Environmental Chemicals, Adiposity, and Bone Accrual Across Adolescence

项目摘要 肥胖和骨质疏松症是一种公共卫生流行病，具有昂贵的共病和有限的治疗选择。 在全球范围内，这些疾病的发病率仍然高得令人无法接受，在美国尤其如此，因为三分之一的美国人 成年人肥胖，25人中就有1人患有骨质疏松症。肥胖和低骨密度是先兆 这些衰弱的疾病，并密切跟踪从童年到成年。确定预防措施 而对早期生活的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，全氟烷基物质和多氟烷基物质(PFAS)以及邻苯二甲酸盐，可能会破坏常见的 同时增加肥胖和低骨密度风险的机制途径。我们的初步数据 在预期的Viva项目队列中(约900名儿童)表明，有较高PFAS血浆水平的儿童 儿童期中期的浓度在青春期早期有较大的中心性肥胖和较低的BMD。在这 建议，我们将扩大这一前期工作。我们将把评估延长到青春期后期，当身体 成分更能预测成年人的身体成分和相关的疾病风险。我们还会另外 研究邻苯二甲酸盐，它们通过与全氟辛烷磺酸类似的机械途径发挥作用。我们还将利用这部小说 说明饮食的步骤，这在对这些化学物质的研究中尚未全面完成，尽管 事实上，同样的西式食物可能是化学暴露的来源，但也预测了患上癌症的风险 肥胖和低骨密度。我们将通过首先确定全氟辛烷磺酸的膳食预测因素和 在儿童中期，然后检查与饮食无关的PFASs和邻苯二甲酸盐的相关性 中心性肥胖与青春期晚期骨密度的关系根据我们的初步数据显示中心性肥胖 与较低的BMD相关，我们还将评估中心性肥胖可能在多大程度上调节 化学物质暴露与骨密度之间的关系。我们预计这将是最全面的基于人口的 儿童时期接触全氟辛烷磺酸和邻苯二甲酸盐对肥胖发生影响的研究 和青春期的低骨密度。通过研究青春期的纵向联系，我们将 克服现有许多关于这些化学物质和肥胖症的流行病学研究的局限性，这 这将是第一个研究这些化学物质对青春期BMD的作用的大型研究。节食，体检 活动性和遗传学并不能解释肥胖症和低骨密度的所有变异性，而且可以 很难修改。确定同时增加肥胖和低BMD风险的可补救因素是公开的 健康优先，因为这将使制定针对这两种情况的预防战略成为可能。 此外，这项建议将推动弗莱施博士研究有毒环境的影响的事业 关于儿童的内分泌发育，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.