There are a sufficient number of short-term studies with these agents suggesting efficacy equal to that seen in the symptomatic treatment of OA using
NSAIDs. Two recent meta-analyses by McAlindon and colleagues and Towheed et al reviewed clinical trials of
glucosamine and
chondroitin in the treatment of
osteoarthritis. The study by McAlindon and co-workers included all double-blind placebo-controlled trials of greater than 4 weeks' duration, testing oral or parenteral
glucosamine or
chondroitin for treatment of hip or
knee osteoarthritis. Thirteen trials (six with
glucosamine, seven with
chondroitin) met eligibility criteria. The authors used global
pain score or the Lequesne index in the index joint as the primary outcome measure and considered the trial positive if improvement in the treatment group was equal to or greater than 25% compared with the placebo group, and was significant (P < or = .05). All 13 studies reviewed were classified as positive, demonstrating large effects, compared with placebo (39.5% [S.D. 21.9] for
glucosamine, 40.2% [S.D. 6.4] for
chondroitin). The authors concluded that clinical trials of these two agents showed substantial benefit in the treatment of
osteoarthritis but provided insufficient information about study design and conduct to allow definitive evaluation. Towheed and colleagues reviewed nine randomized, controlled trials of
glucosamine sulfate in
osteoarthritis. In seven of the randomized controlled trials, in which they compared
glucosamine with placebo,
glucosamine was always superior. In two randomized controlled trials comparing
glucosamine to
ibuprofen,
glucosamine was superior in one and equivalent in one. Methodologic problems, including lack of standardized case definition of
osteoarthritis and lack of standardized outcome assessment led the authors to conclude that further studies are needed to determine if route of administration is important and whether the
therapeutic effect is site specific. A meta-analysis of
chondroitin sulfate trials has also been published. Of the 12 published trials, 4 randomized double-blind placebo or
NSAID-controlled trials with 227 patients on
chondroitin sulfate were entered into the analysis. All four studies showed
chondroitin sulfate to be superior to placebo, with respect to Lequesne index, visual analog scale for
pain and medication consumption. Significant changes (P < or = .05) were seen in those treated from day 60 to the study endpoints (150 to 180 days). Pooled data demonstrated at least 50% improvement in the study variables in the
chondroitin treated group. Discrepancies in some of the study findings reported in the literature may relate to the composition of the nutritional supplements used. Studies in the United States have revealed that a number of preparations claiming to contain certain doses of
glucosamine or
chondroitin sulfate have significantly less (or none) of the dosages described. Accordingly, it is essential that studies performed with these agents use preparations that are carefully defined in manufacture. The amounts generally administered are
glucosamine, 1500 mg, and
chondroitin sulfate, 1200 mg, daily. Although
glucosamine has been described as effective when used alone, it is probably reasonable to use the combination pending further studies. The average cost is approximately $30 to $45 per month. In the interim, what should physicians tell their patients when they ask whether these agents are effective, or whether they should or should not take them? The authors emphasize that these agents are not FDA-evaluated or recommended for the treatment of OA. They are available as health food supplements, and the number of studies of toxicity, particularly with respect to long-term evaluations, is limited. The pros and cons of these agents and the published data are described so that patients can make a reasonably informed decision as to whether they wish to proceed with use of these agents in
therapy. (ABSTRACT TRUNCATED)