Glucosamine and/or chondroitin may not be helpful for patients with osteoarthritis of the hip or knee, according to the results of a network meta-analysis reported in the September 17 issue of the BMJ.

“Osteoarthritis of the hip or knee is a chronic condition mostly treated with analgesics and non-steroidal anti-inflammatory drugs, but these drugs can cause serious gastrointestinal and cardiovascular adverse events, especially with long term use,” write Simon Wandel, from the University of Bern in Bern, Switzerland, and colleagues. “Disease modifying agents that not only reduce joint pain but also slow the progression of the condition would be desirable. Throughout the world for the past 10 years, the cartilage constituents chondroitin and glucosamine have been increasingly recommended in guidelines, prescribed by general practitioners and rheumatologists, and used by patients as over the counter medications to modify the clinical and radiological course of the condition.”

The goal of the study was to assess the impact of supplementation with glucosamine and/or chondroitin on joint pain and on radiologic progression in patients with osteoarthritis of the hip or knee. Using a Bayesian model allowing synthesis of multiple time points, the investigators combined direct comparisons within trials with indirect evidence from other trials. The primary study endpoint was pain intensity, and change in minimal width of the joint space was the secondary endpoint. When a 10-cm visual analog scale was used, the prespecified, minimal clinically important difference between preparations and placebo was −0.9 cm.

The investigators searched electronic databases and conference proceedings from their beginnings to June 2009, and they also contacted appropriate experts and searched relevant Web sites. Inclusion criteria were large-scale, randomized controlled trials enrolling more than 200 patients with knee or hip osteoarthritis and comparing glucosamine, chondroitin, or their combination vs placebo or head to head.

Ten trials meeting eligibility criteria were identified, enrolling a total of 3803 patients. The overall difference in pain intensity vs placebo was −0.4 cm (95% credible interval, −0.7 to −0.1 cm) on the 10-cm visual analog scale for glucosamine, −0.3 cm (95% credible interval, −0.7 to 0.0 cm) for chondroitin, and −0.5 cm (95% credible interval, −0.9 to 0.0 cm) for the combination. The 95% credible intervals crossed the boundary of the prespecified, minimal clinically important difference for none of the estimates. Compared with commercially funded trials, industry-independent trials showed smaller effects (P = .02 for interaction).

For changes in minimal width of joint space, the differences were all very small, with 95% credible intervals overlapping zero.

“Compared with placebo, glucosamine, chondroitin, and their combination do not reduce joint pain or have an impact on narrowing of joint space,” the study authors write. “Health authorities and health insurers should not cover the costs of these preparations, and new prescriptions to patients who have not received treatment should be discouraged.”

Study Limitations

Limitations of this study include use of different instruments to measure joint pain, which made it necessary to calculate effect sizes as a common measure of effectiveness so that outcomes assessed with different instruments would be comparable. Differences in responsiveness of different instruments could potentially threaten the validity of results. In addition, many patients included in the trials may have had radiologic disease too severe to benefit from supplementation or pain too minimal to benefit from analgesic effects.


“Our findings indicate that glucosamine, chondroitin, and their combination do not result in a relevant reduction of joint pain nor affect joint space narrowing compared with placebo,” the study authors note. “Some patients, however, are convinced that these preparations are beneficial, which might be because of the natural course of osteoarthritis, regression to the mean, or the placebo effect.”

“We are confident that neither of the preparations is dangerous,” the study authors conclude. “Therefore, we see no harm in having patients continue these preparations as long as they perceive a benefit and cover the costs of treatment themselves.”

The Swiss National Science Foundation’s National Research Program 53 on musculoskeletal health supported this study. Some of the study authors were supported by the Swiss National Science Foundation and/or the Janggen-Poehn-Foundation. The other study authors have disclosed no relevant financial relationships.

BMJ. 2010;341:c4675.

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