Recent developments in the treatment of osteoarthritis

Abstract

1. Summary Osteoarthritis (OA) is a worldwide heterogeneous group of conditions that lead to joint symptoms and signs which are associated with defective integrity of articular cartilage, in addition to related changes in the underlying bone at the joint margins. The prevalence of the disease after the age of 65 years is about 60% in men and 70% in women. The aetiology of OA is multifactorial, with the end result being mechanical joint failure and varying degrees of loss of joint function. The pathophysiological events associated with OA are beginning to be understood. Inflammatory cytokines such as interleukin-1 (IL-1) and tumour necrosis factor-α (TNF-α) are involved, and these initiate a vicious cycle of catabolic and degradative events in cartilage mediated by metalloproteinases, which degrade cartilage extracellular matrix. The role of inflammation in the pathophysiology and progression of early OA is supported further by the observation that C-reactive protein (CRP) levels are raised in women with early knee OA, and higher levels predicted those whose disease would progress. Nitric oxide (NO) is another potent pro-inflammatory chemical released during inflammation. Cartilage from patients with rheumatoid arthritis (RA) and OA spontaneously produces NO in vitro, and in experimental OA, NO induces chondrocyte apoptosis, thus contributing to cartilage degradation. Hence, dysregulated NO production in humans plays a part in the pathophysiology of the disease. These recent observations suggest that therapy can now be targeted at specific pathophysiological pathways involved in the pathogenesis of OA. The