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New Data on Glucosamine and Chondroitin Sulfate

A recent article in the Journal of the American Medical Association (JAMA 283:1469-75, 2000) by Timothy McAlindon, MD, MPH, MRCP, and colleagues from The Arthritis Center at Boston University School of Medicine concluded that trials of glucosamine and chondroitin preparations for osteoarthritis (OA) demonstrated positive effects, variably ranging from moderate to large. They voiced concerns, however, regarding the validity of such conclusions based on methodological flaws in a number of the studies and possible publication bias. With respect to methodological flaws, the main concerns were inadequate concealment of drug allocation, which affects blinding, and the absence of intent-to-treat analyses. Publication bias concerns were related to sponsorship support, and selective publication of positive trials. Despite these caveats, the authors concluded that some degree of efficacy with respect to symptomatic relief in OA appeared probable for these preparations.

These findings are in concert with conclusions in previous reviews of the use of these agents in OA. It is of interest that the authors found suggestive improvement in their meta-analysis, utilizing studies as short as four weeks' duration. Several studies of four to six months' duration have demonstrated that the efficacy differences between active agent and placebo may be greater than represented in their meta-analysis study.

A recent carefully performed study by Jean-Yves Reginster, MD, PhD, and colleagues in Belgium and presented at the ACR's 63rd Annual Scientific Meeting suggested that glucosamine, in a dose of 1500 mg daily for three years, had a structure-modifying effect on OA of the knee. Glucosamine-treated patients had an increase in joint space, contrasted with loss of joint space in the placebo-treated group. Such structure modification would of course be very exciting, particularly with an agent that appears to have low toxicity. The study has caveats, however, with respect to the radiographic technique used. Although the x-ray methodology was state-of-the-art at the time the study was initiated, more precise reproducible techniques are now available. Small changes in knee position at time of x-ray as utilized may have led to significant differences in apparent joint width. Variations in reproducibility of radiologic findings may have been further accentuated in patients taking glucosamine, who, in the presence of decreased pain, were able to more fully extend their knee, altering the apparent joint space measurement.

The National Institute of Arthritis and Musculoskeletal and Skin Diseases, in collaboration with the National Center for Complementary and Alternative Medicine, has initiated what should be a pivotal study evaluating the symptom-relieving and structure modification effects of these agents. This study, comparing glucosamine, chondroitin sulfate, a mixture of the two agents, a positive NSAID control and placebo, will evaluate symptomatic responses (pain and function) and joint space cartilage structural responses.

Although the mood of the rheumatologic community several years ago was generally skeptical regarding the use of glucosamine and chondroitin sulfate, careful review of studies now suggests that these agents may be of value in the symptomatic treatment of OA. These therapies are not without risk. Glucosamine should not be taken in those with allergy to shellfish, coumadin levels maybe affected by chondroitin sulfate, and recent reports have shown that glucosamine might raise blood insulin levels in diabetics. Since these agents do not fall under the FDA approval process, the rigor of the investigations and claims cited should be carefully scrutinized. Nonetheless, based on the data we now have, it appears not unreasonable for physicians to concur in the use of glucosamine and chondroitin sulfate for OA, after discussing that unknowns remain regarding the efficacy, tolerability, and toxicity of these agents.

July 28, 2000
Roland W. Moskowitz, MD
Contributing author

John J. Cush, MD, and Robert Spiera, MD
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