Serum PFAS and Urinary Phthalate Biomarker Concentrations and Bone Mineral Density in 12-19 Year Olds: 2011-2016 NHANES

Abstract

Context: Per- and polyfluoroalkyl substances (PFAS) and phthalates are 2 families of environmental endocrine disruptors that may be associated with areal lower bone mineral density (aBMD).

Objective: To examine associations between serum PFAS and urinary phthalate biomarker concentrations and their mixtures with aBMD Z-scores in adolescents.

Design, patients, and measures: We examined serial cross-sectional data from male (n = 453) and female (n = 395) 12- to 19-year-old participants in the 2011 through 2016 National Health and Nutrition Examination Survey with measures of serum PFAS, urinary phthalate metabolites, and dual-energy X-ray absorptiometry aBMD Z-scores (total body less head). In sex-specific models, we used linear regression to examine associations of individual PFAS and phthalate biomarkers with aBMD Z-scores, and Bayesian kernel machine regression to examine the association of the overall PFAS/phthalate biomarker mixture with aBMD Z-scores. We replicated the analysis, stratifying by race/ethnicity.

Results: Participants were (mean ± SD) 15 ± 2.1 years of age. In males, each doubling of serum perfluorooctanoate (PFOA), perfluorooctane sulfonate, urinary mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate, and the overall PFAS/phthalate mixture was associated with a lower aBMD Z-score (eg, for PFOA: -0.24; 95% CI, -0.41 to -0.06). Serum PFOA and urinary MiBP were associated with higher aBMD Z-scores in females (eg, for PFOA: 0.09; 95% CI, -0.07 to 0.25). Findings did not differ by race/ethnicity.

Conclusions: Certain PFAS and phthalates may be associated with reduced bone mineral density in adolescent males. Bone mineral density tracks across the life course, so if replicated in longitudinal cohorts, this finding may have implications for lifelong skeletal health.

Keywords: National Health and Nutrition Examination Survey; bone mineral density; children; per- and polyfluoroalkyl substances; phthalates.

Figure 1.

Single-chemical associations from unweighted^a multivariable^b linear regression models of individual serum PFAS and urinary phthalate biomarkers with total body less head aBMD Z-scores in 12- to 19-year-old males (A) and females (B), 2011-2016 National Health and Nutrition Examination Survey (males, N = 453; females, N = 395). ^aModels do not account for the complex sample design, and therefore results cannot be considered generalizable to the US population. ^bAdjusted for age, race/ethnicity, moderate/vigorous physical activity, indoor smoking by a household member, recent sugar-sweetened beverage consumption, recent total dairy consumption, NHANES weights, and NHANES cycle. Models for phthalates were additionally adjusted for urinary creatinine. Abbreviations: aBMD, areal bone mineral density; DEHP, di(2-ethylhexyl)phthalate; MBP, mono-n-butyl phthalate; MBzP, mono-benzyl phthalate; MCNP, mono(carboxynonyl) phthalate; MCOP, mono(carboxyoctyl) phthalate; MCPP, mono-(3-carboxypropyl) phthalate; MEP, mono-ethyl phthalate; MIBP, mono-isobutyl phthalate; PFDA, perfluorodecanoate; PFHxS, perfluorohexane sulfonate; PFNA, perfluorononanoate; PFOA, perfluorooctanoate; PFOS, perfluorooctane sulfonate.

Figure 2.

Associations (95% credible intervals) from unweighted^a Bayesian kernel machine regression models of the overall urinary phthalate metabolite and serum PFAS mixture with total body less head aBMD Z-score^b in 12-19 year old males (A) and females (B), 2011-2016 National Health and Nutrition Examination Survey (males, n = 453; females, n = 395). ^aModels do not account for the complex sample design, and therefore results cannot be considered generalizable to the US population. ^bFrom BKMR models of the association between the overall urinary phthalate metabolite/serum PFAS mixture when all chemical biomarkers are set at a given quantile versus the median. Models are adjusted for age, race/ethnicity, moderate/vigorous physical activity, indoor smoking by a household member, recent sugar-sweetened beverage consumption, recent total dairy consumption, urinary creatinine concentrations, NHANES weights, and NHANES cycle. Abbreviation: aBMD, areal bone mineral density; NHANES, National Health and Nutrition Examination Survey; PFAS, per- and polyfluoroalkyl substances.