Early Life Phthalate and Perfluoroalkyl Substance Exposures and Childhood Bone Health

生命早期邻苯二甲酸盐和全氟烷基物质暴露与儿童骨骼健康

• 批准号: 10062975
• 负责人: Jessie P Buckley
• 金额: $ 42.99万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-01-01 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10062975
• 关键词: 12 year old; 25-hydroxyvitamin D; 8 year old; Address; Adolescence; Adult; Affect; Age; American; Animals; Award; Bayesian Analysis; Bayesian Modeling; Biological; Biological Markers; Biometry; Birth; Body Composition; Bone Density; Bone Development; Bone Diseases; Bone Growth; Bone Resorption; Calcium; Chemical Exposure; Chemicals; Child; Child Welfare; Childhood; Clinical; Cohort Studies; Cross-Sectional Studies; Data; Development; Dietary Intervention; Dual-Energy X-Ray Absorptiometry; Enrollment; Environment; Environmental Epidemiology; Environmental Health; Environmental Impact; Epidemiology; Exposure to; Fostering; Goals; Growth; Health; Height; Human; Impairment; Intake; Intervention; Laboratory Finding; Lead; Life; Longitudinal Studies; Longitudinal cohort study; Measurement; Measures; Mediating; Mediation; Metabolism; Micronutrients; Minerals; Modeling; Modification; National Institute of Environmental Health Sciences; Nature; Nutritional; Ohio; Osteogenesis; Osteoporosis; Outcome Measure; Pediatrics; Poly-fluoroalkyl substances; Predisposition; Pregnancy; Reporting; Research; Research Personnel; Risk Factors; Role; Rotation; Scientist; Serum; Skeletal Development; Testing; Toxic effect; Toxicant exposure; Translations; Visit; Vitamin D; Work; bone; bone health; bone mass; bone strength; bone turnover; calcium intake; career development; chemical association; consumer product; critical period; early adolescence; early childhood; early life exposure; environmental chemical; epidemiology study; exposed human population; follow-up; fracture risk; innovation; modifiable risk; multi-ethnic; novel; nutritional epidemiology; obesogen; phthalates; prenatal; programs; prospective; racial diversity; skeletal; tool; toxicant; urinary

Abstract Phthalates and perfluoroalkyl substances (PFAS) are synthetic chemicals with widespread human exposures that lower bone density in animals. Our preliminary data and limited epidemiologic studies report associations of these chemicals with shorter stature in children as well as lower bone density and altered vitamin D metabolism in adults. Low peak bone mass in adolescence is a strong modifiable risk factor for osteoporosis, a bone disease impacting millions of older Americans. Although early life is a critical period of skeletal growth and bone mass accrual, there are currently no longitudinal studies of phthalate or PFAS exposures in relation to childhood bone density. Therefore, our goal is to test the novel hypothesis that early life phthalate and PFAS exposures adversely impact skeletal growth, bone strength, and vitamin D metabolism in children. Our highly efficient proposal leverages the Health Outcomes and Measures of the Environment (HOME) Study, a prospective, racially-diverse pregnancy cohort study enrolled in Cincinnati, Ohio with existing exposure biomarker, confounder, and height measures from gestation through 8 years of age. Dual-energy X-ray absorptiometry measurements of bone density are currently being collected at an ongoing 12-year follow-up visit. We will additionally measure validated vitamin D and phthalate exposure biomarkers to investigate whether phthalate or PFAS exposures are associated with height trajectories from birth to age 12 years (Aim 1), bone density at age 12 years (Aim 2), and vitamin D biomarker concentrations at ages 8 and 12 years (Aim 3). Further, we will explore the role of chemical and nutritional co-exposures by examining whether height or bone density associations are modified or mediated by vitamin D biomarker concentrations or calcium intake (Aim 4). Using rich longitudinal data and a sophisticated Bayesian modeling approach, we will investigate potential windows of susceptibility (prenatal, early childhood, mid childhood, and early adolescence) as well as effects of cumulative exposures and exposure mixtures. This research will constitute the first systematic assessment of the role of phthalates and PFAS in altering bone health, a significant but understudied component of child well-being with critical importance for life-long risk of fractures and osteoporosis. In addition, this NIEHS ONES Award will support an exceptional Early Stage Investigator to establish an innovative research program specializing in children's environmental health. Finally, our findings will catalyze future research examining environmental impacts on bone health in later adolescence, elucidating biological mechanisms, investigating other environmental bone toxicants, and developing chemical or nutritional interventions with the goal of setting children on a path to healthier, stronger bones throughout life.

抽象的 邻苯二甲酸盐和全氟烷基物质（PFA）是合成化学物质，具有广泛的人类暴露 动物中较低的骨密度。我们的初步数据和有限的流行病学研究报告协会 这些化学物质在儿童以及较低的骨密度和维生素D改变的化学物质中 成人的代谢。青春期低峰骨质量是骨质疏松症的强大可修改风险因素，A 骨骼疾病影响数百万的美国人。尽管早期生活是骨骼生长的关键时期 和骨质量应计，目前尚无有关邻苯二甲酸酯或PFA的纵向研究 到儿童期骨密度。因此，我们的目标是检验邻苯二甲酸盐和PFA早期生命的新假设 暴露会对儿童的骨骼生长，骨骼强度和维生素D代谢产生不利影响。我们的高度 有效的建议利用环境研究的健康结果和措施（家庭）研究， 俄亥俄州辛辛那提的潜在的，种族多样性的怀孕队列研究 从妊娠到8岁的生物标志物，混杂因素和高度测量。双能X射线 目前正在进行的12年随访中，目前正在收集骨密度的吸收测定法测量值 访问。我们还将测量验证的维生素D和邻苯二甲酸盐暴露生物标志物进行研究 从出生到12岁的邻苯二甲酸盐还是PFAS暴露与身高轨迹有关（AIM 1），年龄在12岁时（AIM 2）和8岁和12岁的维生素D生物标志物浓度（AIM） 3）。此外，我们将通过检查身高还是 骨密度关联是通过维生素D生物标志物浓度或钙摄入修饰或介导的 （目标4）。使用丰富的纵向数据和复杂的贝叶斯建模方法，我们将研究 易感性的潜在窗户（产前，幼儿，童年和青春期）以及 累积暴露和暴露混合物的影响。这项研究将构成第一个系统的 评估邻苯二甲酸盐和PFA在改变骨骼健康中的作用，这是一个重要但有研究的 儿童幸福感的组成部分至关重要，这对于寿命骨折和骨质疏松症的风险至关重要。在 此外，这项NIEHS奖将支持一个杰出的早期调查员，以建立一个 专门研究儿童环境健康的创新研究计划。最后，我们的发现将催化 未来的研究研究了青春期后期对骨骼健康的影响，阐明生物学 机制，研究其他环境骨有毒物质，并开发化学或营养 干预措施的目的是使孩子们走上一生更健康，更强壮的骨骼。