Glucosamine for the Treatment of Osteoarthritis

Reginster et al (Lancet 357:251, 2001) conducted a double-blind, placebo-controlled trial to assess the long-term effects of glucosamine sulphate on the progression of structural damage and symptoms in 212 patients with primary knee osteoarthritis of the medial femorotibial compartment. This publication is a follow-up to an abstract presented at the 1999 American College of Rheumatology meeting.

Patients were randomly assigned to receive oral 1500 mg glucosamine sulphate or placebo once daily for 3 years. Radiographically-measured joint space width of the medial compartment of the knee was used as a surrogate measure of cartilage integrity, and the Western Ontario McMaster Arthritis Scale (WOMAC) was used to assess symptoms. Measurements were taken at baseline, 1, and 3 years.

The placebo group had statistically significantly greater joint space narrowing than the glucosamine group, whether analyzed by Intent-to-Treat or by Completer status. For the ITT analysis, placebo treated patients had a net loss of 0.31 mm (95% CI -0.48 to -0.13) of medial joint space, compared to 0.06 mm (95% CI -0.22 to -0.09) in the glucosamine treated group. 30% of patients randomized to placebo had severe mean joint-space narrowing (>0.5mm), compared to 15% of patients receiving glucosamine sulphate. The ITT analysis for the WOMAC demonstrated worsening symptoms in the placebo group (-11.7% [-20.3 to -3.2%]), whereas symptoms in the glucosamine group improved (9.8% [-6.2 to 25.8%]).

Editorial Comment: This study is one of the few in the medical literature to suggest that an agent – in this case, glucosamine sulphate – may slow the progression of OA. As such, it is welcome news since treatment of OA remains inadequate and largely targeted only to relief of symptoms.

There are several caveats to consider in this study, however. First, that preservation of joint space actually reflects preservation of cartilage has not been proven. Concomitant arthroscopic and/or MRI evaluations of cartilage before and after treatment are needed to clarify this putative correlation. Second, the amount of joint space loss during the study period is extremely small (0.3 mm over 3 years in the placebo group) and it is not clear whether this is clinically significant, although the increase in pain in the placebo group would suggest so. Third, knee xrays were done in fully extended views (the state-of-the-art at the time the study was initiated). Semi-flexed views with foot maps for standardization are the current state-of-the-art, and the validity of the current findings will need to be demonstrated according to this more rigorous radiographic method. Finally, glucosamine sulphate is not available in the U.S. and it is not clear whether other formulations of glucosamine will have similar efficacy.

Nonetheless, these data are exciting and perhaps call for more rigorous manufacturing and labeling standards for the multiple glucosamine preparations that are currently available on the neutraceutical shelves.