Early Pb exposure a risk for bone health later in life in African American women

描述（由申请人提供）：拟议的研究旨在首次提供关于环境铅（Pb）暴露的童年史如何影响非洲裔美国妇女日后的骨骼和肌肉组织（CBAM）健康的变革性知识。虽然美国一般人群的血铅浓度（PbB）自停止使用铅作为汽油添加剂以来有所下降，但骨中的铅仍然是数百万妇女的内部暴露来源，特别是在成长期暴露于中等至高水平铅的少数民族。非裔美国妇女的膳食钙含量较低，更有可能是乳糖不耐症，维生素D缺乏和环境铅暴露，这与出生体重较低，姿势平衡差和福尔斯。因此，营养状况和铅暴露的综合风险可能会损害几个骨骼和肌肉参数。这些包括骨矿物质含量（BMC），骨矿物质密度（BMD），出生体重较低影响出生后骨生长和CBAM的结构完整性。较低的结构完整性表明CBAM吸收外部施加的动态载荷的能力降低，从而增加骨折的易感性。能量吸收或阻尼（？）CBAM系统的能力是用我们小组最近开发的一种非侵入性的骨冲击吸收（BSA）工具来测量的。这些铅相关的骨和肌肉参数的有害变化可能共同倾向于发展早期骨质疏松症相关的骨折易感性比那些没有或低铅暴露。此外，铅影响骨形成和成骨细胞过程、激素信号传导途径和生长板软骨细胞成熟的速率，并导致功能性姿势不稳定（FPS），这是跌倒相关骨折和损伤的额外风险。这些研究构成了我们长期核心假设的基础：“生命早期暴露于铅会在精神上影响骨骼健康，其特征在于骨量，骨骼的宏观结构，CBAM的结构完整性承受动态负荷的能力，以及姿势稳定性/平衡，从而使受试者在以后的生活中骨折风险增加”。拟定研究将在我们现有的辛辛那提主要研究（CLS）队列中进行;从而使我们能够利用CLS前瞻性研究的广泛数据资源，这些研究在其早期生活中经历了中度到高度的铅暴露（20世纪70年代末和80年代），现在正接近骨成熟年龄（28-32岁）。解决长期核心假设的第一步是评估骨的宏观结构，BMD，FPS和？，共同和单独用于识别符合或接近文献中福尔斯、骨质疏松相关骨折和无骨折的独立阈值的铅暴露受试者以及CLS年龄范围内的健康受试者。

DESCRIPTION (provided by applicant): The proposed study is designed to provide transformative knowledge for the first time, about how childhood history of environmental lead (Pb) exposure impacts combined bone and musculature (CBAM) health later in life among African American women. While blood lead concentrations (PbB) in the general population of the U.S. have declined since the discontinuation of Pb as a gasoline additive, Pb sequestered in bone continues to be a source of internal exposure for millions of women, especially minorities exposed to moderate to high levels of Pb during their formative years. African-American women have lower dietary calcium, more likely to be lactose intolerant, vitamin D deficient and have environmental Pb exposure that is associated with lower birth weight, poor postural balance and falls. Therefore, combined risks of nutritional status and Pb exposure potentially compromise several bone and muscular parameters. These include bone mineral content (BMC), bone mineral density (BMD), lower birth weight affecting postnatal bone growth and structural integrity of CBAM. Lower structural integrity suggests reduced ability of CBAM to absorb externally applied dynamic loads thereby increasing susceptibility to bone fracture. The energy absorption or damping (?) ability of the CBAM system is measured with a non-invasive, bone shock absorption (BSA) tool recently developed by our group. These Pb associated detrimental changes in bone and muscular parameters could collectively predispose to development of early osteoporosis associated susceptibility to fracture than those with no or lower Pb exposure. Furthermore, Pb affects osteoclastic and osteoblastic processes, hormonal signaling pathways, and the rate of growth plate chondrocyte maturation and contributes to functional postural instability (FPS) as an added risk for fall related fractures and injuries. These studies form the basis for our long-term core hypothesis: "early life exposure to Pb detrimentally affects bone health as characterized by bone mass, macrostructure of the skeleton, and CBAM's structural integrity ability to sustain dynamic load, as well as postural stability/balance thereby predisposing the subjects to increased fracture risk later in life". The proposed study will be carried out with our existing Cincinnati Lead Study (CLS) cohort; thus allowing us to leverage the extensive data resources of our CLS prospective study which has experienced moderate to high levels of Pb exposure during their early life (late1970s and 1980's) and is now approaching bone maturation age (28-32 years).The first step towards addressing the long term core hypothesis is to evaluate the abilities of the proposed measures of bone's macrostructure, BMD, FPS and ?, collectively and individually for identifying Pb exposed subjects who meet or approach the independent thresholds from the literature for falls, and osteoporosis associated fracture and no fracture as well as from healthy subjects within the CLS age range.