Long-term Effects of Glucosamine Sulphate on Osteoarthritis Progression
Abstracts & Commentary
Synopsis: The results of this study are further evidence that glucosamine sulfate in a dose of 1500 mg per day is a safe neutraceutical that alleviates the symptoms of knee osteoarthritis.
Sources: Reginster JY, et al. Lancet. 2001;357:251-256;
McAlindon T. Lancet. 2001;357:247-248.
Glucosamine sulphate is the sulphate derivative of the natural amino-monosaccharide glucosamine and a normal constituent of glycosaminoglyucans in cartilage matrix and synovial fluid. Because several short- to medium-term clinical trials in osteoarthritis have shown that oral administration of glucosamine is safe and associated with reduction in symptoms, Reginster and associates carried out a 3-year, well controlled trial designed to examine the effects of glucosamine (compared to placebo) on both joint symptoms as well as joint structure.
The study subjects were patients older than 50 years of age who had primary knee osteoarthritis of the medial femorotibial compartment. Progression of disease was assessed by serial, standing (weightbearing) x-rays of the joint space. Symptoms were assessed using the WOMAC index, which combines pain, function, and stiffness assessment as reported by questionaire. The study enrolled 212 subjects, who were randomly assigned to receive either 1500 mg of prescription-grade glucosamine or placebo daily.
Reginster et al report that "there was no average loss of joint-space width in the patients receiving glucosamine sulphate. Conversely, patients on placebo had a significant mean and minimum joint-space narrowing after 3 years." Similarly, "There was an improvement in the primary symptom outcome measure represented by the total WOMAC index" in patients taking glucosamine, but "symptoms of patients in the placebo group worsened." For both joint-space changes and symptom differences, the results were assessed to be significant. Nevertheless, there was no correlation between preservation or progression of joint-space narrowing and improvement in symptoms. That is, "patients receiving glucosamine sulfate tended to improve their symptoms regardless of structure outcome."
Comment by Michael K. Rees, MD, MPH
In an accompanying editorial, Dr. Tim McAlindon of the Arthritis Center, Boston University Medical Center, gives high marks to the methodology used by Reginster et al: "In fact, the results are impressive; patients assigned to glucosamine experienced significant improvement in pain and disability that were sustained for the 3 years of the study, whereas the scores among the palcebo group worsened." He further comments that the lack of correlation with joint-space preservation may reflect that the current (and perhaps incorrect) thinking that osteoarthritis is a disorder of progressive hyaline-cartilage loss, when—in fact—more recent evidence suggests the pan-articular nature of knee osteoarthritis and that joint-space loss reflects meniscal extrusion rather than hyaline-cartilage erosion.
The results of this study are further evidence that gluosamine sulfate in a dose of 1500 mg per day is a safe neutraceutical that alleviates the symptoms of knee osteoarthritis. Its mechanism of action is unknown. Because in the United States glucosamine sulfate is considered a food supplement and is not regulated as a medication, the problem faced by our patients is confidence in its supply and the cost thereof. The potential to commit fraud is significant.
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