Constitutional and metabolic factors associated with the development of Hand OA

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 DESCRIPTION (provided by applicant): Hand OA (HOA) is a painful, destructive and deforming polyarticular disorder that impairs an individual's ability to perform manipulative activities of daily life. Its high frequency and strong association with age has been the basis of attribution to inevitable joint degeneration, and of therapeutic nihilism. The severity of HOA can approach that of rheumatoid arthritis, yet in stark contrast to that rarer disorder has been the subject of little research and benefits from no treatments known to effect its development or progression. Involvement of hand joints is the commonest and most heritable manifestation of OA and is a sentinel for the `generalized' OA phenotype. While site-specific biomechanical factors are influential in its development, there is also evidence that bone health and constitutional factors predispose to incidence and progression of HOA. Risk of HOA is doubled in obese individuals, an association more plausibly attributable to systemic factors than the mechanical effect of overload. Indeed, recent epidemiological and clinical data indicate that metabolic syndrome rather than obesity has the greater impact on the initiation and severity of OA. The pathogenesis of metabolic syndrome and OA involve abnormalities in common metabolic intermediates, however, the relationship of these pathways to the development and progression of HOA has been explored to only a limited extent. Recent investigations also indicate that the structural basis for HOA is broader than cartilage loss alone, with distinct pathological pathways that include osteophytosis, marginal and central joint erosion. Also, there is clinical controversy about whether erosive HOA is a separate entity, or simply more advanced disease. We will analyze annually-collected longitudinal radiographic, covariate and outcome data, and biospecimens from the Osteoarthritis Initiative, the largest most comprehensive cohort study of OA, and perform semi- quantitative and computer-aided image measurements across multiple hand joints to evaluate and contrast the roles of structural and metabolic characteristics in the development of radiographic, symptomatic and erosive HOA.