Constitutional and metabolic factors associated with the development of Hand OA

 描述(申请人提供)：手性骨性关节炎(HOA)是一种疼痛、破坏性和变形性的多关节疾病，损害个人进行日常生活操控活动的能力。它的高频率和与年龄的强烈关联一直是归因于不可避免的关节退变和治疗性虚无主义的基础。HOA的严重程度可以接近类风湿性关节炎，但与这种更罕见的疾病形成鲜明对比的是，几乎没有研究的主题，也没有任何已知的治疗方法来影响其发展或进展。手关节受累是骨性关节炎最常见和最可遗传的表现，也是“全面性”骨性关节炎表型的前哨。虽然特定部位的生物力学因素在其发生发展中有影响，但也有证据表明骨健康和体质因素容易导致HOA的发生和发展。肥胖者患HOA的风险增加了一倍，这种关联更有可能归因于系统性因素，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骨性关节炎的开始和严重程度有更大的影响。代谢综合征和骨性关节炎的发病机制涉及常见代谢中间产物的异常，然而，这些途径与骨性骨性关节炎发生发展的关系目前还没有得到很好的研究。最近的研究还表明，HOA的结构基础比单纯的软骨丢失更广泛，有不同的病理途径，包括骨赘、边缘和中央关节侵蚀。此外，对于侵袭性HOA是一个独立的实体，还是仅仅是更晚期的疾病，临床上也存在争议。我们将分析每年收集的纵向放射学、协变量和结果数据，以及来自骨关节炎倡议的生物显微镜，这是最大的、最全面的骨关节炎队列研究，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。 在放射学、症状性和侵袭性骨关节炎的发展过程中。

 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.