Nejm

new england journal of medicine
The
established in 1812

february 23, 2006

vol. 354

no. 8

Glucosamine, Chondroitin Sulfate, and the Two in Combination for Painful Knee Osteoarthritis
Daniel O. Clegg, M.D., Domenic J. Reda, Ph.D., Crystal L. Harris, Pharm.D., Marguerite A. Klein, M.S., James R. O’Dell, M.D., Michele M. Hooper, M.D., John D. Bradley, M.D., Clifton O. Bingham III,M.D., Michael H. Weisman, M.D., Christopher G. Jackson, M.D., Nancy E. Lane, M.D., John J. Cush, M.D., Larry W. Moreland, M.D., H. Ralph Schumacher, Jr., M.D., Chester V. Oddis, M.D., Frederick Wolfe, M.D., Jerry A. Molitor, M.D., David E. Yocum, M.D., Thomas J. Schnitzer, M.D., Daniel E. Furst, M.D., Allen D. Sawitzke, M.D., Helen Shi, M.S., Kenneth D. Brandt, M.D., Roland W. Moskowitz, M.D., and H.James Williams, M.D.

a bs t r ac t
Background

Glucosamine and chondroitin sulfate are used to treat osteoarthritis. The multicenter, double-blind, placebo- and celecoxib-controlled Glucosamine/chondroitin Arthritis Intervention Trial (GAIT) evaluated their efficacy and safety as a treatment for knee pain from osteoarthritis.
Methods

We randomly assigned 1583 patients with symptomaticknee osteoarthritis to receive 1500 mg of glucosamine daily, 1200 mg of chondroitin sulfate daily, both glucosamine and chondroitin sulfate, 200 mg of celecoxib daily, or placebo for 24 weeks. Up to 4000 mg of acetaminophen daily was allowed as rescue analgesia. Assignment was stratified according to the severity of knee pain (mild [N = 1229] vs. moderate to severe [N = 354]). The primary outcomemeasure was a 20 percent decrease in knee pain from baseline to week 24.
Results

The mean age of the patients was 59 years, and 64 percent were women. Overall, glucosamine and chondroitin sulfate were not significantly better than placebo in reducing knee pain by 20 percent. As compared with the rate of response to placebo (60.1 percent), the rate of response to glucosamine was 3.9 percentagepoints higher (P = 0.30), the rate of response to chondroitin sulfate was 5.3 percentage points higher (P = 0.17), and the rate of response to combined treatment was 6.5 percentage points higher (P = 0.09). The rate of response in the celecoxib control group was 10.0 percentage points higher than that in the placebo control group (P = 0.008). For patients with moderate-to-severe pain at baseline,the rate of response was significantly higher with combined therapy than with placebo (79.2 percent vs. 54.3 percent, P = 0.002). Adverse events were mild, infrequent, and evenly distributed among the groups.
Conclusions

Glucosamine and chondroitin sulfate alone or in combination did not reduce pain effectively in the overall group of patients with osteoarthritis of the knee. Exploratoryanalyses suggest that the combination of glucosamine and chondroitin sulfate may be effective in the subgroup of patients with moderate-to-severe knee pain. (ClinicalTrials.gov number, NCT00032890.)
n engl j med 354;8 www.nejm.org february 23, 2006

From the University of Utah School of Medicine, Salt Lake City (D.O.C., C.G.J., A.D.S., H.J.W.); the Hines Veterans Affairs Cooperative Studies ProgramCoordinating Center, Hines, Ill. (D.J.R., H.S.); the Clinical Research Pharmacy Coordinating Center, Albuquerque, N.M. (C.L.H.); the National Center for Complementary and Alternative Medicine, National Institutes of Health, Bethesda, Md. (M.A.K.); the University of Nebraska Medical Center, Omaha (J.R.O.); Case Western Reserve University, Cleveland (M.M.H., R.W.M.); the Indiana University School ofMedicine, Indianapolis (J.D.B., K.D.B.); the Hospital for Joint Diseases, Rheumatology and Medicine, New York (C.O.B.); Cedars-Sinai Medical Center, Los Angeles (M.H.W.); the University of California, San Francisco (N.E.L.); the Presbyterian Hospital of Dallas, Dallas (J.J.C.); the University of Alabama, Birmingham (L.W.M.); the Hospital of the University of Pennsylvania, Philadelphia (H.R.S.);...