Knee Arthritis Did Not Benefit From Supplements

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Main Category: Arthritis / Rheumatology
Also Included In: Complementary Medicine / Alternative Medicine;  Clinical Trials / Drug Trials
Article Date: 01 Oct 2008 - 0:00 PDT

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US scientists found that the dietary supplements glucosamine and chondroitin sulfate were no more effective than placebo at slowing down the rate of cartilage loss in the knees of patients with osteoarthritis; however they also said the trial was probably too short and too small, and spoke more to scientists about how to conduct further research in this area than than to patients.

The two-year multicenter study was the work of rheumatologist Dr Allen D. Sawitzke, associate professor of internal medicine at the University of Utah School of Medicine in Salt Lake City, and colleagues from other research centers throughout the US, and is published online in the October issue of Arthritis & Rheumatism.

Osteoarthritis of the knee is a condition where the cartilage that cover the surfaces of hard bone on the inside of the knee joint, and the synovial fluid in the joint, gradually reduce, resulting in loss of cushioning and lubrication and space between the femur and tibia causing inflammation and pain.

Treatment is limited to symptom relief, wrote the authors, and there are no therapies that slow down the loss of cartilage. Of the 21 million Americans with osteoarthritis, many take the dietary supplements glucosamine and chondroitin sulfate, either alone or in combination, to relieve pain.

For this study, Sawitzke and colleagues evaluated the effect of glucosamine and chondroitin sulfate (alone and in combination), as well as celecoxib and placebo on progressive loss of joint space width (as shown by X-ray) in patients with osteoarthritis of the knee.

The researchers enrolled 572 participants who were already taking part in a 2-year trial to evaluate the pain relieving properties of glucosamine and chondroitin (this was the multicenter, randomized, national clinical trial known as GAIT, which stands for Glucosamine/Chondroitin Arthritis Intervention Trial).

The participants were in 5 groups, each continuing to take either glucosamine at a dose of 500 mg 3 times a day, chondroitin sulfate at a dose of 400 mg 3 times a day, a combination of glucosamine and chondroitin sulfate, celecoxib at a dose of 200 mg a day, or placebo over 24 months. All the participants met the criteria of at least 2 mm of joint space width and certain other radiographic criteria when they started. Patients who had mostly lost cartilage at the sides of the joint (lateral compartment narrowing) were excluded.

The researchers measured the joint space width of each patient by X-ray at the start of the study (baseline) and then at months 12 and 24. The main measure they used in their analysis was the mean change in joint space width from the start of the study.

The results showed that:

• In the placebo group, the mean loss of joint space width at 2 years was 0.166 mm (after adjusting for design and clinical factors).


• No statistically significant difference in mean loss of joint space width was found in any treatment group compared with the placebo group.


• Less severely affected knees (Kellgren-Lawrence grade 2), but not more severely affected knees (Kellgren-Lawrence grade 3), in the treatment groups showed a trend toward improvement relative to the placebo group.

The authors said that the power of the study was hampered by the small size of the sample, the variance of joint space width, and a smaller than expected loss in joint space width. They concluded:

"At 2 years, no treatment achieved a predefined threshold of clinically important difference in JSW [joint space width] loss as compared with placebo. However, knees with K/L grade 2 radiographic OA [osteoarthritis] appeared to have the greatest potential for modification by these treatments."

In a separate statement Sawitzke said:

"At two years, no treatment achieved what was predefined to be a clinically important reduction in joint space width loss."

"While we found a trend toward improvement among those with moderate osteoarthritis of the knee in those taking glucosamine, we were not able to draw any definitive conclusions," he added.

The problem with interpreting these results, explained the statement, is that the joint space width loss of the placebo group was much lower at two years than the 0.4 mm the researchers expected. From previous studies, they expected that a loss of 0.2 mm or less at two years meant a slowed rate of cartilage loss, and because the reduction in rate of joint space loss for all the groups was under this threshold, they had to concluded there was no effect on joint space loss by any of the agents.

Dr Josephine P Briggs, director of the National Center for Complementary and Alternative Medicine, one of the funders of the study, said "the results of the study provide important insights for future research."

Co-investigator Dr Daniel O Clegg said the trial shed light on how osteoarthritis progresses, gave them insight into techniques that can measure joint space width loss more reliably, and on how glucosamine and chondroitin sulfate may potentially affect joint space width. He said it also helped them to identify patients who may respond better in future research.

"The effect of glucosamine and/or chondroitin sulfate on the progression of knee osteoarthritis: A report from the glucosamine/chondroitin arthritis intervention trial."
Allen D. Sawitzke, Helen Shi, Martha F. Finco, Dorothy D. Dunlop, Clifton O. Bingham III, Crystal L. Harris, Nora G. Singer, John D. Bradley, David Silver, Christopher G. Jackson, Nancy E. Lane, Chester V. Oddis, Fred Wolfe, Jeffrey Lisse, Daniel E. Furst, Domenic J. Reda, Roland W. Moskowitz, H. James Williams, Daniel O. Clegg.
Arthritis & Rheumatism, Volume 58 Issue 10, October 2008, pp 3183-3191, Published Online: Sep 29, 2008.
DOI: 10.1002/art.23973

Click here for Abstract.

Source: Journal abstract, University of Utah Health Sciences.

Written by: Catharine Paddock, PhD.


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