title: Osteoarthritis of the knee and hip. Part I: aetiology and pathogenesis as a basis for pharmacotherapy.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  Key features of the pathological joint changes in OA include: cartilage destruction by pro-inflammatory cytokines, matrix metalloproteinases 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 in OA pathogenesis, the source of pain likely stems from the richly innervated synovium, subchondral bone and periosteum components of the joint. Tissue damage during joint degeneration generates nociceptive stimuli. The presence of inflammatory mediators, including bradykinin, prostaglandins and leukotrienes, lowers the threshold of the Aδ and C pain fibres, resulting in a heightened response to painful stimuli.
  
  
  CONCLUSIONS
  It 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.
authors.affiliation: Department of Medicine, McMaster University Faculty of Health Sciences, Hamilton, ON, Canada.
authors.forename: Aleem
authors.initials: A
authors.lastname: Adatia
authors.forename: K D
authors.initials: KD
authors.lastname: Rainsford
authors.forename: Walter F
authors.initials: WF
authors.lastname: Kean
mesh_terms: D018771:Arthralgia; D002358:Cartilage, Articular; D006615:Hip / Q000473:pathology*; D006621:Hip Joint / Q000473:pathology*; D006801:Humans; D018836:Inflammation Mediators; D007717:Knee / Q000473:pathology*; D007719:Knee Joint / Q000473:pathology*; D015207:Osteoarthritis, Hip / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D020370:Osteoarthritis, Knee / Q000188:drug therapy / Q000209:etiology / Q000473:pathology
chemical_list: D018836:Inflammation Mediators