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

基本信息

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
项目类别：
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

项目摘要

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 (PFAS) 是人类广泛接触的合成化学品降低动物的骨密度。我们的初步数据和有限的流行病学研究报告关联这些化学物质会导致儿童身材矮小、骨密度降低和维生素 D 改变成人的新陈代谢。青春期的低峰值骨量是骨质疏松症的一个强大的可改变危险因素，骨病影响着数百万美国老年人。虽然生命早期是骨骼生长的关键时期和骨量增长，目前尚无邻苯二甲酸盐或 PFAS 暴露与相关性的纵向研究到儿童时期的骨密度。因此，我们的目标是检验生命早期邻苯二甲酸盐和 PFAS 的新假设暴露会对儿童骨骼生长、骨强度和维生素 D 代谢产生不利影响。我们的高度有效的提案利用了健康结果和环境措施（HOME）研究，在俄亥俄州辛辛那提市招募的前瞻性、种族多样化妊娠队列研究，具有现有暴露情况从妊娠期到 8 岁的生物标志物、混杂因素和身高测量。双能X射线目前正在持续 12 年的随访中收集骨密度的吸收测量结果访问。我们还将额外测量经过验证的维生素 D 和邻苯二甲酸盐暴露生物标志物以进行调查邻苯二甲酸盐或 PFAS 暴露是否与从出生到 12 岁的身高轨迹相关（Aim 1)、12 岁时的骨密度（目标 2）以及 8 岁和 12 岁时的维生素 D 生物标志物浓度（目标 3）。此外，我们将通过检查身高或体重来探索化学和营养共同暴露的作用。骨密度关联由维生素 D 生物标志物浓度或钙摄入量改变或介导（目标 4）。使用丰富的纵向数据和复杂的贝叶斯建模方法，我们将调查潜在的易感性窗口（产前、儿童早期、儿童中期和青春期早期）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 PFAS 在改变骨骼健康方面的作用，这是一项重要但尚未充分研究的研究儿童福祉的组成部分，对于终生骨折和骨质疏松症风险至关重要。在此外，NIEHS ONES 奖将支持杰出的早期研究人员建立一个专门研究儿童环境健康的创新研究计划。最后，我们的发现将促进未来的研究将检验环境对青春期后期骨骼健康的影响，阐明生物机制，研究其他环境骨毒物，并开发化学或营养旨在让儿童终生拥有更健康、更强健骨骼的干预措施。