Because of its implications for prevention and treatment, how a clinician views osteoarthritis (OA) matters. In most cases, the real problem for the patient is not OA but painful OA. Synovial inflammation in OA results from mechanical damage to the articular cartilage and bone; therefore, it stands to reason that NSAIDs, although they may be symptomatically effective, cannot arrest the underlying process.
Efforts to develop disease-modifying OA drugs (formerly called chondroprotective drugs and now structure-modifying OA drugs) to interrupt or reverse the underlying pathogenetic processes have not succeeded. Foremost among the reasons, in this author’s opinion, is a failure to appreciate sufficiently that common, garden-variety OA—from its earliest stages and in whichever joint it occurs—is a mechanically induced and mechanically driven disease caused by an excessive level of mechanical stress (force/unit area) or by aberrant stress of a physiological magnitude acting on habitually loaded areas of the joint, resulting in local biochemically mediated damage.
In this 3-part article, I review the pathogenesis, diagnosis, and management of OA. This first part offers a contemporary, operational, evidence-based definition of the disease that has evolved from growing knowledge of its causes.1,2 In the second and third parts, to appear in upcoming issues of this journal, I will review the clinical aspects of OA, including diagnosis and diagnostic pitfalls, and approaches to treatment.
TO A DEFINITION
Of note, OA does not develop in all abnormal joints. Among patients who in childhood had hip dysplasia, slipped capital femoral epiphysis, or Legg-Calv-Perthes disease, conditions well known to predispose persons to hip OA, the frequency of OA at a 30-year follow-up evaluation was only 60% to 70%, not 100%.3 Although all patients had hips that were at increased risk for OA, the likelihood that OA would develop in a predisposed person presumably was affected by the severity of the structural abnormality, the amount of unprotected loading, and the adequacy of the mechanisms that normally protect joints from excessive mechanical stress.
Table 1 lists several facts that are relevant to a contemporary definition of OA. Although OA often is said to be a disease of weight-bearing joints (eg, the hip and knee) because most of the load on a synovial joint stems not from the ponderal mass but rather from the strength of contraction of the periarticular muscles, considering the joints as load-bearing joints is more appropriate.
The load across the small joints of the hand that is created by contraction of the powerful flexor digitorum profundus muscle may be roughly comparable to that across the knee or hip. The prevalence of OA is greater in distal interphalangeal joints than in proximal interphalangeal joints or metacarpophalangeal joints, possibly because the load-bearing surface available in the former is only about one-fourth to one-half as large as that in the latter and the underlying cushion of metaphyseal trabecular bone is thinner. Implicated as the cause of OA is not simply the force but also the concentration of that force across the joint and the rate of joint loading.
OA is organ failure of the
OA is the failure of an organ, the synovial joint. Just as the heart can fail because of a primary problem in the endocardium, myocardium, or epicardium, the joint can fail because of a primary problem in any of its tissues—ligaments, meniscus, subchondral bone, periarticular muscle, synovium, nerves, or articular cartilage—and OA can originate in any of them. Therefore, it is to be expected that there are many causes of OA, and there are.
For this reason, OA has no common pathophysiological pathway but only a final common end stage. The inflammatory changes in OA are secondary and are caused by particulate and soluble breakdown products of cartilage and bone.
Not just a“cartilage disease”
Although articular cartilage involvement is prominent in OA (Figure 1), by no means is OA merely a cartilage disease. This concept is reinforced by the generally poor correlation between the severity of cartilage loss (as reflected, eg, by radiographic joint-space narrowing) and the severity of symptoms. Also, among patients with knee OA who underwent an osteotomy (to relieve unacceptably high intra-articular stress), improvement 2 years later was unrelated to whether the articular surface was now hyaline cartilage or fibrocartilage or was denuded relative to that seen at a baseline arthroscopy—ie, the cartilage histology did not seem to affect the patient’s clinical status.4
Chondrocentric definitions that focus on the loss of articular cartilage have not helped understanding of the etiopathogenesis of OA, a concern different from that of the pathogenesis of articular cartilage damage caused by cytokines, tissue-degrading enzymes, and toxic oxygen radicals. Also, most current definitions of OA do not recognize that OA reflects a repair process intended to contain joint damage caused by a local mechanical problem. Under the appropriate conditions (correction of abnormal stress, joint motion, and establishment of a source of cells), joints with OA can heal—with structural and symptomatic improvement.5
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