Early Life Phthalate and Perfluoroalkyl Substance Exposures and Childhood Bone Health

摘要 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 这些化学物质在儿童中具有较矮的身高以及较低的骨密度和改变的维生素D 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烈的可修改的危险因素， 影响数百万美国老年人的骨病。尽管早期生命是骨骼发育的关键时期 和骨量增加，目前还没有关于邻苯二甲酸盐或全氟辛烷磺酸暴露与 儿童时期的骨密度。因此，我们的目标是测试新的假设，即早期生命邻苯二甲酸盐和全氟辛烷磺酸 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。我们的高度重视 有效的提案利用了环境(家庭)研究的健康结果和措施，a 在俄亥俄州辛辛那提登记的前瞻性、种族多样化的怀孕队列研究 生物标记物、混杂物和身高测量从怀孕到8岁。双能X射线 骨密度的骨密度测量目前正在进行一项为期12年的跟踪调查 参观。我们还将测量经过验证的维生素D和邻苯二甲酸盐暴露生物标记物来研究 邻苯二甲酸盐或全氟辛烷磺酸暴露与出生到12岁的身高轨迹有关(目标 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2 3)。此外，我们将通过检查身高或营养联合暴露的作用来探讨化学和营养联合暴露的作用 维生素D生物标记物浓度或钙摄入量改变或调节骨密度相关性 (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 潜在的易感窗口(产前、幼儿期、儿童期中期和青春期早期)以及 累积暴露量和混合暴露量的影响。这项研究将构成第一个系统的 邻苯二甲酸盐和全氟辛烷磺酸在改变骨健康中的作用的评估，一个重要但未被研究的 儿童健康的组成部分，对终身骨折和骨质疏松症的风险至关重要。在……里面 此外，NIEHS One奖将支持一名特殊的早期调查人员建立 致力于儿童环境健康的创新研究项目。最后，我们的发现将催化 未来研究考察环境对青春期后期骨骼健康的影响，阐明生物学 机理，研究其他环境中的骨毒物质，开发化学或营养 干预措施的目标是让儿童在一生中走上更健康、更强壮的骨骼之路。

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.