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.

项目摘要 手骨关节炎是一种痛苦的多节性疾病，会损害个人的表现能力 日常生活的操纵活动。手骨关节炎是很少的研究的主题，很少 治疗选择。局部注射，改变的骨结构和代谢综合征对 手骨关节炎的发病机理。每种和多氟烷基物质（PFA） - 合成产生的 在美国人群中可以普遍检测到的耐油脂化学物质可以留在体内 长时间并影响导致骨关节炎的感染，骨代谢和代谢因子。 PFA在1950年代获得了商业上的可用性。从那以后，骨关节炎的患病率增加了一倍 美国 - 这一发现不能简单地通过长寿或体重指数的增加来解释。 横断面研究表明，暴露于PFA可能会加剧骨关节炎的发育。尽管 先前的研究激发了减少某些PFA的生产的努力，较老的PFA持续存在 环境和较新的PFA正在进入全球市场，并可能出现自己的健康风险。给出 持续使用PFA和污染规模，迫切需要纵向研究 澄清PFA与骨关节炎之间的关系，并确定易感人群以告知公众 健康政策并提出治疗方法。我们的跨学科团队，具有专业知识 骨关节炎和环境健康将受益于每年收集的数据和 骨关节炎倡议的生物测量，这是最大，最全面的队列研究 骨关节炎。此外，我们选择了一个带有射线照相评估的案例 - 霍特样本 骨关节炎和全身性骨骼健康，感染和代谢因素的测量。实现我们的 测试每个PFA和与手骨关节炎有关的PFA的混合物的总体目标，我们将 完整的3个目标使用环境混合物建模。具体来说，我们将确定PFA是否增加 手动骨关节炎的风险（AIM 1），与伯恩疾病的变化更大，关节 软骨和骨头（目标2）。我们还将进行探索性分析，以评估骨骼健康是否 炎症和代谢因子介导PFA和骨关节炎之间的关系。此外， 我们将性别，年龄和肥胖视为效果修饰符，因为研究人员报告了这些相互作用 横断面研究。这项研究的发现将有助于告知公共卫生政策，确定易感性 人群，并建议治疗靶标。