Chondroprotection with Glucosamine and Chondroitin Sulfate
Abstract & Commentary
Synopsis: The use of glucosamine and chondroitin sulfate in combination provide chondroprotective activity for hyaline cartilage in the rabbit instability model.
Source: Lippiello L, et al. In vivo chondroprotection and metabolic synergy of glucosamine and chondroitin sulfate. Clin Orthop 2000;381:229-240.
Lippiello and colleagues in an industry supported study report on a well-designed animal study evaluating the cartilage reparative effects (chondroprotection) of a combination of glucosamine, chondroitin sulfate, and manganese ascorbate. A total of 42 New Zealand rabbits randomized to various treatment groups (control, combination of glu/chond/Mg, glucosamine alone, chondroitin alone, Mg alone) underwent an arthrotomy and transection of the ACL and PCL producing a well-described instability model for osteoarthritis (OA). Articular damage was analyzed by histology and immunohistochemistry. Biochemical evaluation included proteoglycan synthesis by 35-Sulfate incorporation, and degradative activity by IL-1 induced collagenase activity.
Histologically, all groups had some degree of articular damage; however, the combination of glucosamine, chondroitin sulfate, and manganese led to the least severe articular lesions. Combination therapy also produced the greatest increase in proteoglycan synthesis (+96%) as compared to control. Chondroitin sulfate alone, combination therapy, and manganese ascorbate all produced statistically significant decreases in degradative enzyme activity. Glucosamine alone did not produce a change in degradative activity.
Comment By Robert C. Schenck, Jr., MD
The culture of nutritional supplementation requires definition of commonly used terms with which physicians may not readily be familiar. Most agents used initially in the management of OA are nonsteroidal antiinflammatory drugs (NSAIDs) and these medications function to limit or ameliorate the breakdown products from articular degeneration.1 Chondroprotection is used to describe any medication or "compound" that can block progression of degenerative joint disease and stimulate repair of damaged articular cartilage. The theoretical basis of chondroprotection is providing substrate or components of the hyaline matrix, thereby providing a stimulus to increase the synthesis of complete aggrecan macromolecules.
Only recently has interest in glucosamine and chondroitin sulfate increased such that clinical and basic science studies are being performed.2-4 Three recent studies at the Orthopaedic Research Society have focused on the mechanism of glucosamine and chondroitin sulfate on a molecular level. Recent mechanistic studies have given further credence to the use of nutritional supplementation in the management of mild to moderate OA. Mimms and colleagues recently showed increased production of proteoglycans when bovine cartilage explants were cultured with glucosamine and chondroitin sulfate alone and in combination. Mimms et al noted that combination therapy demonstrated the greatest proteoglycan synthesis compared to glucosamine or chondroitin sulfate alone. Mimms et al went on to show the ability of nutritional supplements to prevent interleukin-1 (IL-1) induced aggrecan depletion. Mimms et al concluded that dietary supplementation may play a role in promoting cartilage health, maintenance, and repair. In another study, Sandy and colleagues evaluated the mechanism by which one component of nutritional supplements may affect chondroprotection. Glucosamine was shown to block the aggrecanase response of chondrocytes to IL-1 in an in vitro model using rat chondrosarcoma cells and bovine cartilage explants. These studies are the first independently funded investigations to show a mechanism by which glucosamine and chondroitin sulfate both influence the production of proteoglycans as well as inhibit the degradation of aggrecan, the important components of normal cartilage metabolism. Currently, both European and American nutraceutical companies are carrying out clinical studies on the effectiveness (symptom modification vs disease modification) of nutritional supplementation for (OA) and articular injury, as performed in this study by Lippiello et al. This investment will pay off, as a mechanism of function for nutraceuticals will support their use among skeptical allopathic physicians.
Finally, the concept of disease modification vs. symptom modification is an important distinction when using nutritional supplements.5,6 Disease modifying aspects of glucosamine and chondroitin sulfate, alone or in combination, have been claimed by industry and researchers alike. Symptom modification is generally accepted with the use of these compounds for mild to moderate OA, but independent nonindustry supported studies are still needed. Disease modification in noninflammatory OA would be a significant finding in the use of glucosamine and chondroitin sulfate clinically, and the study by Lippiello et al is a well-designed attempt to show basic science evidence of disease modification.5,7
The true difficulty in sports medicine today is the treatment of articular lesions in the young adult athlete. Currently, when I reconstruct an ACL deficient knee and find an osteochondral contusion (seen in more than 80% of acute ACL injuries), I use a course of glucosamine and chondroitin sulfate for the articular injury as an adjunct to any surgical repair required. Side effects of glucosamine and chondroitin sulfate appear to be minimal and it is well tolerated. Until there are other tested chondroprotective agents, it is a relatively harmless option that has credibility based on long-term clinical studies as well as the basic science evaluations discussed in this review. The use of glucosamine and chondroitin sulfate is currently not included in most treatment algorithms. In the young athlete with an osteochondral injury, chondroprotection is the right treatment direction as there are relative contraindications with NSAIDs. However, only with further study (including independent funding sources) will we know the true efficacy of such nutritional supplements.1
References
1. Buckwalter JA, et al. New approaches to the treatment of osteoarthritis. AAOS Instructional Course Lecture 2000,49:491-494.
2. Mims TT, et al. Effects of dietary supplements on cartilage metabolism and its potential role in osteoarthritis. Trans Orthop Res Soc 2000;46:240.
3. Sandy JD, et al. The mechanism of chondroprotective effect. Trans Orthop Res Soc 2000;46:1009.
4. Patwari P, et al. Mannosamine inhibits aggrecanase-mediated degradation of mechanical properties of cartilage. Trans Orthop Res Soc 2000;46:1084.
5. McAlindon TE, et al. Glucosamine and chondroitin for treatment for osteoarthritis. A systematic quality assessment and meta-analysis. JAMA 2000;283: 1469-1475.
6. Theodosakis J, Adderly B, Fox B. The Arthritis Cure. New York, NY: St. Martins Press; 1997.
7. Kreder HJ. Glucosamine and chondroitin were found to improve outcomes in patients with osteoarthritis. J Bone Joint Surg Am 2000;82:1323.
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