Perfluoroalkyl substances and changes in bone mineral density: A prospective analysis in the POUNDS-LOST study

Background: Recent studies suggested an inverse association between exposures to perfluoroalkyl substances (PFASs) and bone mineral density (BMD). Whether exposures to PFASs are also associated with changes in BMD has not been examined. Methods: Five major PFASs (perfluorooctanesulfonic acid, PFOS; perfluorooctanoic acid, PFOA; per-fluorohexanesulfonic acid, PFHxS; perfluorononanoic acid, PFNA; perfluorodecanoic acid, PFDA) and BMD (g/cm(2)) at six bone sites (spine, total hip, femoral neck, hip intertrochanteric area, hip trochanter, and hip Ward's triangle area) were measured at baseline among 294 participants in the POUNDS-LOST study, a weight-loss trial, of whom a total of 175 participants had BMD measured at both baseline and year 2. Linear regression was used to model the differences or changes in BMD for each SD increment of PFAS concentrations. In a secondary analysis, interactions between PFASs and baseline body mass index (BMI), as well as a BMI-related genetic risk score (GRS) derived from 97 BMI-predicting SNPs were examined in relation to changes in BMD. Results: At baseline, both PFOS and PFOA were significantly associated with lower BMD at several sites. For each SD increase of PFOS, the beta s (95% CIs) for BMD were -0.020(-0.037, - 0.003) for spine, -0.013(-0.026, 0.001) for total hip, -0.014(-0.028, 0.000) for femoral neck, and -0.013(-0.026, 0.000) for hip trochanter. For PFOA, the corresponding figures were - 0.021(-0.038, - 0.004) for spine, - 0.015(-0.029, - 0.001) for total hip, and - 0.015(-0.029, - 0.002) for femoral neck. After adjusting for baseline covariates and 2-year weight change, higher baseline plasma concentrations of PFOS, PFNA, and PFDA were associated with greater reduction in BMD in the hip; the beta s (95% CIs) were -0.005(-0.009, - 0.001), -0.006(-0.010, - 0.001), and -0.005(-0.009, - 0.001), respectively. Similar associations were found in hip intertrochanteric area for all PFASs except PFHxS, with beta s ranging from - 0.006 for PFOA to - 0.008 for PFOS and PFNA. Participants with a higher GRS tended to have less PFAS-related BMD decline in total hip (P-interaction = 0.005) and the hip intertrochanteric area (P-interaction = 0.021). There were similar PFAS-related BMD changes by baseline BMI levels, although the interactions did not achieve statistical significance. Conclusions: This study demonstrated that higher plasma PFAS concentrations were not only associated with a lower BMD at baseline, but also a faster BMD loss in a weight-loss trial setting. Genetic predisposition to larger body size may somewhat attenuate the deleterious effects of PFASs on BMD. Further exploration of the possible impact of PFAS exposures on bone density is warranted.