Mechanisms of joint destruction, pain and disability in osteoarthritis.

Osteoarthritis is characterised by progressive erosion of articular cartilage, and bony overgrowth at the joint margins. Cartilage integrity requires a balance between synthesis and degradation of matrix components, and the latter is augmented in osteoarthritis through the action of chondrocyte-derived metalloproteinases. Synthesis rates also increase but fail to keep pace with the losses. Synovial inflammation, a mild and inconstant feature of osteoarthritis, is more likely to be a consequence of cartilage breakdown than a cause, and its contribution to pain is uncertain. The origins of pain and disability are complex; pathological changes in the joint capsule and periarticular ligaments are a likely source, but nocturnal pain may be related to raised pressure in subchondral bone. In addition to structural damage in the joint, psychosocial factors, muscle weakness, and comorbidities may contribute.