osteoarthritis. In another blood test, levels of a factor called erythrocyte sedimentation rate (ESR) are often elevated in rheumatoid arthritis, but they are generally normal in osteoarthritis. Rheumatoid arthritis also does not usually show up in the fingertips where osteoarthritis is common.

Rheumatoid arthritis is a body-wide (systemic) autoimmune disease that initially attacks the synovium, a connective tissue membrane that lines the cavity between joints and secretes a lubricating fluid.

Click the icon to see an image of osteoarthritis vs. rheumatoid arthritis.

Chondrocalcinosis is a disease in which certain calcium crystals known as CPPD (calcium pyrophosphate dihydrate) are deposited in the joints. It affects about 25% of the population and can accompany and even worsen osteoarthritis. The problem has been called pseudogout or pseudo-osteoarthritis, in the latter case particularly when it affects the knees. A doctor can usually differentiate between the two disorders, however, because chondrocalcinosis usually damages other joints (such as wrists, elbows, and shoulders) that are not usually affected by osteoarthritis. The condition may explain why some patients with osteoarthritis receive benefit from colchicine, a drug used for gout and other crystal-induced joint diseases.

Charcot's joint occurs when an underlying disease, usually diabetes, causes nerve damage in the joint, which leads to swelling, bleeding, increased temperature, and changes in bone. There may be a loss of sensation that leads to an increased risk for injury from overuse.

Risk Factors

Osteoarthritis is the most common type of arthritis. In the U.S., about 12.1% of Americans (21 million people) age 25 and older have osteoarthritis. The prevalence in osteoarthritis increases as people age. Experts estimate that by 2030, 20% of Americans (72 million people) age 65 years and older will be at risk for developing osteoarthritis.

Before age 45, osteoarthritis occurs more frequently in males (although it is not common in younger adults). After age 55, it develops more often in females. In a 2000 study, 33% of women had osteoarthritis compared to 25% of men. Some research suggests that women may also experience greater muscle and joint pain, in general, than men. And, women also tend to be undertreated for pain compared to men. The causes of such differences in pain sensitivity and treatment are largely unknown and most likely are due to a complicated mix of biologic, psychologic, and social factors.

The incidence is highest in lower educational levels. In a 2000 study, 41% of adults with less than a high school education had arthritis compared to 21% of college graduates.

Although the average rate of osteoarthritis among older adults in the U.S. is 60%, it can vary widely in certain geographical regions. In the U.S., the rates in older adults are lowest (34%) in Hawaii and highest (70%) in Alabama. In general, the highest prevalence of arthritis in America occurs in the central and northwestern states.

The rate of osteoarthritis varies by ethnic group. In the U.S., Caucasians and African-Americans have higher rates of arthritis than Hispanics or other ethnic groups. Osteoarthritis also tends to favor specific joints over others in certain ethnic groups. The following are some examples:

Older African-American men are about 33% more likely than Caucasian men to have hip osteoarthritis. In one study, although men in both groups had equal risks for arthritic knees, African-American men were more likely to have arthritis in both knees and to have more severe cases. Although comparable disparities in knee arthritis were observed between African-American and Caucasian women, they might be explained by greater average weight among African-American women. The study could not account for the differences among men, however.
Asians appear to have a higher incidence of osteoarthritis in the knee, an equal risk for osteoarthritis in the spine, and a lower risk for osteoarthritis in the hips than Caucasians.

Genes that determine the angles, amount of force, and other structural factors in the hip joints, or genes that regulate the chemistry in the joints, may account for ethnic differences.

Some researchers suggest that a number of people have anatomical abnormalities, such as mismatched surfaces on the joints, which could be damaged over time by abnormal stress. Legs of unequal length or skewed feet can cause jerky movement and may cause osteoarthritis. One study reported that those whose knees bent inward ("knock-kneed") or outward ("bow-legged"), for example, were more likely to have progressive osteoarthritis of the knee.

Obesity, defined as being 20% over one's healthy weight, places people (particularly women) at increased risk for osteoarthritis. It also worsens osteoarthritis once deterioration begins. This higher risk is due to increased weight on the joints. However, being obese also increases the risk for osteoarthritis in the fingers as well as the knees and hips, suggesting that being overweight may contribute to osteoarthritis in other ways. Some research indicates that obesity may produce an inflammatory response, which is now a major suspect in age-related diseases -- not only osteoarthritis but also heart disease. [See In-Depth Report #53: Weight control and diet.]

Because injuries can trigger the disease process, people whose work or leisure activities place them at risk for muscle and joint injuries may face a higher risk for osteoarthritis later on.

Workers at Higher Risk. Certain occupations that require repeated stressful motions (such as squatting or kneeling with heavy lifting) can contribute to deterioration of cartilage. One study suggested that workers whose jobs require kneeling or squatting for more than an hour a day are at high risk for knee osteoarthritis. (In the study, jobs that involved heaving lifting, climbing stairs, or walking also posed some, but not as high, a risk. Being heavier compounded the chances for osteoarthritis.)

Exercise. There has been some question about the role of strenuous exercise in osteoarthritis. Sports that definitely pose a higher risk for osteoarthritis are those that require repetitive or direct joint impact (such as football), twisting, or both (baseball pitching, soccer).

Marathon runners, however, have a relatively low rate of osteoarthritis. Some scientists speculate that running enhances cartilage health because the rhythmical compression of cartilage expels wastes and promotes absorption of nutrients.

In any case, regular and moderate exercise is important for everyone and does not increase the risk for osteoarthritis. In fact, a 2006 study of middle-aged and elderly people found that recreational weight-bearing exercise (walking, jogging) neither protects against nor increases the risk for osteoarthritis. Furthermore, many factors associated with a sedentary life (muscle weakness, obesity) are associated with a higher risk for osteoarthritis.

Diagnosis

Osteoarthritis is often visible in x-rays. Cartilage loss is indicated by certain images:

If the normal space between the bones in a joint is narrowed.
If there is an abnormal increase in bone density.
If bony projections, cysts, or erosions are evident.
X-rays can also reveal any cysts that might develop in osteoarthritic joints. If other conditions are suspected or if the diagnosis is uncertain, additional tests are necessary.
An MRI may show evidence of osteoarthritis that x-rays miss.

X-rays are a form of electromagnetic radiation (like light); they are of higher energy, however, and can penetrate the body to form an image on film. Structures that are dense (such as bone) will appear white, air will be black, and other structures will be shades of gray depending on density. X-rays can provide information about obstructions, tumors, and other diseases, especially when coupled with the use of barium and air contrast within the bowel.

Blood test results may help diagnose or rule out osteoarthritis. Some examples include:

Elevated levels of rheumatoid factor (specific antibodies in the synovium) and so-called erythrocyte sedimentation rates (ESR or sed rate) indicate rheumatoid arthritis.
Hyaluronic acid (HA), a joint lubricant, is being tested as a potential biomarker for osteoarthritis. High levels of HA may indicate increased risk for osteoarthritis.
Elevated levels of a factor called C-reactive protein, which is produced by the liver in response to inflammation, are proving to be good predictors of osteoarthritic progression in the knee.

If the diagnosis is uncertain or infection is suspected, a doctor may attempt to withdraw synovial fluid from the joint using a needle. There will not be enough fluid to withdraw if the joint is normal. If the doctor can withdraw fluid, problems are likely, and the fluid will be tested for factors that might confirm or rule out osteoarthritis:

Cartilage cells in the fluid are signs of osteoarthritis.
A high white blood cell count is a sign of infection.
High uric acid in the fluid is an indication of gout.

Click the icon to see an animation on gout.

Other factors may be present that suggest different arthritic conditions, including Lyme disease and rheumatoid arthritis.
In people with known osteoarthritis, researchers may look for certain factors in synovial fluid (sulfated glycosaminoglycan, keratin sulfate, and link protein) that can suggest a more or less severe condition.

Prognosis

Osteoarthritis itself is not life-threatening, but a person's quality of life can significantly deteriorate from pain and loss of mobility. The negative effects on activities and physical and mental health are significant regardless of age, educational level, or gender. Only heart disease has a greater impact on work. Five percent of those who leave the work force do so because of osteoarthritis. Unless alleviated by medication or corrected by surgery, advanced osteoarthritis can force the patient to forgo even relatively low-impact activities, such as walking. No treatment can cure osteoarthritis, and none can alter its progression with certainty, but many available therapies can relieve symptoms and significantly improve the quality of life.

Lifestyle Changes

Many doctors suggest first trying lifestyle changes to reduce stress on affected joints. Physical therapy and supportive devices can be helpful. Intensive education on how to protect and care for an osteoarthritic joint may help patients avoid multiple visits to their doctor.

Once osteoarthritis has been diagnosed, patients should reduce shock to the affected joint. Hammering away at deteriorating cartilage is likely to speed up the degeneration. People in occupations requiring repetitive and stressful movement should explore ways to reduce trauma. Adjusting the work area or substituting tasks that produce less stress on joints helps reduce shock.

Joints require motion to stay healthy. Long periods of inactivity cause the arthritic joint to stiffen and the adjoining tissue to atrophy. A moderate exercise program that includes low-impact aerobics and power and strength training has benefits for osteoarthritic patients, even if exercise does not slow down the disease progression. Exercise helps:

Reduce stiffness and increase flexibility. It may also help improve the strength and elasticity of knee cartilage.
Promote weight loss.
Improve strength, which in turn improves balance and endurance.
Reduce stress and improve feelings of well being, which helps patients cope with the emotional burden of pain.

Exercise especially helps patients with mild-to-moderate osteoarthritis in the hip or in the knee. Many patients who begin an aerobic or resistance exercise program report less disability and pain. They are better able to perform daily chores and remain more independent than their inactive peers. Older patients and those with medical problems should always check with their doctor before embarking on an exercise program.

Three types of exercise are best for people with osteoarthritis:

Strengthening exercise
Range-of-motion exercise
Aerobic, or endurance, exercise

Strengthening Exercise. Strengthening exercises include isometric exercises (pushing or pulling against static resistance). Isometric training builds muscle strength while burning fat, helps maintain bone density, and improves digestion.

Some experts encourage patients to emphasize strengthening leg muscles as a first treatment step, before using pain relievers. Patients who rely on painkilling drugs may overuse knees, which do not have muscle tissue sufficiently strong enough to protect the joints from further damage. However, some studies suggest that building up thigh muscles may worsen osteoarthritis in people whose knees are misaligned (for instance those who are "bow-legged" or "knock-kneed"). Such individuals should check with a physical therapist for the best options. Strengthening the thigh muscles is certainly protective for people who have not yet developed osteoarthritis.

Exercise, such as weightlifting, helps build muscle that is usually lost with age and puts stress on bones, helping keep them strong and healthy.

Range-of-Motion Exercise. These exercises increase the amount of movement in a joint and muscle. In general, they are stretching exercises. The best examples are yoga and tai chi, which focus on flexibility, balance, and proper breathing. In one study, older adults who practiced the gentle movement, breathing, and meditation exercises of tai chi for 10 weeks reported less pain than their peers who did not learn the technique.

Click the icon to see an image of cholesterol.

Aerobic (Endurance) Exercise. These exercises help control weight and may reduce inflammation in some joints. Low-impact workouts also help stabilize and support the joint. Cycling and walking are beneficial, and swimming or exercising in water is highly recommended for people with arthritis. (Patients with osteoarthritis should avoid high-impact sports, such as jogging, tennis, and racquetball.)

Click the icon to see an image of exercise.

In addition to exercise, manipulation of muscles and joints by a trained therapist may be helpful. In one study, patients who had a combination of physical therapy and an exercise program reported 30 - 40% improvement after only two to four visits.

Overweight patients with osteoarthritis can lessen the shock on their joints by losing weight. Knees, for example, sustain an impact three to five times the body weight when descending stairs. Losing 5 pounds of weight can eliminate 20 pounds of stress on the knee. The greater the weight loss, the greater the benefit. [See In-Depth Report #53:Weight loss and diet.]

Plant Chemicals. A large study reported significant improvement in symptoms when patients took extracts from avocados and soybeans called saponins. Another study noted that although these substances did not relieve hip pain, they did slow progression of joint deterioration. Soy has chemicals called isoflavones that may have additional benefits, such as preventing bone loss.

Fish Oil and Omega-3 Fatty Acids. Omega-3 fatty acids, which are found in fish oil, canola oil, black currant or primrose seed oils, and flax seeds, have anti-inflammatory properties and may help protect against cartilage deterioration. Supplements of omega-3 fatty acids, such as docosahexaenoic (DHA) and eicosapentaneoic (EPA) acids that are found in fish oil, are available.

Vitamin B3 (Niacin). Some research suggests that vitamin B3 may have some benefits for people with osteoarthritis.

Click the icon to see an image of the benefits of vitamin B3.

Click the icon to see an image of the sources of vitamin B3.

Calcium and Vitamin D. Calcium and vitamin D are important for strong bones. Although osteoarthritis is primarily a disease of joints, bone strength is also important, particularly in older people.

Click the icon to see an image of osteoporosis.

Many experts now recommend 1,000 mg of calcium a day for most adults and 1,200 - 1,500 mg for adolescents. Pregnant women, postmenopausal women not on estrogen therapy, and those on corticosteroids should get 1,500 mg per day; breast feeding women should get 2,000 mg/day. Because calcium supplements increase the risk for kidney stones, an upper limit of 2,500 mg is recommended.

Current guidelines recommend 400 IU of vitamin D per day and 600 IU per day after age 60. Lack of sunlight and unhealthy diets contribute to deficiencies in vitamin D. Good dietary sources include fortified milk, sardines, herring, salmon, tuna, liver, dairy products, and egg yolks. Although supplements are often necessary, vitamin D can be toxic in high doses, and no one should take more than 1,200 IU per day.

Selenium. Selenium is a trace mineral found in grains, nuts, vegetables, and some meats and seafood. Preliminary research suggests that people who do not get enough selenium in their diet may be more likely to develop knee osteoarthritis. Researchers are investigating whether selenium supplements may help protect against osteoarthritis and prevent it from worsening.

Ice. When a joint is inflamed (particularly in the knee) applying ice for 20 - 30 minutes can be effective. If an ice pack is not available, a package of frozen vegetables works just as well.

Heat Treatments. Patients afflicted with osteoarthritis of the hands can relieve pain with hot soaks and warm paraffin application. Osteoarthritis of the hip can be treated with heating pads.

Interestingly, moving to a warm climate does not seem to make much difference. According to one study, people who live in warmer places are actually more sensitive to small shifts in temperature than people who live in cold damp climates, and they experience pain as readily as their northern peers do in response to larger temperature shifts.

A wide variety of devices are available to help support and protect joints:

Splints or braces, worn while the joint is at rest or in use, help align joints and properly distribute weight. They are used most frequently to treat arthritic hands, wrists, knees, ankles, and feet. Many of these devices allow some movement within the affected joint and do not restrict nearby joints. They are usually made from lightweight metal, leather, elastic, foam, and moldable plastic with easy-to-use Velcro straps. Any brace, splint, or other device for joint protection should be custom-fitted by a physical or occupational therapist, or an orthotist. Poorly fitting or improperly used orthoses can cause more harm than good.
Using elastic supports on affected joints may benefit some people. For example, in one study, wearing insoles plus elastic straps supporting the ankle joint helped overweight women with osteoarthritis in the knee. It is important to consult with a doctor about how to use elastic supports.
Wrapping the knee with special therapeutic tape that provides support to specific parts of the joint may be effective. In one trial, patients experienced a 40% reduction in pain within a few days. They wore the tape for 3 weeks, and pain relief continued for 3 more weeks following treatment. The tape should be applied by physical therapists or other trained health professionals. Longer-term studies are needed to determine any continuous benefits.
Wearing shock-absorbing soles in shoes or orthopedic shoes can help in daily activities and during gentle exercise. Heel wedges in the shoes can sometimes help patients avoid knee replacement surgery.
A neck brace or corset may relieve back pain.
A firm mattress also often proves beneficial.
In extreme cases of back pain, lying in traction might be necessary.
Canes, crutches, or walkers offer benefits to patients with advanced arthritis.
Specially designed hip protectors, worn under the clothes, can also protect against hip fractures in elderly patients with impaired mobility who are apt to fall.

Medications

Many medications are available for relieving the symptoms of osteoarthritis. A major analysis indicated that drug therapy is generally more effective than non-drug treatments (surgery, acupuncture). However, a 2006 review of knee osteoarthritis studies found that pain-relief medications generally help only for the first 2 - 3 weeks of treatment. The following are some of the medications used in mild-to-severe cases:

Acetaminophen
Nonsteroidal anti-inflammatory drugs (NSAIDs) or COX-2 inhibitors
Capsaicin
Tramadol
Narcotic pain relievers (oxycodone, oxymorphone, or morphine)
Glucosamine and chondroitin (see Alternative and Complementary Medicine section)

Acetaminophen (Tylenol, Anacin-3, Panadal, Phenaphen, Valadol, and others) is currently the first choice for treating osteoarthritis. However, several major analyses report that acetaminophen is less effective than NSAIDs in reducing moderate-to-severe pain. Because acetaminophen has fewer side effects, most experts suggest trying this drug first, then switching to an NSAID if acetaminophen does not provide sufficient pain relief.

Side Effects. Acetaminophen is inexpensive and generally safe. It poses far less of a risk for gastrointestinal problems than NSAIDs and does not appear to increase the risk for miscarriage (as NSAIDs do), even when used regularly.

It does have some adverse effects, however, and the daily dose should not exceed 4 grams (4,000 mg). Patients who take high doses of this drug for long periods are at risk for liver damage, particularly if they drink alcohol and do not eat regularly.

The kidneys are responsible for removing wastes from the body, regulating electrolyte balance and blood pressure, and the stimulation of red blood cell production.

Nonsteroidal anti-inflammatory drugs (NSAIDs) block prostaglandins, the substances that dilate blood vessels and cause inflammation and pain. There are dozens of NSAIDs:

Over-the-counter NSAIDs include aspirin, ibuprofen (Advil, Nuprin, Motrin IB, Rufen), naproxen (Aleve, Naprosyn), ketoprofen (Actron, Orudis KT).
Prescription NSAIDs include ibuprofen (Motrin), naproxen (Naprosyn, Anaprox), flurbiprofen (Ansaid), diclofenac (Voltaren, Cataflam), tolmetin (Tolectin), ketoprofen (Orudis, Oruvail), nabumetone (Relafen), dexibuprofen (Seractil), indomethacin (Indocin), meloxicam (Mobic, generic).
Topical NSAIDs delivered in gels, creams, or patches do not appear to provide any long-term benefits in reducing arthritic pain. A review of clinical trial data, published in 2004, suggested that guidelines that recommend topical NSAIDs for treatment of osteoarthritis should be revised.

Many experts now recommend that patients use oral NSAIDs for only a short period of time. A 2004 review, published in the British Medical Journal, suggested that long-term use of NSAIDs does not actually reduce osteoarthritis pain and may increase patients’ risk of experiencing side effects. High dosages of NSAIDs can cause heart problems (such as increased blood pressure), kidney problems, and stomach bleeding.

In April 2005, the Food and Drug Administration (FDA) asked drug manufacturers of prescription NSAIDs to include with their products the same boxed warning used for the COX-2 inhibitor celecoxib (Celebrex). This boxed warning emphasizes an increased risk for cardiovascular events and gastrointestinal bleeding in people taking these drugs. The FDA also requested manufacturers of over-the-counter NSAIDs to revise their labels to include more specific language concerning potential cardiovascular and gastrointestinal risks. Due to its proven heart benefits, aspirin was excluded from these labeling revisions.

A 2006 comprehensive report from the U.S. Agency for Healthcare Quality and Research indicated that both NSAIDs and COX-2 inhibitors are equally effective for pain relief and pose similar risks for heart attacks. The report found that one particular NSAID, naproxen (Aleve, Naprosyn), presents less risk of heart attack for some patients. A 2006 Journal of the American Medical Association study suggested that diclofenac (Voltaren, Cataflam) may pose a higher risk for heart attack than other NSAIDs. All patients should talk to their doctors before switching any medications.

Long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) is the second most common cause of ulcers, and the rate of NSAID-caused ulcers is increasing. Such ulcers are also more likely to bleed than those caused by the bacteria H. pylori. NSAID-related bleeding and stomach problems may be responsible for 107,000 hospital admissions and 16,500 deaths each year. Because there are usually no gastrointestinal symptoms from NSAIDs until bleeding begins, doctors cannot predict which patients taking these drugs will develop bleeding.

Among the groups at high risk for bleeding are elderly people, anyone with a history of ulcers of GI bleeding, patients with serious heart conditions, alcohol abusers, and those on certain medications, such anticoagulants ("blood thinners"), corticosteroids, or bisphosphonates (drugs used for osteoporosis). Proton-pump inhibitors may help to prevent and heal ulcers caused by NSAIDs. Proton-pump inhibitors include omeprazole (Prilosec), esomeprazole (Nexium), and lansoprazole (Prevacid)

Click the icon to see an image of a gastric ulcer.

Drugs for Prevention NSAID-Induced Ulcers. If you have NSAID-induced ulcers, follow these steps:

Switch to alternative pain relievers. This is the first step in preventing or healing ulcers caused by NSAIDs. If people cannot change drugs, they should use the lowest NSAID dose possible.
Try proton-pump inhibitors (PPIs). These drugs help reduce NSAID-ulcer rates by as much as 80% compared with no treatment. Brands include omeprazole (Prilosec), esomeprazole (Nexium), lansoprazole (Prevacid), rabeprazole (Aciphex), and pantoprazole (Protonix).
Try misoprostol or Arthrotec. If other drugs are inappropriate, misoprostol protects against the major intestinal toxicity of NSAIDs. It was the first drug approved for preventing NSAID-induced ulcers. It is equally, or even more, effective than some of the PPIs, but it does not heal existing ulcers and has more side effects than PPIs. Patients tend to stop using it. Arthrotec is a combination of an ulcer protective drug called misoprostol and the NSAID diclofenac. One study found that patients taking Arthrotec had 65 - 80% fewer ulcers than those who took NSAIDs alone.

Healing Existing Ulcers. A number of drugs are available to heal NSAID-induced ulcers. Treatment takes about 2 - 6 weeks. Proton-pump inhibitors are the most effective drugs. Others that may be beneficial include sucralfate or H2 blockers, such as famotidine (Pepcid AC), cimetidine (Tagamet), ranitidine (Zantac).

Coxibs inhibit an inflammation-promoting enzyme called COX-2. This drug class was initially thought to provide benefits equal to NSAIDs but cause less gastrointestinal distress. However, following numerous reports of cardiovascular events, as well as skin rashes and other adverse effects, the FDA has been re-evaluating the relative risks and benefits of this drug class. Rofecoxib (Vioxx) and valdecoxib (Bextra) have been withdrawn from the United States market. Celecoxib (Celebrex) is still available, but patients should discuss with their doctors whether this drug is appropriate and safe for them.

A newer COX-2 inhibitor, etoricoxib (Arcoxia) is approved in 60 countries but not the United States. A 2006 Lancet study indicated that etoricoxib is similar to the NSAID diclofenac in risks for heart attack and stroke. (However, diclofenac has already been shown to have a higher risk of heart attack than any other NSAID, so some experts do not find this study result reassuring.) Etoricoxib caused more high blood pressure and fluid retention (edema) than diclofenac. Etoricoxib appeared to pose a lower risk than diclofenac for uncomplicated upper gastrointestinal problems, (obstruction, perforation, bleeding, ulcers), but there was little difference between the two drugs for more serious gastrointestinal complications. In 2007, the FDA rejected an application to market etoricoxib in the U.S.

Capsaicin is a component of hot red peppers and may bring pain relief when used as a skin cream (Zostrix). This is the only skin preparation that does more than just mask pain or reduce it temporarily. Capsaicin seems to reduce a substance in the body, known as substance P, which contributes both to inflammation and the delivery of pain impulses from the central nervous system. A small amount of capsaicin must be applied to the area of inflammation about four times a day. During the first few days of use, the patient will experience a warm, stinging sensation when the cream is applied. This sensation goes away, and pain relief usually begins within 1 - 2 weeks.

Tramadol (Ultram) is a pain reliever that has been used as an alternative to opioids. It has opioid-like properties but is not as addictive. (Dependence and abuse have been reported, however.) It can cause nausea but does not cause severe gastrointestinal problems, as NSAIDs can. Some patients experience severe itching. A combination of tramadol and acetaminophen (Ultracet) is now available and provides more rapid pain relief than tramadol alone with more long-lasting benefits than acetaminophen. Side effects are the same as for each of these drugs.

Narcotics, pain-relieving and sleep-inducing drugs that act on the central nervous system, are the most powerful medications available for the management of moderate to severe pain. There are two types of narcotics:

Opiates, which are derived from natural opium (morphine and codeine).
Opioids, which are synthetic drugs. They include oxycodone (Percodan, Percocet, Roxicodone, Oxycontin), hydrocodone (Vicodin), oxymorphone (Numorphan), and fentanyl (Duragesic).

Although the use of narcotics for arthritic pain is controversial, many studies have suggested that they are rarely addictive for pain sufferers except among patients with a history of substance abuse. Some experts believe that opioids have a place in osteoarthritis treatment when milder drugs are not effective or appropriate. For example, a 2006 study suggested that a fentanyl skin patch may offer pain relief and improved function to some patients with severe knee or hip osteoarthritis who have not been helped by, or who cannot tolerate, NSAIDs or weaker opioids.

The use of such drugs may be beneficial when included as part of a comprehensive pain management program. Such a program involves screening prospective patients for possible drug abuse and then regularly monitoring those who are taking it, adjusting the dose as necessary to achieve an acceptable balance between pain relief and side effects. Common side effects include anxiety, constipation, nausea and vomiting, dizziness, drowsiness, paranoia, urinary retention, restlessness, and labored or slow breathing. Unfortunately, opioid abuse among young people is a major concern.

When pain becomes a major problem and less potent pain relievers are ineffective, doctors may resort to corticosteroid (steroid) injections, usually by administering a shot into the affected joint every 3 months. Corticosteroid shots are useful only if inflammation is present in the joint. Relief from pain and inflammation is of short duration, and this treatment is rarely used for chronic osteoarthritis. These drugs may not be as effective for women as for men.

Corticosteroids mask pain, and the patient must be very careful to avoid over-use of the affected joints. Patients are usually advised not to have more than two or three injections a year, since there is some concern that repeated injections over the long term may be harmful. A reassuring study found no greater disease progression in people who had injections every 3 months for 2 years compared to those who were given sham injections on the same schedule. Because long-term use of corticosteroids has many potentially serious side effects, steroid medications are never given orally or systemically for the treatment of osteoarthritis.

Injections of hyaluronic acid (Hyalgan, Synvisc, Artzal, Nuflexxa) into the joint -- a procedure called viscosupplementation -- is now recommended as one of the treatments for osteoarthritis. Hyaluronic acid is a naturally occurring substance in joints that acts as a lubricant for slow movements and a shock absorber for fast motions. In high amounts, it also may have anti-inflammatory effects.

Patients receive a series of three to five injections once a week.
The drug is injected into the joint.
A health care worker will apply local anesthetic because these viscous (sticky) injections require a large needle.
Patients need to avoid weight-bearing activities for about 48 hours after each shot.

Hyaluronic injections appear to be about as effective as NSAIDs and corticosteroid injections for relieving pain, at least in men, and they have no adverse effects in the stomach or intestines. One study reported that between 39 - 56% of patients were at least nearly free of weight-bearing pain up to 24 weeks after the final injection. In another study, response was judged better or much better for 87% of knees after a second course, which was administered about 8 months later. Nevertheless, a number of studies on viscosupplementation have shown little or no benefits, particularly in women, and more research is needed to determine if they are useful. Injections are also expensive. Accurate placement of the needle directly into the knee joint space is important and may be difficult, even for experienced doctors, if there is no fluid build-up in the joint. Best success rates are with a specific approach into the kneecap called the lateral midpatellar.

Side Effects. Serious adverse reactions are rare. The most common side effects, pain at the injection site and knee pain and swelling, are usually mild and temporary. More research is needed to confirm benefits and long-term risks.

Researchers are studying various drugs that may provide pain relief or stop the disease process itself:

Bisphosphonates such as alendronate (Fosamax) and risedronate (Actonel) help prevent bone loss in people with osteoporosis. They are currently being investigated for osteoarthritis as well. A 2005 study reported that risedronate may delay joint destruction in patients with knee osteoarthritis.
Lidocaine, a local anesthetic, is available in patch form (Lidoderm) and has been used specifically for herpes zoster pain. Early studies indicate that it may provide significant pain relief for osteoarthritis.
Tetracycline antibiotics, such as doxycycline, may have a role to play in treating osteoarthritis. At low concentrations, the drug reduces the production of collagenases, which are enzymes critical to disease development and progression. Initial results from clinical trials suggest that doxycycline may help delay joint space narrowing.
Licofelone is a drug that inhibits both the COX enzyme plus an inflammatory substance called lipoxygenase 5. Early trials indicate it may be effective and safer than either NSAIDs or COX-2 inhibitors.
Diacerein inhibits an inflammatory substance in arthritic joints called interleukin-1b. It has shown promise in clinical trials. A 2006 review indicated that diacerein may be slightly better than NSAIDs for pain relief.
Botulinum toxin type A (Botox) injections may provide sustained pain relief for patients with knee osteoarthritis according to research presented at the 2006 American College of Rheumatology annual meeting.
Nitric oxide increases blood flow in the mucous lining and secretions of mucus and bicarbonate. Combining nitric oxide with NSAIDs may reduce the adverse effects on the gastrointestinal tract.
Trials of gene therapies that either fight joint degradation or strengthen cartilage are in very early stages.

Alternative and Complementary Medicine

Glucosamine hydrochloride and chondroitin sulfate are natural substances that are part of the building blocks found in and around cartilage. Extracts have been used in Europe for more than a decade to reduce pain and improve mobility in patients with osteoarthritis. For many years, researchers in the U.S. have been studying whether these dietary supplements really work for relieving osteoarthritis pain.

In 2006, the New England Journal of Medicine published the results from a major trial sponsored by the U.S. National Institutes of Health. Researchers compared the effects of glucosamine and chondroitin, alone and in combination, with the COX-2 inhibitor celecoxib (Celebrex) in nearly 1,600 patients with knee osteoarthritis. The dietary supplements were also compared with placebo (an inactive substance). Patients took the assigned substance once a day for 6 months.

The results indicated that, for most patients, neither glucosamine nor chondroitin were better than placebo in relieving knee pain. However, for patients with moderate-to-severe pain, a combination of glucosamine and chondroitin was significantly more effective than the other remedies. Celebrex worked best for patients with mild pain.

The next stage of the study will evaluate whether glucosamine and chondroitin, alone and in combination, can halt the progression of knee osteoarthritis.

Research presented at the 2006 American College of Rheumatology annual meeting suggested that chondroitin may prevent joint narrowing in patients with knee osteoarthritis.

Dosage. There are no current standard recommended dosages. Patients in the GAIT trial took 1,500 mg of glucosamine and 1,200 mg of chondroitin.

Side Effects. The safety records of both substances appear excellent. Long-term effects are still unknown, but studies of up to 3 years have reported no significant side effects. However, there are some concerns that glucosamine may affect insulin and blood sugar (glucose) metabolism. Patients with diabetes should not take glucosamine without first talking to their doctors.

Oral Enzymes. People in Europe have used natural enzymes -- including bromelain, trypsin, papain, and rutin -- to treat arthritic pain. Such enzymes have been marketed alone and in combinations (Wobenzym, Phlogenzym). They are not painkillers, and any benefits derived from them may take several weeks.

Ginger (Zingiberaceae). A 2001 study of patients with knee arthritis found that an extract of ginger reduced pain while standing and after walking. By using ginger, patients were able to reduce their pain medications after 6 weeks. Side effects included mild digestive upset.

S-adenosylmethionine (SAMe). S-adenosylmethionine (SAMe, pronounced "Sammy") is a synthetic form of a natural byproduct of the amino acid methionine. It has been marketed as a remedy for both depression and arthritis. Some research suggests that it may work as well as NSAIDs for short-term treatment of osteoarthritis. Other studies suggest that it may help rebuild damaged cartilage.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been several reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

Acupuncture is being increasingly used to reduce osteoarthritis pain. The technique is painless and involves the insertion of small fine needles at select points in the body. Several study reviews have found that acupuncture provides at least short-term pain relief for osteoarthritis of the knee. Other studies have suggested that acupuncture’s benefits are mainly due to a strong placebo effect, or to the psychologically beneficial effects of close contact with health care providers.

In 2004, researchers published results from an important clinical trial that studied the effects of acupuncture on nearly 600 people with osteoarthritis of the knee. The results indicated that acupuncture can relieve pain and improve function. Several 2006 studies of thousands of patients with chronic osteoarthritis pain compared acupuncture to conventional treatment (physical therapy, anti-inflammatory drugs). These studies showed positive results and suggested that acupuncture’s benefits may be sustained for up to 6 months after treatment. In any case, acupuncture appears to be a safe and beneficial addition to standard therapy for certain patients, such as pregnant women, who cannot take most pain medications.

Acupuncture, hypnosis, and biofeedback are all alternative ways to control pain. Acupuncture involves the insertion of tiny sterile needles, slightly thicker than a human hair, at specific points on the body.

Transcutaneous electric nerve stimulation (TENS) uses low-level electrical pulses to suppress pain. Patients are barely aware of the sensation. According to one study, the optimal treatment length is 40 minutes. A variant (sometimes called percutaneous electrical nerve stimulation, or PENS) applies these pulses through a small needle to acupuncture points. A review of trials reported that both methods were better than placebo (sham treatments) in treating osteoarthritis of the knee, although additional well-designed studies are needed.

Low-level laser therapy (LLLT) generates extremely pure light in a single wavelength. It does not produce heat and is painless. Some researchers are combining LLLT with transcutaneous electric nerve stimulation (TENS). Studies report widely varying results, with some showing significant reductions in pain and others reporting no effect. The differences may be due to different approaches, and standardized methods are needed to determine any benefits.

Hydrotherapy, also called spa therapy or balneotherapy, is an ancient therapy that uses bathing in mineral baths for soothing pain. Although many studies report positive results, including improved quality of life, very few have been rigorously conducted. A major analysis reported weak evidence on any real effect on pain or quality of life, but some patients may find comfort from this pleasant therapy.

Surgery

Different surgical procedures are available as a final measure to relieve pain and increase function in patients with osteoarthritis. Certain surgical procedures can help relieve pain if medications fail. Even with these procedures, however, joint replacement may still be needed later on.

Arthroscopy is performed to clean out bone and cartilage fragments that, in theory at least, may cause pain and inflammation. More than 650,000 of these procedures are done on arthritic knees each year in the U.S., and about half of patients report less pain after the procedure.

A rigorous 2002 trial, however, found that arthroscopic knee surgery was no more effective than sham surgery, (in which surgeons only pretended to operate on the knee), for relief of osteoarthritic pain or stiffness. The study, which followed patients at a Veterans Affairs hospital for 2 years, has called into serious question whether the popular procedure has any real benefits for osteoarthritis beyond what might be achieved by a placebo response. Research and debate continues on whether arthroscopy provides true benefits for those with osteoarthritis and, if so, which patients it may most help.

Click the icon to see an illustrated series detailing knee arthroscopy surgery.

When osteoarthritis becomes so severe that pain and immobility make normal functioning impossible, many people become candidates for artificial (prosthetic) joint implants using a procedure called arthroplasty. Hip replacement is the most established and successful replacement procedure, followed by knee replacement. Knee replacement, in fact, has a slightly better long-term success rate than hip replacement. Other joint surgeries (shoulders, elbows, wrists, fingers) are less common, and some arthritic joints (in the spine, for instance) cannot yet be treated in this manner. When two joints, such as both knees, need to be replaced, having the operations done sequentially rather than at the same time may result in fewer complications.

Click the icon to see an illustrated series detailing knee joint replacement surgery.

Candidates. The primary indications for surgery are pain and significant limitations of movement, including walking, that cannot be treated by less invasive therapies. Some experts suggest, however, that joint replacement should be considered earlier rather than as a last resort. They argue that patients who wait until they are severely disabled do not recover as completely as those who have the procedure earlier.

Patients who may not be good candidates are those with the following conditions:

Severe neurologic, emotional, or mental disorders
Severe osteoporosis
Other chronic medical conditions
Obesity

Surgeons often prefer to delay prosthetic implantation in younger patients, because implants wear out and they will require at least one revision procedure later on. Newer, more long-lasting materials, however, may help reduce the rate of re-operations.

Procedure Description. Although the following is mostly a description of hip replacement surgery, the principles are similar for other arthroplasties.

The surgeon removes the ball and socket joint that joins the pelvis and thigh bone (femur) and replaces it with an artificial joint (a prosthesis). It is composed of two pieces:

A cup-like device fits in the hip socket (called the acetabula), which has been hollowed out. This ball-and-socket cup is positioned to form the new joint.
A metal shaft, or stem, with a polished metal ball at the top, is inserted into the narrow center of the femur.

The prosthesis is usually made of a metal alloy and plastic. A ceramic implant may prove to last longer than other materials and be a safe option for younger patients.

There are different options available for attaching it to the adjoining bones:

A cement made of polymethylmethacrylate (usually preferred for older patients who generally have thinner bones).
So-called cementless implants, in which the prosthesis is coated with a porous material that allows bone to grow into and eventually adhere to the device. These implants are usually used for patients younger than age 65, who are likely to need repeat surgery in their lifetime.

Click the icon to see an illustrated series detailing hip joint replacement surgery.

Complications. Complications can occur, and, although uncommon, some can be life-threatening. There is a 1% chance of death within 3 months of an initial procedure and a 2.6% risk after a repeat procedure. The risks are highest in the first 3 months. Those at highest risks for complications are elderly adults, men (compared to women), African-Americans, and those with serious medical conditions.

Specific complications include the following:

Deep blood clots (known as deep vein thrombosis) and pulmonary embolism. Deep blood clots can develop in the legs after this surgery. This poses a very small risk (0.9%) for pulmonary embolism -- a dangerous condition in which the clot travels to the lungs. Anticoagulants (blood thinners) are important for preventing blood clots. These drugs include warfarin and low-molecular weight heparin. Anticoagulant therapy is given during the hospital stay and continued for several weeks at home. The patient also wears specially fitted elastic stockings to help prevent clots. Patients who are overweight are at higher than average risk for post-operative blood clots
Infection. Wound infection occurs in about 0.2% of joint replacements and requires prompt removal of the implant to treat the infection. A new prosthesis must be re-implanted at a later time. Any pre-existing infection must be treated and cured before surgery is performed. (Older women should be aware of urinary tract infections, which may require postponing surgery.) After surgery, patients should take certain precautions. For example, they should take antibiotics before invasive dental procedures or other surgery because bacteria can be introduced into the bloodstream and infect the areas around the artificial joints.
Hip dislocation. Occurs in about 3.1% of first hip procedures. The rate is much higher (14.4%) in revision operations.

Click the icon to see an image of a dislocated hip.

Pain. Thigh pain can occur after hip replacement. Porous hip prostheses are more likely to produce thigh pain than cement implants, although advanced techniques using a tapered shaft are reducing this complication.
Failure. The primary reason for implant failure is osteolysis (bone destruction) caused by long-term wear. The main source of wear is from tiny particles released from the prosthesis.
Other complications. These include uneven leg lengths, nerve damage that can cause numbness or weakness, urinary tract infections, delayed healing, and allergic reactions to the metal. Long-term, there have been rare reports of a possible autoimmune response, in which loose particles released from the prosthetic device trick certain immune system factors into attacking healthy cells. Any incidence of unexplained weight loss and fatigue may be symptoms of this uncommon event.

Rehabilitation. Aside from the surgeon's skill and the patient's underlying condition, the success rate depends on the kind and degree of activity the joint receives following replacement surgery.

The patient is urged and aided into getting out of bed and walking the day after surgery. Most hip replacement patients leave the hospital within a week and can walk with crutches within 2 - 4 weeks, recovering fully in about 3 months.

Physical therapy takes about 6 weeks to rebuild adjoining muscle and strengthen surrounding ligaments. Studies suggest that an exercise program started before surgery and resumed afterward can improve recovery. Continuous passive motion (CPM) is an effective regimen for knee replacement patients. It uses a mechanical device that slowly moves the joint through an arc of motion for an extended period of time. It is used to prevent scar tissue from developing. In one review, a combination of physical therapy and CPM were more beneficial than physical therapy alone.

Limitations After Surgery. While many patients find that joint replacement provides remarkable pain relief and restores some mobility, they need time to adjust to the artificial joint.

Limitations after hip surgery include:

Usually patients with new hips are able to walk several miles a day and climb stairs, but they cannot run.
Prosthetic hips should not be flexed beyond 90 degrees, so patients must learn new ways to perform activities requiring bending down (like tying a shoe).

Limitations after knee surgery include:

Walking distance improves in 80% of patients after knee replacement surgery, but patients still cannot run.
Only slightly more than half of patients report improvement in stair climbing. (Artificial knee joints generally have a range of motion of just 110 degrees.)

Failure Rates. Infection is a major cause of early failure and always requires revision. Improper balancing of the ligaments and other tissues surrounding the joint and resulting poor joint stability is also a common reason for failure of arthroplasties. Surgical expertise is important for avoiding this complication.

Older cement prostheses have a particularly high rate of bone loss and loosening due to cement deterioration. In general, studies report reoperation rates of over 30% after 10 years. Fortunately, advances in cement and prosthetic implants are improving the implant survival rates and reducing the need for revision procedures.

Uncemented arthroplasty using porous material has shown good results for the hip, although it may be less successful for knee replacement. In spite of short-term success, longer experience with this method suggests it may not be superior to cement prostheses. Failure of bone to grow into the porous material is a relatively common event, a problem that does not occur with cement prostheses. Some experts recommend cement implants over cementless ones for total knee arthroplasty.

A repair procedure called arthroplasty revision may be used in cases where the original transplant fails. The specific procedure depends on whether the bone defects that occurred are contained or uncontained.

Contained defects can be repaired with small bone grafts, the use of cement, or oversized cementless implants as required.
Uncontained defects are more severe and may require a large bone graft or specially constructed implants to restore bone.

If a second arthroplasty is required, the potential for complications is magnified: more bone is cut, more blood is lost, and the operation takes longer. Patients are also generally older and more vulnerable to complications.

Resection Arthroplasty. In resection arthroplasty, a false joint of scar tissue is created. This procedure is used most often in treating arthritis of the foot.

Osteotomy. If only a certain section (the medial compartment) of the knee is damaged and deformed by osteoarthritis, the surgeon may choose to perform osteotomy:

A surgeon opens the knee.
The surgeon performs a debridement (removal of damaged tissue) in the joint to eliminate the loose or torn fragments that are causing pain and inflammation.
The bone is then reshaped to remove the deformity.
The procedure may ease symptoms and slow disease progression. It is best used in heavier adults who are under 60 years old.

Hemicallotasis. Hemicallotasis is a procedure for the knee that may be a less invasive alternative to osteotomy. The surgeon attaches the knee with pins to an external frame-like device that lengthens the deformed part of the knee over several weeks. The patient is mobile during this period. Infections at the pin site are the most common complications.

Arthrodesis. If the affected joint cannot be replaced, surgeons can perform a procedure called arthrodesis that eliminates pain by fusing the bones together. The patient must understand, however, that fusing the bones makes movement of the joint impossible. Bone fusion is most often done in the spine and in the small joints of the hands and feet.

Unicompartmental Knee Arthroplasty. Unicompartmental knee arthroplasty (also called unicondylar knee arthroplasty) may be a useful procedure in cases of limited knee damage. It is recommended for relatively sedentary patients who are 60 years or older and not obese. It may relieve pain and delay the need for a total knee replacement. The procedure involves a small incision and insertion of small implants. It retains important knee ligaments, which preserve more movement than a total knee replacement.

Cartilage Transplants. Autologous chondrocyte implantation, also called chondroplasty or the Carticel approach, is used for knees damaged by injuries. In this procedure, arthroscopy is used to first remove cartilage in eroded areas. The results have been good to excellent, although long-term benefits are questionable. Whether it has any benefit for older patients with osteoarthritis is not yet known. Other cartilage transplant procedures are also under study.

Hip Resurfacing. Hip resurfacing is a surgical alternative to total hip replacement. It involves scraping the surfaces of the hip joint and femur and placing a metal cap over the bone. The procedure preserves much of the bone, so that a standard hip replacement can be done years later if needed. It may provide more stability, a faster recovery, and greater range of motion, making it a potentially good option for young, physically active patients.

Resources

www.rheumatology.org -- American College of Rheumatology
www.arthritis.org -- Arthritis Foundation
www.niams.nih.gov -- National Institute of Arthritis and Musculoskeletal and Skin Diseases
www.aaos.org -- American Academy of Orthopaedic Surgeons
www.fda.gov/cder/drug/infopage/cox2 -- FDA NSAID and COX-2 Inhibitor Information

References

Bjordal JM, Klovning A, Ljunggren AE, Slordal L. Short-term efficacy of pharmacotherapeutic interventions in osteoarthritic knee pain: A meta-analysis of randomised placebo-controlled trials. Eur J Pain. 2007 Feb;11(2):125-38.

Cannon CP, Curtis SP, FitzGerald GA, Krum H, Kaur A, Bolognese JA, et al. Cardiovascular outcomes with etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison. Lancet. 2006 Nov 18;368(9549):1771-81.

Chou R, Helfland M, Peterson K, Dana T, Roberts C. Comparative Effectiveness and Safety of Analgesics for Osteoarthritis. Comparative Effectiveness Review No. 4. (Prepared by the Oregon Evidence-based Practice Center under Contract No. 290-02-0024.) Rockville, MD: Agency for Healthcare Quality and Research. September 2006.

Felson DT, Niu J, Clancy M, Sack B, Aliabadi P, Zhang Y. Effect of recreational physical activities on the development of knee osteoarthritis in older adults of different weights: the Framingham Study. Arthritis Rheum. 2007 Feb 15;57(1):6-12.

Laine L, Curtis SP, Cryer B, Kaur A, Cannon CP; MEDAL Steering Committee. Assessment of upper gastrointestinal safety of etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomized comparison. Lancet. 2007 Feb 10;369(9560):465-73.

Langford R, McKenna F, Ratcliffe S, Vojtassak J, Richarz U. Transdermal fentanyl for improvement of pain and functioning in osteoarthritis: a randomized, placebo-controlled trial. Arthritis Rheum. 2006 Jun;54(6):1829-37.

McGettigan P, Henry D. Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase2. JAMA. 2006 Oct 4;296(13):1633-44.

Rintelen B, Neumann K, Leeb BF. A meta-analysis of controlled clinical studies with diacerein in the treatment of osteoarthritis. Arch Intern Med. 2006 Sep 25;166(17):1899-906.

Scharf HP, Mansmann U, Streitberger K, Witte S, Kramer J, Maier C, et al. Acupuncture and knee osteoarthritis: a three-armed randomized trial. Ann Intern Med. 2006 Jul 4;145(1):12-20.

Witt CM, Jena S, Brinkhaus B, Liecker B, Wegscheider K, Willich SN. Acupuncture in patients with osteoarthritis of the knee or hip: a randomized, controlled trial with an additional nonrandomized arm. Arthritis Rheum. 2006 Nov;54(11):3485-93.

Review Date:
3/19/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Rheumatoid arthritis

FitSugar — Wed, 08 Oct 2008 17:35:00 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Symptoms
Complications
Diagnosis
Treatment
Medications
Surgery
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Treatment Approaches

Patients with rheumatoid arthritis who do not respond to single-drug therapy often do better when a combination of drugs is used, indicates a review of 23 clinical trials published in 2007 in the Annals of Internal Medicine. However, the researchers were unable to determine which combinations of drugs work best or which individual drugs are more effective than others.
Combination drug treatment is now becoming a standard approach to treating rheumatoid arthritis while it is still in its early stages. Another 2007 Annals of Internal Medicine study indicated that initial combination therapies slow progression of joint damage more rapidly than single-drug therapy but, after several years, all treatment strategies produce benefits.

Fish Oil for Joint Pain

The omega-3 fatty acids found in fish oil may have anti-inflammatory properties that can help relieve joint pain, indicates a 2007 review in Pain. The researchers found that taking omega-3 fatty acids for 3 - 4 months helped reduce joint pain intensity, minutes of morning stiffness, the number of painful or tender joints, and consumption of non-steroidal anti-inflammatory drugs (NSAIDs). Salmon, mackerel, and herring are types of fish that are particularly high in these fatty acids. Fish oil can also be taken through dietary supplements, but these can interact with some types of prescription medications and may not be safe or appropriate for all patients. (Check with your doctor before taking these or any other supplements.)

Introduction

Rheumatoid arthritis (RA) is a chronic disease in which various joints in the body are inflamed, leading to swelling, pain, stiffness, and the possible loss of function.

Rheumatoid arthritis is an autoimmune disease in which the body's immune system attacks itself. The pattern of joints affected is usually symmetrical, involves the hands and other joints, and is worse in the morning. Rheumatoid arthritis is a systemic (body-wide) disease, involving other body organs, whereas osteoarthritis is limited to the joints. Both forms of arthritis can be crippling.

The process probably develops in the following way:

The disease process leading to rheumatoid arthritis begins in the synovium, the membrane that surrounds a joint and creates a protective sac.
This sac is filled with lubricating liquid called the synovial fluid. In addition to cushioning joints, this fluid supplies nutrients and oxygen to cartilage, a slippery tissue that coats the ends of bones.
Cartilage is composed primarily of collagen, the structural protein in the body, which forms a mesh to give support and flexibility to joints.
In rheumatoid arthritis, an abnormal immune system produces destructive molecules that cause continuous inflammation of the synovium. Collagen is gradually destroyed, narrowing the joint space and eventually damaging bone.
If the disease develops into a form called progressive rheumatoid arthritis, destruction to the cartilage accelerates. Fluid and immune system cells accumulate in the synovium to produce a pannus, a growth composed of thickened synovial tissue.
The pannus produces more enzymes that destroy nearby cartilage, aggravating the area and attracting more inflammatory white cells, thereby perpetuating the process.

This inflammatory process not only affects cartilage and bones but can also harm organs in other parts of the body.

Click the icon to see an image of rheumatoid arthritis.

Causes

Although much has been learned about the process leading to rheumatoid arthritis, researchers have yet to uncover all the factors that lead to this devastating disease. One prevalent theory is that a combination of factors triggers rheumatoid arthritis, including an abnormal autoimmune response, genetic susceptibility, and some environmental or biologic trigger, such as a viral infection or hormonal changes.

The Normal Immune System Response. The inflammatory process is a byproduct of the activity of the body's immune system, which fights infection and heals wounds and injuries:

When an injury or an infection occurs, white blood cells are mobilized to rid the body of any foreign proteins, such as a virus.
The masses of blood cells that gather at the injured or infected site produce factors to repair wounds, clot the blood, and fight any infections.
In the process the surrounding area becomes inflamed and some healthy tissue is injured. The immune system is then called upon to repair wounds by clotting off any bleeding blood vessel and initiating fiber-like patches to the tissue.
Under normal conditions, the immune system has other special factors that control and limit this inflammatory process.

The Infection Fighters. Two important components of the immune system that play a role in the inflammation associated with rheumatoid arthritis are B cells and T cells, both of which belong to a family of immune cells called lymphocytes.

When macrophages recognize foreign particles entering the bloodstream, they are programmed to ingest them, split them into pieces, and bring specific sections of them (antigens) into contact with the surface of the T cell. These antigens are placed within specialized proteins on the surface of the T cell that signal to a T cell and begin a process of immune system inspection. This process involves the interaction of several proteins on B cells and T cells, which seem to signal back and forth.

If the T cell recognizes an antigen as "non-self," it will produce chemicals (cytokines) that cause B cells to multiply and release many immune proteins (antibodies). These antibodies circulate widely in the bloodstream, recognizing the foreign particles and triggering inflammation in order to rid the body of the invasion. T cells can be further categorized as killer T cells or helper T cells. Killer T cells directly attack antigens, such as viruses and tumor cells. Helper T cells recognize antigens that are presented to them by macrophages (or other specialized cells), and can stimulate B cells to mount various kinds of attacks on the antigen. They also produce chemicals (cytokines) that can have a more direct role in the inflammatory process.

For reasons that are still not completely understood, both the T cells and the B cells become overactive in patients with RA. In an immune response it is normal for the antibody response to change over time, particularly if the first antibodies that are made do not eliminate the invading particles. Little by little, the types of antibodies being made undergo changes in an attempt to achieve better recognition and a stronger inflammatory response against a recalcitrant invader. In RA, a complex interaction between activated immune cells and an impaired antigen-elimination process leads to a greater than normal repertoire of what the antibodies recognize. Eventually, antibodies are made that recognize more of the body's own tissues in a stronger or more persistent manner than is healthy, and inflammatory responses are mounted in these tissues.

An antigen is a substance that can provoke an immune response. Typically antigens are substances not usually found in the body.

Cytokines. Cytokines are very important in the destructive process of rheumatoid arthritis, particularly those known as interleukins (ILs) -- notably IL1 and IL6 -- and tumor necrosis factor (TNF). TNF is now known to be the major cause of joint damage and various systemic manifestations of RA, including weight loss.

Leukocytes. The leukocytes, the other major white blood cells in the body, are also spurred into action by the over-zealous T cells. Leukocytes stimulate the production of key players in the inflammatory process, including leukotrienes, prostaglandins, and nitric oxide.

The Hypothalamic-Pituitary-Adrenal Axis and Stress Hormones. Some research suggests that abnormalities in the hypothalamic-pituitary-adrenal axis (HPA axis) may contribute to RA. The HPA system includes two parts of the brain (the hypothalamus and the pituitary) and the adrenal gland.

Click the icon to see an image of the adrenal glands.

The HPA axis regulates a person's response to stress, which includes the release of cortisol (an important stress hormones) and DHEA (a weak male hormone). The cytokines interleukin-6 and TNF-alpha normally stimulate a surge in these hormones, which then block further release of the cytokines. Research suggests, however, that in RA, a defective HPA axis responds to the cytokines with a lower-than-normal release of cortisol and DHEA. Without a strong stress response, the cytokine levels remain high and become destructive, causing inflammation.

Genetic factors play some role in RA, but are clearly not the only important factor. The presence of certain genetic mutations, however, may worsen the disease process. It should be pointed out that defective genes not only can be inherited but they may be changed and mutated by environmental or other factors. More research is needed to determine the specific genetic contributions to this disease.

HLA. HLA (human leukocyte antigen) is a genetically regulated molecule that traps part of antigens and presents them on the surface of cells for destruction by antibodies and T cells. It is designed to recognize self- from non-self cells. A number of HLA genetic forms called HLA-DRB1 alleles are referred to as the RA-shared epitope because of their association with rheumatoid arthritis. These genetic factors do not cause RA, but they may make the disease more severe once it has developed. Genetic variations in the HLA region may also predict drug treatment response to etanercept and the disease-modifying anti-rheumatic drug methotrexate.

Lack of Corticotropin-Releasing Hormone. Some people with RA may have a genetic deficiency of a hormone known as corticotropin-releasing hormone (CRH), which produces corticosteroids, hormones that suppress the inflammatory process.

Infections. Although many bacteria and viruses have been studied, no single organism has been proven to be the primary trigger for the autoimmune response and subsequent damaging inflammation. Higher than average levels of antibodies that react with the common intestinal bacteria E. coli have appeared in the synovial fluid of people with RA. Some experts think they may stimulate the immune system to prolong RA once the disease has been triggered by some other initial infection. Other potential triggers include Mycoplasma, parvovirus B19, retroviruses, mycobacteria, and Epstein-Barr virus.

Chemicals. A number of chemicals are being investigated as triggers of rheumatoid arthritis, but it is very difficult to determine causal effects of any specific trigger.

Risk Factors

Rheumatoid arthritis (RA) is an ancient disease. The condition has been identified in skeletons thousands of years old. According to the Arthritis Foundation, RA affects an estimated 2.1 million Americans.

Although the disease can occur at any age from childhood to old age, it usually starts in young adulthood, with onset peaking between the ages of 20 - 45. Still, about 50,000 children may be afflicted with juvenile rheumatoid arthritis.

Women are more likely to have RA than men. (The risk for women is slightly lower if they have been pregnant.) Women are also at higher risk for the severe type 2 rheumatoid arthritis.

Some people may inherit genes that make them susceptible to RA, but a family history of RA does not appear to increase an individual's risk.

Other factors may place certain susceptible individuals at higher risk for developing RA:

Heavy long-term smoking is a very strong risk factor for RA, particularly in patients without a family history of the disease.
Women who have a shorter fertility time (and so lower levels of reproductive hormones) may be at higher risk.
History of blood transfusions.

Most studies have not found any association between silicone breast implants and rheumatoid arthritis or other autoimmune disease (except possibly Sjögren syndrome).

Reports from a Dutch study suggest that hay fever sufferers have a reduced risk of developing rheumatoid arthritis, and, conversely, arthritis patients are less likely to have hay fever.

Symptoms

The hallmark symptom of rheumatoid arthritis is morning stiffness that lasts for at least an hour. (Stiffness from osteoarthritis, for instance, usually clears up within half an hour.) Even after remaining motionless for a few moments, the body can stiffen. Movement becomes easier again after loosening up.

Swelling and pain in the joints must occur for at least 6 weeks before a diagnosis of rheumatoid arthritis is considered. The inflamed joints are usually swollen and often feel warm and "boggy" when touched. The pain often occurs symmetrically but may be more severe on one side of the body, depending on which hand the person uses more often.

Although rheumatoid arthritis almost always develops in the wrists and knuckles, the knees and joints of the ball of the foot are often affected as well. Indeed, many joints may be involved, including those in the cervical spine, shoulders, elbows, tips, temporomandibular joint (jaw), and even joints between very small bones in the inner ear. Rheumatoid arthritis does not usually show up in the fingertips, where osteoarthritis is common, but joints at the base of the fingers are often painful.

In about 20% of people with RA, inflammation of small blood vessels can cause nodules, or lumps, under the skin. They are about the size of a pea or slightly larger, and are often located near the elbow, although they can show up anywhere. Nodules can occur throughout the course of the disease. Rarely, nodules may become sore and infected, particularly if they are in locations where stress occurs, such as the ankles. On rare occasions, nodules can reflect the presence of rheumatoid vasculitis, a condition that can affect blood vessels in the lungs, kidneys, or other organs.

Fluid may accumulate, particularly in the ankles. In rare cases, the joint sac behind the knee accumulates fluid and forms what is known as a Baker cyst. This cyst feels like a tumor and sometimes extends down the back of the calf causing pain.

Symptoms such as fatigue, weight loss, and fever may accompany early rheumatoid arthritis. Some people describe them as being similar to those of a cold or flu except, of course, RA symptoms can last for years.

In children, juvenile rheumatoid arthritis, also known as Still's disease, is usually preceded by high fever and shaking chills along with pain and swelling in many joints. A pink skin rash may be present.

Complications

Rheumatoid arthritis is not fatal, but complications of the disease may shorten survival by a few years in some individuals. Although type 2 rheumatoid arthritis is progressive and there is no cure, over time the disease becomes less aggressive, and symptoms may even improve.

Treatments for RA are increasingly effective in slowing this debilitating disease, and some may even prevent initial destruction by aggressively reducing inflammation. If bone and ligament destruction and any deformities have occurred, however, the effects are permanent. It is essential, therefore, to seek a doctor's help as soon as symptoms develop. Side effects of the treatments often contribute to the severity of the disease.

Affected joints can become deformed, and the performance of even ordinary tasks may be very difficult or impossible. According to one survey, 70% of patients with rheumatoid arthritis feel the disease prevents them from living a fully productive life. A 2000 study found that about one-third of people with RA stop working within 5 years of onset of the disease.

Rheumatoid arthritis can affect other parts of the body as well as the joints. Some patients with severe disease may then be at higher risk for complications, such as the following:

Peripheral Neuropathy. This condition affects the nerves, most often those in the hands and feet. It can result in tingling, numbness, or burning.
Muscle problems. Many patients have weakness of the muscles.
Anemia. People with RA may develop anemia, which involves a decrease in the production of red blood cells.
Scleritis and Episcleritis. This is an inflammation of the blood vessels in the eye that can result in corneal damage. Symptoms include redness of the eye and a gritty sensation.
Infections. Patients with RA have a higher risk for infections, particularly from some of the immune-suppressing drugs (corticosteroids, anti-tumor necrosis factors, disease modifying drugs) that they take.
Skin Problems. Skin problems are common, particularly on the fingers and under the nails. Some patients develop severe skin complications that include rash, ulcers, blisters (which may bleed in some cases), lumps under the skin, and other problems. Severe skin disease can reflects a more serious case of RA in general.
Osteoporosis. Osteoporosis, a disorder in which bone density decreases, is more common than average in postmenopausal women with RA. The hipbone is particularly affected. The risk for osteoporosis also appears to be higher than average in men with RA who are over 60 years old.
Lung Disease. Patients with RA are susceptible to chronic lung diseases, including interstitial fibrosis, pulmonary hypertension, and other problems. Both rheumatoid arthritis itself and some treatments may cause this damage.
Kidney. Although rheumatoid arthritis only rarely involves the kidney, many of the drugs used to treat it can damage kidneys.
Vasculitis. Vasculitis involves autoimmune inflammatory abnormalities in very small vessels and can affect many organs in the body. Manifestations of vasculitis include mouth ulcers, nerve disorders, rapid worsening of the lungs, inflammation of coronary arteries, and inflammation of the arteries supplying blood to the intestines.
Heart Disease. Inflammation of the heart muscle itself in the sac around the heart can cause many problems. Mounting evidence suggests that RA can increase the risk for heart disease, possibly because of the inflammatory response in RA, which may also injure arteries and heart muscle tissue. Some studies have reported that people with RA are 30 - 50% more likely to suffer heart vessel blockages and 60 - 70% more likely to die as result than people without RA.
Lymphoma and Other Cancers. Research suggests that patients with RA are four times more likely than healthy patients to develop non-Hodgkin’s lymphoma. There has also been concern that some RA treatments may increase the risk for lymphoma. Studies from 2006 indicate that RA’s chronic inflammatory process may play a role in the development of lymphoma. Researchers found that patients with very severe and long-term RA had a substantially increased risk of developing lymphoma. Other 2006 research suggests that RA drugs, such as biologic response modifiers, do not increase lymphoma risk, although they do increase skin cancer risk.
Periodontal Disease. People with RA may be twice as likely as non-arthritic individuals to have periodontal disease. Chronic inflammation and immune dysfunction are central to both diseases.
Pregnancy. Women with RA have an increased risk for premature delivery. They are also three times more likely than healthy women to develop hypertension during the last trimester of pregnancy.

Juvenile rheumatoid arthritis often resolves before adulthood. Patients who experience arthritis in only a few joints do better than those with more widespread (systemic) disease, which is very difficult to treat. Although it can be very serious, very few people die from this condition.

MAS. Macrophage activation syndrome (MAS) is a life-threatening complication of this disorder and requires immediate treatment with high-dose steroids and cyclosporin A. Parents should be aware of symptoms, which include persistent fever, weakness, drowsiness, and lethargy.

Diagnosis

Rheumatoid arthritis can be difficult to diagnose. Many other conditions resemble it and its symptoms can develop insidiously. Blood tests and x-rays may show normal results for months after the onset of joint pain. Even after rheumatoid arthritis has been diagnosed, it is extremely important to determine whether the course of the disease is benign (type 1) or aggressive (type 2) in order to treat the problem appropriately.

Specific findings or presentation more likely to suggest the diagnosis of rheumatoid arthritis include morning stiffness, involvement of three joints at the same time, involvement of both sides of the body, subcutaneous nodules, positive rheumatoid factor, changes in x-rays.

Various blood tests may be used to help diagnose RA, determine its severity, and detect complications of the disease.

Rheumatoid Factor. In RA, antibodies that collect in the synovium of the joint are known as rheumatoid factor. In about 80% of cases of RA, blood tests reveal rheumatoid factor. It can also show up in blood tests of people with other diseases. However, when it appears in patients with arthritic pain on both sides of the body, it is a strong indicator of type 2 RA. The presence of rheumatoid factor plus evidence of bone damage on x-rays also suggests a significant chance for progressive joint damage.

Erythrocyte Sedimentation Rate Test. An erythrocyte sedimentation rate (ESR or sed rate) measures how fast red blood cells (erythrocytes) fall to the bottom of a fine glass tube that is filled with the patient's blood. The higher the sed rate the greater the inflammation. In addition to rheumatoid arthritis, the sed rate can be high in many conditions ranging from infection to inflammation to tumors. The test is used, then, not for diagnosis, but to help determine how serious the condition is.

C-Reactive Protein. High levels of C-reactive protein (CRP) are also indicators of active inflammation. However, because obesity also increases CRP levels, the doctor should consider a patient’s body mass index when evaluating CRP levels during RA diagnosis.

Anti-CCP Antibody Test. The presence of antibodies to cyclic citrullinated peptides (CCP) can identify RA years before symptoms develop. In combination with the test for rheumatoid factor, the CCP antibody test is the best predictor of which patients will go on to develop severe RA. Used in Europe, the test is now beginning to be used somewhat more commonly in the U.S. U.S. laboratories have not yet developed consistent standards for interpreting the test, however.

Tests for Anemia. Anemia is a common complication. Blood tests are needed often to determine the amount of red blood cells (hemoglobin and hematocrit) and iron (soluble transferrin receptor and serum ferritin) in the blood.

Analyzing the synovial fluid might prove to be helpful in detecting markers of joint destruction, but this is not commonly performed. Some investigational examples include the following:

An enzyme called MMP-3 (matrix metalloproteinase 3) is involved with the degradation of cartilage. Its presence in synovial fluid is strongly associated with progressive joint destruction in patients with chronic RA.
High levels urocortin, a member of the peptide family involved in the stress response, may also be a major player in the RA inflammation.

X-Rays. X-rays generally have not been helpful to detect the presence of early rheumatoid arthritis because they cannot show images of soft tissue. The use of a technique known as dual energy x-ray absorptiometry, however, may be useful in detecting early bone loss in rheumatoid arthritis (2 - 27 months after onset). Evidence of damage on x-rays along with elevated rheumatoid factor is a significant predictor for progressive joint destruction.

Ultrasound. Special ultrasound techniques called power Doppler ultrasonography (PDUS) or quantitative ultrasound (QUS) may be helpful in RA. PDUS may be reliable for monitoring inflammatory activity in the joint. QUS, which is used for osteoporosis, can detect bone loss in fingers, which may prove to be a good indicator of early RA.

Magnetic Resonance Imaging. Specially designed magnetic resonance imaging (MRI) equipment called extremity MRI may be able detect bone erosions in the hands of RA patients where x-rays cannot. Further evaluation is necessary.

Symptoms of rheumatoid arthritis can be mimicked by things as benign as a bad mattress or as serious as cancer. A number of rare genetic diseases attack the joints. Physical injuries, infections, and poor circulation are among the many problems that can cause aches and pains. It would be impossible to discuss in this report the dozens of all conditions with symptoms of joint aches and pains.

Osteoarthritis. Osteoarthritis requires some special mention because it is the most common form of arthritis. It differs from RA in several important respects.

Osteoarthritis usually occurs in older people.
It is located in only one or a few joints. (In fact, osteoarthritis is probably most often confused with rheumatoid arthritis if it affects multiple joints in the body.)
The joints are less inflamed.
Progression of pain is almost always gradual.

Gout. Gout also causes swelling and severe pain in a joint, although most commonly starting in one joint. It is particularly difficult to distinguish chronic gout in older people from rheumatoid arthritis, however, since gout in this population can occur in a number of joints. A proper diagnosis can be made with a detailed medical history, laboratory tests, and detection in the affected joint of a salt called monosodium urate (MSU), which identifies gout.


Disease	Specific Subtypes
Osteoarthritis
Infectious Arthritis	Lyme disease, septic arthritis, bacterial endocarditis, mycobacterial and fungal arthritis, viral arthritis
Postinfectious or Reactive Arthritis	Reiter syndrome (a disorder characterized by arthritis and inflammation in the eye and urinary tract), rheumatic fever, inflammatory bowel disease
Crystal Induced Arthritis	Gout and pseudogout
Other Rheumatic Autoimmune Diseases	Systemic vasculitis, systemic lupus erythematosus, scleroderma, Still's Disease (also called juvenile rheumatoid arthritis), Behcet's disease
Other Diseases	Chronic fatigue syndrome, hepatitis C, familial Mediterranean fever, cancers, AIDS, leukemia, bunions, Whipple's disease, dermatomyositis, Henoch-Schonlein purpura, Kawasaki's disease, erythema nodosum, erythema multiforme, pyoderma gangrenosum, pustular psoriasis

Treatment

The treatment of rheumatoid arthritis involves medications and lifestyle changes.

Many drugs are used for managing the pain and slowing the progression of rheumatoid arthritis, but none completely cure the disease. Some experts believe that no single drug will ever cure rheumatoid arthritis because of the many factors that affect the disease at various times. The goals of drug treatment for rheumatoid arthritis include:

Reduce inflammation
Prevent damage to the bones and ligaments of the joint
Preserve movement
To be as inexpensive and as free from side effects as possible over the long-term

The drug categories used for RA include:

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) are the least potent drugs used for RA. These drugs relieve pain by reducing inflammation, but do not affect the course of the disease.
Disease-Modifying Anti-Rheumatic Drugs (DMARDs) are the main drugs used for treating rheumatoid arthritis. They slow the progression of the disease. They are much more effective than NSAIDs but also have more side effects. Methotrexate (Rheumatrex, Trexall) is the most widely used of these drugs.
Biologic Response Modifiers (also known as Biologic DMARDs) are often prescribed to patients who have failed to respond to DMARDs. They may be used alone or in combination with DMARDs such as methotrexate. They modify or block destructive immune factors such as tumor-necrosis factor (TNF). Current anti-TNF drugs include infliximab (Remicade), etanercept (Enbrel), and adalimumab (Humira). Other biologic response modifiers include the interleukin-1 antagonist anakinra (Kineret), the T cell co-stimulation modulator abatacept (Orencia), and rituximab (Rituxan), which targets CD20-positive B cells.
Corticosteroids, or steroids, are powerful anti-inflammatory drugs that are used to quickly reduce inflammation. These drugs include prednisone and prednisolone.

The question of how early and how aggressively to treat RA has been the subject of great debate. Among patients with RA, some will go into remission and remain in remission for the length of their lives even in the absence of treatment, while others will go on to develop active, sometimes severe RA.

Current practice has moved towards treating the disease aggressively while it is in its early stages to help prevent it from reaching a more severe and chronic state. Studies have found less joint damage in patients with early, aggressive treatment, particularly with the use of DMARDs and TNF modifiers in combination with methotrexate. Intensive early dosing of methotrexate may help slow progression of rheumatoid arthritis. Early combination therapy with DMARDs and corticosteroids is also showing good results.

During the first year of treatment, combination therapy appears to reduce the progression of joint deterioration more rapidly and effectively than single drug treatment. In addition, patients who have not been helped by one drug often benefit from a combination of drugs. However, over a longer period of time, it is not clear whether a drug combination approach offers many advantages over single drugs. It is also not certain which combination of drugs works best. Depending on your particular health condition, and how you respond to the drugs prescribed, your doctor may try various treatment strategies.

Medications

Two-thirds of people with RA rank pain as their primary reason for seeking professional help. The most common pain relievers for RA are nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs block prostaglandins, the substances that dilate blood vessels and cause inflammation and pain. There are dozens of NSAIDs:

Over-the-counter NSAIDs include aspirin, ibuprofen (Motrin IB, Advil, Nuprin, Rufen), naproxen (Aleve), ketoprofen (Actron, Orudis KT).
Prescription NSAIDs include ibuprofen (Motrin), naproxen (Naprosyn, Anaprox), flurbiprofen (Ansaid), diclofenac (Voltaren), tolmetin (Tolectin), ketoprofen (Orudis, Oruvail), dexibuprofen (Seractil). In 2004, a new NSAID, meloxicam (Mobic) was approved in the U.S. for the management and treatment of rheumatoid arthritis.

Studies suggest that the best times for taking an NSAID may be after the evening meal and then again on awakening. RA symptoms increase gradually during the night, reaching their greatest severity at the time of awakening. Taking NSAIDs with food can reduce stomach discomfort, although it may slow down the pain-relieving effect.

In April 2005, the Food and Drug Administration (FDA) asked drug manufacturers of prescription NSAIDs to include with their products the same warning label used for the COX-2 inhibitor celecoxib (Celebrex). This "black box" warning, the FDA's strongest warning, emphasizes the increased risks for cardiovascular events and gastrointestinal bleeding associated with these drugs’ use. The FDA also requested manufacturers of OTC NSAIDs to revise their labels to include more specific language concerning potential cardiovascular and gastrointestinal risks. Due to its proven heart benefits, aspirin was excluded from these labeling revisions. In December 2006, the FDA proposed even stronger labeling changes to highlight these drugs’ risk for liver damage as well as alcohol and drug interactions.

Long-term, regular use of NSAIDs can increase the risk for heart attack, especially for people who have a heart condition. Long-term use of NSAIDs is also the second most common cause of ulcers and gastrointestinal bleeding. To reduce the risks associated with NSAIDs, take the lowest dose possible for pain relief.

Other possible side effects of NSAIDs may include:

Upset stomach
Dyspepsia (burning, bloated feeling in pit of stomach)
Drowsiness
Skin bruising
High blood pressure
Fluid retention
Headache
Rash
Reduced kidney function

Long-term use of NSAIDs is the second most common cause of ulcers. Ulcers caused by NSAIDs are more likely to bleed than those caused by the bacteria Helicobacter pylori.

NSAID-related bleeding and stomach problems may be responsible for 107,000 hospital admissions and 16,500 deaths each year. Those at high risk for bleeding include people over age 60, anyone with a history of ulcers of gastrointestinal bleeding, patients with serious heart conditions, people who abuse alcohol, and those who take medications such as anticoagulants (blood thinners) and corticosteroids.

Proton-pump inhibitor (PPI) drugs may help prevent and heal ulcers caused by NSAIDs. PPIs include omeprazole (Prilosec), esomeprazole (Nexium), and lansoprazole (Prevacid).

COX-2 Inhibitors (Coxibs). Coxibs inhibit an inflammation-promoting enzyme called COX-2. This drug class was initially thought to provide benefits equal to NSAIDs but cause less gastrointestinal distress. However, following numerous reports of heart problems, skin rashes, and other adverse effects, the FDA re-evaluated the risks and benefits of this drug class. This lead to the removal of rofecoxib (Vioxx) and valdecoxib (Bextra) from the United States market. Celecoxib (Celebrex) is still available, but patients should ask their doctor whether the drug is appropriate and safe for them. In December 2006, the FDA approved celecoxib for the relief of symptoms of juvenile rheumatoid arthritis in patients ages 2 years and older.

Disease-modifying anti-rheumatic drugs (DMARDs) are the standard treatments for RA. They are used either alone or in combination with newer biologic DMARDs.

DMARDs do not have any common properties other than their ability to slow down the progression of rheumatoid arthritis. Many were used for other diseases and were found accidentally to help RA. DMARDs include:

Methotrexate (considered to be the current standard of care)
Leflunomide
Hydroxychloroquine
Sulfasalazine
Gold
Minocycline
Azathioprine
Cyclosporine

Unfortunately, all DMARDs tend to lose effectiveness over time, even methotrexate. Patients rarely use one drug for more than 2 years. Combining DMARDs with each other or with drugs in other categories offers the best approach for many patients. The addition of a corticosteroid to any combination may also be helpful.

All DMARDs may produce stomach and intestinal side effects, and, over the long-term, each poses some risk for rare but serious reactions. (In some cases, however, they may be less harmful than long-term NSAID treatment.)

Methotrexate. Methotrexate (Rheumatrex, Trexall) acts as an anti-inflammatory drug and is now the most frequently used DMARD, particularly for severe disease. It has a faster mode of action than other DMARDs, (it starts working within 3 - 6 weeks), and its effectiveness as a well proven in studies.

Even this drug loses effectiveness, however, when used alone. It may be more effective when used in combination with other DMARDs or other drugs. Recent studies have focused on combining methotrexate with various biological response modifier drugs, especially for treatment of patients with early aggressive arthritis. The combination appears to work better than single drug therapy.

About 20% of patients withdraw from methotrexate because of its side effects. They include nausea and vomiting, rash, mild hair loss, headache, mouth sores, and muscle aches. Methotrexate reduces levels of folic acid (folate) in the body, which can lead to some of these side effects. Doctors may prescribe folic acid supplements to prevent side effects. However, some research suggests that folic acid may interfere with methotrexate’s effectiveness.

Methotrexate is usually given as pills. Patients who need higher doses can take it as an injection. Methotrexate has fewer serious toxic effects than many DMARDs. Although these severe reactions are rare, they may include:

Kidney and liver damage. People at particular risk for liver damage from methotrexate include those with diabetes, obesity, and alcoholism.
Increased risk for infections
Lung disease occurs in up to 5% of people. People who have poor lung function are most at risk.
The drug increases the risk for birth defects and should not be taken by pregnant women. However, methotrexate will not harm a woman’s chance for future healthy pregnancy.

Leflunomide. Leflunomide (Arava) blocks autoimmune antibodies and reduces inflammation. It also may inhibit metalloproteinases (MMP), which are involved in cartilage destruction. It has the following benefits:

It slows disease progression as early as 6 months into treatment.
Comparison studies with methotrexate report a better quality of life with leflunomide, including more energy, greater vitality, and fewer emotional side effects. (Studies comparing their risk for serious adverse effects are mixed. One, for example, showed fewer problems with leflunomide, while another reported identical rates.)

The combination of methotrexate and leflunomide (which has different effects on the immune system) is very effective compared to either drug alone. (This combination poses a risk for liver toxicity and requires monitoring.)

Reports of adverse effects are comparable to those with methotrexate. Common problems include nausea, diarrhea, hair loss, and rash. Potentially serious side effects include infections and liver injury. Everyone taking leflunomide should be monitored regularly, including blood tests for liver function, and anyone with liver problems should not take this drug. Monitoring of serum concentrations of the most active metabolite of leflunomide may help predict treatment response.

Hydroxychloroquine. Hydroxychloroquine (Plaquenil) was originally used for preventing malaria and is now also used for mild, slowly progressive arthritis. It can help relieve pain and improve mobility. It has one of the least toxic profiles of the DMARDs. The downside is that this drug can take up to 6 months to achieve full benefit. It also does not appear to slow disease progression. One study concluded that joint erosion after 2 years was worse than with no DMARD at all.

As with all DMARDs, gastrointestinal complaints are fairly common. This drug used to be associated with eye and vision problems, but with current lower doses this side effect is rare. If vision problems occur, it is usually with people taking very high doses, those with kidney disease, or those over 60 years of age. Still, you should have regular eye exams while taking this drug and notify your doctor if you experience any sudden changes in vision.

Sulfasalazine. Sulfasalazine (Azulfidine) was developed in the 1930s for treating rheumatoid arthritis, but fell into disfavor when gold treatment emerged. It has regained popularity, however, and is now used for both adult and juvenile RA. It works best when the disease is confined to the joints. Symptom relief occurs within 1 - 3 months.

Side effects are common, particularly stomach and intestinal distress, which usually occur early in the course of treatment. (However, serious gastrointestinal side effects, such as stomach ulcers, occur less frequently with sulfasalazine than with NSAIDs.) A coated-tablet form may help reduce side effects. Other side effects include skin rash and headache. Sulfasalazine increases sensitivity to sunlight. Be sure to wear sunscreen (SPF 15 or higher) while taking this drug. People with intestinal or urinary obstructions or who have allergies to sulfa drugs or salicylates should not take sulfasalazine.

Gold. Gold has been a long-standing DMARD for rheumatoid arthritis, although its use has decreased with the development of disease modifying and biologic drugs. Gold is usually administered in an injected form because the oral form, auranofin (Ridaura), is much less effective. There are two injectable forms of gold: Gold sodium thiomalate (Myochrysine) and aurothioglucose (Solganal). It can take 3 - 6 months before injections have an effect on RA symptoms.

Gold injections cause mouth sores in about a third of patients. Skin side effects include itching and rash, which can be severe in some patients. . The most serious side effects of gold injections, while rare, are kidney damage and decreased white blood cell count. Gold injections are not usually given to pregnant women. It is not definite that gold causes birth defects but doctors generally recommend that women use birth control while receiving this drug.

Minocycline. Minocycline (Minocin) is a tetracycline antibiotic that is usually prescribed for patients with mild RA. It can take 2 - 3 months before symptoms begin to improve and up to a year for full benefit. Side effects include upset stomach, dizziness, and skin rash. Long-term use of minocycline can cause changes in skin color, but this side effect usually disappears once the medication is stopped. Minocycline can cause yeast infections in women. Minocycline increases sensitivity to sunlight and patients should be sure to wear sunscreen. In rare cases, minocycline can affect the kidneys and liver.

Azathioprine. Azathioprine (Imuran) suppresses immune system activity. It takes 6 - 8 weeks for early symptom improvement and up to 12 weeks for full benefit. Azathioprine can cause serious problems with the gastrointestinal tract. About 10 - 15% of patients experience nausea and vomiting, often accompanied by stomach pain and diarrhea. (Taking the medication twice daily, instead of once daily, or taking it after eating may help avoid this problem.) Azathioprine can also cause problems with liver function and pancreas gland inflammation, and can reduce white blood cell count.

Cyclosporine. Like azathioprine, cyclosporine (Sandimmune, Neoral) is an immunosuppressant. It is used for people with RA who have not responded to other drugs. It can take a week before symptoms improve and up to 3 months for full benefit. The most serious and common side effects of cyclosporine are high blood pressure and kidney function problems. While kidney function usually improves once the drug is stopped, mild-to-moderate high blood pressure may continue. Cyclosporine can also cause gout or worsen gout in people who have this condition.

Other common side effects include headache, nausea, vomiting, stomach pain and upset, and swelling of hands and feet. About 10% of patients who take cyclosporine develop tremors, increased hair growth, muscle cramps, and numbing or tingling in hands and feet (neuropathy). Swelling of the gums is also common. Patients should practice good dental hygiene, including regular brushing and flossing.

Biologic response modifiers are drugs made from living cells. These drugs target specific components of the immune system that contribute to the joint inflammation and damage that are part of the rheumatoid arthritis disease process.

Currently approved biologic response modifiers include:

Etanercept (Enbrel). Etanercept is an anti-tumor necrosis factor (anti-TNF) drug. Approved in 1998, etanercept was the first biologic response modifier drug for treatment of rheumatoid arthritis. It is also approved for juvenile RA and psoriatic arthritis.
Infliximab (Remicade). Approved in 1999, infliximab is also an anti-TNF drug. It is used in combination with methotrexate.
Adalimumab (Humira). Adalimumab is another anti-TNF drug. First approved in 2002 as a second-line treatment for RA, adalimumab received additional approvals in 2005 as a first-line treatment for RA and psoriatic arthritis. It is used alone or in combination with methotrexate or other DMARDs. It is also showing promising results in clinical trials for juvenile rheumatoid arthritis.
Anakinra (Kineret). Approved in 2001, anakinra targets interleukin-1 (IL-1), another type of immune factor.
Abatacept (Orencia). Approved in 2005 for adults with moderate-to-severe RA who have not responded to DMARD or anti-TNF drugs. Abatacept is known as a T cell co-stimulation modulator. It blocks T cell activation. It is used alone or in combination with other DMARDs aside from anti-TNF drugs.
Rituximab (Rituxan). Approved in 2006, rituximab targets CD20-positive B cells and blocks their activation. It is used in combination with methotrexate for patients with moderate-to-severe RA who have not responded to anti-TNF therapies.

Some of these drugs are used as first-line treatments for RA. Others are used for patients who have not responded to DMARDs or other types of treatment. Depending on the specific drug, they may be used alone or in combination with the DMARD methotrexate. However, biologic response modifiers are not used in combination with each other, as they can lead to serious infections.

As with other rheumatoid arthritis drugs, these drugs do not cure the disease but can help slow progression and joint damage. In recent clinical trials, some patients have achieved remission using methotrexate in combination with infliximab, adalimumab, or rituximab.

Side Effects and Complications. Etanercept, adalimumab, and anakinra are given by injection and may cause pain at the injection site. To prevent injection reactions, patients are sometimes pretreated with betamethasone, a corticosteroid drug, but some research suggests that the steroid does little good. Infliximab, abatacept and rituximab are given by intravenous infusion. Common infusion reactions include headache, nausea, and flu-like symptoms. Because biologic response modifiers affect the immune system, patients who take these drugs have an increased risk for infections.

Other risks associated with these drugs include:

Anti-TNF drugs (etanercept, infliximab, adalimumab) have been associated with sepsis, pneumonia, and tuberculosis; non-melanoma skin cancer, lymphoma, and other malignancies; lupus; heart failure; blood disorders (including aplastic anemia); palmoplantar psoriasis; lung disease; and liver damage.
Anakinra may cause a sudden drop in white blood cells (leukopenia) that increases the risk for infections.
Abatacept should be used cautiously in patients with chronic obstructive pulmonary disorder (COPD) as it may increase the risk for respiratory complications.
Rituximab has been associated with cases of a rare and deadly brain infection called progressive multifocal leukoencephalopathy (PML). It also may cause hepatitis B reactivation, viral infections, and heart rhythm disturbances and other heart problems.

Corticosteroids work rapidly to control inflammation and pain. Long-time use, however, can have severe adverse effects. Still, they are often used under the following conditions:

Oral corticosteroids, such as prednisolone and prednisone (Deltasone, Orasone), are most often used in combination with DMARDs, which significantly enhances the benefits of DMARDs.
Oral corticosteroids are sometimes used in early stage-RA for patients who cannot tolerate NSAIDs. Studies, in fact, suggest that low-dose corticosteroids may significantly slow joint pain when it is the first drug administered and then used for 2 years. (Even low-dose oral steroids have adverse effects on bone density, blood sugar, and weight.)
Higher doses of corticosteroids are used for flareups of vasculitis and severe reactions to medications.
Corticosteroids may also be used during pregnancy to avoid exposure to more toxic drugs.
Daily, low-dose corticosteroids are also needed in some patients to control their rheumatoid arthritis symptoms.
Corticosteroids are sometimes injected directly into joints for relief of flare-ups when only one or a few joints are affected. Experts suggest no more than three or four injections into a specific joint a year. Steroid injections in the joints may be a safe and effective treatment for juvenile rheumatoid arthritis and reduce the need for oral medication.
Corticosteroid pulse therapy (intravenous administration) may work as well as DMARDs.

Side Effects of Oral Corticosteroids. Serious side effects are associated with long-term use of oral steroids. (Low doses may reduce these risks, but they do not eliminate them.) Osteoporosis is a common and particularly severe long-term side effect of prolonged steroid use. Medications that can prevent osteoporosis include calcium supplements, parathyroid hormone, or bisphosphonates (alendronate etidronate, risedronate). Other adverse effects include cataracts, glaucoma, diabetes, fluid retention, susceptibility to infections, weight gain, hypertension, capillary fragility, acne, excess hair growth, wasting of the muscles, menstrual irregularities, irritability, insomnia, and, rarely, psychosis. Recent research suggests that prednisone can increase the risk of developing non-melanoma skin cancer.

Withdrawal from Long-Term Use of Oral Corticosteroids. Long-term use of oral steroid medications suppresses secretion of natural steroid hormones by the adrenal glands. After withdrawal from these drugs, this so-called adrenal suppression persists and it can take the body a while (sometimes up to a year) to regain its ability to produce natural steroids again. There have been a few cases of severe adrenal insufficiency that occurred when switching from oral to inhaled steroids, which, in rare cases, has resulted in death.

No one should stop taking any steroids without consulting a doctor first, and if steroids are withdrawn, regular follow-up monitoring is necessary. Patients should discuss with their doctor measures for preventing adrenal insufficiency during withdrawal, particularly during stressful times, when the risk increases.

Biologic Drugs. For many years, therapeutic treatment of rheumatoid arthritis focused on T cell mediation. New research is now examining the role of B cells, which become overactive in autoimmune disease, and how B cell depletion may help to reduce disease activity. Other areas of intense research include interleukin receptor antagonists, which target cytokines involved in the inflammatory process.

Many of the current investigational drugs are monoclonal antibodies (MAbs), biologic drugs that are designed to target specific receptors. Promising candidates in late-stage research include tocilizumab (Actemra), golimumab, denosumab, ocrelizumab, ofatumumab, and certolizumab.

Statins. Some research suggests that compounds derived from statins, the highly regarded cholesterol-lowering drugs, may suppress the inflammation responsible for RA damage.

Stem cell transplantation. Stem cells are the early versions of mature, specialized blood cells. Investigators are reporting that transplantation of donated hemopoietic stem cells, which mature into various blood cells, has induced remission in a few children with severe juvenile rheumatoid arthritis. The procedure is promising in select cases, but it can be highly toxic. More studies are needed to determine risks and benefits for RA patients.

Plasmapheresis. A device called the Prosorba column is used to remove inflammatory antibodies from the patient's blood. Small, short-term studies have shown that this therapy may slow or even halt the progression of the disease in a third to a half of patients. Side effects from the Prosorba column may include anemia, fatigue, itching, fever, a drop in blood pressure, and nausea. Nearly all patients experience an immediate flare-up of joint pain that lasts a few days. Some patients develop infection from the catheter used to remove blood. Long-term studies are needed.

Surgery

Certain surgical techniques may be helpful for people with severe deformities or disabilities.

Arthroscopy. Arthroscopy is performed to clean out bone and cartilage fragments that cause pain and inflammation. It is usually performed on the knee, but it also may be done on the hip:

The surgeon makes a small incision and injects a sterile solution to make the joint swell for easier viewing.
A lighted tube, called an arthroscope (which enables the surgeon to view the joint), is then inserted through another small incision.
Through a third incision, the surgeon trims, shaves, or stitches the damaged tissue. (Arthroscopy is most successful when the removal of cartilage only, and not bone, is involved.)

In many cases, the procedure can be done using local anesthetic, and the patient can go home within a day. In the case of knee operations, patients can resume mild activity in a couple of days, but full recovery can take up to 3 months.

Osteotomy. If only a certain section (the medial compartment) of the knee is damaged and deformed, the surgeon may choose to perform osteotomy:

The knee is opened.
A debridement (removal of damaged tissue) is performed in the joint to eliminate the loose or torn fragments that are causing pain and inflammation.
The bone is then reshaped to remove the deformity.

The procedure is best used in heavier adults who are under 60 years old.

Unicompartmental Knee Arthroplasty. Unicompartmental knee arthroplasty (also called unicondylar knee arthroplasty) may be a useful procedure in some cases of limited damage in the knee. It is intended to relieve pain and preserve function as long as possible before a total knee replacement is necessary. The procedure involves a small incision and insertion of small implants. It retains important knee ligaments, which should preserve more movement than a total knee replacement. The procedure is not widely available and is somewhat controversial, since the implants may not be as reliable as those in total knee replacement.

Synovectomy. Synovectomy is a procedure whereby the diseased joint lining is removed. It is used when more conservative measures fail, particularly in the wrist. Studies are suggesting, however, that with the use of lasers for the procedure, eventually synovectomy may prove to be an alternative to DMARD treatments in reducing symptoms and achieving long-term remission.

Joint Replacement Surgery. Eventually, even after these procedures, rheumatoid arthritis may progress to the point that normal functioning is impossible. In such cases, artificial (prosthetic) replacement joint implants may be considered for knees, hips, or other joints. The prosthesis is usually made of a chromium alloy and plastic and may be attached to the adjoining bones using a cement, polymethyl methacrylate, or the prosthesis may be composed of a porous material that allows bone to grow into and eventually adhere to the device.

Although this procedure has usually been performed in people over 60, implants are now lasting 20 years and more and younger patients with severe disability are finding them useful. Uncemented arthroplasty using porous material is showing particularly good results. Studies on hip replacement, for example, now report that after 10 years, 5% of patients require reoperation and 12% of patients report some pain.

Lifestyle Changes

It is important to maintain a balance between rest (which will reduce inflammation) and exercise (which will relieve stiffness and weakness). Studies have suggested that even as little as 3 hours of physical therapy over 6 weeks will help people with RA, and that these benefits are sustained.

The goal of exercise is to:

Maintain a wide range of motion
Increase strength, endurance, and mobility
Improve general health
Promote well-being

In general, doctors recommend the following approaches:

Start with the easiest exercises, stretching and tensing of the joints without movement.
Next attempt mild strength training. (One study found that people with RA who exercised with machines that use compressed air for gentle resistance experienced less pain and increased muscle tone.)
The next step is to try aerobic exercises. These include walking, dancing, or swimming, particularly in heated pools. Avoid heavy impact exercises, such as running, downhill skiing, and jumping.
Tai chi, which uses graceful slow sweeping movements, is an excellent method for combining stretching and range-of-motion exercises with relaxation techniques. It is of particularly value for elderly RA patients who report significantly less pain after practicing this technique.

While traditional guidelines have restricted RA patients to only gentle exercise, recent research suggests that more intense exercise may not only be safe, but may actually produce greater muscle strength and overall functioning. Common sense is the best guide:

If exercise is causing sharp pain, stop immediately.
If lesser aches and pains continue for more than 2 hours afterwards, try a lighter exercise program for a while.
Using large joints instead of small ones for ordinary tasks can help relieve pressure, for instance, closing a door with the hip or pushing buttons with the palm of the hand.

Many patients with RA try dietary approaches, such as fasting, vegan diets, or eliminating specific foods, that seem to worsen RA symptoms. There is little scientific evidence to support these approaches but some patients report anecdotally that they are helpful.

In recent years, a number of studies have suggested that the omega-3 fatty acids contained in fish oil may have anti-inflammatory properties useful for RA joint pain relief. The best source of fish oil is through increased consumption of fatty fish such as salmon, mackerel, and herring. Fish oil supplements are another option, but they may interact with certain medications. If you are thinking of trying fish oil supplements, talk to your doctor first.

Various ointments, including Ben Gay and capsaicin (a cream that use the active ingredient in chilli peppers), may help soothe painful joints.

Orthotic devices are specialized braces and splints that support and help align joints. Many such devices made from a variety of light materials are available and can be very helpful when worn properly.

A number of specially designed appliances and devices are available to ease daily activities.

Although the influence of stress or emotions on the progression of RA is not fully known, having a history of major depression that persists or reoccurs seems to increase the pain, disability, and fatigue. Stress management alone cannot reduce pain, but it may be very helpful in helping people deal with their condition.

One study found that people with RA reported significant clinical improvement after writing about their pain, stress, or other traumatic experiences. Writing for 20 minutes, just a few days a week, resulted in improvement that lasted for months. One study found that spirituality (defined as "a belief in a power outside oneself and one's own existence," as opposed to the practice of any specific religion) is associated with better health, happiness and well-being among RA patients. (Spiritual healing does not appear to offer any advantages.)

People often turn to alternative therapies or nontraditional remedies to relieve the pain of rheumatoid arthritis. Some alternative procedures, such as acupuncture, massage, relaxation techniques, biofeedback, and hypnosis, are not harmful and may be a useful adjunct to standard treatments.

In a small study, acupuncture reduced pain by a third in 73% of patients, and more than half reported at least a 50% improvement in pain. Patients also reduced their use of pain medications. Research presented at the 2006 American College of Rheumatology annual meeting suggested that both electroacupuncture and traditional acupuncture may help reduce joint tenderness.
Balneotherapy, also known as hydrotherapy or spa therapy, is an ancient form of therapy that involves mineral baths to soothe pain, and some patients have reported relief using such baths.
The NIH is conducting clinical trials to examine whether relaxation response, tai chi, stress management, and cognitive-behavioral therapy can help patients with RA feel better.

Herbal remedies used for RA include boswellia, equisetum arvense (horsetail), devil's claw, borage seed oil, and many others. To date, no evidence supports their efficacy.

Researchers are currently conducting studies in animals to determine if supplements extracted from the turmeric spice can help prevent joint inflammation. The U.S. National Institutes of Health is also conducting a clinical trial to compare the clinical effects of the Chinese herb Tripterygium wilfordii Hook F (TwHF) with the pharmaceutical drug sulfasalazine. TwHF is traditionally used in Chinese medicine for its anti-inflammatory properties.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

Resources

www.niams.nih.gov -- The National Institute of Arthritis and Musculoskeletal and Skin Diseases
www.rheumatology.org -- American College of Rheumatology
www.arthritis.org -- The Arthritis Foundation
www.fda.gov/cder/drug/infopage/cox2 -- FDA information on COX-2 inhibitors and NSAIDs
www.clinicaltrials.gov -- Find a clinical trial

References

Chen YF, Jobanputra P, Barton P, Jowett S, Bryan S, Clark W, et al. A systematic review of the effectiveness of adalimumab, etanercept and infliximab for the treatment of rheumatoid arthritis in adults and an economic evaluation of their cost-effectiveness. Health Technol Assess. 2006 Nov;10(42):iii-iv, xi-xiii, 1-229.

Donahue KE, Gartlehner G, Jonas DE, Lux LJ, Thieda P, Jonas BL, et al. Systematic Review: Comparative Effectiveness and Harms of Disease-Modifying Medications for Rheumatoid Arthritis. Ann Intern Med. 2007 Nov 19 [Epub ahead of print]

Firestein GS. In: Harris ED Jr, ed. Kelley's Textbook of Rheumatology. 7th ed. Saunders; 2005.

Furst DE, Breedveld FC, Kalden JR, Smolen JS, Burmester GR, Sieper J, et al. Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2007. Ann Rheum Dis. 2007 Nov;66 Suppl 3:iii2-22.

Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, van Zeben D, Kerstens PJ, Hazes JM,, et al. Comparison of treatment strategies in early rheumatoid arthritis: a randomized trial. Ann Intern Med. 2007 Mar 20;146(6):406-15.

Goldberg RJ, Katz J. A meta-analysis of the analgesic effects of omega-3 polyunsaturated fatty acid supplementation for inflammatory joint pain. Pain. 2007 May;129(1-2):210-23. Epub 2007 Mar 1.

Harris ED Jr. In: Harris ED Jr, ed. Kelley's Textbook of Rheumatology. 7th ed. Saunders; 2005. O’Dell JR. In: Goldman, ed. Cecil Medicine. 23rd ed. Saunders; 2007.

Smolen JS, Aletaha D, Koeller M, Weisman MH, Emery P. New therapies for treatment of rheumatoid arthritis. Lancet. 2007 Dec 1;370(9602):1861-74.

Smolen JS, Keystone EC, Emery P, Breedveld FC, Betteridge N, Burmester GR,. et al. Consensus statement on the use of rituximab in patients with rheumatoid arthritis. Ann Rheum Dis. 2007 Feb; 66(2): 143-50.

Review Date:
1/21/2008
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M. Copyright

adam.com

Scoliosis

FitSugar — Wed, 08 Oct 2008 17:35:13 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Prognosis
Symptoms
Diagnosis
Treatment
Managing Scoliosis
Braces
Surgery
Treatment for Adult Scolios...
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Diagnosing Scoliosis

Scoliosis is diagnosed typically in children 10 - 15 years of age. However, only about 1% of cases actually require treatment. There is a large female preponderance for larger curves that do require treatment.

Defining Scoliosis

Nonstructural scoliosis is a simple side-to-side curve of the spine. Structural scoliosis adds to that simple curve a rotation of the vertebrae, resulting in a twisting of the spine.

Causes

In about 80% of scoliosis cases, the cause is unknown (idiopathic scoliosis). Research has not been able to identify any genetic abnormality that would make a person susceptible to developing scoliosis.

Treatment with Bracing

Bracing has long been the standard treatment to prevent progression of the curvature of scoliosis. However, patient compliance has been a problem, especially for younger patients. Newer braces are now more comfortable and can be worn discretely under the clothing, thus improving patient compliance and treatment results.

Introduction

Scoliosis is the abnormal curvature of the spine. While the normal spine has gentle natural curves that round the shoulders and make the lower back curve inward, scoliosis typically involves a three-dimensional deformity of the spinal column and rib cage. To varying degrees, the spine curves from side-to-side, and some of the spinal bones may rotate slightly, making the hips or shoulders appear uneven. It may develop in the following way:

As a single primary side-to-side curve (resembling the letter C), or
As two curves (a primary curve along with a compensating secondary curve that forms an S shape).

Scoliosis most commonly develops in the area between the upper back (the thoracic area) and lower back (lumbar area). It may also occur only in the upper or lower back. The doctor attempts to define scoliosis by the following characteristics:

The shape of the curve
Its location
Its direction
Its magnitude
Its causes, if possible

Click the icon to see an image of scoliosis.

The severity of scoliosis is determined by the extent of the spinal curvature and the angle of the trunk rotation (ATR) and is usually measured in degrees. Curves of less than 20 degrees are considered mild and account for 80% of scoliosis cases. Curves that progress beyond 20% require medical attention. Such attention, however, usually involves periodic monitoring to make sure the condition is not becoming worse.

Scoliosis affects about 2 - 3% of the population (about 6 million people in the United States). It can occur in adults but is more commonly diagnosed for the first time in children aged 10 - 15 years. About 10% of the adolescent population has some degree of scoliosis, but less than 1% develops scoliosis that requires treatment. The condition also tends to run in families. Among persons with relatives that have scoliosis, about 20% develop the condition.

Among adults, previous reports have indicated a prevalence of scoliosis of up to 32%. But a recent study of 75 healthy adults aged 60 years and older with no known history of scoliosis or prior spine surgery suggested a rate of 68%. However, scoliosis was not linked to physical or social impairment in this population.

Scoliosis is often categorized by the shape of the curve, usually as either structural or nonstructural.

Structural scoliosis. In addition to the spine curving from side to side, the vertebrae rotate, twisting the spine. As it twists, one side of the rib cage is pushed outward so that the spaces between the ribs widen and the shoulder blade protrudes (producing the rib-cage deformity, or hump). The other half of the rib cage is twisted inward, compressing the ribs.
Nonstructural scoliosis. The curve does not twist but is a simple side-to-side curve.

Other abnormalities of the spine that may occur alone or in combination with scoliosis include hyperkyphosis (an abnormal exaggeration in the backward rounding of the upper spine) and hyperlordosis (an exaggerated forward curving of the lower spine, also called swayback).

Click the icon to see an image of kyphosis.

The location of a structural curve is defined by the location of the apical vertebra. This is bone at the highest point (the apex) in the spinal hump. This particular vertebra also undergoes the most severe rotation during the disease process.

The direction of the curve in structural scoliosis is determined by whether the convex (rounded) side of the curve bends to the right or left. For example, a doctor will diagnose a patient as having right thoracic scoliosis if the apical vertebra is in the thoracic (upper back) region of the spine, and the curve bends to the right.

The magnitude of the curve is determined by taking measurements of the length and angle of the curve on an x-ray view.

Vertebrae. The spine is a column of small bones, or vertebrae, that support the entire upper body. The column is grouped into three sections of vertebrae:

Cervical (C) vertebrae are the 7 spinal bones that support the neck.
Thoracic (T) vertebrae are the 12 spinal bones that connect to the rib cage.
Lumbar (L) vertebrae are the 5 lowest and largest bones of the spinal column. Most of the body's weight and stress falls on the lumbar vertebrae.

Each vertebra can be designated by using a letter and number; the letter reflects the region (C=cervical, T=thoracic, and L=lumbar), and the number signifies its location within that region. For example, C4 is the fourth bone down in the cervical region, and T8 is the eighth thoracic vertebra.

Below the lumbar region is the sacrum, a shield-shaped bony structure that connects with the pelvis at the sacroiliac joints. At the end of the sacrum are 2 - 4 tiny, partially fused vertebrae known as the coccyx or "tail bone."

The Spinal Column and its Curves. Altogether, the vertebrae form the spinal column. In the upper trunk the column normally has a gentle outward curve (kyphosis) while the lower back has a reverse inward curve (lordosis).

The Disks. Vertebrae in the spinal column are separated from each other by small cushions of cartilage known as intervertebral disks. Inside each disk is a jelly-like substance called the nucleus pulposus, which is surrounded by a tough, fibrous ring called the annulus fibrosis. The disk is 80% water. This structure makes the disk both elastic and strong. The disks have no blood supply of their own, relying instead on nearby blood vessels to keep them nourished.

Processes. Each vertebra in the spine has a number of bony projections, known as processes. The spinal and transverse processes attach to the muscles in the back and act like little levers, allowing the spine to twist or bend. The particular processes form the joints between the vertebrae themselves, meeting together and interlocking at the zygapophysial joints (more commonly known as facet or z joints).

Spinal Canal. Each vertebra and its processes surround and protect an arch-shaped central opening. These arches, aligned to run down the spine, form the spinal canal, which encloses the spinal cord, the central trunk of nerves that connects the brain with the rest of the body.

Click the icon to see an image of the spine.

Click the icon to see an image of the sacrum.

Click the icon to see an image of the curves of the spine.

Click the icon to see an image of an intervertebral disk.

Click the icon to see an image of the spinal canal.

Causes

In 80% of patients, the cause of scoliosis is unknown. Such cases are called idiopathic scoliosis. (Idiopathic means without a known cause.) Idiopathic scoliosis may be due to multiple, poorly understood inherited factors, most likely from the mother's side. However, the severity often varies widely among family members who have the condition, suggesting that other factors must be present.

Researchers have not been able to identify the specific genetic abnormalities that make a young person susceptible to spinal distortion. Inherited physical abnormalities, problems in coordination, abnormalities in the central nervous system, and other inherited factors may play some role either alone or in combination with other conditions to produce scoliosis.

Physical Abnormalities. Researchers are investigating possible physical abnormalities that may cause imbalances in bones or muscles that would lead to scoliosis. Among them are the following:

Imbalances in Muscles around the Vertebrae. Some research suggests that imbalances in the muscles around the vertebrae may make children susceptible to spinal distortions as they grow.
High Arches. One study showed a higher incidence of abnormally high arches in the feet in people with idiopathic scoliosis, suggesting that altered balance may be a factor in certain cases.

Problems in Coordination. Some experts are looking at inherited defects in perception or coordination that may cause asymmetrical growth in the spine of some children with scoliosis.

Genetic Abnormalities in the Central Nervous System. Genetic defects that cause altered processing in the brain may play a role in producing abnormalities in the growing spine. For example, research has implicated low levels of melatonin, a hormone secreted in the pineal gland in brain. Melatonin is involved with sleep and growth. Researchers speculate that genetic factors that cause reduced blood levels of melatonin may adversely affect muscle tone and development during sleep, perhaps contributing to scoliosis.

Other Biologic Factors. Several other biologic factors are being investigated for some contribution to scoliosis:

Abnormalities in collagen, the critical structural protein found in muscles and bones. Enzymes known as matrix metalloproteinases are involved in the repair and remodeling of collagen. Researchers have found high levels of the enzymes in the disks of patients with scoliosis, which suggests that the enzymes may contribute to curve progression. Elevated levels of the enzymes can cause abnormalities in components in the spinal disks, contributing to disk degeneration.
A possible defective gene responsible for production of fibrillin, an important component of connective tissue, which makes up bones and muscles.
Abnormalities in a protein called platelet calmodulin that binds to calcium. This protein acts like a tiny muscle and pulls clots together. Measuring levels of this protein may eventually help predict whether scoliosis will worsen.

Congenital scoliosis is caused by inborn spinal deformities that may result in the development of absent or fused vertebrae. Kidney problems, particularly having only one kidney, often coincide with congenital scoliosis. The condition usually becomes evident at either age 2 or between ages 8 and 13 as the spine begins to grow more quickly, putting additional stress on the abnormal vertebrae. It is essential to diagnose and monitor such curvatures as early as possible, since they can progress quickly. Early surgical treatment -- before age 5 -- may be important in many of these patients to prevent serious complications.

Adult scoliosis has two primary causes:

Progression of childhood scoliosis.
Degenerative lumbar scoliosis. Degenerative lumbar scoliosis is a condition that typically develops after age 50. With this condition, the lower spine is affected, usually due to disk degeneration. Osteoporosis, a serious problem in many older adults, is not a risk factor for new-onset scoliosis, but it can be a contributing factor. In most cases, however, it is not known why scoliosis occurs in adults.

Scoliosis may be a result of various conditions that affect bones and muscles associated with the spinal column. They include the following:

Muscle paralysis.
Muscle deterioration from diseases such as muscular dystrophy, polio, or cerebral palsy.
Injury to the spinal cord.
Tumors, growths, or other small abnormalities on the spinal column. For example, syringomyelia, a disorder in which cysts form along the spine, can cause scoliosis. These spinal abnormalities may play a larger role in causing some cases of scoliosis than previously thought.
Familial dysautonomia, a rare disorder in Jewish children of Ashkenazi descent. (Only about 500 cases have been reported.)
Stress fractures and hormonal abnormalities that affect bone growth in young, competitive athletes.
Birth defects, including spina bifida (an open spinal cord) and myelomeningocele (a hernia of the central nervous system).
Turner syndrome, a genetic disease in females that affects physical and reproductive development.
Other diseases that can cause scoliosis are Marfan syndrome, Aicardi syndrome, Friedreich ataxia, Albers-Schonberg disease, rheumatoid arthritis, Cushing syndrome, and osteogenesis imperfecta.

Spina bifida is a congenital disorder (birth defect) in which the backbone and spinal canal do not close before birth. In severe cases, this can result in the spinal cord and its covering membranes protruding out of an affected infant's back. Spina bifida may also be nearly inconsequential, or may be repairable through surgery.

Nonstructural scoliosis is usually not a serious problem, since the curve is side to side. It can develop from a number of physical problems, including the following:

Unequal leg length. Injury, a shortened Achilles tendon, or other structural in-born problems can cause this very common condition. Unequal leg length rarely causes any problems and in most cases requires no treatment other than a lift in one of the shoes to equalize the length.
Muscle spasms.

Risk Factors

Risk Factors for Initial Scoliosis. Idiopathic scoliosis, the most common form, occurs most often during the growth spurt right before and during adolescence. (Between 12 - 21% of idiopathic cases occur in children ages 3 - 10 years, and less than 1% in infants.) Mild curvature (under 20 degrees) occurs about equally in girls and boys, but curve progression is 10 times more likely to occur in girls. Being taller than average at earlier ages may put some girls at risk, but other factors must be present to produce scoliosis. A risk factor that affects females is a delayed onset of menstruation, which can prolong the growth spurt period, thus increasing the possibility for the development of scoliosis.

Risk Factors for Curvature Progression. Once scoliosis is diagnosed, it is very difficult to predict who is at highest risk for curve progression. About 2 - 4% of all adolescents develop curvature of 10 degrees or more, but only about 0.3 - 0.5% of teenagers have curves greater than 20 degrees, which requires some medical attention.

People with certain medical conditions that affect the joints and muscles are at higher risk for scoliosis. These conditions include rheumatoid arthritis, muscular dystrophy, polio, and cerebral palsy. Children who receive organ transplants (kidney, liver, heart) are also at increased risk.

In one study, idiopathic scoliosis occurred in about 5% of close family members of children with the condition.

Scoliosis may be evident in young athletes, with a prevalence of 2 - 24%. The highest rates are observed among dancers, gymnasts, and swimmers. The scoliosis may have been due in part to loosening of the joints, delay in puberty onset (which can lead to weakened bones), and stresses on the growing spine. There have also been other isolated reports of a higher risk for scoliosis in young athletes who engage vigorously in sports that put an uneven load on the spine. These include figure skating, dance, tennis, skiing, and javelin throwing, among other sports. In most cases, the scoliosis is minor, and everyday sports do not lead to scoliosis. Exercise has many benefits for people both young and old and may even help patients with scoliosis.

Prognosis

In general, the severity of the scoliosis depends on the degree of the curvature and whether it threatens vital organs, specifically the lungs and heart.

Mild Scoliosis (less than 20 degrees). Mild scoliosis is not serious and requires no treatment other than monitoring.
Moderate Scoliosis (between 25 and 70 degrees). It is still not clear whether untreated moderate scoliosis causes significant health problems later on. Some studies have found no difference in either back pain or survival rates in adult untreated patients versus the general population. In one study, adults with moderate scoliosis had normal lung function, although they had difficulty exercising. (This low exercise tolerance might have been because many patients with scoliosis do not engage in regular physical activity.)
Severe Scoliosis (over 70 degrees). If the curvature exceeds 70 degrees, the severe twisting of the spine that occurs in structural scoliosis can cause the ribs to press against the lungs, restrict breathing, and reduce oxygen levels. The distortions may also affect the heart and possibly cause dangerous changes.
Very Severe Scoliosis (Over 100 degrees). Eventually, if the curve reaches over 100 degrees, both the lungs and heart can be injured. Patients with this degree of severity are susceptible to lung infections and pneumonia. Curves greater than 100 degrees increase mortality rates, but this problem is very uncommon in America.

Some experts argue that simply measuring the degree of the curve may not identify patients in the moderate and severe groups who are at greatest risk for lung problems. Other factors (spinal flexibility, the extent of asymmetry between the ribs and the vertebrae) may be more important in predicting severity in this group.

Scoliosis is associated with osteopenia, a condition characterized by loss of bone mass. About 27 - 38% of adolescent girls who have scoliosis also have osteopenia. Some experts recommend measuring bone mineral density when a patient is diagnosed with scoliosis. The amount of bone loss may help predict how severely the spine will curve. Preventing and treating osteopenia may help limit further curve progression.

If not treated, osteopenia can later develop into osteoporosis. Osteoporosis is a more serious loss of bone density that is common among postmenopausal women. Adolescents who have scoliosis are at increased risk of developing osteoporosis later in life. [See In-Depth Report#18: Osteoporosis.]

Osteoporosis is a condition characterized by progressive loss of bone density, thinning of bone tissue, and increased vulnerability to fractures. Osteoporosis may result from disease, dietary or hormonal deficiency, or advanced age. Regular exercise and vitamin and mineral supplements can reduce and even reverse loss of bone density.

After 20 years or more, scoliosis patients who were previously treated with surgery experience small but significant physical impairment, (mainly mild back problems), compared to their peers without scoliosis. In one study, 65% of patients reported some low back pain compared to 47% of people without a history of scoliosis. In general it was mild, although 45% of patients reported having to take days off from work compared to 19% of nonscolosis patients. In another study, only 1.5% of the scoliosis group had severe debilitating back pain. In general, the quality of life was similar, however. Pain also did not play a major role in social limitations.

The following are some possible causes of later back problems in people with a history of treated scoliosis:

Spinal fusion disease. Patients who are surgically treated with fusion techniques lose flexibility and may experience weakness in back muscles due to injuries during surgery.
Disk degeneration and low back pain. With disk degeneration, the disks between the vertebrae may become weakened and rupture. In some patients, years after the original surgeries, particularly with the first generation of the Harrington rods, the weight of the instrumentation can cause disk and joint degeneration severe enough to require surgery. Treatment may involve removal of the old instrumentation and extension of the fusion into the lower back. Still, most patients do not experience significant back pain from these problems.
Height loss.
Scarred regions. Pain can occur from old scars in the incision areas.
Lumbar flatback. This condition is most often the result of a scoliosis surgical procedure called the Harrington technique, which eliminated lordosis (the inward curve in the lower back). Adult patients with flatback syndrome tend to stoop forward. They may experience fatigue and back and even neck pain.
Rotational trunk shift (uneven shoulders and hips).

Evidence suggests that previous treatment with braces may also cause mild back pain and more days off, but problems appear to be less than with surgery. In one study, dysfunction was comparable to people without a history of scoliosis.

Pain in adult-onset or untreated childhood scoliosis often develops because of posture problems that cause uneven stresses on the back, hips, shoulders, necks, and legs. In one study conducted 20 years after growth had stopped, two-thirds of adults who had lived with curvatures of 20 - 55 degrees reported they experienced back pain. Other studies have reported that adults with a history of scoliosis tend to have chronic and more back pain than the general population.

Nearly all individuals with untreated scoliosis at some point develop spondylosis, an arthritic condition in the spine. The joints become inflamed, the cartilage that cushions the disks may thin, and bone spurs may develop. If the disk degenerates or the curvature progresses to the point that the spinal vertebrae begin pressing on the nerves, pain can be very severe and may require surgery. Even surgically treated patients are at risk for spondylosis if inflammation occurs in vertebrae around the fusion site.

Emotional Impact in Childhood. The emotional impact of scoliosis, particularly on young girls or boys during their most vulnerable years, should not be underestimated. Adults who have had scoliosis and its treatments often recall significant social isolation and physical pain. Follow-up studies of children who had scoliosis without having strong family and professional support often report significant behavioral problems. Fortunately, current treatments are solving many of the problems that previous generations had to deal with, including unsightly bracing and extremely painful surgeries with little pain control.

Emotional Effects in Adults. Of some concern are growing numbers of adults with scoliosis. This group experiences considerable problems in general health, social functioning, emotional and mental health, as well as pain.

Older people with a history of treated scoliosis may carry negative emotional events into adulthood that have their roots in their early experiences with scoliosis. Many studies have reported that patients who were treated for scoliosis have limited social activities and a poorer body image in adulthood. Some patients with a history of scoliosis have reported a slight negative effect on their sexual life. Pain appears to be only a minor reason for such limitation.

Women who have been successfully treated for scoliosis have only minor or no additional risks at all for complications during pregnancy and delivery. A history of scoliosis also does not endanger the child. Pregnancy itself, even multiple pregnancies, does not increase the risk for curve progression. Women who have severe scoliosis that restricts the lungs, however, should be monitored closely.

Some evidence suggests a slightly higher risk for breast cancer and leukemia in patients who had multiple x-rays. Risks are highest in patients who had the largest radiation exposure, such as those who had been surgically treated.

Patients who simply received x-ray series for untreated idiopathic scoliosis or scoliosis caused by uneven length legs or hip abnormalities have a very low risk for future complications.

Click the icon to see an image of an x-ray.

Symptoms

Scoliosis is usually painless. The curvature itself may often be too subtle to be noticed, even by observant parents. Some parents may notice abnormal posture in their growing child that includes:

A tilted head that does not line up over the hips
A protruding shoulder blade
One hip or shoulder that is higher than the other, causing an uneven hem or shirt line
An uneven neckline
Leaning more to one side than the other
In developing girls, breasts appearing to be of unequal size
One side of the upper back being higher than the other when the child bends over, knees together, with the arms dangling down

Scoliosis may be suspected when one shoulder appears to be higher than the other, there is a curvature in the spine, or the pelvis appears to be tilted. The treatment of scoliosis can involve the use of a brace or surgery. Treatment is determined by the cause of the scoliosis, the size and location of the curve, and the stage of bone growth of the patient.

With more advanced scoliosis, fatigue may occur after prolonged sitting or standing. Scoliosis caused by muscle spasms or growths on the spine can sometimes cause pain. Nearly always, however, mild scoliosis produces no symptoms, and the condition is usually detected by the pediatrician or during a school screening test.

Diagnosis

The severity of scoliosis and need for treatment is usually determined by two factors:

The extent of the spinal curvature. (Scoliosis is diagnosed when the curve measures 11 degrees or more.)
The angle of the trunk rotation (ATR).

Both are measured in degrees. These two factors are usually related. For example, a person with a spinal curve of 20 degrees will usually have a trunk rotation (ATR) of 5 degrees. These two measurements, in fact, used to be the cutoff for recommending treatment. However, the great majority of 20-degree curves do not get worse. Patients do not usually need medical attention until the curve reaches 30 degrees, and the ATR is 7 degrees.

Adam's Forward Bend Test. The screening test used most often in schools and in the offices of pediatricians and primary care doctors is called the Adam's forward bend test.

The child bends forward dangling the arms, with the feet together and knees straight. The curve of structural scoliosis is more apparent when bending over. In a child with scoliosis, the examiner may observe an imbalanced rib cage, with one side being higher than the other, or other deformities.

The forward bend test is used most often in schools and doctor's offices to screen for scoliosis. During the test, the child bends forward with the feet together and knees straight while dangling the arms. Any imbalances in the rib cage or other deformities along the back could be a sign of scoliosis.

The forward bend test, however, is not sensitive to abnormalities in the lower back, a very common site for scoliosis. Because the test misses about 15% of scoliosis cases, many experts do not recommend it as the sole method for screening for scoliosis.

Other Physical Tests.

The patient walks on the toes, then the heels, and then jumps up and down on one foot. Such activities indicate leg strength and balance.
The doctor will check leg length and look for tight tendons in the back of the leg, which may cause an uneven leg length or other back problems.
The doctor will also check for neurologic impairment by testing reflexes, nerve sensation, and muscle function.

Proper diagnosis is important. A misjudgment can lead to unnecessary x-rays and stressful treatments in children not actually at risk for progression. Unfortunately, although measurements of curves and rotation are useful, no test exists yet to determine whether a curve will progress.

Inclinometer (Scoliometer). An inclinometer, also known as a Scoliometer, measures distortions of the torso. The procedure is as follows:

The patient bends over, arms dangling and palms pressed together, until a curve can be observed in the upper back (thoracic area).
The Scoliometer is placed on the back and measures the apex (the highest point) of the upper back curve.
The patient continues bending until the curve can be seen in the lower back (lumbar area). The apex of this curve is also measured.
Measurements are repeated twice, with the patient returning to a standing position between repetitions.
If results show a deformity, x-rays probably need to be performed to determine the extent.

Some experts believe the Scoliometer would make a useful device for widespread screening. Scoliometers, however, indicate rib cage distortions in more than half of children who turn out to have very minor or no sideways curves. They are therefore not accurate enough to guide treatment.

Currently, x-rays are the most cost-effective method for diagnosing scoliosis. Experts hope that accurate, noninvasive diagnostic techniques will eventually be developed to replace some of the x-rays used to monitor the progression of scoliosis. To date, imaging techniques under investigation appear to be fairly accurate for detecting scoliosis in the upper back (the thoracic region), but not scoliosis in the lower back (the lumbar region).

X-Rays. If screening indicates scoliosis, the child may be sent to a specialist who takes an initial x-ray and monitors the child every few months using repeated x-rays. X-rays are essential for an accurate diagnosis of scoliosis in that they:

Reveal the degree and severity of scoliosis.
Identify any other spinal abnormalities, including kyphosis (hunchback) and hyperlordosis (swayback).
Help the doctor determine whether skeletal growth has reached maturity.
X-rays taken when patients are bending forward can also help differentiate between structural and nonstructural scoliosis. Structural curves persist when a person bends over, and nonstructural curves tend to disappear. (Muscle spasms or spinal growths may sometimes cause nonstructural scoliosis that shows a curve on bending.)
Children and young adolescents who have mild curves and in older adolescents who have more severe curvatures but whose growth has stopped or slowed need x-rays every few months to detect increasing severity. Young people who are diagnosed with scoliosis should keep their x-rays indefinitely in case they develop back problems later in adulthood and need to be re-examined.

Magnetic Resonance Imaging. Magnetic resonance imaging (MRI) is an advanced imaging procedure that does not use radiation, as x-rays do. It is expensive, however, and not generally used for an initial diagnosis. MRI can, nevertheless, identify spinal cord and brain stem abnormalities, which some studies indicate may be more prevalent than previously believed in children with idiopathic scoliosis. It also may be particularly useful before surgery for detecting defects that could lead to potential complications.

Click the icon to see an image of a MRI scan.

Because frequent x-rays may be required for young children with scoliosis, parents should be sure that x-ray technicians take all necessary protective measures. Experts are concerned about the long-term effects of radiation on sensitive young organs, particularly about a possible increase in the risk for cancer. Studies have reported an increased risk for cancer in women and men who, because of scoliosis, had been exposed to diagnostic x-rays in their childhood and adolescence.

X-ray techniques have become safer in recent years, and technicians can reduce the hazards with the following simple measures:

Directing x-ray beams through the patient from back to front, rather than the reverse.
Using x-ray filters that absorb some of the beam.
Using fast film to reduce exposure by two to six times.
Placing lead aprons or shields over parts of the body that are not being x-rayed.

There are various methods for determining and classifying the extent of the curve.

Cobb Method. The technique known as the Cobb method nearly always calculates the degree of the curve.

On an x-ray of the spine, the examiner draws two lines: One line extends out and up from the edge of the top vertebrae of the curve. The second line extends out and down from the bottom vertebrae.
The technician then draws a perpendicular line between the two lines.
Measuring the intersecting angle determines the degree of curvature.

The Cobb method is limited because it cannot fully determine the flexibility or the three-dimensional aspect of the spine. It is not as effective, then, in defining spinal rotation or kyphosis. It also tends to over-estimate the curve. Other diagnostic tools are needed then to make a more accurate diagnosis.

Classifying the Curve.Classification of the curve allows the doctor to identify patterns that can help determine treatments, particularly specific surgical techniques. The following are examples:

King Classification. The King classification classifies scoliotic curves as one of five patterns, which can help determine surgical treatments. It has limitations, however, and is not very useful for advanced surgical techniques.
Lenke Classification. Lenke classification takes more features of the curve into consideration and is proving to be more reliable. This includes six curve patterns plus additional factors that modify each of these curves.

Three-Dimensional Modeling Techniques. Advanced computer modeling techniques are able to create three dimensional images using x-rays or other two-dimensional images. They allow doctors to observe the spinal distortions and eventually could reduce the number of x-rays currently needed to monitor scoliosis and help surgeons determine optimal surgical procedures.

Even if the curve is accurately calculated, it still remains difficult to predict whether the scoliosis will progress. A recent report indicates that measuring the nerve conduction activity of the muscles supporting the spine may help predict subsequent progression in children with scoliosis. In addition, computer models are being used to better predict risk. One approach requires measuring 21 radiographic and clinical indicators and entering them into a computer program. The technique takes less than 20 minutes per patient, and studies found it to be up to 80% accurate in determining progression of curvature.

One way of predicting whether or not the curvature will progress is knowing when the child will stop growing:

If the child has years to grow, then the spine has more time to progress.
If the child will stop growing within a year, then progression should be very slight. (However, some progression continues in nearly 70% of curves even after the spine has matured.)

Knowing the child's age is, of course, the first step in estimating the end of growth. In addition, other methods can help predict the end of the growth stage. One method is called the Risser sign, which grades the amount of bone in the area at the top of the hipbone. A low grade indicates that the skeleton still has considerable growth; a high grade means that the child has nearly stopped growing and the curve is unlikely to progress much further. The Risser scale differs between genders, and, in boys, a high grade does not always signify the end of progression.

Screening programs for scoliosis, which began in the 1940s, are now mandatory in middle or high schools in many states, but there is considerable debate over whether screening should be routine.

Arguments Against Routine Screening. The U.S. Preventive Services Task Force does not recommend routine screening to detect adolescent scoliosis for the following reasons:

Screening tests are not accurate and depend too much on the skill of the examiner.
Schools often refer children with minor curves who are not at any risk for a progressive or serious condition to doctors, and such over-referrals add considerably to the costs of the health system. In one major study, 94% of the children referred to a doctor by the school did not require treatment. (Over 2,000 children were screened in order to find only 5 children who did need treatment.)
A long-term study of untreated patients with late-onset scoliosis indicates that these patients are productive and functional at a high level at 50-year follow-up. Patients with scoliosis have no greater danger for significant lung problems than the general population until their curves reach 60 - 100 degrees, making early screening unnecessary.

Experts against screening argue that such programs result in early treatments that either will not prevent curve progression and surgery or are unnecessary in the first place since curvatures often do not progress at all.

Arguments for Routine Screening. The American Academy of Orthopaedic Surgeons recommends that girls be screened twice, at ages 10 and 12, and that boys be screened once, at 13 or 14. The American Academy of Pediatrics recommends, however, scoliosis screening at ages 10, 12, 14, and 16 years. (In one study, over 40% of high school sophomores with newly diagnosed scoliosis had shown no signs of the disorder in earlier screening tests.) Other experts make the following arguments for universal screening:

Universal screening is useful for producing information on scoliosis that may eventually lead to knowledge of its cause and ways to prevent it.
Braces have proven to be effective, and early treatment can be important.
Without screening, the chances are slim that children with scoliosis will be diagnosed at an early stage if parents rely only on examinations by a family doctor or pediatrician. Such doctors often do not even look at backs and, if they do, they tend to use only the forward bend test, which is not accurate.

Some experts argue that widespread screening would be cost effective if schools had reasonable guidelines for determining which children should see a doctor for further testing. The following are some suggested guidelines for determining the need for a doctor referral:

Children should be sent to a doctor only if they have a 30-degree curve. (A 20-degree curve with a 5-degree trunk rotation has been the criteria for recommending treatment, although up to 80% of 20-degree curves do not get worse.)
Children with curves between 20 and 30 degrees should be screened every 6 months.

Such guidelines would detect about 95% of all genuinely serious cases while referring only 3% of all children tested for follow-up, thereby cutting costs without jeopardizing children.

Treatment

The treatments for scoliosis are not always straightforward. Some young people do not need treatment at all -- only careful observation. When treatment is warranted, several options, including braces and different surgical procedures, can help.

The general rule of thumb for treating scoliosis is to monitor the condition if the curve is less than 20 degrees. Curves greater than 25 degrees, or those that progress by 10 degrees while being monitored, may require treatment. Whether scoliosis is treated immediately or simply monitored is not an easy decision, however. The percentage of cases that will progress more than 5 degrees can be as low as 5% in certain cases or as high as 50 - 90%, depending on the severity of the curve or other predisposing factors:

Age. In general, the older the child the less likely the curve will progress. Scoliosis in a child under 10, for example, is more likely to progress than scoliosis in an adolescent. Experts estimate that curves less than 19 degrees will progress 10% in girls ages 13 - 15 years and 4% in children older than 15. (In some rare, severe cases, a curve may worsen even after a child has received treatment and stopped growing because of the weight of the body pressing against the abnormal curve.)

Gender. Girls have a higher risk for progression than boys.

Location of the Curvature. Thoracic curves, those in the upper spine, are more likely to progress than thoracolumbar curves or lumbar curves, those of the middle to lower spine.

Severity of the Curvature. The higher the degree of curvature the more likely the chance of progression and the more likely the lungs will be affected. Some experts argue that the degree of the curve alone may not identify patients with moderate and severe scoliosis who are at greatest risk for complications and therefore need treatment. For example, spinal flexibility and the extent of asymmetry between the ribs and the vertebrae may be more important than the curve degree in predicting severity in this group.

Presence of Other Health Conditions. Children in poor health may suffer more from stressful scoliosis treatments than other children. On the other hand, children who have existing conditions and are predispose to lung and heart problems may warrant immediate, aggressive treatment.

For example, a young man of 18 who has a curvature of 30 degrees may require no treatment because his growth has probably almost stopped, and his gender puts him at lower risk. A young girl of 10, however, with the same curvature requires immediate treatment.

In general, the following criteria are used to determine whether a patient should receive braces and conservative therapies or surgery:

Braces tend to be used in children with curvatures between 25 - 40 degrees who still will be growing significantly.
Surgery is suggested for patients with curvatures over 50 degrees, in untreated patients, or when braces have failed. In adults, scoliosis rarely progresses beyond 40 degrees, but surgery may be required if the patient is in a great deal of pain or if the scoliosis causes neurologic problems.

The choice may not be so straightforward in certain cases, and patients should discuss all options with their doctor.

In Children and Adolescents. After a mild curve is detected, a more difficult step is required: predicting whether the curve will progress into a more serious condition. Although as many as 3 in every 100 teenagers have a condition serious enough to need at least observation, progression is highly variable and individual.

In a study of patients whose curves did progress after diagnosis, 34% progressed more than 10 degrees, 18% progressed more than 20 degrees, and 8% progressed more than 30 degrees. Doctors cannot rely on any definitive risk factors for curve progression to predict with any certainty which patients will need aggressive treatment. Some evidence suggests the following factors may help determine patients at lower or higher risk:

Being female, particularly if taller than average.
Being younger at the onset of scoliosis.
Having a greater angle of curvature. For example, at 20 degrees, only about 20% of curves progress. Young people diagnosed with a 30-degree curve, however, have a risk for progression of 60%. With a curve of 50 degrees, the risk is 90%.
Curvatures caused by congenital scoliosis (spinal problems present at birth). These may progress rapidly.
Treatment with growth hormone. (Studies are mixed on whether this treatment poses any significant risk, although strict monitoring is still essential in young patients being given growth hormone.)

Curvatures may be less likely to progress in girls whose scoliosis was low in the back and whose spine was out of balance by more than an inch. Height also comes into play. For example, a shorter-than-average girl of 14 with low-back scoliosis of 25 - 35 degrees but whose spine is imbalanced by over an inch would have almost no risk. The same degree of curvature in the chest region of a tall 10-year old girl whose spine was in balance, however, would almost certainly progress.

In Adults. In rare cases, unrecognized or untreated scoliosis in youth may progress into adulthood, with the following curvatures posing low to high risk:

Curvatures under 30 degrees almost never progress
Predicting progression at curves around 40 degrees is not clear
Curvatures over 50 degrees are at great risk for progression

Managing Scoliosis

Exercise has many health benefits and is important for maintaining strength and muscle tone and stabilizing weight. Stretching exercises may be beneficial in children whose scoliosis is due to uneven leg lengths or a shortened tendon.

Strengthening the Muscles That Turn the Torso. A promising approach focuses on training and strengthening the muscles that turn the torso. Studies using specific equipment (MedX Torso Rotation machine) are showing promise. In a 2003 study, 16 of the 20 patients experienced curve reduction, and no curves progressed. In an earlier study, patients increased strength from 12 - 40%. One girl with a severe lumbar curve required surgery, but the remaining 11 patients had no progression of curvature, and 4 of the patients experienced a reduction in their curvature. Treatment did not involve braces. Clinical trials using this approach are underway. Exercising the torso to build muscle strength is important, in any case, in conjunction with braces.

ASCO Scoliosis Treatment Method. ASCO Scoliosis Treatment Method is a Russian approach that consists of isometric and stretching exercises, vibration, spinal manipulation, and electrical muscle stimulation. Some U.S. centers are reporting success in halting curve progression, but more research is needed to determine possible benefits.

Biofeedback. Researchers have investigated biofeedback on the premise that people receiving a signal to improve posture when slumping may, in some cases, reduce their spinal deformities. (Some experts believe that braces work only because the young patients self-correct their curves by retraining their posture to avoid the discomfort of the brace.)

Chiropractic Care. Several case reports suggest that chiropractic manipulation of the spine may help stop progression of mild curves. However, no rigorous studies have proved this. One small study reported no benefits from chiropractic in girls with spinal curves less than 20 degrees. (About 80% of such curves will not progress significantly without any treatment.)

Airway Ventilation at Night. Some research has focused on the use of airway systems, such as nasal continuous positive airflow pressure, for patients with severe scoliosis and reduced lung capacity. Patients use such systems during the night to force air into the upper airways and into the lungs. In one study, the use of these devices reduced hospitalization and improved lung function, shortness of breath, and fatigue. Such systems also can treat sleep apnea, a common sleep disorder.

Breathing Exercises. Breathing exercises may help improve lung function in children with scoliosis, and signs of lung problems.

When a difference in leg lengths causes secondary scoliosis, adding lifts to the heels may decrease a mild curvature. In one study, this practice reduced the curvature by an average of 5.3 to 7.5 degrees. (Curvatures were all less than 20 degrees.) Patients with the greatest curvature experienced some muscle pain, fatigue, and even nausea during the first few days they were using the lifts, but these symptoms eased within 10 days.

Braces

A brace can prevent further progression of moderate curves of (24 - 40 degrees). However, a brace will almost never reverse an existing curve and is only used to stop progression. One study reported overall success rates of around 74%, but results vary widely depending on the length of time the brace is worn, the type of brace, and the severity of the curve. The great majority of subjects in scoliosis studies are girls. Limited data suggest that in boys compliance rates are low, and braces are not effective.

Compliance with wearing a brace correlates strongly with success rate. In analysis of 34 patients, the compliance rate for the patients whose curve progressed by more than 5 degrees was 62%, while the compliance rate for the patients who did not progress was 85%.

In overweight patients with adolescent idiopathic scoliosis, braces appear to be less effective than in those who are not overweight. In one 10-year multicenter retrospective study, overweight patients were about three times more likely to have an unsuccessful result with braces than were people of normal weight.

A brace is one type of treatment for scoliosis. The brace works by exerting pressure on the back and ribs to push the spine in a straighter position. The brace usually fits snugly around the torso and can come in many styles. In a child who is still growing, bracing is usually recommended to help slow the progression of the curve. The brace is usually worn full-time until the growth of the bones has stopped.

Many experts have questioned whether a brace is any better than nature in halting curvature progress. Early studies found that braces were successful in halting progression in only half of cases (the same rate as no treatment at all). In recent years, however, braces have improved. Many now fit under the arms and can be worn under clothing, so that patients are much more likely to use them for longer periods during the day, which greatly affects their success rates.

Wearing the brace for the prescribed time is difficult but essential for any success. A team approach, with several health professionals involved, is beneficial and often necessary to support the patient through the bracing process. An orthopedic surgeon interprets the x-rays, assesses the potential progression of the scoliosis, and plans the treatment with the patient and family. If a brace is used, an orthotist measures and fits the patient with the device. A physical therapist tailors an exercise program best suited for the patient. A nurse may also coordinate the treatment plans and provide physical and emotional support.

Milwaukee Brace. A full torso brace called the Milwaukee brace was the standard treatment until a decade ago. It is still used particularly for high curves.

The device contains a wide flat bar in front and two smaller ones in back. These bars attach to a ring around the neck that has rests for the chin and back of the head. One study determined that correcting the curve occurs best if the patient lies on their chest when wearing the brace. Some researchers suggest that increasing the tension on the chest straps might add benefit. The brace is also periodically adjusted for growth.

The brace needs to be worn 23 hours a day, with relief during bathing and exercise only. Compliance is a major problem. In one study, only 15% of patients wore the Milwaukee brace as directed. It is a particularly difficult brace to endure wearing; one woman who had worn it for 7 years during adolescence remembered being invisible during her school years, ignored and shunned by other children.

The Boston and TLSO Braces. Molded braces called thoracolumbar-sacral orthoses (TLSOs), most often the Boston brace, come up to beneath the underarms and can be fitted close to the skin so they do not show beneath clothing. It appears to be effective for mid-back and lower curves. In one study, treatment was judged successful in 61% of adolescents who wore Boston braces, and success correlated with wearing the brace more than 18 hours a day. Wearing the brace for 16 hours a day may still be beneficial, although the risk for curve progression is significantly higher the less time the brace is worn. These braces have problems; they are hot, reduce lung capacity by nearly 20%, and cause mild, temporary changes in kidney function.

The Charleston Bending Brace. The Charleston Bending Brace is worn only at night. Some doctors question its value, although it appears to be suitable for small, flexible curves. In a 2002 study, it was equally effective as the Boston brace. Other studies have reported success rates of 56 - 66% in patients who wore the brace as directed. Still, more than 10% of the patients using either brace eventually needed surgery.

Additional Braces in Development. New braces are being developed in an attempt to improve compliance and results. Some examples are:

The Providence brace is a computer-fitted device that is worn only at night. It is specifically designed for the individual curvature abnormalities, and early studies are showing promise.
A bracing method called the SpineCor uses adjustable bands and a cotton vest that allows flexibility. A 2003 study reported that after 2 years, the brace corrected the curve by 5 degrees in more than half the patients, while 38% were stabilized and only 7% had curvature that worsened by more than 5 degrees. A recent trial of 24 girls with idiopathic scoliosis compared the SpineCor with a TLSO-type brace. The study indicated that the SpineCor did not halt curvature progression associated with idiopathic scoliosis during the pubertal growth spurt whereas the TLSO device did.
The custom-fitted TriaC brace exerts pressure in specific areas of the back to allow greater comfort and flexibility. It may be less conspicuous than some of the older braces.

Studies are needed to determine if these or other new braces provide any additional value.

According to a 2003 study, compliance in wearing the brace averages 65% (although it varied from 8 - 90%). Patients were apt to wear them at night but often wore them sporadically during the day. The quality of life can vary by the type of brace worn. In one study, patients who had the Milwaukee brace reported greater impairment than patients with the Boston, TSLO, or Charleston braces. The choice of brace should be one that will be the most effective for a particular patient with the lowest impact on quality of life. Young people often refuse to wear braces, even the newer models, and emotional support from the family and professionals is extremely important to help a child accept the process and sustain compliance. On a positive note, one study reported that brace treatment did not negatively affect the self images of the adolescents who had to wear them.

For children who require braces, an exercise program helps boost well being, improves compliance with treatment, and keeps muscles in tone so that the transition period after brace removal is easier.

An exercise and physical therapy program is important to maintain or achieve the following:

Chest mobility.
Proper breathing. In one study, young girls who wore the Boston brace and performed aerobic exercises for 30 minutes four times a week experienced improved lung function, whereas lung function declined in girls who did not exercise.
Muscle strength (especially in the abdominal muscles).
Flexibility in the spine. One small study showed that patients who performed exercises improving flexibility in the torso experienced less spinal twisting and had improved curvature.
Correct posture. Practicing correct posture, especially in front of a mirror, is an extremely important part of any physical therapy program. A patient who is accustomed to a curved spine may have the sensation of being crooked when first taught to properly align the spine. Practicing in front of a mirror provides a reality check.
Patients must also learn to conduct daily activities while wearing the brace. Patients tend to comply with physical therapy in the period when the brace is first being used. They typically stop exercising when they have gotten used to the brace, however, and resume exercising only near the time the brace is being removed. Patients who don't stay with the program throughout the duration of brace use experience a weakening in the back at the time of removal.

Surgery

The goals of scoliosis surgery are threefold:

Straighten the spine as much as possible in a safe manner
Balance the torso and pelvic areas
Maintain correction

It takes a two-part process to accomplish these goals:

Fusing (joining together) the vertebrae along the curve
Supporting these fused bones with instrumentation (steel rods, hooks, and other devices) attached to the spine

There are many surgical variations that use different instruments, procedures, and surgical approaches to treat scoliosis. All of the operations require meticulous skill. In most cases, success depends less on the type of operation than on the skill and experience of the surgeon. The cause of scoliosis often determines the type of procedure. Parents of patients or adult patients should not be shy in asking the surgeon and hospital about their experience with the specific procedures being considered.

Surgery is usually recommended for the following children and adolescents with idiopathic scoliosis:

All young people whose curve exceeds 50 degrees.
Growing children whose curve has gone beyond 40 degrees. (There is still some debate, however, about whether all children with curves of 40 degrees should have surgery.)
Older children who have surgery tend to experience improved well-being from the changes in their appearance, even if they have no actual improved physical functioning.

Surgery may be required for the following children at as early an age as possible.

Those whose scoliosis is due to inborn abnormalities. (The younger they are when surgery is performed the better their chances for success.)
Children with multiple physical handicaps.

Procedures will differ depending on whether a child has idiopathic scoliosis, or scoliosis due to muscle and nerve disorders (such as muscular dystrophy or cerebral palsy). In the latter cases, children also need a team approach to reduce their risks for serious complications.

Before the operation, a doctor conducts a complete physical examination to determine leg lengths, muscle strength, lung function, and any postural abnormalities. The patient receives training in deep breathing and effective coughing to avoid lung congestion after the operation. The patient should also receive training in turning over in bed in a single movement (called log-rolling) before the operation. Psychologic intervention using cognitive-behavioral methods that help young patients cope may be very helpful in reducing anxiety and pain after surgery.

Patients are encouraged to donate their own blood before the operation for use in possible transfusions. The patient should have no sunburn, rashes, or sores on the back before the operation, which could increase the risk for infection.

Most scoliosis operations involve fusing the vertebrae. The instruments and devices used to support the fusion vary, however.

In the fusion procedure, the surgeon will:

Slice flaps to expose the backs of the vertebrae that lie along the curve.
Remove the bony outgrowths along the vertebrae that allow the spine to twist and bend.
Lay matchstick-sized bone grafts vertically across the exposed surface of each vertebra, being careful that they touch adjoining vertebrae.
Fold the flaps back to their original position, covering the bone grafts.
These grafts will regenerate, grow into the bone, and fuse the vertebrae together.

Depending upon the severity and responsiveness to other treatment, a doctor may recommend surgery for scoliosis. Surgery involves correcting the curve (although not all the way) and fusing the bones in the curve together. The surgeon lays bone grafts across the exposed surface of each vertebra. These grafts will regenerate, grow into the bone, and fuse the vertebrae together. The bones are held in place with one or two metal rods held down with hooks and screws, helping to support the fusion of the vertebrae.

Graft Materials. A surgeon takes bone grafts from the patient's hip, ribs, spine, or other bones (called autografts). This is the best quality bone. However, because autografts are taken directly from the scoliosis patient, the operation is longer and the patient experiences more pain afterward. Researchers are investigating allografts, bone grafts taken from another person or a cadaver. This would reduce the pain and duration of the operation. Allografts, however, pose an increased risk for infection from the donor.

Some surgical centers now perform spinal fusions in adults using a biologically-manufactured human bone protein instead of bone grafts. RhBMP-2 (INFUSE Bone Graft) contains a bone morphogenetic protein (BMP) that helps the body grow its own bone. A surgeon inserts the protein into a pair of thimble-like cages, which are implanted between the spinal vertebrae. The cages help stabilize the spine, while the protein prompts new bone growth. Doctors hope that this new procedure can eliminate the pain of autografts and the risk of infection of allografts. Results from preliminary studies have been promising. BMP treatments are currently approved only for adults.

Healing. The healed fusions harden in a straightened position to prevent further curvature, leaving the rest of the spine flexible. It takes about 3 months for the vertebrae to fuse substantially, although 1 - 2 years are required before fusion is complete. Fusion stops growth in the spine, but most growth occurs in the long bones of the body (such as in the legs), anyway. Patients will most likely gain height from both growth in the legs and from the straighter spine. Patients may walk at a slightly slower pace after fusion, but balance may improve, and sports activities are not restricted after the procedure.

Harrington Procedure. Until 10 years ago, the standard instruments used in fusion procedures were those of the Harrington procedure, first developed in the 1960s:

To support the fusion of the vertebrae, the surgeon uses a steel rod, extending from the bottom to the top of the curve. (More than one rod may be used depending on the type of curve and whether outward curvature of the spine is present.)
The rod is attached by hooks that are suspended from pegs inserted into the bone.
Similar to changing a tire, the steel rod is jacked up and then locked into place to support the spine securely. The surgeon is then ready to fuse the vertebrae together.
After this operation, patients must wear a full body cast and lie in bed for 3 - 6 months until fusion is complete enough to stabilize the spine.
After 1 - 2 years, the steel rod is not really necessary, but it is almost always left in place unless infection or other complications occur.

The Harrington procedure is very difficult to undergo, particularly for young people, and although the operation can achieve a correction of the curve of over 50%, studies have reported a loss in this correction of between 10 - 25% over time. The procedure does not correct the rotation of the spine and, therefore, does not improve an existing rib hump that was caused by the rotation. The operation does not interfere with normal pregnancies and deliveries later in life.

Certain complications may occur from this procedure:

About 40% of Harrington patients have a condition called the flat back syndrome, because the procedure eliminates normal lordosis (the inward curving of the lower back). Flat back syndrome from the Harrington procedure does not cause any immediate pain. In later years, however, the disks may collapse below the fusion, making it difficult to stand erect, and the condition can cause significant pain and emotional distress.
Studies have reported that 5 - 7 years after their surgery, between a fifth and a third of patients who had the Harrington procedure experienced low back pain. (In one study, only 3% had experienced back pain before surgery.) In such cases, however, the pain was not severe enough to interfere with normal activities and did not require additional surgery.
Children younger than age 11 whose skeleton is immature and who have the Harrington procedure have a fairly high risk for a specific curve progression called the crankshaft phenomenon. This condition occurs when the front of the fused spine continues to grow after the procedure. The spine cannot grow longer, so it twists and develops a curvature. In one study that followed patients for 5 - 16 years, crankshaft curve progression was moderate, however, with the Cobb angle averaging 9 degrees and rotation averaging 7 degrees.

Cotrel-Dubousset Procedure. The Cotrel-Dubousset procedure not only corrects the curve but also may help correct rotation, and it does not cause flat back syndrome.

With this procedure, a surgeon cross links parallel rods for better stability in holding the fused vertebrae. Improvement in correction averaged 66% in one study, with a later correction loss reported to be 5%. (Other studies have reported loss of curvature correction at less than 2%.) Over 95% of patients reported the results to be good or very good (only 86% of patients who had the Harrington procedure experienced the same levels of satisfaction). Patients often go home in 5 days and may be back in school in 3 weeks.

Complication rates are similar to the Harrington procedure but with some differences:

Operation time and blood loss are greater than with the Harrington procedure.
Cotrel-Dubousset and other procedures that are designed to reverse the rotation of the spine have less risk for flat back syndrome, but they have a higher risk for spinal imbalance than the Harrington procedure.
Failure rates are about 25% after 10 years, which is very high. Experts hope that the advances in current scoliosis procedures will help reduce the long-term adverse effects.

The Texas Scottish-Rite Hospital (TSRH) Instrumentation. The Texas Scottish-Rite Hospital (TSRH) instrumentation is similar to the Cotrel-Dubousset procedure in that it uses parallel rods and other devices that reverse rotation as well as improve curvature. TSRH, however, uses smooth rods and hooks that are designed to make removal or adjustment easier later on if complications arise. Complications are similar to the Cotrel-Dubousset procedure.

Additional Forms of Instrumentation. Other instrumentation procedures have refined the hardware used in the Harrington and Cotrel-Dubousset operations.

After surgeons developed Luque instrumentation to help maintain normal lordosis, experts hoped that bracing would not be needed afterward. Several studies showed, however, that without braces, correction was lost after this operation, and the procedure may have a higher risk for spinal cord injury than other standard procedures. Luque instrumentation is used primarily in people whose scoliosis is due to problems of nerves and muscles, such as in children with cerebral palsy.
Wisconsin segmental spine instrumentation (WSSI) is as safe as the Harrington rod and nearly as strong as the Luque instrumentation.
The Dorsal Dynamic Spondylodesis (DDS) system, under testing in Germany, is a semirigid system that allows for greater flexibility of the spine.

Instrumentation for Anterior Approach. The anterior approach, in which the surgeon performs the operation by opening the chest wall, requires specific hardware. Halm-Zielke instrumentation, for example, uses TSRH instrumentation with bone grafts constructed from ribs to prop open the spaces between the disks. It allows true three-dimensional curve correction. However, it does not solve specific problems with this approach -- higher risks for kyphosis (an outward curve) and pseudoarthrosis (a false joint at the fusion site). Variants using two rod systems, fusion cages, or other instruments appear to improve this procedure.

Posterior Approach (Through the Back). Many surgeons use a posterior approach for scoliosis, which reaches the surgical area by opening the back of the patient. It has been the gold standard for decades and is generally used with Harrington instrumentation. The posterior approach has advantages and disadvantages:

Advantages. Surgeons are familiar with it, so fusion rates are excellent, curve correction is good, and it has few complications.
Disadvantages. Preadolescent children are at risk for the crankshaft phenomenon (a worsening of the curve) later on. (Newer posterior instrumentation, such as the Isola instrumentation, may prevent this occurrence.) The posterior approach also does not always correct hypokyphosis (the loss of normal outward curvature) in the thoracic (upper) spine. The procedure is not always effective for curves in the thoracolumbar region (where the upper and lower spine meet) and may cause spinal abnormalities there.

Anterior Approach (Through the Front). Increasingly, surgeons are using the anterior approach, in which the surgeon performs the operation through the chest wall (called a thoracotomy). With the anterior approach, the surgeon makes an incision in the chest, deflates the lung, and removes a rib in order to reach the spine. This rib can be used during the operation as a strut to support the spine. It also may be repositioned within the patient until it is used for bone grafting during fusion.

The anterior approach also has its advantages and disadvantages:

Advantages. Because the frontal approach allows the procedure to be performed higher up in the spine than with standard procedures, the patient may have a lower risk for lower-back injury later on. In addition, transfusion rates are much lower with the anterior approach. With increasing experience, the anterior approach is as effective as the posterior approach.
Disadvantages. It is a more recent procedure than the posterior approach, and, among inexperienced surgeons, carries a higher risk for complications than in the more standard posterior approach. One study noted poorer lung function 2 years after surgery than with the posterior approach, possibly because the wide chest incision impairs the chest muscles, which can affect lung function afterward. Anterior instrumentation poses a risk for hyperkyphosis (exaggerated outward curvature) and a higher risk for pseudoarthrosis, a painful condition in which a false joint develops at the fusion site. Hardware failure rates may also be higher in the anterior approach than in the posterior approach. Increasing experience and newer hardware designs are reducing many of these problems.

The Combined Anterior-Posterior Approach. The combination approach uses an anterior approach first, which allows better correction of the problems. The fusion part of the operation is done with the posterior approach. This is a very long and complex procedure. It appears to be safe, however, and is proving to be useful, even in very young patients, for preventing the crankshaft phenomenon. It also may correct large rigid curves and specific severe curves in the thoracic spine.

Researchers are evaluating new approaches to treating thoracic scoliosis in adolescents and children. Researchers in Germany are studying the effects of implanting a vertical expandable prosthetic titanium rib. This implant expands the thoracic cavity, thereby correcting the curvature and allowing spinal, thoracic, and lung growth. Early experience with 15 children showed improvement of thoracic insufficiency syndrome and ability to sit, in addition to greatly improvement cosmetic appearance.

Researchers in the U.S. recently compared the radiographic and clinical outcomes and pulmonary function in patients treated with either anterior thoracoscopic or traditional posterior surgery. The anterior thoracoscopic surgery uses a video-assisted anterior approach and recently developed spinal instrumentation. There were 28 patients in the thoracoscopic group (average, 14.6 years of age) and 23 patients in the posterior fusion group (average, 14.3 years of age). The researchers found no significant differences between the groups in terms of kyphosis, coronal balance, or tilt angle. Advantages of the anterior thoracoscopic approach include the need for fewer vertebral levels fused, less blood loss, and lower transfusion rate, yet the operative time was nearly 2 times longer than for the posterior approach.

While both of these new treatments have shown some early positive results, more research will be needed to determine their true value.

Complication rates are high (nearly 10%) with any of these procedures, including the standard Harrington method and the newer Cotrel-Dubousset procedure.

Complications for all procedures include allergic reactions to anesthesia and the following:

Bleeding. Standard procedures increase the risk for major blood loss during the procedure. Patients are encouraged to donate blood before the operation for use in possible transfusions. Children sometimes require more than one transfusion following surgery. Researchers are investigating various methods for reducing the need for transfusions.

In one study, patients received erythropoietin (rhEPO) before the procedure. RhEPO is a hormone that acts in the bone marrow to increase the production of red blood cells. Patients who received this hormone, particularly those with idiopathic scoliosis, needed fewer transfusions and spent less time in the hospital than those who did not receive rhEPO.

Newer endoscopic techniques are reducing the need for transfusions.

Postoperative Pain. Some pain always follows these procedures, requiring intravenous administration of potent painkillers right after the operation (endoscopic procedures may require only mild pain relievers). Of some concern is a study suggesting that the use of NSAIDs, or nonsteroidal anti-inflammatory drugs (aspirin, Motrin, Advil), for pain relief right after fusion may increase the risk for fusion failure. Until more research is conducted, these common painkillers should not be routinely used immediately after surgery.

Infection. Infection is always a risk with any operation. One study reported changes in the immune system for about 3 weeks after surgery, which indicated a greater risk for infection. Researchers recommended being very vigilant for signs of infection, including in the pancreas and urinary tract. Doctors also recommend antibiotics, given by injection for 2 - 5 days after surgery and by mouth for 1 - 2 weeks longer.

Nerve Damage. Patients often worry about neurologic injuries, but the risk is actually very low. In general, nerve injury occurs in 1% of patients, with the risk highest in adults. If neurologic damage occurs, it most often causes muscle weakness. Paralysis is very rare and can be prevented using monitoring techniques during the operation. Nearly all monitoring procedures use a so-called wake-up test, in which the patient is brought out of anesthesia during or at the end of the procedure and assessed for sensations to be sure no injury has occurred. One simple method is to wake patients up in the middle of their operations and ask them to wiggle their toes. More sophisticated methods measure the electrical activity of the spinal cord; if the monitor indicates a fall in electrical response and possible injury, the surgeon adjusts his techniques to avoid further damage to the spinal cord.

Pseudoarthrosis. If the fusion fails to heal, pseudoarthrosis, a painful condition in which a false joint develops at the site, may develop. In one study, teenagers who smoked and heavier adolescents (over 154 pounds) who had hyperkyphosis (hunchback) were at higher risk for this complication. The anterior approach may pose a higher risk for pseudoarthrosis. One study reported that pseudoarthrosis may be undiagnosed, and rates may average 20% after surgery, therefore acting as a major contributor to post-surgery pain.

Disk Degeneration and Low Back Pain. Fusion in the lumbar area produces great stress on the lower back and eventually can cause disk degeneration. Loss of trunk mobility, balance, and muscle strength from surgical treatments can also cause lower back pain and chronic problems in future years. Patients who are surgically treated with fusion techniques lose flexibility; their back muscles may be weakened if they were injured during surgery. In most cases, however, the consequences are mild to moderate.

Lung Function. Some patients may develop serious lung problems after surgery. These complications are highest in children whose scoliosis is due to neuromuscular problems, such as spina bifida, cerebral palsy, or muscular dystrophy. Lung problems can occur up to 1 week after surgery. Lung function may not become completely normal until 1 - 2 months after surgery.

Other Complications. Other problems can include, but are not limited to, the following:

Hooks dislodging or a fused vertebra fracturing
Gallstones
Pancreatitis (inflammation of the pancreas). Among adolescents, this complication tends to occur more often among those who are older or who have a lower body mass index.
Intestinal obstruction

Click the icon to see an image of gallstones.

Patients must perform breathing and coughing exercises shortly after the procedure and continue them through the recovery process to rid the lungs of congestion. The patient is usually able to sit up the day after the operation, and most patients can move on their own within a week. A brace may be necessary, depending on the procedure. With the anterior approach in the upper back, patients may have some trouble with activities involving the arms and hands -- such as tying shoes and cutting food. In one study, however, occupational therapy using stretching and strengthening exercises allowed for full resumption of daily activities, including dressing, bathing, and grooming, within 3 months.

Patients are often concerned that surgery will stiffen their backs, but most cases of scoliosis affect the upper back, which has only limited movement, so that patients do not notice much difference. It may take a year or more for muscle strength to return. In some cases, the operation cannot completely correct the curve, and one leg may be shorter than the other. Heel lifts may help in this case.

Patients may need a corrective procedure called revision or salvage surgery, usually for one of these reasons:

Failure of the previous procedure
Curvature progression around the fusion site
Disk degeneration
Poor posture alignment

Minimally invasive surgery is an alternative to spinal fusion. These types of surgeries use a few small incisions and cause less scarring than standard open approaches that require wide cuts. However, these surgeries are limited to certain patients and are not yet as frequently performed as spinal fusion surgeries.

Endoscopy. In endoscopy, the surgeon makes small incisions and inserts tubes that contain tiny instruments and cameras through the incisions in order to view and execute the procedure. In most cases, the procedure occurs in two stages:

First, the surgeon uses the anterior approach to remove disk material and loosen the spine.
They follow with a posterior for fusion and instrumentation.

Recovery after surgery is rapid. Most patients are out of bed 2 days after surgery. Endoscopy causes fewer and smaller scars, and an easier recovery, than more invasive surgical approaches.

However, the endoscopic procedure for scoliosis is complicated, and few surgeons are trained to perform it. The surgery is generally used only for single curves in the upper back or for patients with a curve in the upper back and a compensating curve in the lower back. Some surgeons are now able to operate on areas below the diaphragm, including the lumbar spine. The patients must still wear a brace for 3 months after surgery. Long-term studies are required to compare results to those of standard procedures.

Growing Rod Technique. This technique is used for very young children in whom bracing has not helped. Instead of doing spinal fusion, doctors surgically insert a rod into the patient’s back. Additional surgeries are performed every 6 months to extend the rod so that the spine can continue to grow. Some growing rod techniques use a single rod, while others use two rods. Studies suggest that dual rods are stronger than single rods, which may help provide better spinal stability and correction.

Vertebral Body Stapling. Vertebral body stapling is an experimental technique that may prevent curve progression in some young patients with curves less than 50 degrees. It involves stapling the convex (outer) curve of the anterior spine (the side of the spine facing the chest), which helps stabilize and reduce progression of the inner (concave) curve. The procedure uses a special metal device that is clamp-shaped at body temperature but can be straightened when subjected to cold temperatures and inserted into the spine. When warmed up, the staple returns to its clamp shape and supports the spine.

Treatment for Adult Scoliosis

Adults who were surgically treated for scoliosis in their youth are at risk for disk degeneration and spinal fusion failure. In most adults with previous scoliosis, moderate exercise is not harmful and is extremely important for maintaining healthy supportive muscles and preventing disk degeneration. However, people who have only one or two mobile lumbar vertebrae below the area that was fused during surgery should avoid activity or exercise that causes excessive twisting on the spine. Some experts believe this may accelerate spinal degeneration.

In most cases of adult scoliosis, nonsurgical care is preferred if possible. This can include patient education, exercises, and medical treatments. Braces are not useful.

One center reported that epidural steroid injections were a beneficial alternative to surgery in patients with degenerative lumbar scoliosis.

Candidates for Surgery. In general, pain is the most common reason for surgery in adult scoliosis. Surgery may be recommended in the following cases:

Curvatures over 50 degrees with persistent pain.
Surgery is almost always recommended for adults with curvatures over 60 degrees.
Progressive mid and low back curve or low back curve with persistent pain.
Reduced heart and lung function. Most surgeons, however, will not operate on adults with severely impaired lung function and heart failure. Once this has occurred, surgery will not help improve lung capacity and may cause the condition to worsen, at least temporarily.
Significant deformity is present. Adults should not expect to achieve a completely straight spine, however. There is a high risk for nerve damage if the spine is over-corrected, and adult spines are less flexible than children's are. Usually, however, the correction achieves an acceptable cosmetic improvement.

Surgeons prefer to operate on adults under 50 years old, although surgery may be appropriate in some older people.

Standard Scoliosis Procedures in Adult Scoliosis. The procedures involve the following depending on whether the patient had been treated previously or not:

In patients who have not had previous treatment and who have degenerative lumbar scoliosis, the procedure is often a diskectomy (removal of the diseased disks) followed by scoliosis procedures (instrumentation and fusion).
In patients with previously treated scoliosis, the only remedy is removal of the old instrumentation, extension of the fusion, and implementation of new instrumentation and bone grafts.

Surgical procedures in adult scoliosis are complex and undertaken only after careful consideration and all nonsurgical methods have been exhausted. Adults have a much higher risk than children for complications, including pneumonia, infection, poor wound healing, and persistent pain. In addition, procedures in adults often involve fusion in lumbar and sacral areas (the low back), which can cause several complications. Some experts believe that the risks of operations in this area nearly always outweigh any benefits in adults. Most studies on adults have also reported low success rates.

Others argue that without an operation, the back will become unstable and painful. In addition, most studies on adults report on procedures using the old Harrington instrumentation techniques. Advances in instrumentation are increasing success rates in adults.

In a recent study, for example, adults who underwent anterior fusion and instrumentation had excellent results. In another study of newer generation instrumentation, 87% of adult patients reported satisfaction.

Wedge Osteotomy. Researchers are investigating wedge osteotomy in patients with mature spines, as corrective surgery and as an alternative to braces. In this procedure, a surgeon cuts wedges of bone from the concave side of the curve. The surgeon then straightens the spine by inserting a temporary rod and closing the cut sections. The patient needs to wear a brace and restrict activity for about 12 weeks or until the bone has healed. The patient can resume normal activities when a surgeon removes the rod, and the spine is mobile.

Resources

www.scoliosis.org -- National Scoliosis Foundation
www.srs.org -- Scoliosis Research Society
www.scoliosis-assoc.org - - Scoliosis Association
www.aaos.org -- American Academy of Orthopaedic Surgeons
www.niams.nih.gov -- National Institute of Arthritis and Musculoskeletal and Skin Diseases
www.ispine.com -- Information on the spine

References

Akbarnia BA, Marks DS, Boachie-Adjei O, Thompson AG, Asher MA. Dual growing rod technique for the treatment of progressive early-onset scoliosis: a multicenter study. Spine. 2005;30(17 Suppl):S46-S57.

Helenius I, Jalanko H, Remes V, Sairanen H, Salminen S, Holmberg C, et al. Scoliosis after solid organ transplantation in children and adolescents. Am J Transplant. 2006;6(2):324-330.

Hell AK, Campbell RM, Hefti F. The vertical expandable prosthetic titanium rib implant for the treatment of thoracic insufficiency syndrome associated with congenital and neuromuscular scoliosis in young children. J Pediatr Orthop B. 2005;14:287-293.

Hung VW, Qin L, Cheung CS, Lam TP, Ng BK, Tse YK, et al. Osteopenia: a new prognostic factor of curve progression in adolescent idiopathic scoliosis. J Bone Joint Surg Am. 2005;87(12):2709-2716.

Lee WT, Cheung CS, Tse YK, Guo X, Qin L, Lam TP, et al. Association of osteopenia with curve severity in adolescent idiopathic scoliosis: a study of 919 girls. Osteoporos Int. 2005;16(12):1924-1932.

Lonner BS, Kondrachov D, Siddiqi F, Hayes V, Charf C. Thoracoscopic spinal fusion compared with posterior spinal fusion for the treatment of thoracic adolescent idiopathic scoliosis. J Bone Joint Surg. 2006;88A:1022-1034.

Luhmann SJ, Bridwell KH, Cheng I, Imamura T, Lenke LG, Schootman M. Use of bone morphogenetic protein-2 for adult spinal deformity. Spine. 2005;30(17 Suppl):S110-S117.

Thompson GH, Akbarnia BA, Kostial P, Poe-Kochert C, Armstrong DG, Roh J, et al. Comparison of single and dual growing rod techniques followed through definitive surgery: a preliminary study. Spine. 2005;30(18):2039-2044.

Yuan N, Fraire JA, Margetis MM, Skaggs DL, Tolo VT, Keens TG. The effect of scoliosis surgery on lung function in the immediate postoperative period. Spine. 2005;30(19):2182-2185.

Review Date:
4/6/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Osteoporosis

FitSugar — Wed, 08 Oct 2008 17:34:56 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Fractures
Risk Factors
Diagnosis
Lifestyle Changes
Medications
Treatment
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approvals

In 2007, the Food and Drug Administration (FDA) approved zoledronic acid (Reclast) for postmenopausal osteoporosis treatment. Zoledronic acid is given as an injection once a year. A 2007 study in the New England Journal of Medicine indicated that zoledronic acid can significantly reduce the risk of spine, hip, and other fractures.
In 2007, the FDA approved raloxifene (Evista) for prevention of breast cancer in postmenopausal women with osteoporosis and postmenopausal women at high risk for breast cancer. Raloxifene was previously approved for prevention and treatment of osteoporosis.

Calcium and Vitamin D for Osteoporosis Prevention

In 2007, the Food and Drug Administration proposed allowing manufacturers of food and supplements to put a health claim on their products stating that the combination of calcium and vitamin D can reduce the risk of osteoporosis.
In 2007, the National Osteoporosis Foundation updated its daily intake guidelines to recommend 1,200 mg of calcium, and 800 - 1,000 IU of vitamin D3, for adults age 50 and older.
Calcium plus vitamin D is effective in preventing osteoporosis in people age 50 years and older, according to a 2007 review in the Lancet. The researchers found that a minimum of 1,200 mg of calcium and at least 800 IU of vitamin D per day gave the most protection.

Fosamax: Taking a Break (Without Breaking a Bone)

Women at low risk for fracture may be able to temporarily stop taking alendronate (Fosamax) after 5 years, suggests a 2006 study in the Journal of the American Medical Association.

Antidepressants and Osteoporosis Risk

Selective serotonin reuptake inhibitors (SSRIs), the most commonly used class of antidepressants, may increase the risk for bone loss in both older men and women, according to several studies published in 2007 in the Archives of Internal Medicine. SSRIs include fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil). The researchers did not find that other types of antidepressants are associated with reduced bone mineral density.

Introduction

Osteoporosis is a disease of the skeleton in which bones become brittle and prone to fracture. In other words, the bone loses density. Osteoporosis is diagnosed when bone density has decreased to the point where fractures occur with mild stress.

The skeleton consists of groups of bones which protect and move the body.

Until a healthy person is around age 40, the process of breaking down and building up bone by cells called osteoclasts and osteoblasts is a nearly perfectly coupled system, with one phase stimulating the other. As a person ages, or in the presence of certain conditions, this system breaks down and the two processes become out of sync. The reasons why this occurs during aging are not clear. Some individuals have a very high turnover rate of bone, some have a very gradual turnover, but the breakdown of bone eventually overtakes the build-up.

The Function of Bones. The skeleton has a dual function:

It provides structural support for muscles and organs.
It also serves as a depot for the body’s calcium and other essential minerals, such as phosphorus and magnesium.

The skeleton holds 99% of the body’s calcium. The remaining 1% circulates in the blood and is essential for crucial bodily functions, ranging from muscle contraction to nerve function to blood clotting.

Bone Turnover: the Breakdown and Growth of Bones. Like other organs in the body, bone tissue is constantly being broken down and reformed again. This turnover is necessary for growth, for repair of minor damage that occurs from everyday stress, and for the maintenance of a properly functioning body. Two essential cells are involved in this process:

Osteoblast cells are produced by bone cells and are the bone builders. They rebuild the skeleton, first by filling in the holes with collagen, and then by laying down crystals of calcium and phosphorus.
Osteoclast cells are formed from certain blood cells and are responsible for the breakdown, or resorption, of the skeleton. These cells dig holes into the bone and release the small amounts of calcium into the bloodstream that are necessary for other vital functions.

Each year, about 10 - 30% of the adult skeleton is remodeled in this way. The bone build up (formation)-break down (resorption) balance is controlled by a complex mix of hormones and chemical factors. If bone resorption occurs at a greater rate than bone build up, your bone loses density and puts you at risk for osteoporosis.

In women, estrogen loss after menopause is associated with rapid resorption and loss of bone density. This group, then, is at highest risk for osteoporosis and therefore for fracture.

There are two primary kinds of osteoporosis: type I and type II:

Type I. Type I, or high turnover, osteoporosis occurs in 5 - 20% of women, most often between the ages of 50 and 75. This is because of the sudden postmenopausal decrease in estrogen levels, which results in a rapid depletion of calcium from the skeleton. This is associated with fractures that occur when the vertebrae compress together, causing a collapse of the spine. It is also associated with fractures of the hip, wrist, or forearm caused by falls or minor accidents. Women have a higher risk for type 1 osteoporosis than men.
Type II. Type II, or low turnover, osteoporosis (also known as age-related or senile osteoporosis) results when the process of resorption and formation of bone are no longer coordinated, and bone breakdown overcomes bone building. (This occurs with age in everyone to some degree.) Type II osteoporosis affects both men and women and is primarily associated with leg and spinal fractures. Older women can have both type I and type II osteoporosis.

Click the icon to see an image of a compression fracture.

What determines the existence of osteoporosis, whether type I or type II, is the amount of calcium left in the skeleton and whether it places a person at risk for fracture. Someone who has exceptionally dense bones to begin with will probably never lose enough calcium to reach the point where osteoporosis occurs, whereas a person who has low bone density could easily develop osteoporosis despite losing only a relatively small amount of calcium.

Secondary osteoporosis is caused by other conditions, such as hormonal imbalances, diseases, or medications (such as corticosteroids or anti-seizure drugs).

Click the icon to see an image of osteoporosis.

Causes

Because the patterns of reforming and resorbing bone often vary from patient to patient, experts believe several different factors account for this problem. Important chemicals (such as estrogen, parathyroid hormone, and vitamin D) and blood factors that affect cell growth are involved with this process. Changes in levels of any of these factors could play a role in the development of osteoporosis.

Although ordinarily associated with women, sex hormones play a role in osteoporosis in both genders, most likely by controlling the birth and duration of life of both osteoclasts (bone breakers) and osteoblasts (bone builders).

Women and Estrogen. Experts are still puzzled by the rapid decline in bone density after menopause, when a woman’s ovaries stop producing estrogen. Estrogen comes in several forms:

The uterus is a hollow muscular organ located in the female pelvis between the bladder and rectum. The ovaries produce the eggs that travel through the fallopian tubes. Once the egg has left the ovary it can be fertilized and implant itself in the lining of the uterus. The main function of the uterus is to nourish the developing fetus prior to birth.

The most potent form of estrogen is estradiol. Estradiol deficiency appears to be a very strong factor in the development of osteoporosis.
The other important but less powerful estrogens are estrone and estriol.

The ovaries produce most of the estrogen in the body, but it can also be formed in other tissues, such as body fat, skin, and muscle. After menopause, some amounts of estrogen continue to be manufactured in the peripheral body fat. Even though the ovaries have stopped producing estrogens directly, they continue to be a source of the male hormone testosterone, which converts into estradiol.

Estrogen may have an impact on bone density in various ways:

Estrogen’s most important effect on osteoporosis appears to be prevention of bone breakdown (resorption). Some research suggests that estrogen may control the life span of osteoclasts, the cells responsible for bone breakdown.
One study reported that part of estrogen’s beneficial actions may involve maintaining normal levels of vitamin D, an important nutrient in bone protection.

Men and Androgens and Estrogen. In men, the most important androgen (male hormone) is testosterone, which is produced in the testes. Other androgens are produced in the adrenal glands. Androgens are converted to estrogen in various parts of a man’s body, including bone.

Click the icon to see an image of the adrenal glands.

Studies have suggested that the loss of estrogen as well as testosterone may contribute to bone loss in elderly men. In one study, elderly men were first given a drug that blocked their normal hormones and then were given estrogen and testosterone patches. When the estrogen patch was removed, the bone breakdown process accelerated. When both patches were removed, the number of the bone-building cells (the osteoblasts) decreased. In other words, both hormones appeared to be integral to bone function in men.

Low levels of vitamin D and high levels of parathyroid hormone (PTH) are associated with hip fracture in women after menopause:

Vitamin D is a vitamin with hormone-like properties. It is essential for the absorption of calcium into the bone and for normal bone growth. Lower levels result in impaired calcium absorption, which in turn causes an increase in PTH.
Parathyroid hormone (PTH) is produced by the parathyroid glands. These are four small glands located on the surface of the thyroid gland. They are the most important regulators of calcium levels in the blood. When calcium levels are low, the glands secrete more PTH, which then increases blood calcium levels. High persistent levels of PTH stimulate bone resorption (bone loss).

Click the icon to see an image of the benefits of vitamin D.

Click the icon to see an image of the sources of vitamin D.

Click the icon to see an image of the parathyroid glands.

Several studies on family members, including twins, have strongly suggested that genetic factors help determine bone density. Some examples include the following:

Of particular interest are genetic factors that affect vitamin D, a critical nutrient for calcium absorption in the body.
Many studies are looking at abnormalities in genes that may cause deficiencies in estrogen receptors, molecules that help estrogen work on cells. Estrogen is important in maintaining bone density in both men and women.

Corticosteroids. More than 30 million Americans have disorders that are commonly treated using corticosteroid drugs (also called glucocorticoids or steroids). Oral corticosteroids can reduce bone mass in both men and women. It is not clear whether inhaled steroids carry the same risks, but some studies indicate that they may cause bone loss when taken at higher doses for long periods of time. (Children on inhaled steroids may have temporary impaired growth, but they do not appear to be at risk for bone loss.)

Antidepressants. Selective serotonin reuptake inhibitors (SSRIs) -- a class of antidepressants that includes fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft) -- may be associated with bone loss in both older men and women, according to two 2007 studies in the Archives of Internal Medicine. The researchers did not find an increased risk for bone loss with other types of antidepressants.

Diuretics. Diuretics, which are used to treat high blood pressure, have different effects on osteoporosis, depending on the type. Loop diuretics, such as furosemide (Lasix), increase the kidneys’ excretion of calcium, which can lead to thinning bones. Thiazide diuretics, on the other hand, protect against bone loss, but this protective effect ends after use is discontinued.

Contraceptives. Hormonal contraceptives that use progestin without estrogen (such as Depo-Provera injection or other progestin-based contraceptives), can cause loss of bone density. For this reason, the Food and Drug Administration (FDA) recommends that Depo-Provera injections should not be used for longer than 2 years. Some, but not all, studies suggest that combination estrogen-progestin oral contraceptives increase the risk for osteoporosis later in life. Women who take birth control pills should be sure to get adequate calcium and vitamin D from diet or supplements.

Other Medications. Anti-epileptic (anti-seizure) drugs increase the risk for bone loss (as does epilepsy itself). Other drugs that increase the risk for bone loss include the blood-thinning drug heparin, and hormonal drugs that suppress estrogen (such as gonadotropin-releasing hormone agonists). A 2006 study in the Journal of the American Medical Association suggested that long-term (greater than 1 year) use of proton-pump inhibitors (PPIs) may increase the risk for hip fractures. PPIs are used to treat gastroesophageal reflux disease (heartburn) and include omeprazole (Prilosec), lansoprazole (Prevacid), and esomeprazole (Nexium).

Predisposing Medical Conditions. Osteoporosis can be secondary to several other conditions, including alcoholism, diabetes, hyperthyroidism, epilepsy, chronic liver or kidney disease, celiac disease, scurvy, rheumatoid arthritis, leukemia, cirrhosis, gastrointestinal diseases, vitamin D deficiency, hypogonadism (impaired development of reproductive organs), lymphoma, hyperparathyroidism, and rare genetic disorders such as Marfan and Ehlers-Danlos syndrome.

Symptoms

Many people confuse osteoporosis with arthritis and believe they can wait for symptoms such as swelling and joint pain to occur before seeing a doctor. However, the mechanisms that cause arthritis are entirely different from those in osteoporosis. Osteoporosis usually becomes quite advanced before symptoms appear.

All too often, osteoporosis becomes apparent in dramatic fashion: a fracture of a vertebra (backbone), hip, forearm, or any bony site if sufficient bone mass is lost. These fractures frequently occur after apparently minor trauma, such as bending over, lifting, jumping, or falling from the standing position.

Pain, disfigurement, and debilitation are common in the latter stages of the disease. Early spinal compression fractures may go undetected for a long time, but after a large percentage of calcium has been lost, the vertebrae in the spine start to collapse, gradually causing a stooped posture called kyphosis, or a "dowager’s hump." Although this is usually painless, patients may lose as much as 6 inches in height.

Click the icon to see an image of osteoporosis.

Fractures

Bone density loss from osteoporosis is a major cause of disability and death in the elderly, mostly due to subsequent fractures. The lifetime risk of spinal fracture in women is about one in three, and that for hip fracture is one in six. Women at highest risk for fractures are those with low bone density plus a history of fractures, particularly nonviolent fractures.

Click the icon to see an animation about osteoporosis.

Each year, there are an estimated 500,000 spinal fractures, 300,000 hip fractures, 200,000 broken wrists and 300,000 fractures of other bones. About 80% of these fractures occur after relatively minor falls or accidents.

Between 25 - 60% of women older than age 60 develop spinal compression fractures. Studies on men with osteoporosis report that they have a 6% risk for hip fracture and between 16 - 25% risk for any fractures related to osteoporosis.

Click the icon to see an image of a compression fracture.

Click the icon to see an image of a hip fracture.

Unfortunately, studies continue to report inadequate treatment after a fracture. In a major 2003 study, for example, only 8.4% of women who had sustained fractures were tested for osteoporosis. Worse, less than half of these women received any treatment for osteoporosis. Overall, in the study fewer than 4% of men and half of women who had sustained fractures were evaluated and treated according to recommended guidelines. The older a woman was, the less likely she was to have adequate treatment.

Risk Factors for Fracture and Falling. The risk for fracture itself in people with low bone density is compounded by certain features. Having multiple risk factors for osteoporosis itself poses a higher risk for fractures. However, not all older women with osteoporosis develop fractures. There is some evidence that the body partially compensates after menopause by increasing bone strength, which can help offset the risk for fracture.

Falling, of course, is the primary risk factor for fracture. So, additional risk factors for fracture are those that increase the risk for falling. They include:

Having chronic medical problems (emphysema, heart disease, stroke, arthritis, and depression), with the risk increasing with multiple health problems. Such problems may account for 30% of falls in older women.
Taking multiple medications (especially tranquilizers and antidepressants).
Poor physical function, importantly slow gait and reduced muscle strength. Inactivity that results in weak thigh muscles and poor balance particularly puts any older person at risk for fracture and particularly those with low bone density.
Poor concentration or mental impairment.
Impaired vision.
Hazardous environment (such as the presence of throw rugs in the house).

Between 25 - 36% of women who experience a hip fracture die within a year afterward, and about a quarter of the patients require nursing home treatment. The mortality rates after major fractures may be even higher in older men than in older women. Mortality rates after hip fractures declined from the 1960s through the early 1980s, but they have since leveled off. Whether or not medical advances can improve mortality rates in the future, prevention of osteoporosis is extremely important.

Risk Factors

Gender. An estimated 10 million adults in the United States have osteoporosis and another 34 million have low bone mass that places them at risk for developing osteoporosis. A 2004 report from the Surgeon General's office estimates that by 2020, half of all Americans over age 50 could be at risk for this condition. Eighty percent of people with osteoporosis are women. Men start with higher bone density and lose calcium at a slower rate than women, which is why their risk is far lower. Nevertheless, after age 50, bone loss increases and, according to recent studies, more rapidly than previously thought.

Ethnicity. Although adults from all ethnic groups are susceptible to developing osteoporosis, Caucasian and Asian women and men face a comparatively greater risk. About 20% of non-Hispanic white and Asian women older than age 50 have osteoporosis, and over 50% are at risk due to low bone mass. Osteoporosis affects 10% of Hispanic women (49% at risk) and 5% of non-Hispanic black women (35% at risk). Body type can also be a factor. Osteoporosis is more common in women who have a small, thin body frame and bone structure.

Events associated with estrogen deficiencies are the primary risk factors for osteoporosis in women.

Natural and Surgical Causes of Estrogen Deficiency.

Menopause. Within 5 years after menopause, the risk for fracture increases dramatically. Fractures occurring during this period are more likely to occur in the wrist or spine than the hip, but their occurrence is a strong predictor of later severe osteoporosis and hip fracture.
Surgical removal of ovaries.
Missing periods for 3 months or longer.
Never giving birth.
Pregnancy and nursing do not increase the risk for osteoporosis even though during those times calcium is diverted from the mother to the baby. A factor believed to be associated with reduced bone density is elevated at a constant level during nursing, but as the baby is weaned, levels of the factor decline and bone formation is restored.

Female Athlete Triad. In athletes, excessive exercise plays a major role in many cases of anorexia (and, to a lesser degree, bulimia), which in turn increases the risk for low estrogen levels and bone loss. The term "female athlete triad" in fact, is now a common and serious disorder facing young female athletes and dancers and describes the combined presence of the following problems:

Osteoporosis
Amenorrhea (absence or irregular menstruation)
Eating disorders

Some specific risk factors in men include:

Hormonal deficiencies, including both testosterone and estrogen, which occur in older men (although much more slowly than in women). Estrogen deficiencies may also play a major role in osteoporosis in older men. It is unknown yet what normal estrogen levels are in men.
Medical conditions that can reduce testosterone levels, such as prostate cancer treatments, testicular surgery, and mumps.
Hypogonadism, which is a severe deficiency in the primary hormone that signals the process leading to the release of testosterone and other important reproductive hormones.

Of concern, are studies suggesting that men who have osteoporosis and suffer hip fractures are far less likely to be tested and treated for low bone density than are women. In one study, only 27% of men were treated for osteoporosis compared to 71% of women.

Dietary Factors. Diet plays an important role in preventing and speeding up bone loss in men and women. Calcium and vitamin D deficiencies, of course, are important factors in the risk for osteoporosis. Other dietary factors may also be harmful or protective for certain people.

Calcium requires adequate vitamin D in order to be absorbed by the body. In the United States, many food sources of calcium such as milk are fortified with vitamin D.

Click the icon to see an image of the sources of calcium.

Lack of Exercise. Lack of exercise can put thinner people at risk for osteoporosis.

Being Underweight. Being underweight is a risk factor for osteoporosis in men as well as women. (Shortness, thinness, and narrow hips all increase the risk for fracture in people with low bone density.)

Lack of Sunlight. The photochemical effect of sunlight on the skin is a primary source for vitamin D. Bone formation peaks in the summer and bone breakdown increases in the winter. People who avoid sun exposure to prevent skin cancer may be at risk for vitamin D deficiency, particularly it they are elderly.

Click the icon to see an image of the sources of vitamin D.

Smoking. Women who smoke, particularly after menopause, have a significantly greater chance of spine and hip fractures than those who don’t smoke. Men who smoke also have lower bone density.

Diabetes. Diabetes changes bone quality and density and increases the risk for osteoporosis, but the effects differ depending on type:

Type 1 diabetes is associated with a slightly reduced bone density, putting patients at risk for osteoporosis and possibly fracture.
Type 2 diabetes, on the other hand, is associated with an increased bone density. In such cases, the bone quality itself may be impaired, since people with type 2 diabetes are still at higher risk for fractures.

Older patients with any diabetes type are at high risk for falling, which compounds the risk for fracture.

The maximum density that bones achieved during the growing years is a major factor in whether a person goes on to develop osteoporosis. Persons, usually women, who never develop peak bone mass in early life are at high risk for osteoporosis later on. Children at risk for low peak bone mass include children who are:

Born prematurely
Have anorexia nervosa (more common in girls)
Young, highly competitive athletes
Take oral corticosteroid drugs (inhaled steroids, which are common in asthma treatments, appear to pose a very low risk or none at all)
Have certain medical conditions (cystic fibrosis, epilepsy, inflammatory bowel disease, and celiac disease)
Have delayed puberty

Although to a large extent genetics predict bone health, exercise and good nutrition during the first three decades of life (when peak bone mass is reached) are still excellent safeguards against osteoporosis (and countless other health problems).

Diagnosis

About 20 - 30% of Caucasian women in the U.S. can expect to be affected by osteoporosis, including having a spinal fracture, after age 60. Hispanic, Asian, and Native American women have an even higher risk. Nearly all of them are unaware of the condition and so fail to seek a diagnosis. Even worse, studies continue to report inadequate evaluation for osteoporosis even after a fracture.

Evidence suggests that screening for osteoporosis can help prevent fractures. Expert groups now recommend bone density screening for the following people:

All women over age 65.
Any postmenopausal women under 65 years with risk factors for osteoporosis (being thin, being a smoker, having a family history of osteoporosis, corticosteroids use, or any serious high-risk condition, such as hyperthyroidism or early menopause).
Any older men or women who suffer a fracture. (Unfortunately, studies suggest that only a minority of these patients are evaluated and treated for osteoporosis. Men are especially less likely to be tested.)

Whether perimenopausal women should be screened is unclear. (Perimenopause is the period that extends a few years before and after menopause, usually ages 50 - 59.) Some experts believe that women as young as 21 who have strong risk factors for osteoporosis (such as anorexia or absence of menstruation due to over-exercising) should consider being tested. It is also important that older women continue to get bone density tests. A 2006 study found that only 10% of women over age 75 receive bone density screenings, even though they are the age group most likely to have hip fractures.

Bone Densitometry. The standard technique for determining bone density is a form of bone densitometry called dual-energy x-ray absorptiometry (DEXA). DEXA is simple and painless and takes 2 - 4 minutes. The machine measures bone density by detecting the extent to which bones absorb photons that are generated by very low-level x-rays. (Photons are atomic particles with no charge.) Measurements of bone mineral density are generally given as the average concentrations of calcium in areas that are scanned.

A bone density scan measures the density of bone in a person. The lower the density of a bone the higher the risk of fractures. A bone scan, along with a patient's medical history, is a useful aid in evaluating the probability of a fracture and whether any preventative treatment is needed. A bone density scan has the advantage of being painless and exposing the patient to only a small amount of radiation.

Bone mineral density is usually measured at the hip rather than the spine or wrist, which appears to be the most predictive of hip fracture. (Hip fractures are the most dangerous fractures, particularly in women older than sixty.) The bone density in the spine may also be measured. (Spinal bone density in older people however may be misleading. Bone density in this group may increase because of compression on the spinal bones from arthritic changes in the spine. Therefore, bone density measurements may be normal or even high, but the patient may actually be at risk for fracture.)

Click the icon to see an image of a hip fracture.

Ultrasound. Ultrasound techniques measure bone density in the heels, fingers, and leg bones. In early studies, advanced ultrasound techniques, such as quantitative ultrasound (QUS), are promising for improving accuracy in predicting fractures when used with DEXA. Ultrasound itself is less expensive than DEXA and uses no radiation. Ultrasound bone tests are sometimes given at health fairs or other non-medical settings. It should be noted that these results typically vary widely from measurements of the hipbone and are not reliable when used alone.

Quantitative Computed Tomography. Quantitative computed tomography (QCT) scans, a form of CT scans, can provide highly detailed information about spinal density. Radiation doses from this technique are higher than the others. Whether QCT predicts fracture risk accurately is, however, unknown.

Osteoporosis is diagnosed when bone density has decreased to the point where fractures will happen with mild stress, the so-called fracture threshold. This is determined by measuring bone density and comparing the results with the norm. However, low scores on bone density are not very accurate in determining fracture risk without consideration of other risk factors for fracture.

In general, doctors take the following steps to determine osteoporosis:

Bone mineral density ) is measured, typically in the hipbone, using bone densitometry.
Measurements of bone mineral density are given as mg/cm.² This is the average concentration of bone mineral in the areas that are being scanned. In general, bone is normal if results are greater than 833 mg/cm.² Low bone density (osteopenia) is between 833 and 648 mg/cm.² Osteoporosis is diagnosed with results below 648 mg/cm.²

These measurements still do not always indicate the true risk for fracture. The doctor also assesses risk factors and other considerations. The next step is to compare the patient's bone mineral density to normal bone density, which is defined as the average bone mineral density in the hipbones of premenopausal Caucasian women. (This group is used as the basis for the norm because of their high risk and greater proportion in the American population.)

The health professional then uses this comparison to determine her standard deviation (SD) from this norm. Standard deviation results are given as Z and T scores:

A T score gives the standard deviation of the patient in relationship to the norm in young adults. Doctors often use the T-score and other risk factors to determine the risk for fracture.
A Z score gives the standard deviation of the patient in relationship to the norm in her own age group. Z scores may be used to monitor the effects of treatments in women who have been diagnosed with osteoporosis.

For example, the lifetime risks for a younger woman with a specific T-score would be higher than the same scores in an older woman because the younger woman would have a longer time to lose bone density. In general, the T scores in a 55-year-old woman suggest the following degrees of risk for hip fracture.

One standard deviation or less below the norm indicates normal bone mineral density. (This carries a lifetime chance for a hip fracture of up to about 20%, depending on age and other risk factors.)
Between 1 and 2.5 standard deviation s below normal defines osteopenia, which is low bone density. This carries between a 20 - 50% lifetime risk for fracture.
More than 2.5 standard deviation s predicts osteoporosis and over a 60% chance for hip fracture. Additional risk factors increase the risk. They include low weight, smoking, risks for falling, and especially a history of previous fractures. For example, in women 65 years old with low bone density but no adverse factors, the risk for fracture is 4.3% in 1 year and 28.6% over 5 years. In similar women with a previous fracture, the probability of fracture at 1 year is 11% and at 5 years is 71.8%.

Not all older women with osteoporosis develop fractures. There is some evidence that the body partially compensates after menopause by increasing bone strength, which can help offset the risk for fracture. Techniques to measure bone strength may better identify women at higher or lower risk.

Note: Because the standards are based on Caucasian women, they do not necessarily apply to men, children, or to non-Caucasian women. For example, men have a lower risk for fracture at the same standard deviations as women. Researchers are attempting to establish risk guidelines for these groups as well.

Laboratory blood or urine tests for identifying certain markers of bone loss may prove to be useful in certain cases:

High levels of the chemicals deoxypyridinoline and C-telopeptide in the blood may indicate increased risk for hip fracture. These substances are produced when bone is broken down.
A urine test detecting a substance called N-telopeptide may indicate bone loss (although it is not associated with any risk for fracture).

Lifestyle Changes

Because osteoporosis affects such a considerable portion of the female population, total prevention may not be possible, particularly for high-risk groups. Once a woman goes through menopause and more rapid bone depletion occurs, the line between prevention and treatment blurs. Despite their lower risk for osteoporosis, men should also protect their bones with the same healthy lifestyle habits.

Exercise is very important for slowing the progression of osteoporosis. Although mild exercise does not protect bones, moderate exercise (more than 3 days a week for more than a total of 90 minutes a week) reduces the risk for osteoporosis and fracture in both older men and women. Everyone who is in good health should aim for more. Exercise should be regular and life-long. Before beginning any strenuous exercise program, older patients, those at risk or those who have serious medical conditions, should talk to their doctors.

Specific exercises may be better than others, depending on the age group:

Children should begin exercising before adolescence, since bone mass increases during puberty and reaches its peak between ages 20 and 30. Some evidence suggests that exercise may help develop bone mass in teenagers more effectively than high calcium intake. High-intensity exercises may be particularly bone-strengthening in young people. (Such regimes should not be confused with the athlete-triad -- intense competitive exercise, eating disorders, and menstrual irregularities -- that causes osteoporosis in young athletes.)
Weight-bearing exercise applies tension to muscle and bone and, in young people, encourages the body to compensate for the added stress, increasing bone density by as much as 2 - 8% a year. In premenopausal women these exercises are very protective. (Young men need high-intensity exercises to increase bone mass.) Careful weight training is also very beneficial for elderly people, especially women.
Regular brisk long walks improve bone density and mobility and may relieve osteoarthritic pain. High-impact exercises can be very bone-protective in young and middle-aged adults who have no precluding medical or physical conditions. Most older individuals should avoid high-impact aerobic exercises (step aerobics), which increase the risk for osteoporotic fractures. (Older people, particularly women who engage in jumping exercises should do so under supervision.) Although low-impact aerobic exercises such as swimming and bicycling do not increase bone density, they are excellent for cardiovascular fitness and should be part of a regular regimen.
Exercises specifically targeted to strengthen the back help prevent fractures later on in life and can be beneficial in improving posture and reducing kyphosis (hunchback), even in people with existing severe conditions.
Low-impact exercises that improve concentration, balance, and strength, particularly yoga and tai chi, have been found to decrease the risk of falling. In one study, tai chi reduced the risk of falling by almost half.

Exercise plays an important role in the retention of bone density in the aging person. Studies show that exercises requiring muscles to pull on bones cause the bones to retain and possibly gain density.

Click the icon to see an image of osteoporosis.

In 2007, the Food and Drug Administration (FDA) proposed a new health claim for foods and dietary supplements that contain calcium and vitamin D. The FDA’s recommendation will allow manufacturers of these products to state that the combination of calcium and vitamin D can reduce the risk of osteoporosis. Also in 2007, the National Osteoporosis Foundation (NOF) updated its recommendations for getting enough calcium and vitamin D3. The NOF now recommends 1,200 mg of calcium/day and 800 - 1,200 I.U. of vitamin D3/day for adults age 50 and older. (For strong bones, people need enough of both calcium and vitamin D.)

For years, doctors have recommended that women take supplements of calcium plus vitamin D to help maintain bone density and reduce the risk for fractures. Many studies, including a 2007 review in the Lancet, show that a combination of calcium and vitamin D can help prevent osteoporosis. However, a 2006 New England Journal of Medicine study raised some questions about this approach. In the Women’s Health Initiative study, women were randomly assigned to receive either 1,000 mg of calcium carbonate plus 400 IU of vitamin D a day or placebo. The results indicated that daily calcium and vitamin D supplements:

Improve slightly (by 1%) hip bone density
Prevent hip fracture, but only for women who consistently take the supplements. (Another 2006 study supported this finding.)
Do not prevent spine or other types of fractures
Produce a slight increase in the risk of kidney stones

The medical community has differing views on how to interpret these findings. Some doctors recommend that women over age 60 should still consider taking calcium and vitamin D for bone health. Other doctors feel that due to the risks of kidney stones, supplements are beneficial only for women (especially those over age 70) who do not get enough calcium in their diets. Ask your doctor whether or not you should take calcium supplements.

Appropriate Daily Doses. Recommended daily amounts of calcium depend on age and risk factors:

In young people, children ages 3 - 8 should take 800 mg of calcium per day, while children and adolescents ages 9 - 17 need 1,300 mg per day. Teenage girls who do not have enough calcium in their diets should consider taking supplements, which can help build bone density during these critical years.
The standard recommended dose for people over age 50 is about 1,200 mg per day, but actual dosage may be higher or lower depending on risk factors. Even doses of 1,000 mg may help preserve bone in many postmenopausal women without osteoporosis, including during winter months (when bone loss is greatest). In women who have already experienced osteoporosis-related fractures, however, 1,000 mg daily may not add any protective benefits without bone-building medication.
Some experts suggest that all pregnant women, adolescents, and those on corticosteroids take 1,000 - 1,300 mg of calcium every day.
Breast-feeding women should have 2,000 mg per day.

Forms of Calcium Supplements. There are several different kinds of calcium supplements, such as calcium carbonate (Caltrate, Os-Cal, Tums), calcium citrate (Citracal), calcium gluconate, and calcium lactate. Although each kind provides calcium, they all have different calcium concentrations, absorption capabilities, and other actions. Their value in preserving bones depends on many different factors:

Calcium Concentrations. Forty percent of calcium carbonate is actually calcium, whereas calcium citrate is 24% calcium, and calcium gluconate is only 9% calcium.
Calcium Absorption Capabilities. The calcium must also be absorbed from the stomach into the bloodstream. Calcium citrate is better absorbed than many other calcium compounds. It was reported to be the first calcium supplement to preserve bone density after menopause. (Calcium citrate also increases iron absorption. Milk and other calcium compounds tend to reduce iron absorption.) One simple method for testing the absorbency of a particular brand of calcium tablet is to place it in a glass of white vinegar at full strength and check to be sure that it breaks up within 30 minutes. Taking large amounts of antacids can impair calcium absorption. People should take calcium supplements after meals.

Side Effects. Calcium supplements, even at normal doses of about 1,000 mg a day, can increase the risk for kidney stones. People should be careful not to exceed the upper limit of 2,500 mg per day. (Because many commercial foods are now fortified with calcium, this upper limit may be easier to reach than people think.) Calcium may boost the effects of drugs used to treat osteoporosis.

Click the icon to see an image of kidney stones.

Although not a specific side effect of calcium, there has been much public concern about reports of a small amount of lead in calcium supplements. Although exposure to high levels of lead can cause health problems, the amount in such supplements is very small and may pose little or no hazard.

Vitamin D. Vitamin D helps the stomach and the gastrointestinal tract absorb calcium. It also is the essential companion to calcium in maintaining strong bones. Moreover, vitamin D protects against osteoporosis only in combination with calcium.

Click the icon to see an image of the benefits of vitamin D.

Vitamin D is made in the skin using energy from the ultraviolet rays in sunlight. People also can get it from dietary supplements.

As a person ages, vitamin D levels decline. They also fall during winter months and when people have inadequate sunlight. Pollution may also contribute to less sunlight and declining vitamin D levels.

Click the icon to see an image of the sources of vitamin D.

Most current adult guidelines recommend:

400 IU (10 mcg) for people aged 50 - 60.
600 IU (15 mcg) for those over age 70 who do not have sufficient exposure to sunlight. (Evidence suggests that higher doses of vitamin D -- up to 1,000 IU per day -- may help prevent fractures in people with osteoporosis.)

There are various recommendations for daily vitamin D intake. In 2007, the National Osteoporosis Foundation updated its guidelines to recommend 400 - 800 IU of vitamin D3 for adults younger than age 50, and 800 - 1,000 IU of vitamin D3 for adults age 50 and older. Vitamin D3, also called cholecalciferol, is the form of vitamin D that is best for bone health. In addition to supplements, food sources for vitamin D3 include fortified milk, egg yolks, saltwater fish, and liver.

In 2007, the U.S. National Institute of Health’s Office of Dietary Supplements released a report regarding vitamin D and bone health. Researchers were not able to definitely separate the effect of vitamin D from that of calcium, as most clinical trials evaluate the combination of these supplements. The report did indicate that a combination of daily vitamin D3 (700 - 800 IU) and calcium (500 - 1,200 mg) decreases the risks of falls, fractures, and bone loss in elderly people (ages 62 - 85 years).

Sufficient sunlight exposure and drinking milk fortified with vitamin D supply most people’s normal needs for vitamin D. One cup of whole milk provides about 100 IU of vitamin D.

Vitamin D is toxic in doses above 2,000 IU a day. No one should exceed the recommended daily intake of vitamin D except under the direction of a doctor.

Many people could become deficient in vitamin D as they avoid sunlight to prevent skin cancers and instead increase their intake of milk products, such as yogurt and skim milk, which may have little vitamin D. Such individuals may need to take supplements. People with darker skin have a higher risk for vitamin D deficiency than those with lighter skin.

Vitamin D derivatives are being investigated for treating osteoporosis. Calcitriol (Calcijex, Rocaltrol), for example, is a prescription-form of vitamin D that can increase bone mass and decrease the rate of spinal fractures. However, calcitriol increases the risk for high blood calcium levels (hypercalcemia) and requires frequent monitoring.

Vitamin K. Vitamin K has properties that protect bone and prevent fracture. Because intestinal bacteria produce vitamin K, and the vitamin is found in leafy vegetables, deficiencies are rare. Some evidence suggests, however, that people may not be consuming enough of this nutrient. Vitamin K affects blood clotting, and taking supplements is not recommended without first talking to a doctor. Vitamin K2 (menatetrenone), a form of vitamin K, may help prevent fractures in people with osteoporosis.

Click the icon to see an image of the benefits of vitamin K.

Click the icon to see an image of the sources of vitamin K.

Vitamin B12. Studies suggest that people need the right amounts of vitamin B12 and folic acid to maintain their bone mineral density.

Vitamin A. High amounts of dietary vitamin A reduce bone density and may even increase the risk for fracture in postmenopausal women. (A form of vitamin A, retinoic acid, has been found to stimulate bone breakdown.)

The DASH Diet and Low Sodium. Perhaps a good general approach for people at risk for osteoporosis (or almost any adult) is the DASH diet plus sodium (salt) restriction. The DASH (Dietary Approaches to Stop Hypertension) diet is used to help people with hypertension maintain healthy blood pressures. A 2003 study also reported that it might help protect bones and improve cholesterol levels. This diet not only is rich in important nutrients and fiber but also includes foods that contain far more potassium, calcium, and magnesium, than are found in the average American diet. All of these minerals are important for bone protection. The dietary recommendations are as follows:

Avoid saturated fat (although include calcium-rich dairy products that are no- or low-fat). When choosing fats, select monounsaturated oils, such as olive or canola oils. These fats are also found in some fish. Although no one wants to be overweight, even a slight excess of fat helps protect bones. In one study, women who ate more fat in their diet were, on average, better able to absorb calcium than were women who had been put on a low-fat, high-fiber diet.
Choose whole grains over white flour or pasta products. Include nuts, seeds, or legumes (dried beans or peas) daily.
Choose fresh fruits and vegetables every day. Many of these foods are rich in potassium, magnesium, and other minerals that are important for bone (as well as heart) protection.
Choose protein preferably from fish, poultry, or soy products. Soy in combination with fiber-rich foods or supplements may have specific benefits. Oily fish may also be particularly beneficial. They contain omega-3 fatty acids, which have been associated with heart and nerve protection.

Salt Restriction. Reducing salt may protect both the heart and the bones. High sodium intake interferes with calcium retention. Note: Fast foods and commercial snacks are usually high in sodium and have been linked with weak bones.

Dairy Products and Calcium-Rich Foods. Although some studies have reported that dairy products benefit the bones, it is not entirely clear if high-calcium diets reduce the risk for fractures compared to adequate intake of vitamin D. Until more is known, people should be sure their diets have sufficient calcium. Dietary calcium is available from many good sources.

Milk and Dairy Products. The best source of calcium in the diet is from milk fortified with vitamin D. Four glasses of milk provide about 1,200 mg of calcium. (Skim milk and yogurt products, unfortunately, are often low in vitamin D, which is important for calcium absorption.) According to a 2003 study, girls who have low milk intake increase their risk for fracture in adulthood. One report even suggests that milk proteins actually slow bone break down. It is not clear, however, if drinking milk after menopause offers any significant bone protection.
Other Calcium-Rich Foods. Other calcium-rich foods include shrimp, canned salmon or sardines, black strap molasses, calcium-fortified tofu, and almonds. A number of commercial foods, including orange juice and some cereals, are now calcium fortified. Dark green vegetables (broccoli, kale, turnip greens) are rich in calcium but little of it is absorbed (kale is best).

Click the icon to see an image of milk and the facial bones.

Mineral-Rich Fruits and Vegetables.

Potassium. Potassium may be very important for strong bones and may help counteract negative effects of high-protein diets. Potassium-rich fruits include bananas, oranges, prunes, and cantaloupes, and vegetables that contain potassium include carrots, spinach, celery, alfalfa, mushrooms, lima beans, potatoes, avocados, and broccoli.
Magnesium. Some studies have observed that low levels of magnesium may contribute to thinning bones. Some studies suggest that magnesium supplements help suppress the cycle that leads to bone loss. Experts recommend 350 mg a day for supplements. However, excessive magnesium may be harmful in people with diabetes or kidney disease. Foods rich in magnesium include dairy products, spinach, potatoes, beets, nuts, sole, and halibut.
Other Minerals. Phosphorous, boron, and zinc have also been associated with bone protection.

Protein. Protein may be important for frail older people for improving muscle strength. Researchers, meanwhile, have associated both low and high protein intake with bone loss. Protein deficiencies appear to trigger hormonal changes that increase bone breakdown. On the other hand, high protein intake increases urinary calcium loss, which can impair bone density in people with low-calcium diets. High-protein diets, however, do not appear to cause bone loss if calcium intake is also high. The bottom line is to eat enough protein but to balance it with plenty of calcium-rich, and other mineral-rich, foods.

The protein source (meat, soy, or fish) may have some effect on bone density, although the effects are not clear. Studies are mixed on whether protein from meat has a positive or negative effect on bone loss. In any case, the best sources of protein for bone protection may be from oily fish or soy.

Choosing protein from fish (especially oily fish such as sardines, salmon, mackerel, fresh tuna, and herring) is a good option. Oily fish are high in vitamin D, which is bone protective. Such fish are also heart protective. Wild salmon has a much higher vitamin D content than farmed salmon. American brands of canned tuna, meanwhile, generally do not contain significant amounts of vitamin D.
Soy may have some modest protection against bone loss. Soy is high in estrogen-like plant chemicals called isoflavones, which may improve bone health in older women. In particular, the isoflavone genistein is being studied for its effects on bone health. A small 2007 study indicated that genistein supplements, when taken with vitamin D and calcium, may help improve bone density in postmenopausal women with thinning bones. (However, other studies indicate that soy has no effect on bone density in healthy premenopausal women.) Soy food products that also contain calcium, such as tofu, may be particularly beneficial. In such cases, 3 ounces of tofu supply 60% of daily calcium requirements.

Alcohol. Alcohol has different effects on bones depending on how much is consumed. One study found that women older than age 65 who drank one to two drinks (1 - 2 oz) of alcohol weekly had higher bone density than non-drinkers. Alcohol in moderate amounts may reduce parathyroid hormone and increase estrogen levels. Excessive drinking, however, has been associated with brittle bones.

Cola, Coffee, Tea and Caffeine. One study suggested that drinking tea regularly may help protect bones. Nevertheless, there has been some concern that caffeine consumption, particularly from coffee, may increase calcium levels in urine and reduce levels in the body. In one trial, consumption of lots of coffee (9 or more cups per day) was associated with an increased risk of hip fractures in women, but not in men. However, not all studies support a risk. Some evidence suggests that caffeine may pose a danger for bone loss only in elderly thin women -- but not in those who have normal or high weight. Drinking carbonated beverages, particularly cola, may increase the risk for bone fractures in people with low bone density.

Everyone who smokes should quit. The risk for osteoporosis from smoking appears to diminish after quitting.

An important component in reducing the risk for fractures is preventing falls. Risk factors for falling include:

Slow walking
Inability to walk in a straight line
Certain medications (such as tranquilizers and sleeping pills)
Low blood pressure when rising in the morning
Poor vision

Recommendations for preventing falls or fractures from falls in elderly people include:

Exercise to maintain strength and balance if there are no conflicting medical conditions. In one study of older people, this was the single best intervention for preventing falls.
Do not use loose rugs on the floors.
Move any obstructions to walking, such as loose cords or very low pieces of furniture, away from traveled areas.
Rooms should be well lit.
Have regular eye checkups.
Try wearing hip pads. Hip pads are specially designed to protect hipbones against falls and are worn under clothing. Evidence on their protection against fractures is weak, however, particularly since compliance is poor. Nevertheless, newer hip pads that are thinner and made with newer materials may be helpful and more appealing.
Wear thinner, hard-soled shoes. Studies indicate these shoes are just as comfortable as the popular resilient-soled footwear, but they may be difficult to find. Soft-soled high-resilient so-called athletic footwear may contribute to impaired balance and dangerous falls, in part, because these cushioned shoes offer less stability.

Medications

Many drugs are available to treat osteoporosis. Unfortunately, studies continue to report that doctors fail to evaluate and adequately treat both men and women for this condition, even after a fracture. According to one study of women over age 60, fewer than 2% were evaluated for osteoporosis or spinal fracture by their doctors. Among those who were diagnosed, only 36% received appropriate medication. Among adults who had sustained fractures, less than 5% of men and fewer than half of women were evaluated and treated according to recommended guidelines, indicated two other studies. In one of the studies, only 24% of women received treatment for osteoporosis after a fracture. In both studies, the older a woman was, the less likely she was to have adequate evaluation or treatment.

Drugs Used to Treat Osteoporosis. Two types of drugs are used to treat osteoporosis:

Antiresorptive Drugs. Antiresorptives include bisphosphonates, hormone replacement therapy, selective estrogen-receptor modulators (SERMs), and calcitonin. Bisphosphonates are the standard drugs used for osteoporosis. These drugs block resorption (preventing bone break down), which slows the rate of bone remodeling, but they cannot rebuild bone. Because resorption and reformation occur naturally as a continuous process, blocking resorption may eventually also reduce bone formation.
Anabolic, or Bone-Forming, Drugs. Drugs that rebuild bone are known as anabolics. The primary anabolic drug is low-dose parathyroid hormone (PTH), which is administered through injections. This medicine is proving to be very effective in restoring bone and preventing fractions. PTH is still relatively new, and long-term effects are still unknown. Fluoride is another bone-building drug, but it has limitations and is not commonly used.

Both types of drugs are effective in preventing bone loss and fractures, although they vary in their effectiveness and safety.

Bisphosphonates are antiresorptive drugs. They are the primary drugs for preventing and treating osteoporosis. They can help reduce the risk of both spinal and hip fractures, including among patients with prior bone breaks.

Studies indicate that these drugs are effective and safe for at least 10 years. Eventually, however, bone loss continues with bisphosphonates. This may be due to the fact that bone breakdown is one of two phases in a continuous process of rebuilding bone. Over time, just blocking resorption will interrupt this process and impair the second half of the process -- bone formation. Some researchers think that this problem may be overcome by building bone for a couple of years with parathyroid hormone (PTH), then following this treatment with bisphosphonates to prevent the breakdown of bone. (Administering the two drugs simultaneously is not effective because bisphosphonates interfere with the way PTH works.)

A 2006 study of the bisphosphonate alendronate (Fosamax), the most widely used osteoporosis drug, indicated that women at low risk for fracture may be able to stop using the drug after 5 years without increasing their fracture risk for another 5 years. However, the Journal of the American Medical Association study also suggested that it is safer for women at high risk for spine fractures to keep taking alendronate on a continuous basis.

Candidates. National Osteoporosis Foundation guidelines recommend that the following people should take or consider bisphosphonates:

Women with a below-normal bone density of 2.5 standard deviation or greater and no history of fractures
Women with below-normal bone density 1 standard deviation or more and a history of fractures

Brands. Bisphosphonates are available in different forms:

Oral bisphosphonates. These pills include alendronate (Fosamax), risedronate (Actonel), and ibandronate (Boniva). Alendronate and risedronate are taken once a week. In 2005, ibandronate was approved as the first once-monthly pill. Risedronate is also available in a pill that contains calcium. Risedronate and alendronate are approved for both men and women.
Injectable bisphosphonates. In 2007, zoledronic acid (Reclast) was approved as the first once-yearly injection treatment for osteoporosis. The injectable form of ibandronate (Boniva), approved in 2006, requires injections 4 times a year. Injectable bisphosphonates are an alternative for patients who may have difficulty swallowing pills or sitting upright after oral bisphosphonate treatment.

Side Effects. The most distressing side effects of bisphosphonates are gastrointestinal problems, particularly stomach cramps and heartburn. These symptoms are very common and occur in nearly half of all patients. Other side effects may include irritation of the esophagus (the tube that connects the mouth to the stomach) and ulcers in the esophagus or stomach. Some patients may experience muscle and joint pain. To avoid stomach problems, doctors recommend:

Take the pill on an empty stomach in the morning with 6 - 8 ounces of water (not juice or carbonated or mineral water).
After taking the pill, remain in an upright position. Do not eat or drink for at least 30 - 60 minutes. (Check your drug’s dosing instructions for exact time.)
If you develop chest pain, heartburn, or difficulty swallowing, stop taking the drug and see your doctor.

Osteonecrosis (bone death) of the jaw is a rare side effect that has occurred mainly in patients who received intravenous bisphosphonates for cancer treatment (not osteoporosis). Many of these patients had major dental procedures before developing osteonecrosis. However, this bone decay condition has also been reported in some patients who have taken bisphosphonates by mouth (mainly alendronate). Symptoms may include jaw pain or swelling, gum infections, and poor healing of the gums. Talk to your doctor or dentist if you experience any jaw or gum discomfort while taking a bisphosphonate drug.

Raloxifene (Evista) belongs to a class of drugs called selective estrogen-receptor modulators (SERMs). These drugs are similar, but not identical, to estrogen. Raloxifene provides the bone benefits of estrogen without increasing the risks for estrogen-related breast and uterine cancers. Raloxifene was approved in 1997 to prevent osteoporosis in postmenopausal women, and in 1999 for the treatment of osteoporosis in postmenopausal women. In 2007, the Food and Drug Administration approved raloxifene for prevention of breast cancer in postmenopausal women with osteoporosis, as well as postmenopausal women at high risk for invasive breast cancer.

While there are many SERM drugs, raloxifene is the only one approved for both treatment and prevention of osteoporosis. Only postmenopausal women who have or are at risk for osteoporosis should take this drug. Studies indicate that raloxifene can stop the thinning of bone and help build better quality and stronger bone.

A thrombus is a blood clot that forms in a vessel and remains there. An embolism is a clot that travels from the site where it formed to another location in the body. Thrombi or emboli can lodge in a blood vessel and block the flow of blood in that location, depriving tissues of normal blood flow and oxygen. This can result in damage, destruction (infarction), or even death of the tissues (necrosis) in that area.

Side Effects. Raloxifene increases the risk for blood clots in the veins. Because of this side effect, raloxifene also increases the risk for stroke (but not other types of heart disease). These side effects, though rare, are very serious. Women should not take this drug if they have a history of blood clots, or if they have certain risk factors for stroke and heart disease. More common mild side effects include hot flashes and leg cramps.

Produced by the thyroid gland, natural calcitonin regulates calcium levels by inhibiting the osteoclastic activity, the breakdown of bone. The drug version is derived from salmon and is available as a nasal spray (Miacalcin) and an injected form (Calcimar). Calcitonin is not used to prevent osteoporosis. It treats osteoporosis. It may be effective for spinal protection (but not hip) in both men and women. Calcitonin may be an alternative for patients who cannot take a bisphosphonate or SERM. It also appears to help relieve bone pain associated with established osteoporosis and fracture.

Side Effects. Side effects include headache, dizziness, anorexia, diarrhea, skin rashes, and edema (swelling). The most common adverse effect experienced with the injection is nausea, with or without vomiting. This occurs less often with the nasal spray. The nasal spray may cause nosebleeds, sinusitis, and inflammation of the membranes in the nose. Also, many people who take calcitonin develop resistance or allergic reactions after long-term use.

Although high persistent levels of parathyroid hormone (PTH) can cause osteoporosis, daily injections of low and intermittent doses of this hormone actually stimulate bone production and increase bone mineral density. In clinical studies, teriparatide (Forteo), a drug made from selected amino acids found in parathyroid hormone, reduced the risk for spinal and non-spinal fractures by 50 - 65%. It may prove to be a very useful drug for men with osteoporosis. Unlike most treatments for osteoporosis, including bisphosphonates, the benefits may persist even after the injections have been stopped.

Although the treatment requires injections, researchers are investigating a nasal spray version of PTH. In addition to easing patient discomfort, there is some preliminary evidence that nasal-administered PTH may be better absorbed than injections. Side effects of PTH are generally mild and include nausea, dizziness, and leg cramps. No significant complications have been reported to date.

Early animal studies did report bone tumors in mice that were given parathyroid long-term. Such effects have not been observed in humans to date. However, people with Paget disease, (a disorder in which bone thickens but also, oddly, weakens), should not take parathyroid hormone, since they are at higher than normal risk for bone tumors.

Hormone replacement therapy (HRT) is sometimes used to prevent osteoporosis. A Women’s Health Initiative (WHI) study found that women who received estrogen, or estrogen plus progestin, therapy had fewer fractures than women who received placebo.

However, WHI studies have also shown that estrogen increases the risk for breast cancer, blood clots, strokes, and heart attacks. For this reason, women need to balance the benefits that HRT has on bone-loss protection, with the risks it carries for other serious health conditions. The Food and Drug Administration recommends that women first try other medications for prevention of osteoporosis.

HRT is available in many different forms, including pills and skin patches. [See In-Depth Report #40: Menopause.]

New SERMs. Bazedoxifene (Viviant) is a new selective estrogen receptor modulator (SERM) that is in phase III clinical trials. In research presented at the 2007 annual meeting of the American Society for Bone and Mineral Research (ASBMR), bazedoxifene reduced new cases of non-spine fracture by 52% compared to placebo.
Biologic Drugs. Denosumab is a humanized monoclonal antibody injectable drug currently in phase III studies. It targets the RANK ligand, a protein involved with cells that break down bone (osteoclasts). Results presented at the 2007 ASBMR meeting indicated that denosumab may help increase bone mineral density by as much as 10.6%. Odanacatib is another biologic drug showing promise in phase IIB trials. Odanacatib inhibits cathepsin K, a protein that also plays a role in osteoclast activity.
Strontium. Strontium, a chemical element found in bone, may help increase bone formation and decrease bone resorption. NB S101 is a strontium drug currently in phase II trials.

Treatment

Nonsurgical treatments for fractures include braces, plaster cases, and manipulation of the fracture. Such approaches have not been well studied to determine an optimal method, and patients should discuss all options with their doctors.

Reconstructive surgery is usually used for hip fractures and should be performed within 48 hours, assuming the patient has no other complicating medical conditions. After surgery, the patient should be mobilized within the first day. In one study, protein supplements helped people with hip fractures recover more quickly and reduced bone loss.

Percutaneous vertebroplasty and kyphoplasty are surgical procedures used to lessen pain. Research to date suggests that they are safe and provide pain relief for many patients. In some cases they may increase height. There have been few controlled trials, however, and more research is needed to determine long-term effects.

Percutaneous Vertebroplasty. Percutaneous vertebroplasty involves the injection of a cement-like bone substitute into damaged vertebrae. It is proving useful for stabilizing the spine and relieving pain in patients with spinal compression fractures due to osteoporosis or cancer. Success rates of over 90% have been reported. Serious complications occur in fewer than 1% of cases.

Kyphoplasty. Kyphoplasty is a variant of percutaneous vertebroplasty that may help prevent kyphosis (hunchback) in patients whose spines have collapsed. The procedure inserts a balloon into the fractured vertebrae. As the balloon inflates, the spine is moved upward, to its original location. The balloon is then removed, and the bone and the core of the newly-erect vertebrae are filled with cement. In one 2003 study, short-term symptom relief improved by 70% and was immediate. Long-term effectiveness is not yet known.

Resources

www.nof.org -- National Osteoporosis Foundation
www.niams.nih.gov/Health_Info/Bone -- National Institutes of Health, Osteoporosis and Related Bone Diseases
www.menopause.org -- North American Menopause Society
www.asbmr.org -- American Society for Bone and Mineral Research
www.niams.nih.gov -- National Institute of Arthritis and Musculoskeletal and Skin Diseases

References

Agency for Healthcare Research and Quality. Effectiveness and Safety of Vitamin D in Relation to Bone Health, Structured Abstract. August 2007. Rockville, MD.

Bilezikian JP. Osteonecrosis of the jaw -- do bisphosphonates pose a risk? N Engl J Med. 2006 Nov 30;355(22):2278-81.

Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007 May 3;356(18):1809-22.

Black DM, Schwartz AV, Ensrud KE, Cauley JA, Levis S, Quandt SA, et al. Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA. 2006 Dec 27;296(24):2927-38.

Diem SJ, Blackwell TL, Stone KL, Yaffe K, Haney EM, Bliziotes MM, et al. Use of antidepressants and rates of hip bone loss in older women: the study of osteoporotic fractures. Arch Intern Med. 2007 Jun 25;167(12):1240-5.

Haney EM, Chan BK, Diem SJ, Ensrud KE, Cauley JA, Barrett-Connor E, et al. Association of low bone mineral density with selective serotonin reuptake inhibitor use by older men. Arch Intern Med. 2007 Jun 25;167(12):1246-51.

Marini H, Minutoli L, Polito F, Bitto A, Altavilla D, Atteritano M, et al. Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women: a randomized trial. Ann Intern Med. 2007 Jun 19;146(12):839-47.

Tang BM, Eslick GD, Nowson C, Smith C, Bensoussan A. Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet. 2007 Aug 25;370(9588):657-66.

Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006 Dec 27;296(24):2947-53.

Review Date:
11/1/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Obesity

FitSugar — Wed, 08 Oct 2008 17:35:32 -0700

Overview

Signs and Symptoms
What Causes It?
Risk Factors
Preventive Care
What to Expect at Your Provider's Office
Treatment Options
Other Considerations
Supporting Research

HEALTH GUIDE REFERENCE FROM A.D.A.M

Being overweight or obese puts you at risk for a number of diseases, including heart disease, diabetes, high blood pressure, stroke, gallbladder disease, osteoarthritis, and respiratory disorders. The risk of developing these diseases is even higher when weight is concentrated near the waist.

Obesity is an increasing problem. According to the National Institutes of Health, 60% of American adults are overweight and 25% are considered obese, while about 25% of American children are overweight or obese. And the numbers are rising. Taking weight off, and keeping it off, is difficult. Many people who lose weight later gain back some or all of the excess pounds.

Despite growing research on obesity, there are no medications, herbs, or supplements that can help you lose a significant amount of weight, and all have some side effects. The only way to lose weight is to reduce the amount of calories you eat and increase the time and intensity of your exercise. These actions have many health benefits in addition to helping you lose weight.

Signs and Symptoms

Obesity is usually determined by body mass index, or BMI, using a formula that calculates a ratio of your height to your weight.

BMI 25 - 29.9 (overweight)
BMI 30 and above (obese)

A high waist to hip ratio (indicating that fat is centered around the waist) increases the risk for developing serious, even life-threatening conditions associated with obesity. Generally, for men a ratio of .90 or less is considered safe. For women, .80 or less is considered safe.

Conditions that may accompany obesity include:

High cholesterol (including high triglyceride levels)
Diabetes
High blood pressure
Sleep apnea (episodes when a person stops breathing while asleep)
Osteoarthritis
Gallstones

What Causes It?

A number of factors contribute to obesity.

Diet: Eating high-fat, high-calorie foods causes weight gain.
Lack of exercise: Sedentary people don't burn as many calories as active people.
Genetics: Your genes may influence how much fat your body stores and where it store it, although genes alone do not mean you will be obese.
Age: People gain weight as they get older, because they tend to be less active and to lose muscle mass.
Psychological issues: Some people overeat when they are upset or stressed.
Medications: Some drugs, such as corticosteroids, blood pressure medication, and tricyclic antidepressants, can cause you to gain weight.
Medical problems: Rarely, obesity is due to a medical problem such as Cushing's syndrome (where the adrenal glands produce too much hormone) or hypothyroidism (where the thyroid gland doesn't produce enough hormone). Conditions such as osteoarthritis cause people to be less active, which can lead to weight gain.

Risk Factors

The following factors may increase an individual's risk for becoming obese:

Living in an industrialized country, especially the United States
Having family members who are overweight or obese
Not being physically active
Overeating
Eating a high-fat diet
Taking certain prescription medications (see "Causes")
Having a hormone disorder, such as Cushing's syndrome or hypothyroidism (underactive thyroid)
Being emotionally stressed (from the death of a loved one, for example), which may cause a person to overeat

Preventive Care

The best way to prevent obesity and maintain a normal weight is to eat a healthy diet and exercise daily. Keeping a food and exercise journal, where you record what you eat and how long you exercise, is an excellent way to get started.

Organizations such as the American Diabetes Association, the American Heart Association, and the American Dietetic Association have developed guidelines that promote weight loss and healthy eating. These guidelines recommend that no more than 30% of a person's total calorie intake should come from fats. Overall, you should eat a wide variety of foods, especially fruits and vegetables, in order to stay healthy and maintain proper weight.

Many studies show that exercise -- from moderate to intense -- helps prevent obesity. The Centers for Disease Control and Prevention and the American Academy of Sports Medicine recommend at least 30 minutes of moderate aerobic activity (such as a brisk walk) at least 5 days a week. You don't have to exercise for 30 minutes at a time; 10 minutes, done three times a day, is also effective. In fact, any exercise -- from taking the stairs to cleaning the house or working in the garden -- is beneficial.

What to Expect at Your Provider's Office

Health care practitioners use BMI to diagnose obesity. To determine BMI, weight in kilograms is divided by height in meters, squared. You can find online BMI calculators that do the math for you. As previously noted in the "Signs and Symptoms" section, the following BMI ranges are most often used as indications that a person is overweight or obese:

BMI 25 - 29.9 (overweight)
BMI 30 and above (obese)

Your doctor may also measure your blood pressure and percentage of body fat, and may order blood tests to check cholesterol levels and determine how well your thyroid is functioning.

Treatment Options

Losing weight -- and then maintaining a healthy weight -- involves a combination of diet, exercise, and other lifestyle modifications. Although some medications, herbs, and supplements may help you lose a little weight, you still must eat fewer calories and exercise more to see any real effect. For severe obesity, bariatric surgery (which physically restricts the amount of food a person can eat) may be an option.

Lifestyle

To lose weight, you must eat fewer calories and increase your physical activity to burn more calories. The key to losing and keeping off weight is to set realistic weight loss goals that are achievable. The changes you make to your eating and exercise habits will need to last throughout your life.

Exercise

Exercise can help you lose weight, especially in the first six months, and to maintain your desired weight in the long-term. Exercise not only contributes to weight loss, it also decreases abdominal fat and increases heart health, lowers blood pressure, and helps keep blood sugar in check.

If you are not used to exercising, start slowly and build up to the goal of 30 minutes a day for at least 5 days a week. An ideal exercise program includes aerobic activity (walking, swimming, biking), strength training (lifting weights), and flexibility (stretching). If you are severely obese or have other medical problems, talk to your doctor before starting a new exercise program.

You may be sore at first. Some muscle soreness is normal. However, if you experience pain that lasts more than 2 hours after your workout, see your doctor before continuing.

Drug Therapies

Some medications help promote weight loss, but there are no drugs to cure obesity. Weight loss medications should be used in addition to diet, exercise, and other lifestyle modifications. Many of these drugs are available by prescription only and some have serious side effects.

Over-the-counter Medications

Orlistat (Alli) -- The FDA has approved Alli as the only over-the-counter weight loss drug. It reduces the amount of fat your body can absorb from foods. Side effects include oily stools, flatulence, and diarrhea. Alli also blocks you body from absorbing some vitamins and nutrients, so you should take a multivitamin daily.

Prescription Medications

Sibutramine (Meridia) -- boosts metabolism, enhances energy level, and promotes a feeling of fullness. Side effects include dry mouth and insomnia; cannot be taken by people with a history of stroke, seizures, or heart, liver, or kidney diseases. Meridia is moderately effective; studies show that people who take Meridia lost about 10 pounds more than those who just followed a low-calorie diet.
Orlistat (Xenical) -- reduces the absorption of fat from foods; side effects include oily stools, flatulence, and diarrhea. Recently approved for over-the-counter sale in the U.S.
Phentermine -- suppresses appetite; serious potential side effects include pulmonary hypertension and heart valve defects. Phentermine is similar to an amphetamine and should not be taken by people with high blood pressure, heart disease, glaucoma, or those taking antidepressant medications

Surgical Procedures

Bariatric or weight-loss surgery may be considered in cases where people are severely obese and lifestyle changes have not worked. Physicians carefully select individuals for surgery, and patients must undergo psychological testing and counseling. Bariatric surgery reduces the amount of food that can be taken into the stomach. People who have had bariatric surgery must be monitored by their doctor afterward to make sure they get enough essential nutrients. Procedures include:

Roux-en Y procedure (gastric bypass) -- permanently reduces the size of the stomach; vomiting is the most common side effect
Gastric banding -- An adjustable silicone band is placed around the stomach, decreasing the amount of food that can be eaten. The band can be adjusted or removed.

Complementary and Alternative Therapies

Diet

Diet plans are enormously popular. They range from traditional low-fat, high-carbohydrate diets to high-protein, high-fat, low-carbohydrate diets. The truth is, no specific diet works for everyone, and no diet works without the other essential components of weight loss -- exercise and stress management.

The U.S. Department of Health and Human Services says a healthy diet

Emphasizes fruits, vegetables, whole grains, and fat-free or low-fat dairy products
Includes lean meats, poultry, fish, beans, eggs, and nuts
Is low in saturated fats, trans fats, cholesterol, salt, and added sugar

Among many weight-loss plans available, the ones that generally result in a balanced diet include the Weight Watchers plan, the South Beach Diet, and the American Heart Association No Fad Diet. Beware of diets that promise quick, substantial weight loss; they often don't contain enough of the nutrients your body needs to stay healthy, and you're more likely to go off the diet and engage in binge eating, gaining the weight back. Weight loss of about 1 to 2 pounds per week is considered safe and sustainable. Before attempting any diet, it is important to consult a healthcare practitioner to determine which plan is right for you.

Nutrition and Supplements

Most evidence for using these supplements in weight loss is either scant or mixed. None of these supplements will work for significant weight loss without changes to diet and exercise habits. Talk to your healthcare provider before using these supplements.

5-Hydroxytryptophan (5-HTP) (600 - 900 mg per day) -- 5-HTP is thought to reduce hunger cravings by boosting serotonin levels in the central nervous system, which may reduce appetite and lessen food cravings. However, 5-HTP has been associated with eosinophilia myalgia syndrome (EMS), a rare and potentially fatal blood disorder, although it isn't clear whether 5-HTP actually contributes to developing the disorder. In addition, people who take antidepressants or herbs and supplements with antidepressant effects (such as St. John's wort and SAMe) should avoid 5-HTP. Talk to your doctor before taking 5-HTP.

Fiber -- may help lower insulin levels (insulin controls the amount of sugar in the blood) and help you feel fuller.

Conjugated linoleic acid (CLA) -- Preliminary human and animal studies suggest that CLA may help control weight by reducing body fat and enhancing lean body mass. However, the benefit appears to be slight, there is some question as to whether CLA can increase insulin resistance in overweight people (a precursor to developing diabetes), and studies show mixed results for weight loss.

Zinc (15 - 20 mg per day) -- may increase lean body mass and decrease or keep stable the amount of fat. The reason may be that zinc increases levels of leptin, a hormone in the body that helps you feel full.

Chitosan (1,500 mg three times per day) -- Chitosan is a fiber-like supplement made from the shells of crustaceans such as shrimp and crab. While some studies have found that chitosan (in addition to a low-calorie diet) reduces weight, it is unclear whether the supplement itself, the low-calorie diet, or a combination of both led to the weight loss. Other studies have shown mixed results.

Pyruvate (22 - 44 g per day) -- Pyruvate is a substance that occurs naturally in the body, where it is converted to lactic acid. There is some evidence that it may help reduce body fat, possibly by increasing the body's metabolic rate. Other studies show no effect.

Hydroxycitric acid (HCA) (2.5 g per day) -- This substance, extracted from the fruit Garcinia cambogia, is similar to citric acid (found in oranges and citrus fruits). In test tubes, HCA stops carbohydrates from being stored as fat, and some animal tests indicate HCA can suppress appetite. However, studies in humans show mixed results.

7-keto or 7-keto-DHEA (3-acetyl-7-oxo-dehydroeplandrosterone) (100 mg two times per day) -- 7-keto is a substance related to DHEA, a substance in the body that is the precursor to male and female hormones. DHEA has been studied as a weight-loss supplement, but results are mixed and there is some concern over DHEA's hormone-like effects on the body. One preliminary trial suggested that 7-keto may help enhance weight loss for people who are already dieting and exercising, without risk of the side effects of DHEA (7-keto is not converted to hormones in the body). However, more studies are needed to determine whether 7-keto has any real effect on weight loss. People who have had or are at risk of hormone-related cancers should not take 7-keto without their doctor's supervision.

Chromium (600 mcg per day) -- Chromium or chromium picolonate is a popular supplement among bodybuilders and those trying to lose weight and build more lean muscle mass. However, results from scientific studies have been mixed, and its effects are small compared to those of exercise and a well-balanced diet. Chromium may improve blood sugar (also a risk factor for heart disease), particularly in those with diabetes and glucose intolerance, but should not be taken for that purpose without a doctor's supervision. In addition, large doses of chromium can cause kidney damage.

Glucomannan (1 g three times per day, 1 hour before each meal) -- Glucomannan is a kind of insoluble fiber that appears to reduce blood sugar levels and may help to promote weigh loss. People with diabetes should not take glucomannan without their doctor's supervision.

Herbs

Psyllium (Plantaginis ovatae) -- Psyllium, a kind of soluble fiber, may reduce hunger cravings by making you feel full. For this reasons, incorporating psyllium and other sources of fiber into your diet may aid weight loss.

Green tea (Camellia sinensis) -- Researchers have theorized that polyphenols (chemical substances found in plants that have antioxidant properties, protecting cells in the body against damage) found in green tea extract may boost metabolism and help burn fat. However, studies have shown mixed results so far. In addition, the extracts used in the studies have contained caffeine, which could be responsible for increasing metabolism and promoting weight loss. If you are sensitive to caffeine or have anxiety or heart problems, you may want to limit how much green tea you consume.

Guggul (Commiphora mukal, 25 mg of guggulsterones three times per day) -- a common ingredient in several Ayurvedic medicines used to treat obesity. Studies suggest that overweight people who take these Ayurvedic remedies lose slightly more weight compared to those who do not take them. Guggul can cause mild diarrhea and nausea, and may interact with the following medications: blood-thinning drugs (anticoagulants), birth control pills, thyroid hormone, tamoxifen, and estrogens. People who take these medications should not take guggul. In addition, people who have or have had hormone-sensitive cancers (breast, ovarian, or prostate cancer) should not take guggul.

Cayenne or capsaicin (Capsicum frutescens, 6 - 10 g per meal) -- Preliminary evidence indicates that capsaicin (the substance that makes chili peppers taste hot) may reduce hunger and help the body burn fat, particularly when eating a high-fat diet. More research is needed to confirm these early findings, however.

Hoodia (Hoodia gordonii) -- A number of media reports on hoodia have suggested it could be an effective weight-loss supplement. However, the only evidence that exists is a single, unpublished study funded by the manufacturer of the supplement, so no one knows whether hoodia works or even whether it is safe. In addition, news reports now suggest that most hoodia supplements on the market today contain little if any of the actual herb. Until more research is done and trusted sources exist to provide the herb, hoodia is best avoided.

Homeopathy

Few studies have examined the effectiveness of specific homeopathic remedies, and there is no single or combination homeopathic remedy that will help all people lose weight. However, individualized homeopathic therapy can be designed to aid weight loss by addressing metabolism, digestion, and elimination. Before prescribing a remedy, homeopaths take into account a person's constitutional type -- your physical, emotional, and intellectual makeup. An experienced homeopath assesses all of these factors when determining the most appropriate remedy for an individual.

Acupuncture

Many studies have found both acupuncture and acupressure can improve weight loss slightly. Acupuncture is believed to promote weight loss by stimulating points on the body that boost serotonin levels. (Elevated serotonin levels are thought to suppress appetite.) One well-designed study found that people who received electrical acupuncture of the ear (auricular acupuncture) reduced their appetite.

Cognitive Behavioral Therapy

Besides changing diet and exercise habits, successful weight loss often requires additional behavioral adjustments to keep the weight off. That might include setting reasonable weekly or monthly goals -- how much exercise or how much weight loss is desired, for instance -- and finding ways to reward yourself for successes that don't involve food. Working with both a dietician and a behavioral specialist can help you put these practices into play.

It also helps to reduce the stress that leads to overeating by practicing relaxation exercises, such as yoga, meditation, or tai chi.

Finally, it is hard to lose weight without support. Support groups such as Overeaters Anonymous or Weight Watchers can help you stay focused on your goals and allow members to share success and encourage each other.

Hypnosis

Although studies are mixed, some evidence indicates that hypnosis (especially when used in combination with cognitive behavioral therapy, exercise, and a low-fat diet) may help overweight or obese people lose weight.

Other Considerations

Pregnancy

Pregnant women should not take any herbal remedies or over-the-counter or prescription medications for weight loss.

Obese women who become pregnant are at an increased risk for the following:

Gestational diabetes -- a diabetic condition that appears during pregnancy and usually goes away after the birth of the baby
High blood pressure
Preeclampsia -- a potentially fatal condition causing high blood pressure, fluid retention, and protein in the urine; may cause abdominal pain and vomiting
Caesarean sections
Fetal distress -- a condition in which the baby does not receive enough oxygen

Prognosis and Complications

People who are overweight or obese increase their risk for developing the following conditions:

Type 2 diabetes
High blood pressure
Coronary artery disease
High cholesterol
High levels of triglycerides (fat) in the blood
Heart failure
Respiratory problems (such as sleep apnea)
Circulatory problems (such as varicose veins)
Gallbladder disease
Breast cancer (after menopause) and endometrial cancer
Prostate cancer
Colorectal cancer
Osteoarthritis

Eating and exercise habits are hard to change. Many people are able to lose at least 20 pounds with diet and exercise plans, but only about 10 - 20% can maintain that weight loss for a long period of time. Losing just 15 - 20 pounds, however, can reduce the risk of serious complications, such as diabetes and heart failure, by 10 - 25%.

Supporting Research

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Bhattacharya A, Rahman MM, McCarter R, O'Shea M, Fernandes G. Conjugated linoleic acid and chromium lower body weight and visceral fat mass in high-fat-diet-fed mice. Lipids. 2006 May;41(5):437-44.

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Bray GA, Blackburn GL, Ferguson JM, et al. Sibutramine produces dose-related weight loss. Obes Res. 1999;7:189-198.

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Chantre P, Lairon D. Recent findings of green tea extract AR25 (Exolise) and its activity for the treatment of obesity. Phytomedicine. 2002;9:3-8.

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Review Date:
3/24/2007
Reviewed By:
Steven D. Ehrlich, N.M.D., private practice specializing in complementary and alternative medicine, Phoenix, AZ. Review provided by VeriMed Healthcare Network.

A.D.A.M. Copyright

adam.com

Skin wrinkles and blemishes

FitSugar — Wed, 08 Oct 2008 17:34:59 -0700

In This Report

Highlights
Introduction
Blemishes
Risk Factors
Prevention
Treatment
Resurfacing Treatments
Implant Procedures
Plastic Surgery
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Smoking and Skin Damage

The skin of smokers ages more rapidly than the skin of non-smokers, even in areas of the body not exposed to sunlight, according to a 2007 study. Women in the study who smoked also had much lower levels of vitamin E secretions in their skin. Vitamin E may protect the skin from sun damage.
There may be an association between smoking and higher frequency of a type of acne (noninflammatory acne) in adult women, according to a European study.

Antioxidants and Your Skin

A study in the Journal of Nutrition found that a combination of antioxidants and trace elements supplementation raises the risk of skin cancer in women, but not in men.

Ultraviolet Radiation

Overall, exposure to ultraviolet radiation from sunlight (radiation referred to as UVA or UVB) accounts for about 90% of the symptoms of premature skin aging.
UVB primarily affects the outer skin layers. It is most intense when sunlight is brightest. People receive slightly over 70% of their yearly UVB dose during the summer.
UVA penetrates more deeply and efficiently. The intensity of UVA rays is less dependent on the time of day and season of the year than that of UVB rays.

Vitamin D

A report analyzing studies of vitamin D supplementation found that people who take vitamin D supplements live longer than those who do not. People who avoid sunlight are at risk for vitamin D deficiency.

Introduction

As you age, your skin undergoes progressive changes:

The cells divide more slowly, and the inner layer of skin (the dermis) starts to thin. Fat cells beneath the dermis begin to shrink. In addition, the ability of the skin to repair itself decreases with age, so wounds heal more slowly. The thinning skin becomes vulnerable to injuries and damage.
The deeper layer of the skin, which provides scaffolding for the surface skin layers, loosens and unravels. Skin then loses its elasticity (ability to stretch). When pressed, it no longer springs back to its initial position. Instead, older skin sags and forms furrows.
The sweat- and oil-secreting glands atrophy (waste away), leaving the skin without a protective layer of water and fat. The skin's ability to stay moisturized then decreases, and it becomes dry and scaly.
Frown lines (those between the eyebrows) and crow's feet (lines that spread from the corners of the eyes) appear to develop because of permanent small muscle contractions. Habitual facial expressions also form characteristic lines.
Gravity makes the situation worse, contributing to the formation of jowls and drooping eyelids. Eyebrows, surprisingly, move up as a person ages, possibly pulled up by forehead wrinkles.

Wrinkles can have a profound impact on self-esteem. The stigma attached to looking old is evidenced by the more than $12 billion Americans spend each year on cosmetics to hide the signs of aging. Our society places a premium on youthfulness, and age discrimination in the workplace, although illegal, has stalled many people's careers. Indeed, the emotional consequences of aging explain in large part why the cosmetics industry and plastic surgeons thrive.

The sun is the most important cause of prematurely aging skin (a process called photoaging) and skin cancers. Overall, exposure to ultraviolet radiation from sunlight (radiation referred to as UVA or UVB) accounts for about 90% of the symptoms of premature skin aging. Most of these effects occur by age 20:

Even small amounts of UV radiation trigger the processes leading to skin wrinkles.
Long-term repetitive exposure to sunlight adds up, and likely is responsible for the vast majority of unwanted consequences of aging skin, including basal cell and squamous cell cancers.
Intense exposure to sunlight in early life is an important cause of melanoma, a particularly aggressive type of skin cancer.

Initial Damaging Effects of Sunlight. Ultraviolet radiation penetrates the layers of the skin. Both UVA and UVB rays cause damage leading to wrinkles, lower immunity against infection, aging skin disorders, and cancer. They appear to damage cells in different ways, however.

UVB is the main cause of sunburns, and primarily affects the outer skin layers. UVB is most intense at midday when sunlight is brightest. People receive slightly over 70% of their yearly UVB dose during the summer. We receive only 28% during the remainder of the year. Window glass filters out UVB.
UVA penetrates more deeply and efficiently. The intensity of UVA rays is less dependent on the time of day and season of the year than that of UVB rays. For example, you receive only about half of your yearly UVA dose during the summer months, with the balance spread over the rest of the year. Window glass does NOT filter out UVA.

Both UVA and UVB rays cause damage to the body, including genetic injury, wrinkles, aging skin disorders, and skin cancers. Exactly how they cause this damage is not yet fully understood.

Processes Leading to Wrinkles. Even small amounts of UV radiation trigger the processes that can cause wrinkles:

Sunlight damages collagen fibers (the major protein that gives structure to the skin). Sunlight also causes damage to elastin, a protein in the skin that normally maintains springiness and strength of tissue beneath the skin.
In response to this sun-induced elastin accumulation, the body produces large amounts of enzymes called metalloproteinases. One study indicated that when people with light to moderate skin color are exposed to sunlight for just 5 - 15 minutes, the metalloproteinase levels in their body remain high for about a week.
The normal function of these metalloproteinases is generally positive -- to remodel the sun-injured tissue by producing and repairing collagen. This is an imperfect process, however, and some of metalloproteinases produced by sunlight actually degrade (break down) collagen. The result is an uneven formation (matrix) of disorganized collagen fibers called solar scars. Repetition of this imperfect skin rebuilding causes wrinkles.
An important event in this process is the over-production of oxidants, also called free radicals. These are unstable molecules that are normally produced by chemical processes in the body, a process called oxidation. Environmental damage, however, causes an overproduction of oxidants. Excessive amounts of oxidants damage the body's cells and even alter their genetic material. Oxidation may contribute to wrinkling by activating the specific metalloproteinases that degrade connective tissue.

In addition to sunlight, other factors may hasten the formation of wrinkles:

Cigarette Smoke. Smoking produces oxygen-free radicals, which accelerate wrinkles and aging skin disorders, and increase the risk for non-melanoma skin cancers. Studies also suggest that smoking and subsequent oxidation produce higher levels of metalloproteinases, the enzymes associated with wrinkles.

Air Pollution. Ozone, a common air pollutant, may be a particular problem for the skin. One study reported that it might deplete the amount of vitamin E in the skin. This vitamin is an important antioxidant.

Rapid Weight Loss. If weight loss occurs too rapidly, the volume of fat cells that cushion the face are also decreased before chemicals in the skin can react. This not only makes a person look gaunt, but can cause the skin to sag.

Blemishes

This report covers three types of blemishes: Liver spots, purpura, and seborrheic keratoses (or warts).

Liver spots (known as lentigos, or sun-induced or pigmented lesions) are flat brown spots on the skin. They are almost universal signs of aging. Occurring most noticeably on the hands and face, these blemishes tend to enlarge and darken over time. The extent and severity of the spots are determined by a combination of skin type, sun exposure, and age. These spots are harmless, but should be distinguished from lentigo maligna, which is an early sign of melanoma.

Liver spots or age spots are a type of skin change that are associated with aging. The increased pigmentation may be brought on by exposure to sun, or other forms of ultraviolet light, or other unknown causes.

Treating Liver Spots. Liver spots do not require treatment, although some people are distressed by their appearance. Treatments may include the following:

Trichloroacetic acid (a chemical peel).
Tretinoin (Retin A) alone or in a combination with Mequinol (Solagé). Tretinoin is related to vitamin A, and is also effective in treating wrinkles.
Gentle freezing with liquid nitrogen (cryotherapy).
Laser treatment. Specific lasers, such as the Nd:YAG, are effective in eliminating 80% of liver spots in one treatment. It may be more effective than cryotherapy and have fewer side effects.
Bleaching creams -- these are commonly available but are not as satisfactory as peels, and high concentrations can sometimes cause permanent loss of skin color.

Purpura occurs when tiny capillaries (blood vessels) break and leak blood into the skin. In older people, the condition (called senile or actinic purpura) is usually caused by fragile blood vessels. The capillaries appear as flat purplish patches. These patches are called petechiae when they are smaller than 3 mm (about a tenth of an inch). When they are greater than 3 mm, they are referred to as ecchymoses. Patients typically complain of a rash, which may appear reddish at first but gradually change color, turning brown or purple.

Treatment. Although there is no specific treatment for purpura, patients are advised to avoid trauma, including vigorous rubbing of the skin, which may be sufficient to damage the capillaries. Emollients that soften the skin may be helpful. Some doctors also recommend vitamin C, but its effectiveness is unproven.

Seborrheic keratoses, (also called seborrheic warts), are among the most common skin disorders in older adults. Their cause or causes are unknown. They usually appear on the head, neck, or trunk and can range in size from 0.2 - 3 cm (a little over an inch). They are well defined and appear to be pasted onto the skin, but their appearance can vary widely:

They can be smooth with tiny, round, pearl-like formations embedded in them.
They can be rough and warty.
They can be brown or black.

Seborrheic keratoses sometimes look like melanoma, since they can have an irregular border, but they are always benign. A dermatologist can tell the difference between them, although experts warn that melanomas may "hide" among these benign lesions and go unnoticed without close inspection. In general, seborrheic keratoses have a uniform appearance while melanomas often have a smooth surface that varies in height, color density, and shading. In some cases, keratoses may cause itching or irritation. They can be easily removed with surgery or freezing. Vitamin D3 ointment is also showing promise in clinical trials.

Risk Factors

Exposure to Sun in Childhood. It is estimated that 50 - 80% of skin damage occurs in childhood and adolescence from intermittent, intense sun exposure that causes severe sunburns. In spite of this now well-known effect, many people still believe that a tan in children signifies health. And even though many parents are concerned about sun exposure, they still rely too much on sunscreen and not enough on protective clothing.

The Elderly. Most people over 70 have at least one skin disorder. Many have three or four. Everyone experiences skin changes as they age, but a long life is not the sole determinant of aging skin. Family history, genetics, and behavioral choices all have a profound impact on the onset of aging-skin symptoms.

Of all the risk factors for aging skin, exposure to UV radiation from sunlight is by far the most serious. Indeed, the vast majority of undesirable consequences of aging skin occur in individuals who are repetitively exposed to the sun, including the following:

Outdoor workers, such as farmers, fishermen, construction workers, and lifeguards
Outdoor enthusiasts
Sunbathers
People who regularly attend tanning salons or use tanning beds (One study indicated that regular use significantly increases the risk for non-melanoma skin cancers. Fair-skinned women under age 50 may be at particular risk.)

Experts have devised a classification system for skin phototypes (SPTs) based on the sensitivity to sunlight. It ranges from SPT I (lightest skin plus other factors) to IV (darkest skin). People with skin types I and II are at highest risk for photoaging skin diseases, including cancer. It should be noted, however, that premature aging from sunlight can affect people of all skin shades.


Skin Type	Tanning and Burning History
I	Always burns, never tans, sensitive to sun exposure
II	Burns easily, tans minimally
III	Burns moderately, tans gradually to light brown
IV	Burns minimally, always tans well to moderately brown
V	Rarely burns, tans profusely to dark
VI	Never burns, deeply pigmented, least sensitive

The common belief is that women are at greater risk for wrinkles than men. Some evidence suggests, however, that given the same risk factors, men and women in the same age groups have comparable risks for skin photoaging. In a French study, the evidence of moderate-to-severe photoaging was observed in the following:

Twenty two percent of women and 17% of men ages 45 - 49
Thirty six percent of women and 38% of men by age 54
Nearly half of both men and women by age 60

Some studies report that men are more likely to develop non-melanoma skin cancers.

Heavy smokers are almost five times more likely to have wrinkled facial skin than nonsmokers, according to one study. The skin of smokers in areas of their bodies not exposed to sunlight also seems to age more rapidly, compared to non-smokers in the same age group, according to a 2007 study. In fact, heavy smokers in their 40s often have facial wrinkles more like those of nonsmokers in their 60s.

Studies of identical twins have found smokers to have thinner skin (in some cases by as much as 40%), more severe wrinkles, and more gray hair than their non-smoking twins. Even worse, cigarette smokers are more prone to skin cancers, including squamous cell carcinoma and giant basal cell carcinomas. A European study found an association between smoking and higher frequency of a particular type of acne in adult women. The study also found that women who smoked had much lower levels of vitamin E secretions in their skin. Vitamin E is an antioxidant that may help protect the skin from sun damage. [See In-Depth Report #41: Smoking.]

Prevention

The best long-term prevention for overly wrinkled skin is a healthy lifestyle.

Eat Healthy. A diet with plenty of whole grains, fresh fruits and vegetables, and the use of healthy oils (such as olive oil) may protect against oxidative stress in the skin. One study reported that people over age 70 years had fewer wrinkles if they ate such foods. Diet played a role in improving skin regardless of whether the people in the study smoked or lived in sunny countries. Benefits from these foods may be due to high levels of anti-oxidants found in them.

Exercise. Daily exercise keeps blood flowing, which brings oxygen to the skin. Oxygen is an important ingredient for healthy skin.

Reduce Stress. Reducing stress and tension may have benefits on the skin.

Quit Smoking. Smoking not only increases wrinkles, but smokers have a risk for squamous cell cancers that is 50% higher than nonsmokers' risk. Smokers should quit smoking to prevent many health problems, not just unhealthy skin.

The following are some daily measures for skin protection:

Don't wash your face too often with tap water. (Once a day is enough.) It strips the skin of oil and moisture. In addition, chlorinated water, particularly at high temperatures, poses special risks for wrinkles.
Wash your face with a mild soap that contains moisturizers. Avoid alkaline soaps, especially with deodorant.
Pat the skin dry and immediately apply a water-based moisturizer.
Always apply sunscreen, even if going outdoors for short periods.
Avoid drinking alcohol within 3 hours of bedtime. Alcohol increases the risk for leaks in the capillaries, which allows more water in and causes sagging and puffiness. Capillary leakage increases when one is lying down.
Lie on the back when sleeping. This helps offset the effects of gravity.

One of the most important ways to prevent skin damage is to avoid episodes of excessive sun exposure. The following are some specific guidelines:

Use sunscreens that block out both UVA and UVB radiation. However, do not rely only on sunscreen for sun protection. Wear protective clothing and sunglasses in addition.
Avoid exposure particularly from 10 a.m. to 4 p.m., when sunlight pours down 80% of its daily UV dose.
Avoid reflective surfaces, such as water, sand, concrete, and white-painted areas. Clouds and haze are not protective and in some cases may intensify UVB rays.
Ultraviolet intensity depends on the angle of the sun, not heat or brightness. So the dangers are greater the closer to the summer-start date. For example, in the Northern Hemisphere, UV intensity in April (2 months before summer starts) is equal to that in August (2 months after summer begins).
The higher the altitude the quicker one sunburns. One study suggested, for example, that an average complexion burns in 6 minutes at an altitude of 11,000 feet at noon, compared with 25 minutes at sea level in a temperate climate.
Avoid sun lamps and tanning beds or salons. They provide mostly high-output UVA rays. Some experts believe that 15 - 30 minutes at a tanning salon is as dangerous as a day spent in the sun. People should not be misled by advertising claims of "safe" tanning or promotions offering unlimited tanning.

Sunscreens. The use of sunscreens is complex, and everyone should understand how and when to use them. The bottom line is not that people should avoid sunscreens or sunblocks, but that they should always use them in combination with other sun-protective measures.

Protective Clothing. Wearing sun-protective clothing is extremely important and protects even better than sunscreens. Special clothing is now available for blocking UV rays and is rated using SPF ratings or a system called the UPF (ultraviolet protection factor) index, with 50 UPF being the highest. (According to one study, this is a very reliable indicator of protection.) The clothing is expensive, however. The following are some tips for everyone:

Adults and children should wear hats with wide brims. Even wearing a hat, however, may not be fully protective against skin cancers on the head and neck.
People should look for loosely fitted, unbleached, tightly woven fabrics. The tighter the weave, the more protective the garment.
Washing clothes over and over improves UPF by drawing fabrics together during shrinkage. An easy way to assess protection is simply to hold the garment up to a window or lamp and see how much light comes through. The less the better.
Everyone over age 1 should wear sunglasses that block all UVA and UVB rays.

Chemical Tanners. Some research suggests that melanin and dihydroxyacetone (DHA), the active ingredients in many self-tanning lotions, may help filter out UVA and UVB radiation and are therefore protective against sun damage More research is underway. A preliminary study funded by the National Cancer Institute found that people who received numerous daily injections of melanotan-1 (MT-1) before going in the sun or a tanning bed tanned more quickly and showed fewer signs of sun-related damage. MT-1 is a synthetic version of the hormone melanin, which helps produce the skin's natural pigment (color).

In choosing a sunscreen, look at the ingredients. Preparations that help block UV radiation are sometimes classified as sunscreens or sunblocks, according to the substances they contain. In general, sunscreens contain organic formulas and sunblocks inorganic formulas. However, the term sunblock is used less and less as sunscreens increasingly contain both kinds of ingredients:

Organic formulas contain UV-filtering chemicals such as octocrylene, octyl salicylate, homosalate, and octyl methoxycinnamate (block UVB), avobenzone-Parsol 1789 (blocks UVA), cinoxate, ethylhexyl p-methoxycinnamate (blocks UVB and small amounts of UVA), oxybenzone, benzophenone-3 (blocks UVA/UVB). People should look for a wide-spectrum sunscreen that contains combinations of these ingredients and filter both UVA and UVB. Of note: para-amino benzoic acid (PABA), once a popular ingredient, is now used infrequently. PABA may actually break down in the presence of UV exposure and release harmful oxidants. In addition, many people have an allergic reaction to it. Some products contain PABA derivatives, such as padimate O or octyl dimethyl PABA. It is not known if they have the same effects.
The Food and Drug Administration approved Anthelios SX in July 2006. This new sunscreen prevents sunburn and protects against ultraviolet A and B rays. The product contains ecamsule, an ingredient not previously marketed in the United States.
Inorganic formulas contain the UV-blocking pigments zinc oxide or titanium dioxide. Zinc and titanium oxides lie on top of the skin and are not absorbed. They prevent nearly all UVA and UVB rays from reaching the skin. Older sunblocks are white, pasty, and unattractive, but current products use so-called microfine oxides, either zinc (Z-Cote) or titanium. They are transparent and nearly as protective as the older types. Microfine zinc oxide may be more protective and less pasty-colored than microfine titanium oxide.

Inexpensive products work as well as expensive ones with the same ingredients. Unfortunately, there are still no standards for sunscreens, and even those claiming UVA protection may offer very little. In one study, the average UVA protection from a wide range of brands was only 23%. In fact, the average protection of brands not making the claim was 37%!

Organic formulas and inorganic microfine oxides do not protect against visible light, which is a problem for people who have light-sensitive skin conditions, including actinic prurigo, porphyria, and chronic actinic dermatitis. Inorganic sunscreens that protect against visible light and are still cosmetically acceptable are now available in Europe, but not yet in the US.

Calculating the SPF. The sun protection factor (SPF) on all sunscreen labels is a ratio based on the amount of UVB (not UVA) radiation required to turn sunscreen- or sunblock-treated skin red compared to non-treated skin. For instance, people who sunburn in 5 minutes and who want to stay in the sun for 150 minutes might use an SPF 30. The formula would be: 30 (the SPF number) times 5 (minutes to burn) = 150 minutes in the sun.

Protection offered by sunscreens may be classified as follows:

Minimal: SPF 2 to 11.
Moderate: SPF 12 through 29.
High: 30+. (Although some sunscreens claim SPFs higher than 30, the added protection at such higher levels is insignificant.)

SPF Levels by Age Group. Certain groups should have higher or lower SPFs depending on age and other factors:

Although sunscreens are safe in most toddlers and children, they should not be the first and only lines of defense. In fact, experts are worrying that by relying too much on sunscreen and not providing other protective measures, parents may actually be increasing their children's risk for melanoma. All young children should be well covered with clothing, sunglasses, and hats as the first line of defense against sunburn. Children should be kept out of the sun during peak sunlight periods. Sunscreens should not be used on babies younger than 6 months without consulting a doctor.
Older children and adults (even those with darker skin) benefit from using SPFs of 15 and over. Some experts recommend that most people should use SPF 30 on the face and 15 on the body.
Adults who burn easily instead of tanning and anyone with risk factors for skin cancer should use at least SPF 30.

Timing and Amount of Application. You should apply sunscreen or sunblock liberally as follows:

Adults should include sunscreen with a daily skin regimen, even if going outdoors for only a short time.
Apply a large amount to all exposed areas, including ears and feet. To achieve protection as indicated by the sunscreen's SPF, experts recommend half a teaspoon each for the head, neck, and each arm and a teaspoon each for the chest area, the back, and each leg.
Apply initially 30 minutes before venturing outdoors for best results. (This allows time for the sunscreen to be absorbed. Then reapply every 15 - 30 minutes while being in the sunlight.
Also reapply each time after exercise or swimming. (Choose a waterproof or water-resistant formula even if activities don't include swimming. Waterproof formulas last for about 40 minutes in the water, whereas water-resistant formulas last half as long.)
Insect repellents reduce sunscreen SPFs by up to one-third. Use higher SPFs and very liberal application when applying both.

Possible Hazards of Sunscreens, Sun Avoidance, or Both. When used generously and appropriately, sunscreen products and sun avoidance help reduce the severity of many aging skin disorders, including squamous cell cancers. There are certain concerns, however.

Sunscreen Use May Not Protect Against Basal Cell and Melanoma Cancers and May Even Increase the Risk. Although sunscreens help prevent squamous cell carcinomas and other skin disorders, sunscreens do not appear to provide protection against melanoma and some basal cell cancers. In fact, some studies have reported a higher association with sunscreen use and these skin malignancies, though not all studies report such negative results.

The reasons for this possible increased risk are unclear, though some theories include the following:

Until recently, many sunscreens blocked only or mostly UVB rays and not UVA, the more deeply penetrating rays now known to be especially dangerous. Past studies may not have reflected the effects of the broad-spectrum sunscreens now available, which block both UVA and UVB.
People who apply sunscreens may feel safe and stay out longer during high sun-exposure hours than is safe. Even if a person doesn't sunburn, UVA rays can still penetrate the skin and do harm.
People may not put on enough sunscreen. According to a 2002 study, people generally apply only 20 - 60% of the recommended amount, which can provide significantly less protection than the given SPF. (Of note, a 2003 study reported that when applied at the recommended amount, a broad-screen sunscreen prevents DNA damage from UV exposure. However, omitting it even once resulted in significant cell injury.)

Sunscreen Use May Increase the Risk for Health Problems Related to Sunlight Deficiencies. There is some major concern that underexposure to sunlight, due to the use of sunscreens or sun-avoidance measures, may produce other health problems, such as the following:

Vitamin D Deficiency. Vitamin D is found in only a few foods, such as fortified dairy products and fish, but it is produced in the skin in response to UVB sunlight. A medical literature review published in the journal Nutrition and Cancer reported that UVB rays may outshine dietary supplements for building the body's vitamin D reserves. Without an appropriate mix of diet and supplements, vigorous sun protection measures may increase a person's risk for developing vitamin D deficiency. Vitamin D is important for prevention of rickets, osteoporosis, and some cancers, including melanoma. People who need to avoid sunlight and whose diet is low in foods that contain vitamin D should check with their doctor about taking supplements. People with darker skin are at higher risk for deficiencies from sun protection than those with whiter skin. Note: vitamin D is toxic in high doses. Most doctors recommend 200 IU a day (for young adults) to 600 IU a day (above age 70). Doses up to 2,000 IU a day are considered safe. A report analyzing studies of vitamin D supplementation found that people who take vitamin D supplements live longer than those who do not. The researchers looked at 18 studies. They found that participants who received vitamin D supplements were, on average, 7% less likely to die during the study they were in, compared with those receiving "sugar pills."
Other Cancers. Although sunlight is implicated in skin cancers, it is also associated with lower risks for breast, prostate, ovarian, and colon cancers. Some protection against these cancers may be related to vitamin D production by sunlight.
Depression. Many people suffer from SAD (seasonal affective disorder), a form of depression that generally occurs in winter and is associated with exposure to less sunlight.

The bottom line is that some sunlight is important and even necessary for a healthful and high-quality life. Adults may benefit from daily moderate tanning (20 - 30 maximum minutes of exposure during lower-risk hours) over several days to slowly build up pigment in the skin.

Treatment

An increasing number of dermatology patients are looking for a way to improve the appearance of their skin. As a result, more and more products have become available to treat skin wrinkles and blemishes. From vitamins and supplements to exfoliants and chemical peels -- the options can be overwhelming. In some cases, more than one approach may be needed.

Antioxidants are substances that hunt oxygen-free radicals, the unstable particles that can damage cells. Free radicals may also cause sun damage and even skin cancers. Exposure to sunlight depletes antioxidants in the skin, and therefore they must be replaced.

Antioxidant ointments, creams, and lotions ("topical products") may help reduce the risk of wrinkles and protect against sun damage. Unlike sunscreens, they build up in the skin and are not washed away, so the protection may last. Selenium, coenzyme Q10 (CoQ10), and alpha-lipoic acid are types of antioxidants that come in topical form. Many are proving to be very beneficial for the skin.

Vitamin A. Vitamin A is important for skin health. UV radiation produces vitamin A deficiencies in the skin. Topical products containing natural forms of vitamin A (retinol, retinaldehyde) or vitamin A-related products called retinoids (tretinoin, tazarotene) may help repair skin damage due to sunburn and natural aging.

Tretinoin (Retin-A). Tretinoin (known commercially as Retin-A) is the only topical agent approved for treating photoaging and is available in prescription form (Avita, Renova, Differin). The June 2004 issue of Dermatology Surgery reported that tretinoin (0.25% concentration) was an effective and well-tolerated treatment for photodamaged facial skin. This drug produces a rosy glow and reduces fine and large wrinkles, liver spots, and surface roughness. It also may help prevent more serious effects of ultraviolet radiation. Patients may apply tretinoin to the face, neck, chest, hands, and forearms, and should do so at least twice a week. Noticeable improvement takes 2 - 6 months. Because Retin-A increases a person's sensitivity to the sun, patients should apply just a tiny amount at bedtime, and wear sunblock during the day. Patients should also avoid overexposure to the sun. Almost all patients experience redness, scaling, burning, and itching after 2 or 3 days that can last up to 3 months. In women who experience irritation, a daytime moisturizer or low-dose corticosteroid cream, such as 1% hydrocortisone, may help. There is some concern that overuse of high-dose tretinoin may cause excessive skin thinness over time. Studies now suggest that low concentrations (as low as .02%) of tretinoin can produce significant improvements in wrinkles and skin color, with less irritation than the higher doses.
Retinol. Retinol, a natural form of vitamin A, could not, until recently, be used in skin products because it was unstable and easily broken down by UV radiation. Stable preparations are now sold over the counter. In the right concentrations, retinol may be as effective as tretinoin, and studies indicate that it has fewer side effects. An animal study suggests that adding antioxidant creams (such as those containing vitamins C or E) may offer added protection against degradation of retinol, but not tretinoin. The Food and Drug Administration warns that over-the-counter retinol skin products are unregulated. The amount of active ingredients is unknown, and some preparations, in fact, may contain almost no retinol.
Tazarotene. Tazarotene (Tazorac, Zorac, Avage) is a retinoid used for acne and psoriasis. It has now been approved for treating wrinkles, skin discoloration, and blemishes due to photoaging. One short-term study suggested that it may be as effective as tretinoin and even slightly better at high doses. At such high doses, however, it can cause very severe irritation. Redness and peeling may be reduced by administering tretinoin first to get the skin acclimated. A randomized study of 562 patients with facial photodamage found that a daily application of tazarotene 0.1% cream resulted in a minimum 1 grade improvement in fine and coarse wrinkling, uneven skin color, pore size, skin roughness, and overall photodamage. More research is needed to determine if it produces any long-lasting significant benefits.

Warning: Pregnant women and those who may become pregnant should avoid any vitamin A derivative (a product related to vitamin A). For example, oral tretinoin causes birth defects, and women should avoid even topical Retin-A when pregnant or trying to conceive.

Vitamin C. Vitamin C, or ascorbic acid, is a very potent antioxidant. Most studies on the effects of antioxidants on the skin have used this vitamin. In laboratory studies, large amounts of vitamin C reduced skin swelling and protected immune factors from sunlight. It may even promote collagen production. Vitamin C by itself is unstable, but products that solve the delivery problem are now available (such as Cellex-C, Avon's Anew Formula C Treatment Capsules, Physician Elite, and others). More research is needed.

Antioxidants Under Investigation for Skin Care. Other antioxidants are also being investigated for their value in skin protection. Most available brands, however, contain very low concentrations of these antioxidants. In addition, they are also not well absorbed and have a short-term effect. New delivery techniques, however, may prove to offset some of these problems.

Vitamin E. Studies suggest that topical vitamin E, particularly alpha tocopherol cream (a form of vitamin E), decreased skin roughness, length of facial lines, and wrinkle depth. Studies on mice have also reported reductions in UV-induced skin cancer with its use.
Both green and black tea may provide some protection against skin cancers and photoaging. There is also some evidence that pomegranate and soy extracts may help rejuvenate aging skin.
Aloe, ginger, grape seed extract, and coral extracts contain antioxidants and are promoted as being healthy for the skin, although evidence of their effects on wrinkles is weak.

A small study found that taking vitamin C and E supplements by mouth -- at the same time -- may help reduce sunburn, although it doesn't work as well as sunscreen. Taking the vitamins separately did not have any effect. Vitamin C and E are also antioxidants.

One of the basic methods for improving skin and eliminating small wrinkles is exfoliation (also called resurfacing), which is the removal of the top layer of skin to allow regrowth of new skin. Methods for doing this run from simple scrubs to special creams to intensive peeling treatments, including laser resurfacing. People with darker skin are at particularly higher risk for scarring or discoloration with the more powerful exfoliation methods.

Abrasive Scrubs. Scrub gently with a mildly abrasive material and a soap that contains salicylic acid to remove old skin so that new skin can grow. The motion should be perpendicular to the wrinkles. Use textured material or cleansing grains with microbeads. Organic materials, such as loofahs or sea sponges, may harbor bacteria. Avoid cleansing grains that contain pulverized walnut shells and apricot seeds, which can scratch skin on a microscopic level. Cleansing grains with microbeads don't have sharp edges and remove skin without cutting it. Exfoliation using scrubs, however, can worsen certain conditions, such as acne, sensitive skin, or broken blood vessels.

Topical Alpha Hydroxy Acid and Similar Substances. Alpha hydroxy acids (AHA) ease the shedding of dead skin cells and may even stimulate the production of collagen and elastin. Their natural forms are:

Lactic acid (milk)
Glycolic acid (sugar cane)
Malic acid (found in apples and pears)
Citric acid (oranges and lemons)
Tartaric acids (grapes)

Most alpha hydroxy acid products contain glycolic acid. Skin care products are also made from polyhydroxy acids (PHAs) and beta hydroxy acids (BHAs). Research suggests that PHA products may cause less skin irritation than AHA or BHA products.

Acid concentrations in over-the-counter AHA preparations are 2 - 10%. One clinical study suggested that 8% concentrations showed modest skin improvement Some examples include Avon's Anew Intensive Treatment (8% glycolic), Pond's Age Defying Complex (8%), Elizabeth Arden's Alpha-Ceramid Intensive Skin Treatment (3 - 7.5%), and BioMedic's home product (10%). Prescription strength creams contain at least 12% glycolic acid, and glycolic acid peels of 30 - 70% concentration may be administered in a doctor's office at weekly or monthly intervals.

Response to AHA varies, and the treatment is not without risk, particularly in high-concentration products. Side effects from over-the-counter creams, prescription products, and professional AHA peels can include burns, itching, pain, and possibly scarring. Studies also suggest that AHA may increase susceptibility to sun damage, even at concentrations as low as 4%. Such effects can persist up to a week after a person stops using the product. Experts advise that people purchase products with AHA concentrations of 10% or less. Chemical peels of up to 60% are available without prescription on the Internet. Such concentrations are not recommended, except under a doctor's supervision. If any adverse effects occur, stop using the product immediately. Always avoid sunlight or use proper sun protection when using these products.

Copper Peptides. Certain copper-containing compounds may protect skin and help repair it. Note: copper is a toxic metal. When using products containing copper, buy only those that contain peptides (small protein fragments) that bind to copper. Most studies have been conducted on the copper peptide glycyl-l-histidyl-l-lysine:copper (II) or GHK-Cu. It is currently used in a number of products (such as CP Serum, Neutrogena's Visibly Firm, ProCyte's Neova).

Furfuryladenine. Furfuryladenine (Kinetin, Kinerase) is a naturally occurring growth hormone found in plant and animal DNA. It has antioxidant and anti-aging properties. Some small laboratory studies suggest that furfuryladenine may delay the onset and decrease the effects of aging on skin. However, there are no well-conducted human studies to support this suggestion.

Vitamin K. Microsponge-based vitamin K is said to clear bruises spider veins, and other small blood vessel damage. Vitamin K is important for blood clotting.

Moisturizers help prevent dryness, bruising, and tearing. They have no effect on wrinkles by themselves. Moisturizers should be applied while the skin is still damp. These products retain skin moisture in various ways:

Occlusives, such as petroleum jelly, prevent water from evaporating.
Humectants, including glycerin, act by pulling water up to the surface of the skin from deep tissues. People with oily skin generally should use the humectant type.
More powerful compounds, such as monolaurin (Glylorin), contain mixtures of fatty molecules (lipids), which may help restore the skin's natural barriers against moisture loss and damage.

Most moisturizers contain combinations of these compounds. They usually have other ingredients as well, such as alpha hydroxy acids, sunscreens, collagen, and keratin. Collagen and keratin leave a protein film and temporarily stretch the skin. They range widely in price, and a major consumer organization found little difference in general between the more and less expensive products.

The skin under the eyes is very thin and does not produce as much of the protective oils that keep skin soft and supple. Manufacturers market their under-eye gels as being able to reduce puffiness and dark circles. The creams typically work in one of two ways:

By temporarily constricting blood vessels to prevent the build-up of fluids
By firming the skin with an invisible film

Never rub the creams under the eyes, as this may cause more wrinkles to form. Instead, apply these products with a light tapping motion to stimulate the skin.

Cosmetics, if properly applied, can be surprisingly effective in camouflaging the signs of aging skin, including wrinkles and age spots. Moreover, they offer additional benefits by retarding water loss and providing a physical barrier to UV radiation. However, as women age, less is more.

Here are some suggestions for older women:

Moisturizers. Apply moisturizers before foundation. If reddish discoloration is extensive or the skin is sallow, tinted moisturizers may be helpful and can be worn alone or under foundation.

Foundations. Caking on make-up will cause cracks at the wrinkle lines and only increase the appearance of aging. Try to cover large areas of the face with a moderate-coverage foundation that has a matte or semi-matte finish. Facial powder reflects light and thus minimizes wrinkles, but people with dry skin should avoid it.

Correcting Color. When blemishes are especially prominent, applying color correctors under the foundation can be very effective:

Green neutralizers mask red lesions.
Yellow will camouflage dark circles and bruises.
Mauve (a purplish-pink color) helps neutralize sallow skin or yellowish blemishes.
A white, pearled base helps to minimize wrinkles.

Blushes. Blushes and color washes can help conceal the spidery network of dilated capillaries on the nose and cheeks. Powder blushes are preferred because they blend easily on top of foundation.

Eyes. Powder eye shadows applied on top of a moisturizer are better than cream-based shadows. Light-colored shadow, applied along the upper eyelid crease and above the iris (the colored part of the eye) is best for offsetting the appearance of deep-set eyes. You should then apply a slightly deeper shade of the same color to the lower part of the eyelid, and draw it out to the corner.

Lips. A lip-setting cream or facial foundation should be applied before lipstick to help prevent it from bleeding into surrounding wrinkles. Try using a stiff bristle brush instead of a lip pencil. The brush will help keep the lipstick on and prevent bleeding. (Some women use the pencil itself for the full lip, which gives color but appears natural.) Some make-up artists recommend cream lipsticks instead of matte.

The Food and Drug Administration (FDA) does not regulate herbal remedies and dietary supplements. In other words, the manufacturers and distributors of such products do not need FDA approval to sell their products. In addition, any substance that affects the body's chemistry can, like any drug, produce side effects that may be harmful. There have been numerous reported cases of serious and even deadly side effects from herbal products.

Overexposure to sunlight can damage skin. The following natural remedies may cause extra sensitivity to light (photosensitivity):

St. John's wort (Hypericum perforatum) is a popular herbal remedy for depression. People who are sensitive to light should not use it. A case report suggests that St. John's wort may cause skin reactions in patients who have laser treatment.
Kava (Piper methysticum) is an herb used to calm nerves and reduce stress. In addition to photosensitivity, it can cause liver damage.
Yohimbe (Pausinystalia yohimbe) is used to treat erectile dysfunction. Both the herb and the pharmaceutical drug (yohimbine) can cause sensitivity to light.
Essential oils in many botanical aromatherapy products can trigger photosensitivity. Avoid citrus oils (grapefruit, lemon, lime, and orange) as well as bergamot, cumin, ginger, and angelica root oils.

Resurfacing Treatments

There are many choices for skin resurfacing (also called exfoliation), and the patient must consider several different factors that affect the choice. Resurfacing can achieve the following:

Removal of abnormal tissue and rough skin
Stimulation of new skin growth
Stimulation of collagen and elastin production

In addition to determining the skill of the surgeon and the safety of the procedure, the patient must discuss the desired depth of the resurfacing and the capability of each procedure to reach this depth safely. All resurfacing procedures require a healing period afterward, during which the skin is red and sensitive. The deeper the procedure, the higher the risk for complications, including delayed healing, infection, loss of pigment (skin color), and scarring.

If you make the decision to pursue intensive treatments, consider the following factors, among others, and discuss them with your dermatologist or plastic surgeon:

The ability of the procedure to safely reduce wrinkles
The ease and safety record of the procedure
The skill of the doctor
The length of recovery
Possible complications
How long the benefits will last

A person's age also helps determine the procedure:

For people in their 30s, a simple chemical peel is sufficient.
After age 40, people may benefit from collagen or fat implants.
At age 50 and over, plastic surgeons recommend laser resurfacing and customized treatments for individual needs.

In older individuals, combination procedures may be beneficial. Some examples include the following:

Laser surgery may be used for deep lines (such as those around the mouth) and chemical peels used over the rest of the face.
For enhancing the eye by correcting droopy eyelids, bags, and a "sinking" brow, combinations of eyelift (blepharoplasty), Botox, and laser resurfacing may be used.

Chemical peels, also known as chemosurgery, help restore wrinkled, lightly scarred, or blemished facial skin. Much like chemical paint strippers, chemical peels strip off the top layers of skin, and new, younger-looking skin grows back. The procedure is very effective for the upper lip but cannot be performed around the eyes. Partial peels are often done in conjunction with a face-lift. Combinations of the topical antioxidants, such as tretinoin and vitamin C, along with a chemical peel, may be particularly effective.

The Procedure.

A dermatologist applies chemicals to the skin. They include trichloroacetic acid, high concentrations of alpha hydroxy or beta hydroxy acids, or combinations of all three.
In some cases, tretinoin or alpha hydroxy is applied 4 - 6 weeks before, and starting one day after, the peel. Such treatments can enhance the effects of a peel and reduce the risk of discoloration in people at risk for this complication. Tretinoin is being tested as a chemical peel.
A crust or scab generally forms within 24 hours after surgery. You can remove this scab by gently cleansing with soap and water.
The skin takes 6 - 7 days to heal.
After the scab disappears, the visible skin is deep red but gradually lightens as it regenerates.

Complications. Complications include white heads, cold sores, infection, scarring, numbness, and permanent discoloration, particularly in people with darker skin. Refinement of chemical peel techniques are now permitting doctors to reach deeper skin, improvements which make it easier to apply peels to non-facial skin and to individuals with darker skin.

Dermabrasion affects deeper layers of skin than chemical peels, and may be useful for removing disfiguring marks, such as deep acne scars or deep wrinkles. As with chemical peels, it is effective for wrinkles on the upper lip and chin, and cannot be used around the eyes. Some doctors prefer dermabrasion to lasers for skin surfacing of people with darker skin colors.

Standard Dermabrasion. Standard dermabrasion uses a rotating brush that removes the top layers of a person's skin. As with chemical peels, dermabrasion selectively strips away the upper layers of skin, leaving the underlying skin layers exposed. Similar to chemical peels, after the procedure, the treated skin oozes and forms a scab, a reaction that looks and feels uncomfortable, but only temporary. Postoperative care is similar for both procedures.

Microdermabrasion. A gentler variation called microdermabrasion uses very tiny crystals to polish the skin and a vacuum technique to remove them. It has largely replaced the older dermabrasion, and, in fact, was the fourth most common non-surgical cosmetic procedure performed in 2005, with over a million done. Results are similar to light chemical peels. Patients can have this procedure done on their lunch hour and return to work. Only mild redness occurs after treatment, although for best results five or six repetitive treatments are needed every 1 - 2 weeks. To date, overall patient satisfaction has been very high.

Lasers are currently the most effective exfoliation tools for eliminating wrinkles. Their unique advantages over other resurfacing methods are their ability to tighten the skin. A successful procedure can make patients look 10 - 20 years younger, and the results can last up to 10 years.

The procedure is most beneficial for the following areas:

It is best around the mouth and eyes. Recent evidence suggests CO₂ lasers may be even better than dermabrasion for the upper lip.
It is slightly less beneficial for the area around the nose.

Used alone, current laser therapy does not eliminate crow's feet, broken blood vessels, or dark circles under the eye. The evidence of the effects of lasers on acne scars is incomplete.

Standard laser dermabrasion is too harsh for thinner skin layers, such as on the neck. Newer and gentler laser techniques, however, stimulate collagen without removing skin layers, and may prove to be useful for necklines.

The Laser Resurfacing Procedure. In general the procedure works in the following way:

Laser pulses penetrate the skin quickly, vaporizing water and surface skin without damaging the deeper layers, allowing new top skin to grow.
In addition, the laser delivers enough heat to shorten collagen fibers, restoring some elasticity to the skin.

Choice of Lasers. The lasers used depend on skin type and severity of the condition. Some of the more common laser types are:

The carbon dioxide (CO₂) laser. This is the most powerful laser treatment and is used for deep wrinkles and skin imperfections. People who have had silicone injections should not have CO₂ procedures, which can burn and scar the skin over the implanted area.
The erbium: YAG (Er:YAG). This laser is gentler than the CO₂ laser, and is effective for mild wrinkles and for providing a smooth skin texture. It has a shorter recovery time. Some experts have even found the YAG laser as effective in removing deep wrinkles as CO₂ when used to sufficient depth. A variable pulse YAG laser can shift between pulses that destroy skin tissue to those that heat the skin. This process effectively resurfaces the skin with fewer side effects than CO₂ laser therapy.
Pulsed dye laser. Pulsed dye laser uses yellow light, which is easily absorbed by hemoglobin, the molecule that gives blood its red color. Pulsed dye laser treatments are used to treat skin blemishes that are due to blood vessel abnormalities, such as port-wine stains.

A gentle laser procedure called non-ablative laser resurfacing (NLite), also called photorejuvenation, is now approved for the treatment of all facial wrinkles. The procedure uses light energy to gently stimulate new collagen, and possibly elastin production, without removing the skin tissue itself. Its effects are less pronounced than those of other laser procedures. However, because it does not injure the external layers of skin, it can be used on delicate skin areas, such as the neck and around the eyes. It also causes very little irritation afterward.

Some surgeons are using combination techniques that employ more than one laser technology in one session, to achieve different effects. For example, one combination technique uses CO₂, YAG, pulsed-dye laser, and one other laser technology to both improve wrinkles and clear under-eye dark circles and acne scarring. Pretreatment with botulinum (Botox) injections before laser resurfacing significantly improved the treatment of crow's feet in one study.

Post-Procedure Recovery. The procedure itself is relatively painless, but the redness and irritation that occur during the healing process can be severe. Non-ablative laser resurfacing does not have the same severe after-effects as other laser treatments. For 8 - 9 days, the face looks skinned and swollen, and requires continuous moisturizing. Some doctors suggest that people with very sensitive skin, who cannot tolerate the necessary medications and lubricants, should avoid laser resurfacing. Redness and sensitivity can persist for 1 - 4 months. The patient must stay out of the sun as much as possible during this time, and should always avoid sunbathing and damaging their skin again. Early research suggests that silicone dressings may reduce post-procedure pain and crusting.

Complications. Scarring and infections can occur in about 1% of procedures. The risk of complications depends on the experience of the surgeon. People with a history of herpes simplex may experience flare-ups of fever, facial pain, and flu-like symptoms for 5 or 6 days after the procedure. In addition, people with darker skin may wish to avoid the procedure, because it can cause unpredictable and dramatic lightening of the skin.

A new skin rejuvenation technology, called Plasma Skin Resurfacing, or Portrait Plasma, was introduced in February 2005. The technology uses plasma energy (heat and light energy) to rejuvenate the skin from the deeper layers outwards. While new skin regenerates, the outer layers of the skin act as a natural bandage. When the outer layers peel off in the week after treatment, the new skin emerges. The process prevents or minimizes the raw appearance that follows laser treatments. This system uses radio waves to "excite" nitrogen gas, resulting in the release of energy. According to the manufacturer, skin regeneration using the Portrait Plasma system is rapid, and satisfaction with the procedure appears high. Long-term follow-up studies are not available yet for this new method. In 2006, the Food and Drug Administration approved this method for the treatment of wrinkles on other areas of the body, besides the face.

Cold Ablation. Cold ablation, called coblation for short, delivers saline (salt water) to the skin, through which a cool electric current is passed. A subsequent reaction heats and vaporizes the top shallow layer of skin. The procedure is very specific and appears to minimize any damage to other areas of the skin.

Radiofrequency Resurfacing. A promising technique uses low radiowave energy to resurface the skin. Preliminary research indicates that this procedure may eventually be as effective as laser surgery in reducing severe wrinkles around the eyes and mouth, with minimal pain and a shorter recovery time. In one study, one radiofrequency treatment with only a skin anesthetic resulted in tighter facial skin for 14 out of 15 patients within 12 weeks. All but one patient returned to normal activity immediately afterward. A small clinical trial published in Dermatology Surgery found that a noninvasive radiofrequency technique called NARF safely and effectively improved drooping lower eyelids.

Intense Pulsed Light. Intense pulsed light (IPL) uses filters to deliver different wavelengths of light. Doctors use it to treat a number of photoaging skin problems, and it appears to have long-term effects. Typically, four to six treatments are performed over a four-month period. Each treatment takes 15 - 20 minutes. Unlike laser light, which uses one color wavelength (such as green or red), intense pulsed light starts with a full spectrum of light. It then allows the doctor to selectively block off specific wavelengths, depending on how shallow or deep the procedure should go. IPL machines are less expensive and safer than lasers.

Implant Procedures

Implants, also called injectable fillers, are becoming a common means of erasing wrinkles and folds. Several materials are being used for deep wrinkles, depression under the eyes, lip enhancements, and acne scars.

After being banned from the market in 1992, silicone is making a comeback in research settings as a potential permanent wrinkle eraser. Scientists are looking into a new microdroplet technique (the use of very small drops) combined with purified silicone as a way to eliminate any danger. The past problems with silicone occurred when it was mixed with a foreign substance, like mineral oil, or when it was injected in large doses.

Most implants to date, however, are not completely satisfactory. Collagen implants and biologic fillers from animal, bacterial, or human sources do not provide long-lasting benefits. Synthetic fillers are permanent but may cause an allergic reaction, which can lead to chronic problems. Such reactions are rare, but they can be painful and unattractive.

The U.S. Food and Drug Administration (FDA) approved the Juvéderm product line in June 2006. Juvéderm is an injectable treatment of moderate-to-severe facial wrinkles and folds. Juvéderm products are gels made from hyaluronic acid. They are injected into the face. Doctors report good results after a single treatment with Juvéderm, and the results last for at least 6 months.


Name and Material Used	Procedure	Specific Areas Affected	Benefits	Drawbacks
Collagen implants. Collagen is the protein that forms the structures in the body (such as skin, bones, cartilage). The implant procedure has typically used bovine (cow) collagen. A form of human collagen (CosmoDerm, CosmoPlast) has now been approved.	Injected into target wrinkles with needle and syringe. Several weeks after injection, cow collagen breaks down and is replaced by newly created human collagen.	Wrinkles around the eyes and mouth. It is used to give lips greater fullness.	Very simple with faster recovery than many other implant techniques.	Wrinkles form again, and require repeat treatments 3 - 12 months later. Rarely, severe allergic reactions occur. Should not be used by children, pregnant women, and people with a history of autoimmune disease.
Microlipoinjection. Fat tissue from the patient's own thigh or abdomen.	Injected into target wrinkles with needle and syringe.	Deep wrinkles around the nose and mouth, folds in the forehead, and wrinkles on the hands.	No allergic or immune reaction because substance is patient's own fat.	Body eventually absorbs the fat, resulting in a need for multiple injections. Some studies suggest that 70% of the fat may still be in place after at least a year.
Gore-Tex. Highly porous (full of tiny holes) and inert (not chemically active) synthetic material.	Requires some surgery. Tiny patches are inserted under the skin to fill out wrinkles. Skin cells and blood vessels pass through the porous material easily, reducing the risk of severe irritation.	Deep wrinkles.	Material does not break down.	Possible scarring from surgical procedure. Allergic reactions are rare but can occur even with chemically inactive materials.
Artecoll. Contains PMMA, or polymethylmethacrylate, an inert substance, enclosed in tiny droplets of natural collagen.	Material is injected. Body absorbs collagen. PMMA remains and stimulates new collagen growth.	Deep wrinkles.	Although part of the implant is a natural collagen implant, it does not degrade as quickly as a full collagen implant.	Repeat treatments may still be needed. Possible allergic reaction.
Hyaluronic acid. Natural (non-animal) substance acts like a molecular sponge to absorb water. The FDA approved Restylane in 2003, Captiva, Hylaform-Plus, and Hylaform in 2004, and Juvéderm in 2006.	Gel is injected under the skin.	Moderate-to-severe wrinkles.	Low risk for allergic reaction. May last longer than cow collagen.	Repeat treatments needed.
Poly-L-lactic acid. Synthetic polymer. Approved in US as Sculpta. Approved in other countries as New-Fill.	Material is injected under the skin.	Approved in U.S. only for patients with facial fat loss due to HIV. Approved in other countries for wrinkles.	Low risk of allergies. Treatment effects can last 18 - 24 months.	Doctors require special training.

The popularity of Botox injections has skyrocketed in the United States. Between 2004 and 2005, the number of procedures performed jumped 16 percent. Botox injection was the number one non-surgical cosmetic procedure in 2005, with more than 3.2 million injections. Botulinum, the deadly toxin found in uncooked foods, is also a powerful muscle-relaxant. Tiny amounts of a purified form (Botox) are injected into wrinkles to relax the surrounding muscles. It may benefit forehead and frown lines, crow's feet, lower eyelids, lines on the side of the nose, and the area between the upper lip and the nose. It is also useful for treating involuntary muscle movements that can occur after a face-lift.

The injections need to be repeated every few months, since the effects wear off. The treatment decreases the ability to frown or squint and may cause the corners of the mouth to turn down. When used for areas around eyes, it produces a rounder appearance afterward, which patients should be aware of before they undertake the procedure.

The drug does not cross the blood-brain barrier, and, to date, the only side effects are temporary muscle weakness near the injection site. Although there have been some reports that Botox can reduce migraine and tension headaches, Botox also causes headaches in about 1% of cases. In some cases, the headaches can be very severe and long lasting (from 8 days to a month). Some researchers suggest that either a contaminated batch of Botox or a specific injection technique may be the cause, but additional investigation is needed.

Plastic Surgery

In 2005, there were over 2.1 million cosmetic surgeries, up 1% from the year before. Most of these surgeries were liposuction and breast surgeries. However, over 200,000 each of eyelid and nose surgeries were performed. Facial plastic surgeries range from being fairly minimal, such as a brow lift, to a full face-lift.

Several face-lift procedures (called rhytidectomies) are available. Face-lifts can provide individuals with a more youthful look. The degree of improvement, however, depends on many factors, including age, bone structure, skin type, and personal habits, such as smoking and sunbathing.

The Procedure. When a face-lift is a relatively simple procedure, it can take about 2 hours under local anesthetic in a doctor's office. Complicated face-lifts are done under general anesthesia in a hospital and can take 3 - 6 hours. The face-lift procedure may be one of the following:

Superficial musculoaponeurotic system (SMAS) is the most common face-lift procedure. The surgeon makes an incision at the hairline and separates the skin from the underlying tissue and muscles. The muscles are tightened and excess fat and tissue, such as fat under the chin and neck, are removed.
The endoscopic subperiosteal or subgaleal face-lift is a less invasive surgical technique. The surgeon raises facial structures rather than cutting away flaps of skin. Only a few half-inch incisions are made, and scarring is minimal. Not all individuals are candidates for this procedure, however.

Neither SMAS nor the endoscopic version is effective for the middle part of the face, particularly the deep lines (naso-labial folds) that run down from the nose beside the mouth. Some time after the SMAS face-lift, the upper face begins to age again while the lower area keeps its shape, causing the face to look imbalanced. Researchers are looking at other approaches, such as one called composite face-lift, that lift most muscles in the face.

Recovery Process. Recovery normally lasts from several weeks to several months. Swelling and discoloration are common. Some patients report tingling or numbing sensations after surgery. These sensations generally decrease as damaged nerves regenerate.

Complications. A face-lift is not without risks. A postsurgical hematoma is a collection of blood that can occur after a face-lift. In one study, major hematomas occurred in 2.2% of patients and minor hematomas in 6.65% of patients. They generally develop within 2 weeks of the surgery and require draining. Even minor hematomas need fast treatment to prevent greater complications. Such complications can include infection, changes in skin color, fluid buildup, and prolonged recovery time.

Other less common complications may include the following:

Infection
Excessive bleeding
Imbalanced facial muscles
Delayed healing
Scarring
Permanent injury to the nerves that control facial movements

These complications are rare, particularly with a skilled surgeon, but the more complex the face-lifts, the greater the risk.

Blepharoplasty. Blepharoplasty is the primary surgical procedure for eye lifts. Results usually last 5 -10 years. Although simple, it has potential complications, including permanent difficulty in closing the eyes or making a stern expression. Newer techniques, however, are preventing this complication. Assuming the surgeon is experienced, laser surgery is now preferred to the standard surgical scalpel approach. Laser surgery reduces bleeding and bruising, and both the operation and recovery are faster. Temporary blurred or double vision is common. More serious complications include infection, bleeding, dry eyes, difficulty in closing the eyes, and pulling down of the lower lids. Rare cases of blindness have been reported.

Transconjunctival Upper Blepharoplasty. An innovative procedure called transconjunctival upper blepharoplasty removes fat from the membrane that lines the eyelids (the conjunctiva) and is an effective technique for treating both the upper and lower eyelids. Unlike traditional blepharoplasty, this procedure does not cause scarring in the nasal area. In patients who have scars from previous surgeries, transconjunctival removal of fat can also make existing scars less obvious. Long-term side effects and effectiveness of this procedure have not been studied.

Laser Liposculpture and Platysma Resurfacing. A procedure called laser neck and jowl liposculpture and platysma resurfacing may prove to be an alternative to face-lifts. The procedure requires only a one-inch incision under the chin and removing excess fat. After the fat is removed, the surgeon tightens the platysma, the thin muscular sheet under the skin of the neck, which improves the shape of the neck. Only local anesthetic is needed, and the patient can return to normal activities in 2 days. The patient's skin should be elastic enough to be able to reform without sagging.

Resources

www.aad.org -- American Academy of Dermatology
www.asds.net -- American Society for Dermatologic Surgery
www.plasticsurgery.org -- American Society of Plastic and Reconstructive Surgeons
www.surgery.org -- American Society for Aesthetic Plastic Surgery
www.skincarephysicians.com/agingskinnet -- Aging Skin Net

References

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Review Date:
10/23/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

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