Glucosamine Sulfate Proves Beneficial in Slowing Progression of Knee OA
Pavelka, et. al. (Arch Intern Med 162:2113, 2002) recently published the results of a 3-year, randomized, placebo controlled clinical trial assessing the ability of glucosamine sulfate to slow structural damage in patients with knee osteoarthritis (OA).
Methods: 202 patients with mild to moderately severe primary knee OA of the medial femorotibial compartment were randomized to receive either oral glucosamine sulfate (1500mg daily) or placebo. Anteriorposterior, weight-bearing radiographs of the knee in the fully extended position were taken at baseline and 1, 2, and 3 years and assessed by 2 independent readers. Symptom severity was measured using the Lequesne and WOMAC indices. Patients with obesity (body mass index of >27), history of trauma to the knee joint, or other rheumatic diseases were excluded.
Results: The cumulative joint space narrowing at the end of 3 years [mean (95% confidence intervals) = 0.19mm (-0.29, 0.09) for the placebo group and 0.04mm (-0.06, 0.14) for the glucosamine sulfate group, P = .001. The Lequesne index scores improved substantially in the glucosamine sulfate group compared to the placebo group, [-1.7 (-2.2, 1.2) and -0.82 (-1.1, 0.51) respectively]. Adverse events were similar in both groups and most frequently included gastrointestinal symptoms, musculoskeletal pain, and cardiovascular events (increased blood pressure and recurrent episodes of preexisting ischemic heart disease). Consumption of acetaminophen, the only allowed rescue medication, did not vary significantly between the two groups.
Conclusion: These data confirm the results of a prior study by Reginster et. al. (read summary) whereby long-term treatment with glucosamine sulfate appears to slow the progression of structural damage to the joint in patients with knee osteoarthritis.
Editorial Comments: It is encouraging that the results of this trial are consistent with those of Reginster et. al. in a similarly designed trial. A weakness of both studies is the use of radiographs of the knee in the fully extended position. Knee pain may reduce the ability of patients to fully extend the knee. Because glucosamine has analgesic properties, it is possible that a decrease inpain over the course of the study may have enabled subjects to extend the knee more fully, thus creating artifactual increases (or less robust decreases) in joint space width over time. However, this method of knee xray was state-of-the-art at the time this study was begun. A glucosamine study utilizing a radiograph technique of semi-flexed knees is currently in progress in the U.S., and it will be interesting to see whether the results are identical to those of the prior two glucosamine trials.
Another flaw in the current study of Pavelka et. al. is the exclusion of obese patients. Obesity is a risk factor for incedent, as well as progressive, knee OA. Therefore, it is essential to evaluate the efficacy of glucosamine in these patients as well.