The meta-analysis led by Stephan Reichenbach from the University of Bern, Bern, Switzerland and colleagues involves 20 trials of 3846 patients. The trials included in the analysis are only those that were randomized or quasi-randomized, controlled trials that compared chondroitin with placebo or with no treatment in patients with osteoarthritis of the knee or hip.

Chondroitin is a glycosaminoglycan (GAG) composed of a chain of alternating sugars (N-acetylgalactosamine and glucuronic acid).   In the United States, an estimated 21 million of men and women suffer osteoarthritis.   Chondroitin and glucosamine is the common formula used by osteoarthritis patients because the efficacy of conventional treatments is limited and poor.

Osteoarthritis, a common form of arthritis, is a joint disease that mostly affects cartilage, which is the slippery tissue covering the ends of bones in a joint.   People with osteoarthritis often have joint pain and reduced motion.   Conventional treatments aim to relieve pain and stiffness while chondroitin is believed to repair the damaged cartilage.

The researchers say in their report that the 20 trials used for the analysis "revealed a high degree of heterogeneity,” indicating that the meta-analysis is difficult and the result that chondroitin is ineffective at treating osteoarthritis may not be as reliable as desired.

Reichenbach and colleagues write that "Small trials, trials with unclear concealment of allocation, and trials that were not analyzed according to the intention-to-treat principle showed larger effects in favor of chondroitin than did the remaining trials."

Their conclusion that use of chondroitin was no more effective than use of placebo at treating osteoarthritis is based on analysis of only three trials with large sample sizes and an intention-to-treat analysis, which included about 1500 patients.

The authors conclude that large-scale, methodologically sound trials indicate that the benefit of chondroitin is minimal or nonexistent.   They say use of chondroitin in routine clinical practice should be discouraged.   But they also acknowledge that for 9 trials, they had to use approximations to calculate the effect and low trial quality and heterogeneity among the trials made interpretation of results difficult.

In response, the Natural Products Association, an industry group, was quoted by the New York Times as saying: “Clearly, research has demonstrated that chondroitin, especially when taken with glucosamine, has shown a benefit for those suffering from osteoarthritis. To discourage its use as a treatment option is ill-considered, particularly when the alternatives are limited or nonexistent.”

Experts caution that the current analysis is based on results of trials on chondroitin, which may not be applicable to the formula commonly used in the US.   In the U.S., chondroitin is always sold together with glucosamine for treatment of osteoarthritis.  

Chondroitin and glucosamine as a supplement has become so popular in the U.S. that it prompted the government to fund a 4-year study to determine the efficacy of chondroitin and glucosamine on osteoarthritis.

The study included a total of 1,583 people aged 40 or older with knee pain and documented x-ray evidence of osteoarthritis. Participants were about 59 years of age, on average, and nearly two-thirds of participants were women. Of the 1,583 participants, 1,229 or 78 percent experienced mild pain and 354 or 22 percent experienced moderate-to-severe pain.

The study published in a Feb. 2006 issue of in the New England Journal of Medicine found the following cited from http://nccam.nih.gov/research/results/gait/qa.htm
 

    * Participants taking the positive control, celecoxib, experienced statistically significant pain relief versus placebo--about 70 percent of those taking celecoxib had a 20 percent or greater reduction in pain versus about 60 percent for placebo.   

 * Overall, there were no significant differences between the other treatments tested and placebo.

* For a subset of participants with moderate-to-severe pain, glucosamine combined with chondroitin sulfate provided statistically significant pain relief compared to placebo--about 79 percent had a 20 percent or greater reduction in pain versus about 54 percent for placebo. According to the researchers, because of the small size of this subgroup these findings should be considered preliminary and need to be confirmed in further studies.

    * For participants in the mild pain subset, glucosamine and chondroitin sulfate together or alone did not provide statistically significant pain relief.

Researchers led by rheumatologist Daniel O. Clegg, M.D., of the University of Utah, School of Medicine, Salt Lake City, conducted the study known as the Glucosamine/chondroitin Arthritis Intervention Trial (GAIT) at 16 sites across the United States.   That study was funded by the National Center for Complementary and Alternative Medicine (NCCAM) and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), components of the National Institutes of Health (NIH).

In an accompanying editorial, David T. Felson, MD, MPH, from Boston University School of Medicine, whose research grants came from both the National Institutes of Health and Merck & Co. writes that chondroitin is unlikely to have an effect on osteoarthritis, but he says that patients should not be discouraged from using it if they find it helpful.

"Because no frequent or severe adverse effects have been reported, chondroitin sulfate should not be considered dangerous. If patients say that they benefit from chondroitin, I see no harm in encouraging them to continue taking it as long as they perceive a benefit," he writes.

Regardless of what researchers found, at least 7 million of American men and women take chondroitin, alone or combined with other supplements, for joint pain, ABC News cited current industry figures as suggesting.   A scientist affiliated with foodconsumer.org comments that the huge number of patients who use the supplement suggests that this supplement may have an effect on osteoarthritis.

Experts suggest that patients may try chondroitin, which has no reported side-effects, for four to six weeks before going to receive conventional treatments, which are known to have a limited and poor therapeutic effect on osteoarthritis while adverse effects are common.

For more information on osteoarthritis, read http://www.niams.nih.gov/hi/topics/arthritis/oahandout.htm.

For more information on chondroitin/glucosamine, read http://nccam.nih.gov/research/results/gait/qa.htm

For the editorial accompanying the study report, read http://www.annals.org/cgi/content/full/146/8/611

For more details on the meta-analysis, read http://www.annals.org/cgi/content/abstract/146/8/580