Environmental Factors Associated with the Development of Osteoarthritis

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.