Osteoarthritis of the knee and hip. Part I: aetiology and pathogenesis as a basis for pharmacotherapy

Objectives Osteoarthritis (OA) of the knee and hip is among the most frequent and debilitating arthritic conditions. Aside from surgical intervention in severe cases, conventional treatment involves relieving painful symptoms with non-steroidal anti-inflammatory drugs (NSAIDs), narcotic and non-narcotic (weak) analgesics and physical therapy. To obtain insight into the extent of pathological changes in hip and knee OA we reviewed current literature on the pathogenesis of this state as a basis for current pharmacotherapy options. Key findings Key features of the pathological joint changes inOA include: cartilage destruction by pro- inflammatory cytokines, matrixmetalloproteinases and prostaglandins, which promote a catabolic environment; subchondral bone remodelling and resorption; hypertrophic differentiation of chondrocytes; neovascularisation of synovial tissue; and focal calcification of joint cartilage. Despite the central involvement of hyaline cartilage inOApathogenesis, the source of pain likely stems fromthe richly innervated synovium, subchondral bone and periosteum components of the joint. Tissue damage during joint degeneration generates nociceptive stimuli. The presence of inflammatorymediators, including bradykinin, prostaglandins and leukotrienes, lowers the threshold of the Ad and C pain fibres, resulting in a heightened response to painful stimuli. SummaryIt is our opinion that it is important to base and centre the management of OA patients on the severity of patient- important outcomes, rather than purely an assessment of damage to the joint. The joint damage, as interpreted from radiographs, is not necessarily representative of the symptoms experienced. The management of OA primarily comprises pharmacological therapy, surgical interventions and various non- pharmacological interventions.