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Pathogenesis of osteoarthritis

Richard F. Loeser, MD
Section Editor
David Hunter, MD, PhD
Deputy Editor
Monica Ramirez Curtis, MD, MPH


In the past, osteoarthritis (OA) was considered to be simply a degenerative “wear and tear” process and therefore often misnamed as degenerative joint disease. However, the pathogenesis of OA is much more complex than just wear and tear and the term “osteoarthritis,” where “-itis” is indicative of an inflammatory process, is indeed correct [1,2]. There are a variety of factors that play an important role in the pathogenesis of OA, including biomechanical factors, proinflammatory mediators, and proteases. By understanding the mechanisms driving joint tissue destruction in OA and identifying the key factors involved, new targets for therapy are emerging that will go beyond symptomatic relief to slowing or stopping the progression of OA [3].

This topic will review the pathogenesis of OA. The diagnosis, treatment, and other issues related to OA are discussed separately. (See "Initial pharmacologic therapy of osteoarthritis" and "Treatment of osteoarthritis resistant to initial pharmacologic therapy" and "Nonpharmacologic therapy of osteoarthritis" and "Overview of surgical therapy of knee and hip osteoarthritis" and "Investigational approaches to the management of osteoarthritis" and "Clinical manifestations and diagnosis of osteoarthritis".)


Classically, inflammatory arthritis was defined in part based on cellular inflammation represented by increased numbers of leukocytes in the affected joint tissues and synovial fluid. Classic cellular inflammation is not prominent in osteoarthritis (OA), where the number of leukocytes in the joint fluid is normally low, and rarely exceeds 1000 to 2000 cells per milliliter. This is in contrast to forms of inflammatory arthritis, such as rheumatoid arthritis (RA), where the number of synovial fluid leukocytes will commonly exceed 2000 and will be accompanied by a more extensive synovial infiltrate of leukocytes with synovial fibroblast proliferation resulting in pannus formation. Although synovial inflammation is also present in OA and in some individuals can be indistinguishable from RA, the inflammatory component of OA is best appreciated at the molecular level and is characterized by the presence of a host of proinflammatory mediators, including cytokines and chemokines, that are part of an innate immune response to joint injury [2].

As will be further discussed below, proinflammatory factors appear to be driving the production of the proteolytic enzymes responsible for the degradation of the extracellular matrix that results in joint tissue destruction. Although destruction and loss of the articular cartilage is a central component of OA, all joint tissues are affected in some way, indicating that OA is a disease of the joint as an organ [4]. Mechanical factors certainly play a key role in OA and there is some debate in the field as to the extent to which OA is mediated by abnormal joint mechanics. However, the balance of evidence suggests that rather than simply causing joint tissue damage by wear and tear, excessive or abnormal joint loading also stimulates joint tissue cells to produce proinflammatory factors and proteases that mediate joint tissue destruction. (See 'Inflammatory mediators' below and 'Proteases' below.)


Osteoarthritis (OA) is one of the most common causes of chronic disability in adults due to pain and altered joint function that result from characteristic pathologic changes in the joint tissues and their processing in a biopsychosocial context (figure 1). The pathological findings described below are present to varying degrees in all people with OA, suggesting a common response of the joint to a variety of insults.


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Literature review current through: Sep 2016. | This topic last updated: Jun 21, 2016.
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