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OSTEOARTHRITIS: SYMPTOM CONTROL AND RETARDING DISEASE PROGRESSION

Chondroitin sulfate appears to produce a slow but gradual reduction of the clinical symptoms of OA. Multiple human clinical trials lasting from a few weeks to 3 years have shown that chondroitin sulfate can significantly alleviate symptoms of pain and improve function in patients with OA of the knee (Bourgeois et al 1998, Bucsi & Poor 1998, Fioravanti et al 1991, Lazebnik 2005, Mazieres et al 2001, Morreale et al 1996, Oliviero et al 1991, Rovetta 1991) and that these effects last months after the cessation of treatment (Mazieres et al 2005), as well as being evident with intermittent treatment (Uebelhart et al 2004).

A meta-analysis of 7 trials of 372 patients taking chondroitin sulfate found at least 50% improvement in pain and function in the chondroitin sulfate group compared with placebo (Leeb et al 2000). A meta-analysis of 1 5 trials of the use of glucosamine and/or chondroitin raised quality issues about many studies, but found moderate to large clinical effects from these agents, suggesting that they do have efficacy in treating OA (McAlindon et al 2000).

There is also evidence from double-blind clinical trials that chondroitin can reverse, retard or stabilise the pathology of OA (Volpi 2005), as evidenced by stabilisation of the joint space (Uebelhart et al 1998b), less progression of erosions (Rovetta et al 2002, Verbruggen et al 1998) and improved articular cartilage thickness (Pipitone et al 1992) and interarticular space, as observed by X-rays (Conrozier 1998, Michel et al 2005, Uebelhart et al 2004). A subanalysis of patients involved in the GAIT study (see below and Glucosamine monograph) further suggests that chondroitin sulfate may have differential effects on OA symptoms depending on the degree of radiographic involvement, and that chondroitin may provide improvements in knee pain in patients with relatively early radiographic disease (Clegg et al 2005). Comparisons with NSAIDs Although chondroitin appears to be at least as effective as NSAIDs in treating the symptoms of OA (Fioravanti et al 1991, Morreale et al 1996), it has a slower onset of action, taking 2-4 months to establish an effect (Leeb et al 2000, Morreale et al 1996). Chondroitin may, however, provide benefits that persist after treatment is stopped (Mazieres et al 2001, Morreale et al 1996). Combined use of chondroitin sulfate and glucosamine sulfate Chondroitin and glucosamine are frequently marketed together in combination products and some studies suggest that this combination is effective in treating symptoms (Das & Hammad 2000, Leffler et al 1999, McAlindon et al 2000, Nguyen et al 2001) and reducing joint space narrowing (Rai et al 2004). These findings are supported by an in

vitro study on horse cartilage that found that a combination of glucosamine and chondroitin was more effective than either product alone in preventing articular cartilage glycosaminoglycan degradation (Dechant et al 2005), as well as an in vivo study on rats that found that the combined treatment prevented the development of cartilage damage and was associated with a reduction in IL-1 -beta and matrix metalloprotease-9 synthesis (Chou et al 2005). The recent GAIT trial (see Glucosamine monograph) provides further evidence that glucosamine and chondroitin are more effective when given in combination than when either substance is given alone, with the combined treatment being more effective than the COX-2 inhibitor celecoxib for treating moderate to severe arthritis compared with chondroitin alone (Clegg et al 2006).

A small RCT has suggested that the addition of high-molecular-weight hyaluronate to glucosamine and chondroitin may provide additional benefits to the use of glucosamine and chondroitin alone (Bucci et al 2005). Topical preparations A topical preparation containing chondroitin with glucosamine and camphor has been shown to reduce pain from OA of the knee in one RCT (Cohen et al 2003).

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