Letter from Dr. Verges, Professor of Pharmacology University of Madrid, Scientific Director Bioiberica
With regard to the article: “Meta-analysis: Chondroitin for Osteoarthritis of the Knee or Hip” published in the Annals of Internal Medicine, I would like to make a series of considerations I find of interest for the use of chondroitin sulfate (CS) in daily clinical practice.
The aim of the aforesaid meta-analysis is to assess the effect of CS on pain in osteoarthritic patients. It concludes that its effect is minimal or non-existent and that its use should be discouraged.
The parameter used in this study is pain, but it should be borne in mind that CS is not an analgesic. Specifically, CS presents an anti-inflammatory effect, which in turns results in pain reduction and improvement of joint function. This anti-inflammatory effect has been observed in different experimental models1,2,3.
At the same time, in the GAIT trial4, also cited by the authors as one of the recent, large-scale trials on CS, the patients in the CS group presented a statistically significant improvement on joint effusion / swelling, thus evidencing an effect on inflammation.
Also in this trial, the subgroup of patients with moderate-to-severe pain experienced significant pain reduction when administered the combination CS plus glucosamine. On the other hand, the positive control (celecoxib) was not superior to placebo in this subset of patients.
In the other two recent large scale trials5,6 cited by the authors of this meta-analysis, the main outcome measure studied was joint space narrowing. CS evidenced in these two trials that it was able to preserve intra-articular joint space, as opposed to the placebo group. In the case of the trial by Michel et al., specifically designed to assess the disease modifying effect of CS, the assessment of pain was secondary and therefore, the included patients had very low baseline pain, making it difficult to evaluate the effect of the product on this parameter. In the case of the second study6, given that it has not been published, we have not been able to determine the levels of baseline pain in these patients.
It is also noteworthy that different clinical trials and a meta-analysis on CS published in the J Rheumatol7 concluded that CS was able to improve joint function (Lequesne index) as well as pain, thereby indirectly indicating that CS may have an effect on inflammation.
Another indirect sign of the clinical efficacy of CS is the reduction in the consumption of analgesics and NSAIDs8 in daily clinical practice. Evidently, this means important safety and pharmacoeconomical advantages. We should not forget that osteoarthritis is a chronic pathology, which mainly affects the elderly, often affected by high blood pressure, diabetes, etc. In these cases, the use of analgesics and NSAIDs needs to be carefully monitored for safety reasons.
As regards safety, all the clinical trials, meta-analyses and pharmacosurveillance conducted in Europe over 10 years have never reported any serious adverse events or pharmacological interactions with other drugs. This is an important matter in this clinical framework: old patients who may suffer concomitantly of high blood pressure, diabetes, etc. in whom the use of analgesics and NSAIDs is not exempt of risks.
Obviously, a better knowledge of the osteoarticular pathology to understand underlying mechanisms of osteoarthritis, a better or worse response on pain, etc, as well as ongoing clinical trials will provide more knowledge on this issue.
To my knowledge, and according to the data published in the literature, CS acts on inflammation preserving intra-articular joint space and helps improve functional capacity, reduce pain and at the same time reduces analgesic and NSAID consumption. Considering also its safety in the current clinical framework, I feel that its clinical use should be encouraged.
Dr. Josep Vergés MD, MSc, PhD
Professor of Pharmacology, Faculty of Medicine, University of Nancy (France)
Professor of Pharmacology, Faculty of Medicine, Autonomous University of Madrid (Spain)
Scientific Director BIOIBERICA
(1) Ronca F. et al. Anti-inflammatory activity of chondroitin sulfate. Osteoarthritis Cartilage 1998 (6); Supplement A:14-21.
(2) Monfort J, et al. Chondroitin sulfate and hyaluronic acid (500-730 KDa) inhibit stromelysin-1 synthesis in human osteoarthritic chondrocytes. Drugs Exptl Clin Res 2005; vol. 31(2): 71-76.
(3) Omata T, et al. Effects of Chondroitin sulfate-C on Articular Cartilage Destruction in Murine Collagen-induced Arthritis. Arzneim.-Forsch./Drug Res. 50(I), 148-153 (2000).
(4) Clegg DO, et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med. 2006 Feb 23;354(8):795-808.
(5) Michel B, et al. Chondroitins 4 and 6 sulfate in osteoarthritis of the knee. A randomized, controlled trial. Arthritis Rheum 2005, 52 (3): 779-786.
(6) Kahan A. STOPP (STudy on Osteoarthritis Progression Prevention): a new two-year trial with chondroitin 4&6 sulfate (CS). Accessed at www.ibsa-ch.com/eular_2006_amsterdam_vignon-2.pdf on 18 September 2006.
(7) Leeb F, et al. A meta-analysis of chondroitin sulfate in the treatment of osteoarthritis. The Journal of Rheumatology 2000; 27: 1: 205-211.
(8) Lagnaoui R et al. Less use of NSAIDs in long-term than in recent chondroitin sulphate users in osteoarthritis: a pharmacy-based observational study in France. Therapie. 2006 Jul-Aug;61(4):341-6.