NIAMS-Funded Analysis of Glucosamine/Chondroitin Sulfate Trials Shows Probable Usefulness for OsteoarthritisIndependent, High-Quality Clinical Trials Recommended

Connie Raab, Kelli Carrington, NIAMS Office of Communications and Public Liaison, RaabC@mail.nih.gov, carringk@mail.nih.gov

A systematic analysis of clinical trials on glucosamine and chondroitin sulfate for treating osteoarthritis (OA) has shown that these compounds may have some efficacy against the symptoms of this most common form of arthritis, in spite of problems with trial methodologies and possible biases. The study, by Timothy E. McAlindon, D.M., and colleagues at the Boston University School of Medicine, published in the March 15, 2000, issue of the Journal of the American Medical Association (JAMA),* recommends that additional, rigorous, independent studies be done of these compounds to determine their true efficacy and usefulness.

"About 21 million adults in the United States have OA," says Stephen I. Katz, M.D., Ph.D., director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), which funded this study and has helped launch a major clinical trial on the compounds in OA, along with the National Center for Complementary and Alternative Medicine (NCCAM), both parts of the federal government's National Institutes of Health (NIH). "Effective treatments are key to improving the quality of life of Americans affected by this common disorder."

OA, also called degenerative joint disease, is caused by the breakdown of cartilage, which cushions the ends of bones within the joint. It is characterized by pain, joint damage, and limited motion. It generally occurs later in life, and most commonly affects the hands and large weight-bearing joints, such as the knees and hips.

The Boston researchers point out that glucosamine and chondroitin sulfate have received significant media attention and have been used in Europe for OA for over 10 years. The researchers say that physicians in the United States and the United Kingdom have been skeptical about these products, probably because of well-founded concerns about the quality of scientific trials conducted to test them. Glucosamine and chondroitin sulfate, which are sold in the United States as dietary supplements, are natural substances found in and around the cells of cartilage. Researchers believe these substances may help in the repair and maintenance of cartilage.

The Boston University team located 37 studies of the compounds in osteoarthritis by a thorough review of the scientific literature going back more than three decades. Of these, 15 trials published between 1980 and 1998 met their criteria: double-blind, randomized placebo-controlled trials that lasted four or more weeks, tested glucosamine or chondroitin for osteoarthritis of the knee or hip, and reported data that the team could extract on the effect of treatment on OA symptoms. Six of the 15 trials involved glucosamine and 9 used chondroitin. The team used only trials of four or more weeks duration because of evidence that it may take several weeks for the compounds to have a therapeutic benefit. Only one of the 15 trials was completely independent of manufacturer support.

The team's analysis of the trials had two key facets: a quality assessment to evaluate each of the clinical trials and a meta-analysis, which enabled them to integrate the data from different trials. The trials studied had many methodological flaws and biases, including those that tended to inflate the benefits of the compounds. The team was also concerned that trials having small or negative effects might not have been published, but after contacting study authors and other experts, they could locate no unpublished negative results.

Based on data from the trials, the researchers calculated an overall "effect size" for the two compounds: the figure 0.2 is considered a small effect; 0.5, moderate; and 0.8, large. The researchers calculated an effect size for glucosamine of 0.44 and for chondroitin sulfate of 0.78, but reported that these values "were diminished when only high-quality or large trials were considered."

"The results of this analysis performed by Boston University researchers underscore the critical public health need to test these agents in a rigorous way," said Dr. Stephen E. Straus, director of the NCCAM. "The NCCAM and NIAMS have jointly initiated the largest multicenter study to date of glucosamine and chondroitin sulfate in order to provide Americans with definitive answers about their effectiveness for osteoarthritis," Straus concluded. The University of Utah School of Medicine is coordinating a nine-center effort in over 1,000 patients, with recruitment to begin later this year.

In the meantime, says Dr. McAlindon, he would not discourage patients from trying these compounds, "but there is a possibility that they might not work," and that substances labeled as these compounds might not even contain them, due to a lack of regulation. Both the Arthritis Foundation and the American College of Rheumatology have issued statements** urging patients with osteoarthritis not to stop proven treatments and disease-management techniques and to let their physicians know if they are considering use of these compounds.

The mission of the NIAMS is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases, the training of basic and clinical scientists to carry out this research, and the dissemination of information on the progress of research in these diseases. More information on NIAMS is available at www.nih.gov/niams/. The NIH multicenter study is described at http://www.nih.gov/niams/news/nccam-15.htm. References: *McAlindon TM, LaValley MP, Gulin JP, Felson DM. Glucosamine and Chondroitin Sulfate for Treatment of Osteoarthritis: A Systematic Quality Assessment and Meta-analysis. JAMA. 2000;283:1469-1475. Accompanying editorial: Towheed TE, Tassos PA. Glucosamine and Chondroitin for Treating Symptoms of Osteoarthritis: Evidence is Widely Touted but Incomplete. JAMA. 2000;283:1483-4.

**These statements are available at http://www.arthritis.org/resource/statements/glucosamine.asp and http://www.rheumatology.org/patients/hotline/970127.html, respectively.

To interview Dr. McAlindon, contact Rebecca Sullivan, Boston University, (617) 638-8491.