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Am Fam Physician. 2001;63(5):854-856

to the editor: I read the article on osteoarthritis by Drs. Manek and Lane1 with great interest as it is commonly encountered in my practice. These authors detail a treatment algorithm ranging from patient education and acetaminophen treatment to joint replacement surgery, with a heavy emphasis on the use of nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 (COX-2) enzyme inhibitors and co-therapy to protect against gastric and duodenal ulcers. Unfortunately, the full risks of NSAID therapy are not detailed, and minimal attention is given to the therapeutic use of glucosamine and chondroitin sulfates.

It is well accepted that NSAIDs can lead to gastrointestinal toxicity ranging from dyspepsia to serious gastrointestinal hemorrhage. It has been estimated that NSAID-induced gastrointestinal hemorrhage leads to at least 103,000 hospitalizations and 16,500 deaths each year, with direct costs of complications exceeding $2 billion annually.2 Lesser known is the increased risk of gastrointestinal hemorrhage with concurrent use of selective serotonin reuptake inhibitors (SSRIs) and NSAIDs, giving an adjusted rate ratio of 3.0 (95 percent CI; range: 2.1 to 3.4).3 In addition, NSAIDs are associated with acute and chronic renal failure, although the actual incidence is unknown.2

Glucosamine and chondroitin sulfates are marketed as nutritional supplements in the United States and have been purported to be effective in the treatment of persons with osteoarthritis in various studies over the past three to four decades. In a recent meta-analysis,4 glucosamine and/or chondroitin demonstrated positive effects compared with placebo. Discrepancies in some of the study findings reported in the literature may relate to the composition and quality of the nutritional supplements used. A large number of preparations claiming certain doses of glucosamine or chondroitin sulfate have significantly less (or none) of the dosages described; however, some products have been independently tested for potency with the results posted on the following Web site:

The cost of some nutritional supplements has decreased greatly with competition that is unavailable with patent-protected proprietary pharmaceuticals. For instance, the cost of supplementation with one product independently tested for potency (Sundown Osteo-Bi-Flex Maximum Strength) containing 1,500 mg of glucosamine sulfate and 1,200 mg of chondroitin sulfate has been quoted as less than $20 per month.5 For patients who pay medication costs out of pocket, this price compares favorably with the price of other prescription products, with the advantage of having a safer side effect profile without the risk of gastrointestinal hemorrhage.

A bias against nutritional supplements has been described elsewhere.6 They state there should be only three important questions when evaluating a potential treatment: “Does it work?” “What are the adverse effects?” and “How much does it cost?” Glucosamine and chondroitin sulfates appear to have answered these questions favorably and should be considered as a therapeutic option in the treatment of persons with osteoarthritis.

in reply: We welcome Dr. Woliner's comments and concerns regarding the management of osteoarthritis. Nonsteroidal anti-inflammatory drugs (NSAIDs) are an accepted and appropriate part of treatment for patients with symptomatic osteoarthritis unless it is medically contraindicated. We kept in line with the state-of-the-art guidelines from the American College of Rheumatology.1 Patients who require NSAID therapy should be carefully assessed for factors that increase their risk of gastrointestinal complications, including increased age, concomitant anticoagulant or corticosteroid use and a past history of NSAID-associated gastrointestinal events. If a patient is responsive to a standard NSAID therapy, then assessment should be made for the lowest possible effective dose and shortest duration of NSAID therapy on an individual basis. This would help to reduce the incidence of NSAID-induced ulcers.2

For patients who are unable to tolerate NSAID therapy, the newer cyclooxygenase-2 (COX-2) enzyme inhibitors are a good alternative. Celecoxib (Celebrex) and rofecoxib (Vioxx) are the first COX-2–specific inhibitors to receive FDA labeling for the treatment of patients with osteoarthritis and have been shown to significantly reduce the incidence of endoscopically identified gastroduodenal ulcers when compared to standard NSAID therapy.3,4

Glucosamine and chondroitin sulfates have been studied in a number of short-term trials in Europe and Asia, with results suggesting efficacy in the treatment of patients with symptomatic osteoarthritis. A meta-analysis5 included 13 double-blind, placebo-controlled trials, of more than four weeks' duration, testing glucosamine sulfate or chondroitin sulfate for the treatment of patients with osteoarthritis of the hip or knee. The main finding of this meta-analysis is that glucosamine and chondroitin are likely to be effective therapies for the symptomatic management of patients with osteoarthritis. However, definitive analysis of the results was inconclusive because of study design and conduct.6 For example, a detailed description of the patients enrolled in the trials was not provided, making it difficult to generalize results from the meta-analysis to individual patients.

We should also emphasize that these agents are not FDA labeled for the treatment of patients with osteoarthritis. Because most of the published trials have been of a relatively short duration, the long-term efficacy and toxic effects of glucosamine and chondroitin have not been established. Large well designed, randomized, controlled trials are needed to determine whether these nutraceuticals can modify the radiologic progression of osteoarthritis.

The National Institutes of Health is sponsoring the first U.S. study evaluating glucosamine and chondroitin in patients with osteoarthritis of the knee. Until such high quality independent studies are completed and the results compared to existing trial data, the actual efficacy and utility of these preparations for the treatment of patients with osteoarthritis are still in question.

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This series is coordinated by Kenny Lin, MD, MPH, deputy editor.

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