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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 at the Boston University School of Medicine1, recommends that additional, rigorous, independent studies be done of glucosamine and chondroitin compounds to determine their true efficacy and usefulness.
"About 21 million adults in the United States have osteoarthritis," says Stephen I. Katz, M.D., Ph.D., director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). NIAMS funded this glucosamine and chondroitin sulfate study, and has helped launch a major clinical trial on glucosamine and chondroitin sulfate compounds in osteoarthritis. NAIMS along with the National Center for Complementary and Alternative Medicine (NCCAM), both parts of the federal government's National Institutes of Health (NIH) both believe that glucosamine and chondroitin sulfate are potential "effective treatments that are key to improving the quality of life of Americans affected by osteoarthritis."
Osteoarthritis, also called degenerative joint disease, is caused by the breakdown of cartilage, which cushions the ends of bones within the joint. Osteoarthritis is characterized by pain, joint damage, and limited motion. Osteoarthritis generally occurs later in life, and most commonly affects the hands and large weight-bearing joints, such as the knees and hips.
Since the 1950s, the standard treatment for osteoarthritis has been the administration of acetaminophen or non-steroidal, anti-inflammatory drugs (NSAIDs). Acetaminophen, an analgesic, worked well to mask the pain associated with osteoarthritis, but ignored the etiology of the disease. Similarly, NSAIDs treat the symptoms of the disease (pain and inflammation) but ignore the mechanisms responsible for its development. Recently, evidence has arisen that NSAIDs may in fact directly inhibit cartilage regeneration; aggravating the disease they are meant to treat.3 Also, the negative effects of long-term NSAID use on the gastrointestinal tract have been well known for years. Clinical trials have been conducted directly comparing glucosamine therapy to standard NSAID treatment for osteoarthritis.4,5 Results indicated that pain relief was more rapid with NSAIDs, but was eventually significantly greater with glucosamine, and glucosamine had much greater tolerability by the study patients.
The Boston researchers point out that glucosamine and chondroitin sulfate have received significant media attention and have been used in Europe for osteoarthritis for over 10 years. The researchers say that physicians in the United States and the United Kingdom have been skeptical about glucosamine and chondroitin sulfate, 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 glucosamine and chondroitin sulfate may help in the repair and maintenance of cartilage.
The Boston University team located 37 studies of glucosamine and chondroitin sulfate in osteoarthritis by a thorough review of the scientific literature going back more than three decades. Of these, 15 glucosamine and chondroitin sulfate 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 osteoarthritis 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 glucosamine and chondroitin sulfate compounds to have a therapeutic benefit. Only one of the 15 glucosamine and chondroitin sulfate 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 glucosamine and chondroitin sulfate clinical trials and a meta-analysis, which enabled them to integrate the data from different trials. The glucosamine and chondroitin sulfate 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 glucosamine or chondroitin sulfate negative results.
Based on data from the glucosamine and chondroitin sulfate trials, the researchers calculated an overall "effect size" for glucosamine and chondroitin sulfate: 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 glucosamine and chondroitin sulfate 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 glucosamine and chondroitin sulfate 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 glucosamine and chondroitin sulfate, "but there is a possibility that they might not work," and that substances labeled as glucosamine and chondroitin sulfate might not even contain them, due to a lack of regulation. Both the Arthritis Foundation and the American College of Rheumatology have issued statements6 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 glucosamine and chondroitin sulfate.
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 glucosamine and chondroitin sulfate multicenter study is described at http://www.nih.gov/niams/news/nccam-15.htm.
For decades, European physicians and scientists have shown a marked interest in glucosamine and its ability to benefit osteoarthritic patients. Animal tissue culture studies have demonstrated that glucosamine has the ability to increase the water-retaining properties of cartilage and synovial fluid, improving their lubricating and shock-absorbing functions. Additionally, glucosamine may stimulate the repair of damaged cartilage by increasing collagen deposition. These effects appear (at least in animal models) to demonstrate the ability of exogenous glucosamine to counter the degenerative changes seen in osteoarthritis. European clinical trials have unanimously shown the efficacy of glucosamine administration to sufferers of osteoarthritis. Every study has shown positive results with decreases in pain and inflammation and increases in mobility being common. No significant side effects have been demonstrated with regular use of glucosamine.2
Despite such overwhelming evidence for the benefits of glucosamine, American doctors have, until very recently, ignored it as a potential treatment for osteoarthritis. As glucosamine has become readily available in health food stores in recent years, news about its benefits have spread rapidly through the patient population. This great popular interest, and a general increased openness to alternative therapies, has given birth to scientific interest in glucosamine in the United States. Recent studies have agreed with the results of earlier trials, demonstrating the benefits of glucosamine in osteoarthritis treatment. However, many physicians continue to adhere to the traditional therapy of analgesics and NSAIDs, despite studies on the negative effects of NSAIDs on cartilage and the gastrointestinal tract, and direct comparison studies showing an equal or increased benefit of glucosamine over NSAIDs.2
In conclusion, it is clear that glucosamine can provide a clear therapeutic benefit in osteoarthritis with minimal, if any, side effects. These points challenge the rationale of traditional therapy with anti-inflammatory agents. It is important for anyone considering glucosamine therapy for osteoarthritis to consult with their physician so they may recommend the proper dosage and rule out any potential complications.2