Reichenbach et al.39 performed a meta-analysis of CS for OA of the knee or hip in 20 trials involving 3,846 patients. After analyzing the small and large studies, they found the trial quality to generally be low. They concluded that with the large-scale, methodologically sound trials, CS had minimal to nonexistent symptomatic benefit. They discouraged CS use by itself in routine clinical practice.
Leeb et al.40 performed a meta-analysis of 7 trials of CS including 372 patients. They cited the difficulties in design with co-mixing of medications in several studies using the visual analog scale and Lequesne's index. The findings in the CS groups were significantly superior to those in the placebo groups. They called for better and longer time periods for symptom-modifying evaluations.
The Cochrane Review is perhaps the most thorough of the meta-analyses performed on glucosamine's effect on OA.41 Updated in January 2005, this meta-analysis followed 3 selection criteria: they were RCTs, they were either placebo controlled or comparative, and they were blinded (single or double were both accepted). Twenty articles were found to meet the selection criteria, representing 2,570 patients. Cumulatively, these articles showed that glucosamine induced a 28% improvement from baseline in pain and a 21% improvement in function by use of Lequesne's index. In 8 articles that showed adequate allocation concealment, glucosamine failed to show a benefit for either pain or function. The Cochrane Review confirmed the safety findings of the incorporated studies, finding glucosamine to have adverse events equal to the placebo. Although these conclusions were significant for the number of studies they incorporate, they did have their limitations. This review was designed to include a broad selection of clinical trials, accepting short-term studies, comparative control studies, and single-blind studies. In accepting these lower-quality articles, the power of the pooled results was negatively impacted.
Other Sulfur-Containing Compounds
S-adenosylmethionine (SAMe) and methylsulfonylmethane (MSM) are market leaders among the sulfur-containing compounds advertised for joint health. Despite the public interest in these compounds, few well-designed studies have been completed. An open-label study in 1987 showed that SAMe increased joint mobility with no evaluation of pain or function.42 Subsequent double-blind placebo-controlled studies have supported the use of SAMe and shown it was effective as many anti-inflammatory and pain-relieving drugs.[43], [44] and [45]
In 2004 Najm et al.46 compared the efficacy of SAMe with Celebrex (Pfizer) for the symptoms of OA. In the first month of their 4-month study, celecoxib showed significantly more reduction in subjective pain reports by the participants (P = .024). By the second month, both study arms were equally effective in reducing pain (P < .01). This study noted increased functional health measures and increasing joint mobility in both treatment groups, without significant differences in side effects. These trends were not shown to be statistically significant.
Despite the presence of several studies suggesting the efficacy of MSM in reducing joint pain and enhancing mobility,[47] and [48] the literature on MSM is deficient. With a paucity of research, as well as the short length of follow-up, it is difficult to recommend MSM at this time as an efficacious therapy for OA. Kim et al.49 showed significant decreases in WOMAC pain (decrease of 25% from baseline) and physical function subcategories with MSM versus placebo. Improved performance of MSM users was seen in activities of daily life as measured by the Short Form 36 score (P = .05), but this study found no significant improvement in the total aggregate WOMAC score at 3 months.
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