Class Act: Is there clinical evidence for the use of chondroitin sulfate in the treatment of osteoarthritis?

October 17, 2008

images1.jpgClass act is a feature of Clinical Correlations written by NYU 3rd and 4th year medical students. Prior to publication, each commentary is thoroughly reviewed for content by a faculty member.

Commentary by Jillian Borman, MS-4, Reviewed by Svetlana Krasnokutsky, MD, Clinical Instructor, NYU Department of Medicine

Osteoarthritis (OA) is one of the most common causes of joint pain in the aging population. The pain of OA, which is generally worsened with joint use and alleviated with rest, is typically described as a deep ache localized to the affected joint. (1) Using the National Health and Nutrition Examination Survey I (NHANES I) and the 2005 population estimates from the Census Bureau, it has been estimated that 26.9 million adults over the age of 25 years are afflicted with clinical OA of at least one joint. This estimate is up from the 1995 estimate of 21 million.(2) The prevalence of osteoarthritis in the United States will likely continue to rise due to the aging population and the fact that people are living longer than ever before.

While there are a variety of options for symptomatic treatment, which range from weight loss and non-steroidal anti-inflammatory drugs (NSAIDs) to glucocorticoid injections and total joint replacement, not all patients are helped by these treatments. Recently many patients have turned to chondroitin sulfate, a widely available dietary supplement, which is currently not approved by the U.S. Food and Drug Administration for use in OA. Chondroitin sulfate, the predominant glycosaminoglycan found in articular cartilage, allows the cartilage to withstand tensile stresses during loading conditions. In vitro, chondroitin sulfate acts as a competitive inhibitor to prevent enzymes from degrading the cartilage, increases proteoglycan production, and counters the destructive effect of interleukin 1ß.(3) Administration of chondroitin sulfate exogenously is thought to have an anti-inflammatory effect, though its efficacy in the treatment of OA remains controversial due to the lack of consistent findings among reliable scientific studies.(4)

In 2006, the New England Journal of Medicine published the results of a randomized, multicenter, double blind, placebo-controlled trial that studied the efficacy of chondroitin sulfate in the treatment of OA. The study included more than 1,500 participants with symptomatic knee osteoarthritis with a primary outcome measure of a 20 percent decrease in knee pain at 6 months. The investigators found that the rate of response to chondroitin sulfate was not significantly higher than the rate of response to placebo in the analysis of the primary outcome. However, participants using chondroitin sulfate had a significant decrease in the incidence of joint swelling, effusion, or both. Furthermore, in a subgroup of patients with moderate to severe knee pain, results for the primary outcome demonstrated that when chondroitin sulfate was used with glucosamine, the combination was significantly more effective than placebo.(5)

The Annals of the Rheumatic Diseases published the results of another randomized, multicenter, double-blind, placebo-controlled study in 2007 that included over 300 patients with symptomatic knee osteoarthritis. The primary outcome measures used by these investigators were the mean variation of pain on activity and the mean variation of Lequesne’s Index Score at the end of the 6 months of treatment compared with the score at inclusion. Lequesne’s Index Score allows patients to score pain or discomfort, stiffness, difficulty performing daily activities, and their maximum walking capacity. The results failed to show that chondroitin sulfate was effective on the two primary outcome measures, though it was slightly more effective than placebo on quality of life.(6)

A 2007 meta-analysis examined the effects of chondroitin sulfate in 20 randomized or quasi-randomized trials of 3846 patients with knee or hip OA.(7) When all 20 trials, which had a high degree of heterogeneity, were evaluated, chondroitin was statistically significantly more effective than placebo in terms of pain relief (patients were also allowed other analgesics/anti-inflammatory medications). However, when only the studies that used an intention-to-treat analysis were examined (3 largest studies, 1553 subjects), chondroitin had no effect on symptoms. Effects of chondroitin on the rate of cartilage loss have also been examined in some of the studies comprising this meta-analysis. The chondroitin-treated groups had statistically significantly less radiographic joint space narrowing compared with placebo groups in combined results from five trials. The effects, however, were small and of uncertain clinical significance.

In summary, chondroitin sulfate should not be a first-line therapy for OA at this juncture, but may be considered in patients with moderate–to-severe disease who have failed other treatments. Patients should also be advised that when chondroitin sulfate is used in combination with glucosamine, its efficacy may be improved. The current evidence for treating OA with chondroitin sulfate continues to be limited and further research needs to be completed, though it appears that any possible benefit will be small.

References:

1. Brandt KD. Osteoarthritis. In:Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL. Harrison’s Principles of Internal Medicine, 16th ed. New York, NY: McGraw-Hill; 2005:2036-2045.

2. Lawrence RC, Felson DT, Helmick CG, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis Rheum 2008;58:26-35.

3. Fioravanti A, Collodel G. In vitro effects of chondroitin sulfate. Adv Pharmacol 2006; 53:449-465.

4. Toshihiko T, Sakai S, Akiyama H, Linhardt RJ. Immunological activity of chondroitin sulfate. Adv Pharmacol 2006;53:403-415.

5. Clegg DO, Reda DJ, Harris CL, et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med 2006;354:795-808.

6. Mazieres B, Hucher M, Zaim M, Garnero P. Effect of chondroitin sulfate in symptomatic knee osteoarthritis: a multicentre, randomized, double-blind, placebo-controlled study. Ann Rheum Dis 2007; 66:639-645.

7. Reichenbach S; Sterchi R; Scherer M; Trelle S; Burgi E; Burgi U; Dieppe PA; Juni P. Meta-analysis: chondroitin for osteoarthritis of the knee or hip. Ann Intern Med 2007;146:580-90.

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