Association of perfluoroalkyl substance (PFAS) on vitamin D biomarkers in a highly exposed population of the Veneto Region in Italy

Perfluoroalkyl substances (PFASs) raise concerns about their environmental accumulation. Experimental data have suggested that PFASs interfere with bone metabolism from the early stages of life. However, mechanisms underlying this association are unclear. The aim of this study was to evaluate the possible association between environmental exposure to PFAS and vitamin D (VitD), serum calcium and parathyroid hormone (PTH) levels in subjects residing in high-exposure area of the Veneto Region of Italy. In this cross-sectional observational study, 1174 subjects who previously adhered to the 2016-2018 Regional Surveillance Plan for plasma levels of PFASs were recalled in 2023 and evaluated for demographic, anthropometrics and blood analyses. Data on nutritional habits and VitD supplementation were obtained by a dedicated questionnaire. Serum concentrations of PFASs, calcium, 25-hydroxy-vitamin D (25OH-VitD) and PTH were determined from blood sampling. Perfluorooctanoic acid (PFOA), perfluorooctanesulfonate (PFOS) and perfluorohexanesulfonic acid (PFHxS) were the only three PFASs, of 12, quantifiable in at least 90% of the samples and considered for further analyses. Generalized additive models, using linear regression and smoothing thin plate splines, detected a positive association between serum calcium and all considered PFAS (PFOA: β = 0.03; CI 95% 0.01-0.06; PFOS: β = 0.06; CI 95% 0.02-0.09, PFHxS: β = 0.04; CI 95% 0.01-0.06). Estimated degrees of freedom (EDF) analysis showed the approximately linear association between serum calcium with PFOA (EDF = 1.89) and PFHxS (EDF = 1.21), but not for PFOS (EDF = 3.69). Differently, PFAS levels showed no association with either 25-hydroxy-vitamin D or PTH, except for ln-transformed 25OH-D and PFOS (β = 0.04; CI 95% 0.00-0.08). Stratified analyses confirmed the positive association between all considered PFAS and calcium in subjects not taking a VitD supplementation. Results show that high exposure levels to PFAS may interfere with calcium metabolism, independently of lifestyle and dietary factors. Further elucidation on the mechanisms underlying calcium homeostasis disruption, including multiple binding-equilibrium with serum albumin, remains to be addressed.