Endocrine disrupting chemical mixtures and bone health in adolescence

摘要 青春期骨密度低与青春期骨折和 成年期以及骨质疏松症风险的增加，骨质疏松症是一种影响1000多万人的慢性骨骼疾病 美国的老年人大多数美国人都暴露在全氟烷基物质、邻苯二甲酸盐和 有机磷酸酯，合成内分泌干扰物(EDCs)，对骨骼有不良影响 实验室研究。在有限的横断面研究中，在人类中，这些内分泌细胞与较低的骨密度有关。 在我们的初步数据中，与12岁时较低的BMD有前瞻性的关联。然而，很少有研究 评估了内分泌细胞与青春期骨骼健康的关系，青春期是骨骼快速矿化的时期 这可能对环境暴露高度敏感，并对成人骨密度有很强的预测作用。因此， 我们建议的首要目标是确定是否暴露于单个内分泌干扰物或其混合物 导致青春期骨骼累积量和强度降低。我们将在卫生部门内解决我们的目标 环境(家庭)研究的结果和措施，这是一项关于母亲和母亲的预期出生队列研究 他们的孩子在俄亥俄州辛辛那提注册。这项家庭研究积累了详细的纵向接触 生物标记物测量和协变量数据的参与者从怀孕到12岁。我们会 在大约17岁时对225名参与者进行新的跟踪访问，以测量EDC 生物标志物；进行详细的骨骼评估；收集关于饮食、体力活动、 人体测量和青春期状况。使用这些数据，我们将确定EDC暴露是否 结合外周定量计算机断层扫描测量体积骨密度，骨几何形状， 和17岁时的强度应变指数(目标1)；面骨密度的双能X线吸收测量法 17岁和12至17岁的骨密度累积率(目标2)；17岁的骨折史 (目标3)。我们将阐明终生累积EDC暴露的影响，并确定高峰期 应用包括贝叶斯和滞后核机器在内的复杂统计方法的敏感度 回归分析和潜伏期分析。这项工作将为制定有针对性的干预措施提供信息 优化青春期的骨健康，长期目标是降低骨折和骨质疏松的风险 在一生中。

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.