Constitutional and metabolic factors associated with the development of Hand OA

 描述（由申请人提供）：手OA（HOA）是一种疼痛、破坏性和变形性多关节疾病，损害个体进行日常生活操作活动的能力。它的高频率和与年龄的强烈联系一直是归因于不可避免的关节变性和治疗虚无主义的基础。HOA的严重程度可以接近类风湿性关节炎的严重程度，但与此形成鲜明对比的是，这种罕见的疾病几乎没有研究，并且没有已知的治疗方法可以影响其发展或进展。手关节受累是OA最常见和最易遗传的表现，是“泛发性”OA表型的标志。虽然特定部位的生物力学因素对其发展有影响，但也有证据表明骨骼健康和体质因素易导致HOA的发生和进展。肥胖个体HOA的风险增加一倍，这种关联更可能归因于全身因素，而不是超负荷的机械效应。事实上，最近的流行病学和临床数据表明，代谢综合征而不是肥胖对OA的发生和严重程度有更大的影响。代谢综合征和OA的发病机制涉及常见代谢中间产物的异常，然而，这些途径与HOA的发生和进展的关系仅在有限程度上进行了探索。最近的研究还表明，HOA的结构基础比单独的软骨损失更广泛，具有不同的病理途径，包括骨赘病，边缘和中央关节侵蚀。此外，临床上对于糜烂性HOA是否是一个独立的实体，或者仅仅是更晚期的疾病存在争议。我们将分析每年收集的纵向放射学、协变量和结局数据，以及来自骨关节炎倡议（最大最全面的OA队列研究）的生物标本，并对多个手关节进行半定量和计算机辅助图像测量，以评估和对比结构和代谢特征的作用。 在影像学、症状性和糜烂性HOA的发展中。

 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.