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: 9043813
• 负责人: Timothy E McAlindon
• 金额: $ 70.37万
• 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/9043813
• 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; Health; IL18 gene; IL5 gene; IL7 gene; IL8 gene; Image; Image Analysis; Incidence; Individual; Inflammation; Inflammatory; Influentials; Insulin; Insulin Resistance; Interleukin-1 beta; 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; joint destruction; 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（由应用提供）：手OA（HOA）是一种痛苦，破坏性和变形的多关节疾病，会损害个人进行日常生活的操纵活动的能力。它的高频和与年龄的牢固关联一直是不可避免的关节变性和热虚无主义的基础。 HOA的严重程度可以接近类风湿关节炎的严重性，但是与这种稀有疾病形成鲜明对比的是很少的研究和受益，而没有已知的治疗方法会影响其发育或进展。手关节的参与是OA的最常见，最可遗传的表现，是“概括” OA表型的前哨。尽管位点特异性的生物力学因素在其发育中受到影响，但也有证据表明，骨骼健康和宪法因素易于发病和进展。 HOA的风险在肥胖个体中增加了一倍，这种关联比系统因素更可取，而不是超负荷的机械效应。确实，最近的流行病学和临床数据表明，代谢综合征而非肥胖对OA的主动性和严重程度的影响更大。代谢综合征和OA的发病机理涉及常见代谢中间体的异常，但是，这些途径与HOA发展和进展的关系仅在有限的程度上探索了。最近的投资还表明，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，包括骨植物学，边际和中央关节侵蚀。同样，关于侵蚀性HOA是独立的实体还是更晚期疾病也存在临床争议。我们将分析每年收集的纵向射线照相，协变量和结果数据，以及来自骨关节炎倡议的生物测量，这是OA的最大最全面的队列研究，并进行半定量和计算机辅助的图像测量，以评估和对比结构和形成构成结构和构成框架的尖动。 在射线照相，有症状和侵蚀性HOA中。