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Update on Glucosamine and Chondroitin Sulfates for Degenerative Joint Disease

Introduction
Osteoarthritis continues to be a painful and disabling condition for many of our patients. Medical treatments remain limited primarily to pain-control medication and surgery. Fortunately, certain promising alternative therapies have received a good deal of attention from the scientific research community. In the WSCC Clinics Protocol on Glucosamine and Chondroitin Sulfate1, adopted in 2001, the case was made for selecting either glucosamine, 1500 mg per day, or chondroitin sulfate, 800-1200 mg per day, as the initial choice of dietary supplement therapy for osteoarthritis. This recommendation was based on the strength of evidence from several randomized controlled trials (RCTs) and two meta-analyses. Since then new studies have been published that improve our understanding of the value of these supplements.

New Glucosamine Research
One of the most promising results discussed in the WSCC Clinics Protocol were the findings reported early in 2001 of a three-year Belgian RCT of glucosamine, in which the treatment group did not experience the deterioration of radiographic knee changes seen in the placebo group at the end of the trial2. In 2002, a second long-term RCT was published reporting similar benefits in a group of Czech subjects3. In addition to experiencing significant symptom relief, subjects receiving 1500 mg per day of glucosamine averaged no progressive joint space narrowing after three years, while in comparison the placebo group lost a significant amount of joint space and had only a modest reduction in pain. While a few subjects taking glucosamine did not experience these protective joint space effects, almost three times as many in the placebo group developed severe narrowing, defined as greater than 0.5 mm in three years. A follow-up analysis revealed that subjects with initially milder joint narrowing received the greatest protection from glucosamine 4. As in the prior long-term study, no significant side effects from the supplement were reported.

Osteoarthritis of the temporomandibular joint (TMJ) was treated with glucosamine in a recent Canadian RCT5. Glucosamine therapy (1500 mg per day) was compared to ibuprofen (1200 mg per day) in this 90-day trial, which resulted in equal improvement in both groups measured by assessments of pain and TMJ function. As reported in other trials, subjects treated with glucosamine did not experience a return of pain for 30 days after treatment was stopped, which represents a remarkable "carry-over" effect. This study also demonstrates that glucosamine may benefit patients with osteoarthritis in areas other than the knee.

A recent short-term study conducted in Great Britain did not report significant pain reduction from glucosamine therapy for osteoarthritis of the knee6. After six months of supplementation with 1500 mg per day, the glucosamine group had a small but significant improvement in knee flexion, but self-assessment of pain was not different from that in the placebo group, many of whom experienced pain reduction as well. These patients had more severe osteoarthritis than those in most of the successful trials of glucosamine, and other reports suggest glucosamine is more effective in mild to moderate cases4. This study is only the second RCT to report disappointing results from glucosamine therapy, compared with at least sixteen double-blind studies reporting significant positive outcomes.

Clinicians and patients alike are interested to learn whether glucosamine might be helpful in joint disorders other than osteoarthritis, but until recently this type of investigation had not been attempted. An Australian group has just reported results of a RCT of glucosamine hydrochloride therapy on people with "regular" knee pain7. Subjects, who averaged 42-43 years of age, were selected for the presence of knee pain "more often than not" while pursuing the activities of daily living. About half of the subjects had prior medical workups for their knee pain that indicated some degree of cartilage damage, but this study did not perform any further diagnostic evaluations on any subject. Deviating from most prior glucosamine studies, this three-month trial supplied glucosamine as the hydrochloride rather than the salt. Until this study appeared, only one trial of glucosamine hydrochloride monotherapy had been published, and the earlier study reported only marginal effects of glucosamine hydrochloride against osteoarthritis discomfort8. Glucosamine-treated subjects in the new study reported some significant improvements compared to the placebo group in discomfort relief and quality of life, but performance of either a "duck-walk" or a stair climb did not improve. It is tempting to speculate that glucosamine, having a more impressive record of significant benefit, may have had greater potential to improve both discomfort and function had it been used in this study.

As described in the WSCC Protocol, animal studies have questioned whether glucosamine is safe for use in patients with diabetes or other glucose intolerance disorders. To date no formal human investigations have been carried out to determine whether this concern is valid. It appears from the long-term studies described above that glucosamine produces no significant changes in plasma glucose among healthy subjects, but anecdotal reports of elevated blood glucose readings by diabetics taking glucosamine suggest that patients with that disease monitor their glucose levels carefully while using glucosamine.

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