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Glucosamine and Chondroitin Sulfate for Osteoarthritis Pain

Taking glucosamine and chondroitin sulfate together may relieve pain and improve function in people with moderate-to-severe knee-pain associated with osteoarthritis, according to a recent report on the Glucosamine-chondroitin Arthritis Intervention Trial (GAIT) study.

Results of the study, which examined the effects of glucosamine and chondroitin sulfate, alone or in combination, and daily Celebrex (celecoxib) alone, compared with placebo, was published in the February 23 issue of The New England Journal of Medicine (NEJM) and reported by MedPage Today on February 22, 2006.

According to researchers Daniel O Clegg, MD, of the University of Utah School of Medicine, and colleagues, glucosamine and chondroitin sulfate (taken alone or together) did not significantly reduce mild knee-pain associated with osteoarthritis, compared with placebo. However, in people with moderate-to-severe knee-pain, the combined drugs significantly reduced pain and improved function, according to the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index.

Also, the study showed that treatment with Celebrex (celecoxib) was associated with a "much faster time to response" compared with glucosamine and chondroitin sulfate taken alone or in combination.

Clinical Trial

Researchers in this multi-center, double-blind, placebo- and celecoxib-controlled study recruited 1,583 people with symptomatic knee osteoarthritis. Participants were mainly women (64.1%) and had an average age of 58.6 years.

Participants were randomly assigned to receive either glucosamine (1,500 mg daily), chondroitin sulfate (1200 mg daily), both glucosamine and chondroitin sulfate daily, celecoxib (200 mg daily) or placebo for 24 weeks. They were also permitted Tylenol (acetaminophen; up to 4000 mg daily) as "rescue analgesia".

Knee-pain was classified by severity: 1,229 participants had "mild" knee-pain, and 354 participants had "moderate-to-severe" knee-pain. The study's primary outcome measure was a 20% decrease in knee-pain from baseline to week 24.

Among the study groups, a 20% decrease in WOMAC pain score was reported by:

  • 70% of participants randomized to Celebrex (223 of 318);
  • 67% of participants randomized to glucosamine plus chondroitin sulfate (211 of 317);
  • 64% of participants in the glucosamine group (203 of 317);
  • 65% of participants in the chondroitin sulfate group (208 of 318);
  • 60% of participants in the placebo arm (188 of 313).

When researchers analyze the data by pain severity, 79.2% of participants who received glucosamine plus chondroitin sulfate scored a 20% pain decrease, versus 69.4% of participants with moderate-to-severe pain who received Celebrex.

Similarly, participants with moderate-to-severe pain receiving combination treatment posted significant improvements in the WOMAC function score, compared with participants with moderate-to-severe pain receiving Celebrex.

Interpreting Results

The study provides valuable information for orthopedists who routinely recommend the popular supplements glucosamine and chondroitin, according to Deryk Jones, MD, section head for sports medicine and cartilage restoration at the Ochsner Clinic in New Orleans.

"When you look at the results for the patients with moderate-to-severe pain, all pain parameters went down and those decreases were statistically significant," Dr Jones said. The findings suggest that using glucosamine and chondroitin sulfate "isn't going to make a difference for patients with mild pain, but [in] those with severe symptoms the treatment could be helpful."

The researchers advise caution in interpreting their results: "Our finding that the combination of glucosamine and chondroitin sulfate may have some efficacy in patients with moderate-to-severe symptoms is interesting but must be confirmed by another trial."

With regard to treatment, they add, "In making therapeutic decisions, physicians and patients alike should be aware of our data suggesting that celecoxib has a much faster time to response than glucosamine, chondroitin sulfate, or the two in combination."

Accompanying Editorial

In an editorial published in the same issue of NEJM, Marc C. Hochberg, MD, MPH, of the University of Maryland in Baltimore, urged careful interpretation of the study results for the moderate-to-severe pain group, because "[Celebrex], the active control, had no significant effect in this subgroup."

Dr Hochberg pointed out some limitations of the study, including the high attrition rates (20%) in the placebo group; high attrition in the chondroitin sulfate group and the glucosamine group; and an a high response in the placebo group.

Dr. Hochberg also wrote that it was "disappointing" that the study authors did not use the Rottapharm brand of glucosamine sulfate:

"In the most recent meta-analysis of eight randomized trials in which either glucosamine hydrochloride or glucosamine sulfate not manufactured by Rottapharm was compared with placebo, differences between the groups in the WOMAC scores did not reach significance.

"On the other hand, when the Rottapharm brand of glucosamine sulfate was compared with placebo in seven randomized trials and Lequesne's Disease Severity Index was used to assess outcomes, glucosamine sulfate was found to be significantly better at reducing pain and improving function."

Dr Hochman concluded, "If patients choose to take dietary supplements to control their symptoms, they should be advised to take glucosamine sulfate rather than glucosamine hydrochloride." For people with severe pain, he advised that "taking chondroitin sulfate with glucosamine sulfate may have an additive effect."

He concluded that, if after three months the supplements confer no benefit, treatment should be stopped.

GAIT was supported by grants from the National Center for Complementary and Alternative Medicine and the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Sources:Glucosamine, Chondroitin Sulfate, and the Two in Combination for Painful Knee Osteoarthritis, Clegg DO, New England Journal of Medicine, volume 354, pages 795-808, 2006. Nutritional Supplements for Knee Osteoarthritis-Still No Resolution. Hochberg MC, New England Journal of Medicine, volume 354, pages 858-860, 2006.

Posted: March 2006