Identifying periods of susceptibility to perfluoroalkyl substances and bone mineral density in early adolescence: the HOME Study

Abstract

BACKGROUND AND AIM: Perfluoroalkyl substance (PFAS) exposures may affect childhood bone mineral density (BMD), but no studies have assessed periods of heightened susceptibility. We estimated associations of individual PFAS and their mixture during gestation and three times during childhood with BMD in early adolescence. METHODS: We examined 222 mother-child pairs enrolled in a prospective pregnancy and birth cohort in Cincinnati, OH from 2003-2006. We measured concentrations of perfluorooctanoic acid (PFOA), perfluorononanoic acid, perfluorohexanesulfonic acid, and perfluorooctanesulfonic acid in maternal serum collected at 16 weeks gestation and child serum collected at age 3, 8, and 12 years. At age 12 years, we measured areal BMD at six skeletal sites with dual x-ray absorptiometry and calculated height-, age-, sex-, and population ancestry-specific BMD Z-scores. Using linear regression, we estimated covariate-adjusted differences in BMD Z-scores per doubling of PFAS concentrations at each period. Using hierarchical Bayesian kernel machine regression (hBKMR), we estimated period-specific associations and posterior inclusion probabilities (PIPs) to determine periods of heightened susceptibility to PFAS mixtures. RESULTS:Associations were strongest for PFOA and forearm (1/3 distal radius) BMD, with differing periods of susceptibility for males and females. Among males, forearm BMD Z-score differences (95% confidence interval) per doubling of PFOA were -0.26 (-0.50, -0.02), -0.33 (-0.68, 0.02), -0.24 (-0.61, 0.13), and -0.00 (-0.30, 0.29) for gestation and ages 3, 8, and 12, respectively. Among females, the corresponding estimates were -0.12 (-0.38, 0.15), -0.07 (-0.44, 0.30), -0.30 (-0.76, 0.17), and -0.44 (-0.81, -0.07). Patterns were generally similar but weaker for other PFAS and skeletal sites. Period-specific PIPs from hBKMR models were highest for the PFAS mixture at age 8 for males (0.76) and age 12 for females (0.62). CONCLUSIONS:PFOA and PFAS mixtures were associated with lower BMD in early adolescence. Susceptibility to PFAS may occur earlier in life for males compared with females. KEYWORDS: Chemical exposures, Children's environmental health, Mixtures analysis, PFAS, Endocrine disrupting chemicals, Environmental epidemiology