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

• 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
• 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

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.

摘要 青春期低骨矿物质密度（BMD）与青春期骨折相关， 以及骨质疏松症的风险增加，这是一种影响1000多万人的慢性骨骼疾病 大多数美国人暴露于全氟烷基物质，邻苯二甲酸酯， 有机磷酸酯，合成内分泌干扰化学品（EDCs），有不利的骨骼影响， 实验室研究在有限的横断面研究中，这些内分泌干扰物与人体骨密度降低有关 并且在我们的初步数据中，与12岁时较低的BMD前瞻性相关。然而，很少有研究 已经评估了青春期内分泌干扰物与骨骼健康的关系，青春期是骨骼快速矿化的时期 这可能是高度敏感的环境暴露，并强烈预测成人骨密度。因此 我们建议的首要目标是确定暴露于单个EDCs或其混合物是否 会导致青春期骨骼增长和强度降低。我们将在卫生部内实现我们的目标。 结果和环境措施（HOME）研究，一项针对母亲和 他们的孩子就读于俄亥俄州的辛辛那提。HOME研究积累了详细的纵向暴露 从怀孕到12岁的参与者的生物标志物测量和协变量数据。我们将 对225名约17岁的参与者进行新的随访访视，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， 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 与体积BMD，骨几何形状， 和17岁时的强度应变指数（目标1）;双能X线骨密度仪测量17岁时的区域BMD。 年龄17岁和12至17岁的aBMD增加率（目标2）;以及17岁时的骨折史 (Aim 3）。我们将阐明终生累积EDC暴露的影响，并确定 敏感性，应用复杂的统计方法，包括贝叶斯和滞后核机 回归分析和潜在轮廓分析。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 在生活中。

项目成果

Bone Accrual During Adolescence: Do Endocrine-Disrupting Chemicals Play a Role?

青春期的骨骼应计：干扰内分泌化学物质是否起作用？

• DOI: 10.1210/clinem/dgac391
• 发表时间: 2022-09-28
• 期刊: The Journal of clinical endocrinology and metabolism