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Efficacy of Glucosamine and Chondroitin for Treatment of Osteoarthritis
To the Editor: In their meta-analysis of randomized, placebo-controlled trials, Dr McAlindon and colleagues1 report that both glucosamine sulfate (GS) and chondroitin sulfate (CS) are likely to be effective therapies for the symptomatic treatment of osteoarthritis (OA). However, they also assert that the symptomatic benefit may be less than predicted because of methodological flaws and probable publication bias. As representatives of one of the major European manufacturers of highly purified CS, we wish to point out that the clinical development of such agents requires great financial investment. Therefore, without the support of pharmaceutical industries, it would be almost impossible for physicians and researchers to investigate the clinical effect of any active principle. Publication is the last step for a researcher, who is responsible for content and quality of the results. Therefore, we disagree that supported clinical trials are necessarily associated with publication bias.
One of our first clinical studies on the efficacy of CS began in Europe 15 years ago. At that time, validated parameters for efficacy in OA were unknown or not well defined. The first guidelines for conducting clinical trials in OA were published in 1994.2 After this date, our clinical studies (references 9, 10, 20, 32, and 49 in the article by McAlindon et al) have been carried out in agreement with the new procedures.
Furthermore, McAlindon et al did not consider several relevant studies3-4 in their meta-analysis, and they misrepresent others. For instance, the studies they cite by Bourgeois et al did report intention to treat (ITT) analysis, as did those of Bucsi and Poor and Pavelka et al. The Lequesne algofunctional index also was used in these trials.
We do appreciate the effort to provide an overview of CS, but we think that before discrediting the quality of serious studies, the data should be analyzed more carefully. We are aware that more studies are necessary to provide scientific support, and some are already in progress. Nevertheless, incomplete information is bound to confuse physicians and their patients about the benefits of these therapies.
Giuseppe Mautone, PhD
IBSA, Institut Biochimique SA
Pambio-Noranco, Switzerland
1. McAlindon TE, LaValley MP, Gulin JP, Felson DT. Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. JAMA. 2000;283:1469-1475. FREE FULL TEXT
2. Lequesne M, Brandt K, Bellamy N, Moskowitz CJ, Pelletier JP. Guidelines for testing slow acting drugs in osteoarthritis. J Rheumatol. 1994;21:65-73.
3. Morreale P, Manopulo R, Galati M, Boccanera L, Saponati G, Bocchi L. Comparison of the anti-inflammatory efficacy of chondroitin sulfate and diclofenac sodium in patients with knee osteoarthritis. J Rheumatol. 1996;23:1385-1391. ISI | PUBMED
4. Malaise M, Vignon E, Uebelhart D, Marcolongo R. Efficacy and tolerability of 800 mg oral CS 4&6 in the treatment of knee osteoarthritis: a randomized, double-blind, multicentre study. Eular Rheumatol Litera. 1998;27(suppl 2):64.
To the Editor: In their systematic quality assessment and meta-analysis of the effectiveness of GS and CS for the treatment of OS, Dr McAlindon et al1 did not mention that shark cartilage serves as a major source of these products.
The United Nations Food and Agricultural Organization report that virtually 70% of the world's fisheries (including shark fisheries) are fully exploited to overexploited, depleted, or in a state of collapse.2 In the United States, which is one of the few countries that effectively manages any of its fisheries, the number of some species of coastal sharks has been reduced by 75% to 85% over the past 20 years.3 Sharks are caught for their fins (to be used in soup), their cartilage (to be used in supplements), and their meat, as well as inadvertently through the use of long-line fishing. In 1995, more than 100 million sharks from the 400 known species were killed.3 Furthermore, unregulated fisheries in other countries and in international waters support a thriving, worldwide gray-market trade in shark skeletons.4
In the midst of the largest global extinction since the demise of the dinosaurs 65 million years ago, when more than 5000 species are lost per year (10,000 times the naturally occurring rate of extinction),5 we must take special care to preserve all creatures and promote biodiversity. Given that many currently available pharmaceutical and "neutraceutical" products are derived from or patterned after molecules found in plant and animal species, we must balance a respect for human, plant, and animal life and ensure that a continuing source of effective organismal products are available for patients.
Martin Donohoe, MD
Center for Ethics in Health Care
Oregon Health Sciences University
Portland
1. McAlindon TE, LaValley MP, Gulin JP, Felson DT. Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. JAMA. 2000;283:1469-1475. FREE FULL TEXT
2. Greenpeace International. Dead ahead—industrial fishing fleets set course for disaster. May 1998. Available at: http://www.greenpeace.org/~oceans/globaloverfishing/deadahead.html. Accessed March 30, 2000.
3. Benchley P. Sharks. Audubon. May-June 1998:53-57.
4. Rivlin MA. Bad to the bone. Amicus J. Spring 2000:12-18.
5. Wilson EO. Threats to biodiversity. Sci Am. 1989;261:108-116.
In Reply: Dr Mautone expresses concern that we did not give credit to some trials for ITT analyses even when this was stated in the text of our article. In Reichelt's study, the ITT results for the primary outcome measure are not reported—the trials by Rovati and Bucsi gave no indication of an ITT approach. For the study by Bourgeois et al, we would like to acknowledge that this was indeed misclassified in the table in our article, as Mautone points out.
We also agree with Mautone that the support of the pharmaceutical industry is critical in advancing research in therapeutic compounds. Of course, this poses a dilemma in a meta-analysis because it has been shown repeatedly that industry involvement in clinical trials is more frequently associated with positive results.1-2 We also emphasize that we used quality evaluation in our analyses to help evaluate the overall weight of evidence for efficacy of these compounds. This critical component of meta-analytic methodology should not be viewed as an attempt to discredit individual trials or investigators, nor was this our intent.
Timothy E. McAlindon, DM, MPH; Michael P. LaValley, PhD; David T. Felson, MD, MPH
The Arthritis Center
Boston University School of Medicine
Boston, Mass
1. Rochon PA, Gurwitz JH, Simms RW, et al. A study of manufacturer-supported trials of nonsteroidal anti-inflammatory drugs in the treatment of arthritis. Arch Intern Med. 1994;154:157-163. ABSTRACT
2. Friedberg M, Saffran B, Stinson TJ, Nelson W, Bennett CL. Evaluation of conflict of interest in economic analyses of new drugs used in oncology. JAMA. 1999;282:1453-1457. FREE FULL TEXT
Letters Section Editors: Stephen J. Lurie, MD, PhD, Senior Editor; Phil B. Fontanarosa, MD, Executive Deputy Editor.
JAMA. 2000;284:1241.
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