Environmental Chemicals, Adiposity, and Bone Accrual Across Adolescence

项目摘要 肥胖症和骨质疏松症是公共卫生流行病，伴随着昂贵的合并症和有限的治疗选择。 这些疾病的发病率在全球范围内仍然高得令人无法接受，在美国尤其如此， 成年人肥胖，二十五分之一患有骨质疏松症。肥胖症和低骨密度（BMD）是 从儿童期到成年期都有密切的联系。确定预防措施 而在生命早期进行干预对于遏制这些流行病至关重要。有动物数据表明化学物质 在环境中，全氟烷基和多氟烷基物质（PFAS）和邻苯二甲酸酯可能会破坏常见的 机制途径，同时增加肥胖和低BMD的风险。我们的初步数据 在前瞻性Viva项目队列（约900名儿童）中， 在儿童中期浓度有更大的中心性肥胖和较低的BMD的青春期早期。在这 建议，我们将扩大这一先前的工作。我们将把评估延长到青春期后期， 更强地预测成人身体组成和相关疾病的风险。我们还将 检查通过与PFAS类似的机制途径起作用的邻苯二甲酸酯。我们也会用小说 考虑饮食的步骤，这在这些化学物质的研究中还没有全面完成，尽管 事实上，同样的西式食物，可能是一个来源的化学接触也预测风险， 肥胖和低BMD。我们将通过首先确定PFAS的饮食预测因子来实现这些目标， 邻苯二甲酸酯在儿童中期，然后检查PFAS和邻苯二甲酸酯的关联独立于饮食， 青春期晚期的中心性肥胖和BMD。根据我们的初步数据，中枢性肥胖 与较低的BMD相关，我们也将评估中枢性肥胖可能介导的程度 化学品暴露与BMD的关系。我们预计这将是最全面的基于人口的 迄今为止测试儿童暴露于PFAS和邻苯二甲酸酯对肥胖症发展的作用的研究 和低骨密度。通过研究青春期的纵向联系，我们将 克服了许多现有的这些化学物质和肥胖症的流行病学研究的局限性， 将是第一个大型研究，以检查这些化学物质对青春期骨密度的作用。饮食，体力 活动和遗传并不能解释肥胖和低BMD的所有变异性，而且可以 很难修改。确定增加肥胖和低BMD风险的可补救因素是一个公共问题。 卫生优先事项，因为这将有助于制定针对这两种疾病的预防战略。 此外，这一建议将推动弗莱施博士的职业生涯调查的影响，有毒环境 儿童期内分泌发育，重点是青春期前后的健康。

PROJECT ABSTRACT Obesity and osteoporosis are public health epidemics with costly comorbidities and limited treatment options. Rates of these disorders globally remain unacceptably high, and this is particularly true in the US where 1 in 3 adults are obese and 1 in 25 has osteoporosis. Adiposity and low bone mineral density (BMD) are precursors to these debilitating disorders and track closely from childhood to adulthood. Identifying preventive measures and intervening in early life is critical to curb these epidemics. There are suggestive animal data that chemicals in the environment, per- and polyfluoroalkyl substances (PFASs) and phthalates, may disrupt common mechanistic pathways to concomitantly increase risk of both adiposity and low BMD. Our preliminary data within the prospective Project Viva cohort (~900 children) suggest that children with higher PFAS plasma concentrations in mid-childhood have greater central adiposity and lower BMD by early adolescence. In this proposal, we will expand this prior work. We will extend evaluation through late adolescence, when body composition more strongly predicts adult body composition and related disease risks. We will additionally examine phthalates which act through similar mechanistic pathways as PFASs. We will also employ the novel step of accounting for diet, which has not been comprehensively done in studies of these chemicals, despite the fact that the same Western-style foods that may be a source of chemical exposure also predict risk for adiposity and low BMD. We will accomplish these objectives by first identifying dietary predictors of PFASs and phthlalates in mid-childhood, then examining associations of PFASs and phthalates independent of diet on central adiposity and BMD in late adolescence. Based on our preliminary data suggesting that central adiposity is associated with lower BMD, we will also evaluate the extent to which central adiposity may mediate associations of chemical exposures on BMD. We expect this to be the most comprehensive population-based study to date testing the role of childhood exposures to PFASs and phthalates on development of adiposity and low BMD through adolescence. By examining longitudinal associations across adolescence, we will overcome limitations of many of the existing epidemiologic studies of these chemicals and adiposity, and this will be the first large study to examine the role of these chemicals on BMD in adolescence. Diet, physical activity, and genetics do not explain all of the variability in adiposity and low BMD, and moreover can be difficult to modify. Identifying remediable factors that increase risk of both adiposity and low BMD is a public health priority because this will enable development of preventive strategies to target both conditions. Furthermore, this proposal will advance Dr. Fleisch's career investigating the impact of the toxic environment on endocrine development in childhood with a focus on peripubertal health.