Endocrine disrupting chemical mixtures and bone health in adolescence

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Abstract Low bone mineral density (BMD) during adolescence is associated with fractures in adolescence and adulthood as well as increased risk of osteoporosis, a chronic bone disease affecting more than 10 million older adults in the U.S. The majority of Americans are exposed to perfluoroalkyl substances, phthalates, and organophosphate esters, synthetic endocrine disrupting chemicals (EDCs) that have adverse skeletal effects in laboratory studies. In humans, these EDCs are associated with lower BMD in limited cross-sectional studies and prospectively associated with lower BMD at age 12 years in our preliminary data. However, few studies have assessed relationships of EDCs with bone health in adolescence, a period of rapid bone mineralization that may be highly sensitive to environmental exposures and is strongly predictive of adult BMD. Therefore, the overarching objective of our proposal is to determine whether exposure to individual EDCs or their mixtures causes reduced bone accrual and strength in adolescence. We will address our aims within the Health Outcomes and Measures of the Environment (HOME) Study, a prospective birth cohort study of mothers and their children enrolled in Cincinnati, Ohio. The HOME Study has amassed detailed longitudinal exposure biomarker measures and covariate data on participants from gestation through 12 years of age. We will conduct a new follow-up visit of 225 participants at approximately 17 years of age to measure EDC biomarkers; perform detailed skeletal assessments; and collect information on diet, physical activity, anthropometry, and pubertal status. Using these data, we will determine whether EDC exposures are associated with peripheral quantitative computed tomography measures of volumetric BMD, bone geometry, and strength strain index at age 17 years (Aim 1); dual-energy X-ray absorptiometry measures of areal BMD at age 17 years and rate of aBMD accrual from age 12 to 17 years (Aim 2); and fracture history at age 17 years (Aim 3). We will elucidate the impact of lifetime cumulative EDC exposures and identify periods of heightened susceptibility by applying sophisticated statistical approaches including Bayesian and lagged kernel machine regression and latent profile analysis. This work will inform the development of targeted interventions for optimizing bone health in adolescence with the long-term goal of reducing risk of fractures and osteoporosis throughout life.