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
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
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
John J. Cush, MD, and Robert
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