Environmental Factors Associated with the Development of Osteoarthritis

项目总结 手部骨关节炎是一种疼痛的多关节疾病，会损害个人的执行能力 日常生活中的操纵性活动。手部骨关节炎一直是很少有研究的主题，也很少有 治疗选择。局部炎症、骨骼结构改变和代谢综合征是 手部骨性关节炎的发病机制。全氟和多氟烷基物质(PFAS)--合成 在美国人群中普遍检测到的抗油化学物质--可以在体内停留一段时间 时间长，影响炎症、骨代谢，以及导致骨关节炎的代谢因素。 全氟辛烷磺酸在20世纪50年代开始商业化。从那时起，骨关节炎的患病率在#年翻了一番 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，暴露于全氟辛烷磺酸可能会加剧骨关节炎的发展。而当 先前的研究激发了减少某些全氟辛烷磺酸产量的努力，但较旧的全氟辛烷磺酸仍在 新的全氟辛烷磺酸正在进入全球市场，可能会带来自身的健康风险。vt.给出 鉴于全氟辛烷磺酸的持续使用和污染规模，迫切需要进行纵向研究，以 阐明全氟辛烷磺酸与骨性关节炎的关系，并确定易感人群以告知公众 卫生政策和建议的治疗方法。我们的跨学科团队在以下方面拥有专业知识 骨关节炎和环境健康，将受益于每年收集的丰富数据和 来自骨关节炎倡议的生物样本，这是关于 骨性关节炎。此外，我们选择了手部放射学评估的病例队列样本。 骨关节炎以及全身骨骼健康、炎症和代谢因素的测量。为了实现我们的目标 总体目标是测试每一种全氟化铝及其混合物是否与手部骨关节炎有关，我们将 使用环境混合建模完成3个目标。具体地说，我们将确定全氟化肥是否会增加 手部骨关节炎发生的风险(目标1)，与关节疾病负担的较大变化有关 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了PFAS和骨性关节炎之间的关系。此外， 我们将考虑性别、年龄和肥胖作为影响因素，因为研究人员在 横断面研究。这项研究的发现将有助于为公共卫生政策提供信息，识别易感人群 人口，并建议治疗目标。

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.