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Osteoarthritis

From the Journal Arthritis & Rheumatism Volume 58 Issue 10, Pages 3183 - 3191

The effect of glucosamine and/or chondroitin sulfate on the progression of knee osteoarthritis: A report from the glucosamine/chondroitin arthritis intervention trial

Allen D. Sawitzke 1 *, Helen Shi 2, Martha F. Finco 1, Dorothy D. Dunlop 3, Clifton O. Bingham III 4, Crystal L. Harris 5, Nora G. Singer 6§, John D. Bradley 7, David Silver 8, Christopher G. Jackson 1, Nancy E. Lane 9, Chester V. Oddis 10, Fred Wolfe 11, Jeffrey Lisse 12, Daniel E. Furst 13, Domenic J. Reda 2, Roland W. Moskowitz 6¶, H. James Williams 1, Daniel O. Clegg 1||

1University of Utah School of Medicine, Salt Lake City
2Hines VA Cooperative Studies Program Coordinating Center, Hines, Illinois
3Northwestern University Feinberg School of Medicine, Chicago, Illinois
4Johns Hopkins University, Baltimore, Maryland
5Albuquerque VA Cooperative Studies Program Clinical Research Pharmacy Coordinating Center, Albuquerque, New Mexico
6Case Western Reserve University, Cleveland, Ohio
7Indiana University, Indianapolis
8Cedars Sinai Medical Center, Los Angeles, California
9University of California, Davis, Sacramento
10University of Pittsburgh, Pittsburgh, Pennsylvania
11Arthritis Research Center, Wichita, Kansas
12University of Arizona, Tucson
13University of California, Los Angeles

*Correspondence to Allen D. Sawitzke, University of Utah School of Medicine, 30E 1900 S SOM 4B200, Salt Lake City, UT 84132

ClinicalTrials.gov identifier: NCT00032890.
Dr. Bingham has received consulting fees from Merck and McNeil (less than $10,000 each).
§Dr. Singer has received consulting fees, speaking fees, and/or honoraria from Bristol-Myers Squibb (less than $10,000) and from Abbott Immunology (more than $10,000); she has received grants and/or contracts through the University of California, Davis from the Alliance for Lupus Research, Pfizer, Merck, Endo, Zymogenetics, Serono, Genentech, Amgen, and Roche.
¶Dr. Moskowitz has received speaking fees and honoraria from Bioiberica (more than $10,000).
||Dr. Clegg has received consulting fees, speaking fees, and/or honoraria from Bioiberica (less than $10,000), and has received grants and contracts through the University of Utah from Bioiberica.
setDOI("ADOI=10.1002/art.23973")

Funded by:
NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases and National Center for Complementary and Alternative Medicine); Grant Number: N01-AR-2236

Abstract


Objective

Osteoarthritis (OA) of the knee causes significant morbidity and current medical treatment is limited to symptom relief, while therapies able to slow structural damage remain elusive. This study was undertaken to evaluate the effect of glucosamine and chondroitin sulfate (CS), alone or in combination, as well as celecoxib and placebo on progressive loss of joint space width (JSW) in patients with knee OA.


Methods

A 24-month, double-blind, placebo-controlled study, conducted at 9 sites in the United States as part of the Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT), enrolled 572 patients with knee OA who satisfied radiographic criteria (Kellgren/Lawrence [K/L] grade 2 or grade 3 changes and JSW of at least 2 mm at baseline). Patients with primarily lateral compartment narrowing at any time point were excluded. Patients who had been randomized to 1 of the 5 groups in the GAIT continued to receive glucosamine 500 mg 3 times daily, CS 400 mg 3 times daily, the combination of glucosamine and CS, celecoxib 200 mg daily, or placebo over 24 months. The minimum medial tibiofemoral JSW was measured at baseline, 12 months, and 24 months. The primary outcome measure was the mean change in JSW from baseline.


Results

The mean JSW loss at 2 years in knees with OA in the placebo group, adjusted for design and clinical factors, was 0.166 mm. No statistically significant difference in mean JSW loss was observed in any treatment group compared with the placebo group. Treatment effects on K/L grade 2 knees, but not on K/L grade 3 knees, showed a trend toward improvement relative to the placebo group. The power of the study was diminished by the limited sample size, variance of JSW measurement, and a smaller than expected loss in JSW.


Conclusion

At 2 years, no treatment achieved a predefined threshold of clinically important difference in JSW loss as compared with placebo. However, knees with K/L grade 2 radiographic OA appeared to have the greatest potential for modification by these treatments.


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