Environmental Factors Associated with the Development of Osteoarthritis

与骨关节炎发展相关的环境因素

• 批准号: 10558833
• 负责人: Jeffrey B Driban
• 金额: $ 65.94万
• 依托单位: TUFTS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10558833
• 关键词: Address; Affect; Age; Architecture; Area; Articulation; Automobile Driving; Biological Assay; Body mass index; Bone Spur; Bone structure; Cartilage; Characteristics; Chemicals; Clinical; Clothing; Cohort Studies; Cross-Sectional Studies; Data; Data Set; Degenerative polyarthritis; Development; Diagnosis; Disease; Endocrine Disruptors; Environment; Environmental Health; Environmental Pollutants; Environmental Risk Factor; Exposure to; Functional disorder; Furniture; Goals; Hand; Hand Osteoarthritis; Hand' s disease; Health; Health Policy; Impairment; Incidence; Individual; Inflammation; Inflammation Mediators; Insulin Resistance; Interleukin-1 beta; Joints; Kellgren-Lawrence grade; Life; Longevity; Longitudinal Studies; Macrophage; Marketing; Measures; Mediating; Metabolic; Metabolic syndrome; Mission; Modeling; National Institute of Arthritis, and Musculoskeletal, and Skin Diseases; Obesity; Outcome; Oxidative Stress; Pain; Pain Research; Participant; Pathogenesis; Pathway interactions; Patient Self-Report; Peroxisome Proliferator-Activated Receptors; Poly-fluoroalkyl substances; Population; Predisposition; Prevalence; Production; Proliferating; Public Health; Reporting; Research; Research Personnel; Resistance; Risk; Risk Factors; Sampling; Serum; Severities; Strategic Planning; Structure; Sum; Synovitis; Testing; Therapeutic; Thumb structure; Time; Tissues; United States; Up-Regulation; Width; adipocyte differentiation; articular cartilage; base; bone; bone health; bone loss; bone metabolism; burden of illness; cohort; fatty acid oxidation; interest; mast cell; modifiable risk; novel; peer; perfluorooctane sulfonate; perfluorooctanoic acid; primary outcome; radiological imaging; response; secondary analysis; sex; therapeutic target

PROJECT SUMMARY Hand osteoarthritis is a painful polyarticular disorder that impairs an individual's ability to perform manipulative activities of daily life. Hand osteoarthritis has been the subject of little research and has few therapeutic options. Local inflammation, altered bone structure, and metabolic syndrome are pivotal to the pathogenesis of hand osteoarthritis. Per- and poly-fluoroalkyl substances (PFAS) – synthetically produced grease-resistant chemicals universally detectable in the United States population – can stay in the body for a long time and affect inflammation, bone metabolism, and metabolic factors that contribute to osteoarthritis. PFAS became commercially available in the 1950s. Since then, the prevalence of osteoarthritis has doubled in the United States – a finding that cannot simply be explained by increases in longevity or body mass index. Cross-sectional studies demonstrate that exposure to PFAS may exacerbate osteoarthritis development. While prior research has inspired efforts to reduce the production of certain PFAS, older PFAS persist in the environment, and newer PFAS are entering the global markets and may present their own health risk. Given the ongoing use of PFAS and the scale of contamination, there is an urgent need for longitudinal studies to clarify the relationship between PFAS and osteoarthritis and to identify susceptible populations to inform public health policies and suggest therapeutic approaches. Our interdisciplinary team, which has expertise in osteoarthritis and environmental health, will benefit from the wealth of annually collected data and biospecimens from the Osteoarthritis Initiative, the largest and most comprehensive cohort study of osteoarthritis. Furthermore, we selected a case-cohort sample with radiographic assessments of hand osteoarthritis and measures of systemic bone health, inflammation, and metabolic factors. To achieve our overall goal of testing whether each PFAS and a mixture of PFAS relate to hand osteoarthritis, we will complete 3 aims using environmental mixture modeling. Specifically, we will determine if PFAS increase the risk for hand osteoarthritis incidence (Aim 1) and relate with greater changes in disease burden, articular cartilage, and bone (Aim 2). We will also perform exploratory analyses to assess whether bone health, inflammation, and metabolic factors mediate the relationship between PFAS and osteoarthritis. Furthermore, we will consider sex, age, and obesity as effect modifiers because investigators reported these interactions in cross-sectional studies. The findings from this study will help inform public health policies, identify susceptible populations, and suggest therapeutic targets.

项目概要 手部骨关节炎是一种痛苦的多关节疾病，会损害个人的工作能力 日常生活中的操作活动对手部骨关节炎的研究很少。 局部炎症、骨治疗结构和代谢综合征是关键 全氟烷基物质和多氟烷基物质（PFAS）——合成产生的手部骨关节炎的发病机制。 在美国人中普遍可以检测到的抗油脂化学物质——可以在体内停留一段时间 时间长了会影响炎症、骨代谢以及导致骨关节炎的代谢因素。 自 20 世纪 50 年代 PFAS 上市以来，骨关节炎的患病率翻了一番。 美国——这一发现不能简单地用寿命或体重指数的增加来解释。 横断面研究表明，接触 PFAS 可能会加剧骨关节炎的发展。 先前的研究激发了减少某些 PFAS 生产的努力，但旧的 PFAS 仍然存在于 环境，而新型 PFAS 正在进入全球市场，并可能带来自身的健康风险。 鉴于 PFAS 的持续使用和污染规模，迫切需要进行纵向研究 澄清 PFAS 与骨关节炎之间的关系，并确定易感人群以告知公众 我们的跨学科团队拥有以下方面的专业知识： 骨关节炎和环境健康，将受益于每年收集的大量数据和 来自骨关节炎倡议的生物样本，这是最大、最全面的队列研究 此外，我们选择了一个病例队列样本，对手进行放射学评估。 骨关节炎和全身骨骼健康、炎症和代谢因素的措施以实现我们的目标。 测试每种 PFAS 和 PFAS 混合物是否与手骨关节炎相关的总体目标，我们将 使用环境混合物模型完成 3 个目标具体来说，我们将确定 PFAS 是否会增加。 手部骨关节炎发病风险（目标 1），并与疾病负担、关节疾病负担的更大变化相关 软骨和骨骼（目标 2）。我们还将进行探索性分析，以评估骨骼健康、 炎症和代谢因素介导 PFAS 与骨关节炎之间的关系。 我们将性别、年龄和肥胖视为影响调节因素，因为研究人员报告了这些相互作用 这项研究的结果将有助于为公共卫生政策提供信息，识别易感人群。 人群，并提出治疗目标。