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Am Fam Physician. 2000;62(4):849-851

Glucosamine sulfate has been advertised as an effective treatment in patients with osteoarthritis. It has been recommended as a safe alternative to nonsteroidal anti-inflammatory drugs, although it is not recommended by the American College of Rheumatology for this indication. Further studies are needed, particularly in older patients.

Rindone and associates conducted a study to determine the effectiveness of glucosamine in reducing pain in patients with osteoarthritis of the knee. Patients were eligible if they had a history of osteoarthritis of the knee and radiographic findings consistent with the disease. Knee radiographs were rated by a radiologist; grading ranged from grade zero (no arthropathy) to grade 4 (severe arthropathy). Patients who were not ambulatory, had been previously treated with glucosamine or chondroitin singly or in combination, and whose radiographic findings were rated as less severe than grade 1 were excluded from the study. Of the 114 patients enrolled in the study, data were analyzed on 98, who were randomized in a double-blind design to receive 500 mg of glucosamine three times daily or a placebo for two months. Glucosamine was given with or without food. Patients who were taking other analgesics were instructed to continue taking them for the duration of the study. Participants were evaluated at the beginning of the study and at 30 and 60 days after starting treatment. Pain intensity was assessed with a visual analog scale that measured pain intensity at rest and while walking. Side effects were noted at each visit.

No statistical difference was noted between the glucosamine group and the placebo group in mean scores for pain while resting or walking; 17 patients (34 percent) in the glucosamine group reported side effects compared with 11 patients (23 percent) in the placebo group. Most side effects were mild and self-limiting, and included loose stools, nausea, heartburn and headache. The rate of withdrawal from both groups because of side effects was not statistically different.

The results of this study conflict with several other trials recently completed. Patients in this study tended to have had osteoarthritis longer than participants in other trials and to be older and heavier, with more pronounced arthropathy when radiographic grading was used as an assessment tool. Patients in this study had more severe disease than patients in other studies, suggesting more pronounced joint pathology. Perhaps patients with more severe pathology do not respond as readily as patients with less severe arthropathy. Theoretically, this explanation makes sense because glucosamine is believed to be a precursor of proteoglycans that are thought to help cartilage retain water and promote formation of an elastic layer, improving cartilage function. Older patients may have more damaged cartilage that is less responsive to the effects of glucosamine. The length of treatment time with glucosamine in this study was similar to that in the other studies that demonstrated efficacy. The addition of chondroitin sulfate has been shown to stimulate the production of proteoglycans and hyaluronic acid and to inhibit the proteolytic enzymes that may damage cartilage. Only one study compared the combination of chondroitin sulfate with glucosamine. Efficacy was demonstrated during eight weeks of therapy. It is uncertain if chondroitin contributed to the reduction in pain demonstrated in this study because other trials have suggested that three to six months of treatment is needed to derive any benefit. The National Institutes of Health plans further studies to compare the efficacy of glucosamine, glucosamine and chondroitin combination therapy, and placebo in the treatment of patients with osteoarthritis.

The authors conclude that in a select patient population showing radiographic evidence of osteoarthritis of the knee, glucosamine was no better than placebo in reducing the intensity of pain.

editor's note: Patients are being bombarded with information and advertisements about glucosamine as a medicine that relieves osteoarthritis pain and improves mobility. A review of some studies conducted in the United States, and a larger number of studies conducted in Europe hint that some patients with osteoarthritis may benefit from glucosamine therapy. Glucosamine is thought to be chondroprotective, as well as an agent that restores cartilage by providing the material needed for chondrocytes to regenerate cartilage tissue. Some researchers have documented decreased joint pain and less joint tenderness and swelling when glucosamine is used for a period of four to 10 weeks. Short-term adverse effects can include mild gastrointestinal upset, skin rash and headache. Chondroitin, made from shark cartilage, is thought to inhibit free radical activity in the joint space that degenerates joint cartilage and collagen. The research demonstrating chondroitin's efficacy usually involves intra-articular injection, but oral formulations are being strongly promoted, especially in combination with glucosamine. Further study is needed of these agents—alone or in combination—to determine their roles in the treatment of patients with osteoarthritis. Meanwhile, many of our patients will be using these preparations.—r.s.

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