Constitutional and metabolic factors associated with the development of Hand OA

与手部 OA 发生相关的体质和代谢因素

• 批准号: 8886165
• 负责人: Timothy E McAlindon
• 金额: $ 77.04万
• 依托单位: TUFTS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2018-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8886165
• 关键词: Activities of Daily Living; Advanced Glycosylation End Products; Age; Biological Markers; Biomechanics; Bone Density; Bone Spur; C-reactive protein; Cartilage; Cartilage Diseases; Characteristics; Clinical; Clinical Data; Cohort Studies; Computer Assisted; Computer-Assisted Image Analysis; Constitutional; Data; Degenerative polyarthritis; Dermal; Development; Disease; Distal; Enthesopathies; Epidemiology; Equation; Finger joint structure; Fluorescence; Fractals; Frequencies; Glucose; Hand; Hand Osteoarthritis; IL18 gene; IL5 gene; IL7 gene; IL8 gene; Image; Image Analysis; Incidence; Individual; Inflammation; Inflammatory; Influentials; Insulin; Insulin Resistance; Investigation; Joints; Leptin; Life; Measurement; Measures; Mechanics; Metabolic; Metabolic Pathway; Metabolic syndrome; Modeling; Morphology; Natural History; Obesity; Outcome; Pain; Pathogenesis; Pathologic Processes; Pathway interactions; Phenotype; Predisposing Factor; Prevalence; Preventive; Principal Component Analysis; Radial; Rare Diseases; Research; Research Personnel; Resources; Rheumatoid Arthritis; Risk; Risk Factors; Role; Sampling; Sentinel; Serum Proteins; Severities; Site; Skin; Testing; Therapeutic; Therapeutic Intervention; Thick; Thumb structure; Tissues; Width; adipokines; adiponectin; advanced disease; age related; base; blood glucose regulation; bone; bone health; glycation; public health relevance; resistin; statistics; tool

 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.

 描述（由申请人提供）：手部 OA (HOA) 是一种疼痛性、破坏性和变形性多关节疾病，会损害个人进行日常生活操作活动的能力，其发生频率高且与年龄密切相关，是其不可避免的基础。 HOA 的严重程度可以接近类风湿性关节炎，但与这种罕见的疾病形成鲜明对比的是，这种疾病的研究很少，也没有从中获益。已知影响其发展或进展的治疗方法是 OA 最常见和最具遗传性的表现，也是“普遍”OA 表型的前哨，虽然部位特异性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导致 HOA 的发生和进展，肥胖个体的 HOA 风险加倍，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。流行病学和临床数据表明，代谢综合征而非肥胖对 OA 的发生和严重程度影响更大。代谢综合征和 OA 的发病机制涉及常见代谢中间体的异常，然而，这些途径与 OA 发生和进展的关系。最近的研究还表明，HOA 的结构基础比单纯的软骨损失更广泛，具有不同的病理途径，包括骨赘增生、边缘和中央关节侵蚀。此外，关于 HOA 是否存在临床争议。糜烂性 HOA 是一个单独的实体，或者只是更晚期的疾病，我们将分析每年收集的纵向放射学数据、协变量和结果数据以及来自骨关节炎倡议（最大、最全面的 OA 队列研究）的生物样本，并进行半定量和定量研究。多个手关节的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 放射学、症状性和糜烂性 HOA 的发展。