Glucosamine and CS
The highly publicized Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT) was published in the New England Journal of Medicine early in 2006 (Table 4).31 The multicenter trial assigned 1,583 patients to randomly receive 1,500 mg glucosamine; 1,200 mg CS; both GH and CS; 200 mg of celecoxib (Celebrex; Pfizer, New York, NY); or placebo for 24 weeks. Patients were allowed to take up to 4,000 mg of acetaminophen for rescue analgesia daily (no pain medications were taken within 24 hours of clinical examination). All patients in the study were aged at least 40 years, had both clinical evidence (knee pain for most days of the month for ≥6 months) and radiographic evidence of OA (osteophytes ≥1 mm), and WOMAC scores from 125 to 400. The primary outcome measure was a 20% decrease in the summed score for the WOMAC pain subscale from baseline to week 24. Over 40 secondary outcome measures were included in the study
In the subgroup of 79 patients with moderate to severe pain (determined by a score of 300-400 on the WOMAC pain scale), GH and CS significantly reduced knee pain. In this subgroup of patients receiving GH and CS, 79% showed a 20% reduction in knee pain, whereas only 54.3% of the placebo group showed this improvement. However, GH and CS were not found to be significantly better than placebo in reducing knee pain by 20% from baseline in the pooled analysis of patients. Adverse effects were mild, infrequent, and evenly distributed across all groups tested, supporting the safety of these nutritional supplements.
Celecoxib was found to yield a statistically significant decrease in pain scores in the combined mild pain and moderate/severe pain subgroups but failed to have a significant effect on the pain scores in the moderate/severe pain subgroup. Celecoxib was also found to yield a faster decrease in pain scores, showing substantial decreases in pain scores at 4 weeks of treatment. Overall, celecoxib was found to have a significant effect on 6 of the 42 outcome measures followed in the study, whereas glucosamine and CS were found to have a significant effect on 14 of the 42 outcome measures.
This study, the largest and most rigorous of its kind, showed that GH and CS had a significant effect on patients with more severe OA. Questions remain about the usefulness of glucosamine and CS in mild OA and their effect on other parameters such as joint function, stiffness, and joint space narrowing. Limitations of the study noted by the authors were the high rate of response to placebo (60%) and the relatively mild degree of OA pain among the participants. Concomitant treatments, such as physical therapy, were not clarified. These limitations decreased the ability of the study to detect the benefits of treatment. Studies with alternative medical therapies have shown a higher placebo response rate.32 Celecoxib at 200 mg/d had noticeably smaller effects in the GAIT study compared with earlier studies.
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