Clinical aspects, pathology and pathophysiology of osteoarthritis.

Osteoarthritis (OA) is the most common joint disorder, and there is evidence that a majority of individuals over the age of 65 have radiographic and/or clinical evidence of OA. The most frequently affected sites are the hands, knees, hips and spine. Importantly, the symptoms are often associated with significant functional impairment, as well as signs and symptoms of inflammation, including pain, stiffness and loss of mobility 1. Anatomic analysis and application of histopatho-logical and imaging techniques have helped to define the natural history of OA with respect to the structural alterations in the articular cartilage 1-6. They also have demonstrated that OA is not exclusively a disorder of articular cartilage. Multiple components of the joint are adversely affected by OA, including the peri-articular bone, synovial joint lining and adjacent supporting connective tissue elements 1-6. The characteristic structural changes in OA include the progressive loss of articular cartilage, increased subchondral plate thickness, formation of new bone at the joint margins (osteophytes) and the development of subchondral bone cysts 7-9. In addition, at the junction of the articular hyaline cartilage and adjacent subchondral bone, in the region of the so-called tidemark, there is a remnant of calcified cartilage. As OA progresses, there is evidence of vascular invasion and advancement of this zone of calcified cartilage into the artic-ular cartilage that further contributes to a decrease in artic-ular cartilage thickness 2,10-14. These structural alterations in the articular cartilage and peri-articular bone may lead to modification of the contours of the adjacent articulating surfaces 7-9,15,16. These changes, as well as the accompanying alterations in subchondral bone remodeling and modulus, may further contribute to the development of an adverse biomechanical environment and enhance the progression of the articular cartilage deterioration 15-19. Multiple factors have been shown to affect the progression of OA, including the presence of polyarticular disease, increasing age, associated intra-articular crystal deposition, obesity, joint instability and/or malalignment, muscle weakness and peripheral neuropathy 1,20-22. These factors can be segregated into categories that include hereditary contributions , mechanical factors and the effects of ageing. There are several lines of evidence indicating that genetic factors contribute to the risk of OA 23,24. These include the results of epidemiological studies, analysis of patterns of familial clustering, twin studies and the characterization of rare genetic disorders. For example, twin studies have shown that the influence of genetic factors may approach 70% in certain skeletal sites. Linkage analyses and …