Per- and Polyfluoroalkyl Substances and Knee Osteoarthritis: Data From the Osteoarthritis Initiative

To examine whether concentrations of specific per- and polyfluoroalkyl substances (PFAS) and a mixture of PFAS relate to incident knee osteoarthritis (KOA) and knee pain progression.

Among a case-cohort sample from the OA Initiative (n = 1,878), we examined associations of serum concentrations of eight PFAS with odds of developing over the subsequent 48 months (1) symptomatic KOA and (2) a clinically meaningful change in the Western Ontario and McMaster Universities OA Index knee pain score. 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 outcomes, accounting for sociodemographics.

Fifty-eight percent of participants were female with a mean age of 62 years and body mass index of 28.6 kg/m². Participants with higher perfluorooctanoic acid (continuous) had greater odds of incident symptomatic KOA (odds ratio [OR] per interquartile range [IQR] 1.12, 95% confidence interval [CI] 1.04-1.21). Participants in the highest quartiles of perfluorononanoic acid (PFNA) had greater odds of incident symptomatic KOA [OR for the third quartile 1.63, 95% CI 1.29-2.07; fourth quartile 1.55, 95% CI 1.19-2.01). Perfluorooctanoic acid may have a nonlinear relationship with the greatest chance of incident symptomatic KOA with serum concentrations between 5.19 and 6.88 ng/mL (OR 1.55, 95% CI 1.21-1.97). Participants with greater perfluorooctanoic acid and PFNA (continuous) had greater odds of knee pain progression (OR per IQR: perfluorooctanoic acid 1.10, 95% CI 1.03-1.18; PFNA 1.06, 95% CI 1.01-1.11). Mixture models showed perfluorooctanoic acid and PFNA were among the PFAS with the strongest positive weights for both outcomes.

In a large cohort at risk for KOA, higher perfluorooctanoic acid and PFNA serum concentrations may be associated with a greater likelihood of symptomatic KOA incidence and knee pain progression.