Donohoe MT. Arthritis, shark cartilage, and the protection of threatened species. JAMA 2000;284:1241 (letter).
Vol. 284 No. 10, September 13, 2000JAMA / /
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Efficacy of Glucosamine and Chondroitin for Treatment of Osteoarthritis
To the Editor: In their meta-analysis of randomized, placebo-controlledtrials, Dr McAlindon and colleagues1 report that both glucosaminesulfate (GS) and chondroitin sulfate (CS) are likely to be effectivetherapies for the symptomatic treatment of osteoarthritis (OA).However, they also assert that the symptomatic benefit may beless than predicted because of methodological flaws and probablepublication bias. As representatives of one of the major Europeanmanufacturers of highly purified CS, we wish to point out thatthe clinical development of such agents requires great financialinvestment. Therefore, without the support of pharmaceuticalindustries, it would be almost impossible for physicians andresearchers to investigate the clinical effect of any activeprinciple. Publication is the last step for a researcher, whois responsible for content and quality of the results. Therefore,we disagree that supported clinical trials are necessarily associatedwith publication bias.
One of our first clinical studies on the efficacy of CS beganin Europe 15 years ago. At that time, validated parameters forefficacy in OA were unknown or not well defined. The first guidelinesfor conducting clinical trials in OA were published in 1994.2After this date, our clinical studies (references 9, 10, 20,32, and 49 in the article by McAlindon et al) have been carriedout in agreement with the new procedures.
Furthermore, McAlindon et al did not consider several relevantstudies3-4 in their meta-analysis, and they misrepresent others.For instance, the studies they cite by Bourgeois et al did reportintention to treat (ITT) analysis, as did those of Bucsi andPoor and Pavelka et al. The Lequesne algofunctional index alsowas used in these trials.
We do appreciate the effort to provide an overview of CS, butwe think that before discrediting the quality of serious studies,the data should be analyzed more carefully. We are aware thatmore studies are necessary to provide scientific support, andsome are already in progress. Nevertheless, incomplete informationis bound to confuse physicians and their patients about thebenefits 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-analysisof the effectiveness of GS and CS for the treatment of OS, DrMcAlindon et al1 did not mention that shark cartilage servesas a major source of these products.
The United Nations Food and Agricultural Organization reportthat virtually 70% of the world's fisheries (including sharkfisheries) are fully exploited to overexploited, depleted, orin a state of collapse.2 In the United States, which is oneof the few countries that effectively manages any of its fisheries,the number of some species of coastal sharks has been reducedby 75% to 85% over the past 20 years.3Sharks are caught fortheir fins (to be used in soup), their cartilage (to be usedin supplements), and their meat, as well as inadvertently throughthe use of long-line fishing. In 1995, more than 100 millionsharks from the 400 known species were killed.3 Furthermore,unregulated fisheries in other countries and in internationalwaters support a thriving, worldwide gray-market trade in sharkskeletons.4
In the midst of the largest global extinction since the demiseof the dinosaurs 65 million years ago, when more than 5000 speciesare lost per year (10,000 times the naturally occurring rateof extinction),5 we must take special care to preserve all creaturesand promote biodiversity. Given that many currently availablepharmaceutical and "neutraceutical" products are derived fromor patterned after molecules found in plant and animal species,we must balance a respect for human, plant, and animal lifeand ensure that a continuing source of effective organismalproducts are available for patients.
Martin Donohoe, MD
Center for Ethics in HealthCare
OregonHealthSciencesUniversity
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: 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 givecredit to some trials for ITT analyses even when this was statedin the text of our article. In Reichelt's study, the ITT resultsfor the primary outcome measure are not reported—the trialsby Rovati and Bucsi gave no indication of an ITT approach. Forthe study by Bourgeois et al, we would like to acknowledge thatthis was indeed misclassified in the table in our article, asMautone points out.
We also agree with Mautone that the support of the pharmaceuticalindustry is critical in advancing research in therapeutic compounds.Of course, this poses a dilemma in a meta-analysis because ithas been shown repeatedly that industry involvement in clinicaltrials is more frequently associated with positive results.1-2We also emphasize that we used quality evaluation in our analysesto help evaluate the overall weight of evidence for efficacyof these compounds. This critical component of meta-analyticmethodology should not be viewed as an attempt to discreditindividual 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.
Update, 2012
California joins other states such as Hawaii, Washington, and Oregon in banning the sale and trade of shark fins.
Public Health and Social Justice Website