BACKGROUND: Osteoarthritis is a major problem in primary care, but its optimal management is unclear. Nonsteroidal anti-inflammatory drugs (NSAIDs), analgesics, and intra-articular corticosteroids have significant toxicity and do not alter disease progression; thus, many patients have turned to glucosamine and chondroitin.
POPULATION STUDIED: The authors of this meta-analysis reviewed 15 randomized double-blind placebo-controlled trials of glucosamine and chondroitin (both together and separately) for patients with osteoarthritis of the knee or hip. Trials were included if they were longer than 4 weeks in duration and used an accepted osteoarthritis outcome measure. A total of 1710 patients were enrolled; no information was provided on age, sex, severity of osteoarthritis, or other treatments, making generalizability to a typical family practice difficult.
STUDY DESIGN AND VALIDITY: The authors’ search included MEDLINE, the Cochrane Controlled Trials Registry, rheumatology meeting abstracts, citation lists from review articles, and consultation with experts. Two trained reviewers independently examined outcomes, quality, and financial sponsorship of the articles. Disagreements were resolved by discussion. A pooled effect size was calculated by dividing the difference in mean outcomes between treatment group and control group by the standard deviation of the outcome value in the control group. The resulting effect measure combines pain outcomes with disability outcomes. Publication bias was addressed by funnel plots and regression of effects on the inverse of study variance.
OUTCOMES MEASURED: The primary outcome measured was improvement in symptoms at 4 weeks, measured by either a pain scale or a disability index. The article did not address other outcomes important for osteoarthritis, such as quality of life, cost, side effects, or radiographic progression of osteoarthritis.
RESULTS: Interrater reliability of the reviewers was excellent. The quality of the available studies was relatively poor, with only 2 employing intention-to-treat analysis. None of the studies reported independent funding from a governmental or not-for-profit organization, and there was evidence of a publication bias toward positive trials. Glucosamine showed an effect size of 0.44 (95% confidence interval [CI], 0.24-0.64), and chondroitin had an effect size of 0.96 (95% CI, 0.63-1.3). An effect size of 0 indicates equivalency with placebo, with less than 0.2 indicating a small effect, 0.2 to 0.8 a moderate effect, and greater than 0.8 a large effect. The studies were heterogenous; one trial with chondroitin seemed to be significantly different from the others. Excluding that trial weakened but did not eliminate the pooled effect of chondroitin. Shorter duration of treatment was associated with a lower effect size. Poorer-quality studies showed a larger effect than better-quality studies.
The authors of this meta-analysis provide weak evidence that glucosamine and chondroitin are more efficacious than placebo in reducing pain or disability from osteoarthritis, but this finding is limited by the lack of information about clinical characteristics of the patients, details of treatments employed, and the poor quality of the literature. Upcoming National Institutes of Health trials may better delineate some of these issues. However, in the absence of good-quality information, clinicians should consider prescribing glucosamine and chondroitin in view of the apparent safety1 of these agents and the toxicity and incomplete effectiveness associated with standard therapies for osteoarthritis.