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Principal Investigator: Jessie P Buckley
Organization: UNIV OF NORTH CAROLINA CHAPEL HILL
Fiscal Year: 2024
Award: $554,037
Funding agency: National Institute of Environmental Health Sciences
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.
Terms: <0-11 years old><12 year old><12 years of age><12-20 years old><17 year old><17 years of age><2-dimensional><21+ years old><3-D><3-Dimensional><3D><Active Follow-up><Adolescence><Adolescent><Adolescent Youth><Adult><Adult Human><Affect><Age><American><Animals><Anthropometry><Autoregulation><Back><Biological Markers><Biostatistical Methods><Birth><Blood><Blood Reticuloendothelial System><Bone Density><Bone Diseases><Bone Mineral Density><Bone Mineralization><CAT scan><CT X Ray><CT Xray><CT imaging><CT scan><Chemical Exposure><Chemicals><Child><Child Youth><Childhood><Children (0-21)><Chronic><Clinic><Clinical><Cohort Studies><Computed Tomography><Concurrent Studies><Cross Sectional Analysis><Cross-Sectional Analyses><Cross-Sectional Studies><Cross-Sectional Survey><DEXA><DXA><Data><Development><Diet><Disease Frequency Surveys><Dorsum><Dual-Energy X-Ray Absorptiometry><Dual-Energy Xray Absorptiometry><Endocrine><Endocrine Disrupter><Endocrine Disrupting Chemicals><Endocrine Disruptors><Endocrine disrupting agent><Enrollment><Environment><Environmental Exposure><Epidemiology><Esters><Evaluation><Exposure to><Fire Retardants><Flame Retardants><Forearm><Fracture><Future><Geometry><Gestation><Goals><Health><History><Homeostasis><Human><Individual><Intervention><Intervention Strategies><Laboratory Study><Life><Long-term cohort study><Longitudinal cohort study><Longterm cohort study><Measures><Modern Man><Morphology><Mothers><Ohio><Organophosphates><Osteoporosis><Outcome><PFAS><Participant><Parturition><Peripheral><Physical activity><Physiologic calcification><Physiological Calcification><Physiological Homeostasis><Poly-fluoroalkyl substances><Population><Predisposition><Pregnancy><Process><Prospective Studies><Puberty><Public Health><Radial><Radius><Recording of previous events><Risk><Risk Factors><Risk Reduction><Site><Susceptibility><Techniques><Tomodensitometry><Urine><Visit><Work><X-Ray CAT Scan><X-Ray Computed Tomography><X-Ray Computerized Tomography><Xray CAT scan><Xray Computed Tomography><Xray computerized tomography><active followup><adolescence (12-20)><adulthood><age 12 years><age 17 years><ages><bio-markers><biologic marker><biomarker><bone><bone disorder><bone fracture><bone geometry><bone health><bone imaging><bone mass><bone scanning><bone strength><bone turnover><catscan><chemical association><clinical significance><clinically significant><computed axial tomography><computer tomography><computerized axial tomography><computerized tomography><consumer product><critical period><design><designing><developmental><diets><early adolescence><early adulthood><early childhood><emerging adult><endocrine disrupting compound><enroll><epidemiologic><epidemiological><follow up><follow-up><followed up><followup><fracture risk><histories><indexing><innovate><innovation><innovative><interventional strategy><juvenile><juvenile human><kids><male><malleable risk><modifiable risk><non-contrast CT><noncontrast CT><noncontrast computed tomography><older adult><older adulthood><pediatric><perfluorinated alkyl substances><perfluoroalkyl substances><perfluoroalkylated substances><phthalates><polyfluorinated alkyl substances><polyfluoroalkyl substances><prospective><reduce risk><reduce risks><reduce that risk><reduce the risk><reduce these risks><reduces risk><reduces the risk><reducing risk><reducing the risk><risk-reducing><seventeen year old><seventeen years of age><sex><skeletal><skeletal imaging><three dimensional><tool><twelve year old><twelve years of age><two-dimensional><youngster>