Does glucosamine sulfate affect progression of symptoms and joint structure changes in osteoarthritis?

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Reginster JY, Leroisy R, Rovati LC, et al. Long-term effects of glucosamine sulfate on osteoarthritis progression: a randomized, placebo-controlled clinical trial. Lancet 2001; 357: 251-56.


BACKGROUND: Traditional treatments for osteoarthritis, including acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), and steroids all have potentially serious side effects and do not affect the progression of the disease. Glucosamine sulfate shows promising short-term positive effects on symptoms and quality of life, but the long-term effects on the progression of osteoatrhritis are unknown.

POPULATION STUDIED: The investigators in Belgium enrolled 212 patients older than 50 years with established mild to moderate osteoarthritis of the medial tibiofemoral compartment of the knee and similar mild to moderate symptom severity. Patients were not enrolled if they had other rheumatologic diseases, severe articular inflammation, traumatic knee lesions, a body mass index greater than 30, or if they received corticosteroids in the 3 months preceding enrollment. The demographics of both groups were similar at the start and the end of the study and reflect patients commonly seen in a primary care setting.

STUDY DESIGN AND VALIDITY: Patients in this study were randomized to receive either placebo or 1500 mg glucosamine sulfate daily for 3 years. Rescue analgesia (acetaminophen or NSAIDs) was allowed in both groups. Weight-bearing antero-posterior radiographs of each knee were taken at baseline and 1 and 3 years after the start of the study. The mean joint-space width of the medial and lateral compartments of the tibiofemoral joint was measured by a single independent blinded reader. A visual analog scale version of the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index was used to assess the severity of joint pain, stiffness, and limitation of physical function. Results for patients who dropped out of the study were calculated by either extrapolating their data forward or by assigning values for the average joint-space change of the placebo group who did finish (worst-case scenario).

OUTCOMES MEASURED: The primary outcome was the mean joint-space change of the medial compartment of the tibiofemoral joint and change in the total WOMAC index of pain, stiffness, and functional mobility after 3 years. Secondary outcomes included use of rescue medications, withdrawal rates, and adverse effects.

RESULTS: Of the 355 patients screened, 212 were enrolled and randomly assigned to receive glucosamine sulfate or placebo. Withdrawals were similar in both groups, and patients in both groups showed more than 70% compliance with study treatment. The mean joint-space change was -0.31 mm narrowing in the placebo group and 0.07 mm improvement in the glucosamine sulfate group (0.38 mm difference; 95% confidence interval, 0.02-0.73 mm). Compared with baseline WOMAC index values, symptoms worsened in the placebo group and improved in the glucosamine sulfate group (9.8% decline vs 24.3%, improvement; P=.016). The most significant changes were in pain and function. Change in stiffness was similar in both groups. However, symptom improvement did not correlate with joint-space change, with some patients in the glucosamine sulfate group showing an improvement of symptoms and worsened joint-space narrowing. Use of rescue analgesia, adverse events, and withdrawal from the study were similar in both groups.


More of our patients older than 50 years with osteoarthritis of the knees are considering using glucosamine sulfate, and this study allows us to reassure them that the long-term use of this product is an effective treatment that can improve symptoms and slow the course of progression. Although this study used standardized preparations of glucosamine sulfate available in Europe, this product is considered a dietary supplement in the United States, and quality and consistency may vary between brands. Patients should be advised to purchase this product from reputable sources and should be told that symptom improvement may take several months.

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