Subset of original GAIT patients
The ancillary study was concurrently conducted on a subset of the patients who were enrolled in the prospective, randomized GAIT trial. The primary objective was to investigate whether these dietary supplements could diminish OA structural damage of osteoarthritis. The results show none of the agents had a clinically significant effect on the rate of joint space loss.
“The mean JSW (joint space width) loss at 2 years in knees with OA in the placebo group, adjusted for design and clinical factors, was 0.166 mm. No statistically significant difference in mean JSW loss was observed in any treatment group compared with the placebo group,” Dr. Sawitzke said.
The researchers noted a nonsignificant trend toward improvement (versus placebo) in treated Kellgren/Lawrence grade 2 knees but not in grade 3 knees.
The study design defined “clinically important” JSW loss as ≥0.2mm loss at 2 years. The researchers had expected a joint space loss of 0.4 mm with placebo, and the study was based on that assumption. However, even the placebo group did not reach this level of damage. Total JSW loss among treatment groups were as follows:
- 0.013 mm (glucosamine)
- 0.107 mm (chondroitin sulfate)
- 0.111 mm (celecoxib)
- 0.166 mm (placebo)
- 0.194 mm (glucosamine and chondroitin sulfate)
According to Dr. Sawitzke, associate professor of internal medicine at the University of Utah School of Medicine, “At 2 years, no treatment achieved what was predefined to be a clinically important reduction in [JSW] loss. [Although] we found a trend toward improvement among those with moderate OA of the knee in those taking glucosamine, we were not able to draw any definitive conclusions.”
The original GAIT study found that the supplements produced no more pain relief than placebo.2 A subset of the original GAIT participants with moderate-to-severe OA knee pain appeared to receive significant pain relief when they took combination glucosamine and chondroitin sulfate.
GAIT II patients continued treatment for additional 18 months
In the ancillary study, GAIT patients were offered the opportunity to continue their original study treatment for an additional 18 months. Participants remained on their originally assigned GAIT treatment: 500 mg of glucosamine three times a day, 400 mg of chondroitin sulfate three times a day, combination of the two supplements, 200 mg of celecoxib daily, or placebo.
X-rays were obtained at study entry and again at 1 and 2 years. JSW was measured on 581 knees from 357 patients. None of the trial groups showed significant improvement. The group taking glucosamine had the least change in JSW, followed by the groups taking chondroitin sulfate, celecoxib, placebo, and the combination of both dietary supplements.
Supplement makers not in step with GAIT
In response to the Sawitzke et al report, the Council for Responsible Nutrition (CRN), the lead trade association representing the dietary supplement industry, characterized the GAIT II results as “perplexing and extremely inconsistent with an existing large body of evidence that shows a benefit from glucosamine and chondroitin supplementation.”
CRN vice president for regulatory affairs Andrew Shao, PhD, said, “The results are also inconsistent with the first arm of GAIT, as well as with a series of previously published clinical trials which examined the same outcome—the narrowing of the space between joints—and demonstrated clear benefit. This trial was a follow-up to the original GAIT trial, using only a small subset of the original cohort of patients. In addition, anecdotal reports from consumers overwhelmingly indicate that glucosamine and chondroitin or their combination is effective.”
References
1. Sawitzke AD, Shi H, Finco MF, et al. The effect of glucosamine and/or chondroitin sulfate on the progression of knee osteoarthritis. A report from the Glucosamine/Chondroitin Arthritis Intervention Trial. Arthritis Rheum. 2008;58:3183-3191.
2. Clegg DO, Reda DJ, Harris CL, et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. New Engl J Med. 2006;354:795-808.