Osteoarthritis Treatment - Glucosamine/Chondroitin Sulfate
Abstract 1975 Glucosamine Sulfate Significantly Reduces Progression of Knee Osteoarthritis Over 3 Years
Reginster, Deroisy, Paul, Lee, et al.
Glucosamine sulfate is a component of normal human cartilage. It is sold in the U.S. as a nutritional supplement but is approved in Europe as a drug. This study investigated the potential for prolonged administration of glucosamine to slow progression of OA of the knee. 212 patients with knee OA were randomized to receive either placebo (n=106) or 1.5 gm of daily glucosamine sulfate (n=106) for 3 years. Disease progression was assessed by measurement of joint space width obtained by extended view standing knee xrays. The average joint space width at study entry was 5 mm. The two groups were comparable for demographics and disease characteristics at baseline.
The placebo group had a statistically significantly higher rate of joint space narrowing than the glucosamine group, whether analyzed by Intent-to-Treat or by Completer status. For the ITT analysis, placebo patients demonstrated 0.24 mm loss of joint space, while the glucosamine group had an increase in joint space width of 0.12 mm. The percent of patients who had joint space narrowing greater than 0.5 mm after 3 years was 38% in the placebo group, but only 22% of the glucosamine group (p .044). HAQ scores and WOMAC scores were also statistically significantly better in the glucosamine group compared to placebo.
Editorial Comment: This is the first study that claims to demonstrate a disease modifying effect of a drug for OA (as measured in the knee). Some caution is recommended in interpreting these data, however. This study was performed before the reproducibility of serial knee xrays was worked out. Current recommendation for long-term studies of knee OA in the U.S. require standing view of the knees but in a semi-flexed position, preferably with fluroscopic positioning, and using an individualized foot map for each patient. These results will have to be confirmed in another trial(s) using this rigorously validated technique. Nonetheless, they are encouraging since no disease modifying agent for OA currently exists.
Abstract 1111 Beneficial Effect of Cartilage Disease-Modifying Agents Tested in Chondrocyte Cultures and a Rabbit Instability Model of Osteoarthritis
L Lippiello, J Woodward, R Karpman, T Hammad Phoenix, AZ, Edgewood, MD
Using rabbit instability model of osteoarthritis, Hammad etal compared the dietary supplements to retard the progression of cartilage lesions. Surgical instability (Hulth) was induced in 36 (2-3 Kg) NZW rabbits. Following surgery, rabbits were divided into four groups; (1) 12 (controls) were fed a standard diet of Teklad, (2) 12 were fed 2% by weight *Cosamin DS, (3) & (4) 6 each were fed comparable levels of chondroitin sulfate or glucosamine HCL, respectively. Animals were exercised for one hour, 3 times per week, sacrificed at 16 weeks, and the weight-bearing portion of the medial condyles quantitatively assessed with a modified Mankin grading system using Safranin-O staining. Lesions were grouped as mild (1-3), moderate (4-7), or severe (>8).
The Cosamin DS® fed rabbits had no severe lesions and a significant reduction in moderate lesions (p<0.003) compared to controls. Groups 3 & 4 receiving monotherapy demonstrated fewer severe and moderate lesions than the control group, although to a lesser extent than the combination therapy. A combination of glucosamine HCL and low molecular weight chondroitin sulfate had a synergistic effect in stimulating proteoglycan synthesis. Necropsy showed no apparent organ pathology.
*Cosamin DS® is a combination glucosamine HCL and low molecular weight chondroitin sulfate.
Editorial Comment: This study is one of the few that have examined the combination of glucosamine and chondroitin sulfate and that examined a disease modification outcome. These results are encouraging but will need to be verified in humans since this model is an artificial way of inducing OA.