Objective: To explore whether biologic levels of specific per- and polyfluoroalkyl substances (PFAS) and a mixture of PFAS-reflecting the overall effect and accounting for correlations among PFAS-relate to incident hand osteoarthritis (HOA) and progression.
Methods: Among a case-cohort sample from the Osteoarthritis Initiative (n = 1,878), we examined associations of eight PFAS in serum with odds of developing over the subsequent 4 years (1) symptomatic HOA and (2) an increased number of joints with radiographic osteoarthritis (Kellgren-Lawrence ≥2; yes/no). We used weighted logistic regression to assess single PFAS (continuous and quartiles) and quantile g-computation to assess the PFAS mixture in relation to our primary outcomes.
Results: Participants were primarily female (58%) and on average aged 62 years and overweight (mean body mass index = 28.6 kg/m2). Participants with higher perfluorodecanoic acid (PFDA) and perfluorononanoic acid (PFNA; continuous variables) had greater odds of incident symptomatic HOA (odds ratio [OR] [95% confidence interval (CI)] per interquartile range increment: PFDA 1.12 [1.05-1.20]; PFNA 1.07 [1.00-1.13]), but associations were not monotonic when these PFAS were represented in quartiles. Participants with higher perfluorohexane sulfonic acid had lower odds of incident HOA (eg, OR 0.94 [95% CI 0.88-1.00] per interquartile range increment). We observed no other consistent associations between PFAS and either outcome.
Conclusion: We observed possible associations of PFDA and PFNA serum concentrations with symptomatic HOA incidence, but we otherwise found no consistent evidence that greater PFAS concentrations relate to a greater chance of developing HOA incidence or progression.
© 2025 The Author(s). Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.