Endocrine disrupting chemical mixtures and bone health in adolescence

内分泌干扰化学混合物与青春期骨骼健康

基本信息

批准号：
10874040
负责人：
Jessie P Buckley
金额：
$ 59.99万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-03 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10874040
关键词：
12 year old 17 year old 3-Dimensional Adolescence Adolescent Adult Affect Age American Animals Anthropometry Back Biological Markers Biostatistical Methods Birth Blood Bone Density Bone Diseases Chemical Exposure Chemicals Child Childhood Chronic Clinic Clinical Cohort Studies Cross-Sectional Studies Data Development Diet Dual-Energy X-Ray Absorptiometry Elderly Endocrine Endocrine Disruptors Enrollment Environment Environmental Exposure Epidemiology Esters Evaluation Exposure to Flame Retardants Forearm Fracture Future Geometry Goals Health Homeostasis Human Individual Intervention Laboratory Study Life Longitudinal cohort study Measures Morphology Mothers Ohio Organophosphates Osteoporosis Outcome Participant Peripheral Physical activity Physiologic calcification Poly-fluoroalkyl substances Population Predisposition Pregnancy Process Prospective Studies Puberty Public Health Radial Recording of previous events Risk Risk Factors Risk Reduction Site Techniques Urine Visit Work X-Ray Computed Tomography bone bone geometry bone health bone imaging bone mass bone strength bone turnover chemical association clinically significant consumer product critical period design early adolescence early childhood emerging adult follow-up fracture risk indexing innovation male modifiable risk phthalates prospective sex skeletal tool two-dimensional

项目摘要

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.

抽象的青春期骨矿物质密度（BMD）低与青春期骨折有关，成年后患骨质疏松症的风险增加，骨质疏松症是一种影响超过 1000 万人的慢性骨病美国老年人大多数美国人都接触全氟烷基物质、邻苯二甲酸盐和有机磷酸酯、合成内分泌干扰化学物质 (EDC) 对骨骼有不良影响实验室研究。在人类中，在有限的横断面研究中，这些 EDC 与较低的 BMD 相关我们的初步数据显示，这与 12 岁时骨密度较低有关。但很少有研究评估了 EDC 与青春期骨骼健康的关系，青春期是骨骼快速矿化的时期可能对环境暴露高度敏感，并且强烈预测成人 BMD。因此，我们提案的首要目标是确定是否接触单独的 EDC 或其混合物导致青春期骨质增生和强度减少。我们将在健康领域实现我们的目标环境结果和措施（HOME）研究，一项针对母亲和儿童的前瞻性出生队列研究他们的孩子在俄亥俄州辛辛那提就读。 HOME 研究积累了详细的纵向曝光参与者从妊娠期到 12 岁的生物标志物测量和协变量数据。我们将对 225 名年龄约为 17 岁的参与者进行新的随访，以测量 EDC 生物标志物；进行详细的骨骼评估；并收集有关饮食、身体活动的信息，人体测量学和青春期状态。使用这些数据，我们将确定 EDC 暴露是否与体积 BMD、骨几何形状的外周定量计算机断层扫描测量相关， 17 岁时的强度应变指数（目标 1）；双能 X 射线吸收法测量面积 BMD 17 岁和 12 至 17 岁的 aBMD 累积率（目标 2）； 17岁时有骨折史（目标 3）。我们将阐明终生累积 EDC 暴露的影响，并确定高浓度时期通过应用复杂的统计方法（包括贝叶斯和滞后内核机）来确定敏感性回归和潜在概况分析。这项工作将为制定有针对性的干预措施提供信息优化青春期的骨骼健康，长期目标是降低骨折和骨质疏松症的风险一生。