Doubts Cast on Glucosamine-Chondroitin Trial Results

The publication this week of the second part of the Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT) has led to controversy.

The first part of the GAIT trial sought to determine whether these dietary supplements were effective in the treatment of pain caused by knee osteoarthritis and found that, in general, the combination of glucosamine (GLU) and chondroitin (CS) was the most effective treatment to reduce pain in patients suffering from mild to severe pain due to osteoarthritis (OA) [1].

The results of the second part of the GAIT trial, which was designed to determine whether GLU, CS, or a combination of the two could diminish the structural damage caused by OA, are inconsistent, mainly due to methodological limitations.

- The sample size was much smaller than initially planned.

Though the trial was designed so that 86% of the total number of patients would finish the trial, thus allowing differences to be detected, only 55% of them actually completed the entire two-year treatment period.

- Low sensitivity of the radiographic method.

The radiographic technique showed a precision error of 0.16 mm, which is exactly the amount of joint space lost by the placebo group in 2 years. A loss of 0.4 mm was initially considered to be clinically significant. - A progression of the disease was not observed in the placebo group in the two-year trial (no significant loss in joint space was detected). This inconsistency invalidates the interpretation of all the results. Moreover, these results are not consistent with a series of previously published clinical trials which examined the same outcome [2-7] – the narrowing of the space between joints – and demonstrated the clear benefits of GLU and CS supplementation. A meta-analysis study was recently published that endorsed the efficacy of CS as a way to stop the progression of OA[8]. The study analyzed four clinical trials carried out on a total of 1088 patients with knee osteoarthritis and concluded that CS at a dose of 800 mg reduced the loss of intra-joint space with an effect size of 0.26 (p < 0.0001), which represents a statistically significant effect.

Although future trials will need to include a more in-depth study of a radiographic methodology that makes it possible to accurately measure the progression of OA, the bottom line is that there is a large body of evidence supporting the use of glucosamine and chondroitin as a safe and effective treatment for OA. 1. 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 2. Reginster JY, et al. A two-year prospective, randomized, double-blind, controlled study assessing the effect of chondroitin 4&6 sulfate (CS) on the structural progression of knee osteoarthritis: STOPP (Study on Osteoarthritis Progression Prevention). Accepted for publication in the ACR journal Arthritis and Rheumatism. 3. Uebelhart D, Thonar EJ, Delmas PD, et al. Effects of oral chondroitin sulfate on the progression of knee osteoarthritis: a pilot study. Osteoarthritis Cartilage 1998;6 (Suppl A): 39–46 4. Uebelhart D, Malaise M, Marcolongo R, et al. Intermittent treatment of knee osteoarthritis with oral chondroitin sulfate: a one-year, randomized, double-blind, multicenter study versus placebo. Osteoarthritis Cartilage 2004;12:269–76 5. Michel BA, Stucki G, Frey D, et al. Chondroitins 4 and 6 sulfate in osteoarthritis of the knee: a randomized, controlled trial. Arthritis Rheum 2005;52: 779–86 6. Verbruggen G. et al. Systems to assess the progression of finger joint osteoarthritis and the effects of disease modifying osteoarthritis drugs. Clinical Rheumatology 2002; 21 (3): 231-241 7. Verbruggen G, et al. Chondroitin sulfate: S/DMOAD (structure/disease modifying anti-osteoarthritis drug) in the treatment of finger joint OA. Osteoarthritis Cartilage 1998; 6, (Supplement A): 37-38 8. The rate of decline of joint space width in patients with osteoarthritis of the knee: a systematic review and meta-analysis of randomized placebo-controlled trials of chondroitin sulfate. Curr Med Res Opin. 2008, 24 (11): 3029-3035.

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