Etiopathogenesis of osteoarthritis.

Because of the implications for prevention and treatment, how a clinician views osteoarthritis (OA) matters. We view OA as an attempt to contain a mechanical problem in the joint and as failed repair of damage caused by excessive mechanical stress on the joint. OA is organ failure of the synovial joint. Because of insufficient focus on reduction of the habitually loaded contact area of the joint and on aberrant loading, we believe that therapeutic efforts aimed at pathogenetic mechanisms in OA have been misdirected: neither the large role that a reduction of excessive levels of mechanical stress plays in promoting the healing response in OA nor the evidence that relief of joint pain and improvement in function, rather than the appearance of the articular surface, are the most important outcomes of the healing process have been sufficiently emphasized. Various mechanical abnormalities can trigger the processes involved in repair and attempts by the joint to contain the mechanical insult, but without a return to mechanical normality, attempts at healing will fail. In our view, drugs may be helpful symptomatically, but cannot accomplish this. In our view, as long as the joint remains in the same adverse mechanical environment that got it into trouble in the first place, it is unlikely that a drug that inhibits a specific enzyme or cytokine in the pathways of cartilage breakdown, or further stimulates the already increased synthesis of cartilage matrix molecules will solve the problem of OA. Also, because the subchondral bone is critically important in containing the mechanical abnormalities that damage the cartilage, emphasis on cartilage repair alone is likely to be futile. On the other hand, if the abnormal stresses on the joint are corrected, intervention with a structure-modifying drug may be superfluous.