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非洲裔美国妇女童年环境铅（Pb）暴露史如何影响晚年骨骼和肌肉组织（CBAM）健康的变革性知识。虽然美国普通人群的血铅浓度（PbB）自铅作为汽油添加剂停止使用以来有所下降，但骨中隔离的铅仍然是数百万妇女体内接触铅的来源，特别是少数民族在成长期暴露于中高水平的铅中。非裔美国女性饮食中的钙含量较低，更容易出现乳糖不耐症、维生素D缺乏症，并且接触环境中的铅，这与出生体重低、姿势平衡差和跌倒有关。因此，营养状况和铅暴露的综合风险可能会损害一些骨骼和肌肉参数。这些因素包括骨矿物质含量（BMC）、骨矿物质密度（BMD）、影响出生后骨生长和CBAM结构完整性的低出生体重。较低的结构完整性表明CBAM吸收外部动态载荷的能力降低，从而增加骨折的易感性。CBAM系统的能量吸收或阻尼（?）能力是用我们小组最近开发的一种无创骨冲击吸收（BSA）工具来测量的。这些与铅相关的骨骼和肌肉参数的有害变化可能比没有或低铅暴露的人更容易发生与骨折相关的早期骨质疏松症。此外，铅影响破骨细胞和成骨细胞过程、激素信号通路和生长板软骨细胞成熟的速度，并导致功能性姿势不稳定（FPS），增加跌倒相关骨折和损伤的风险。这些研究形成了我们长期核心假设的基础：“早期生活暴露于铅会对骨骼健康产生不利影响，其特征是骨量、骨骼宏观结构、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容易增加骨折风险。”拟议的研究将与我们现有的辛辛那提先导研究（CLS）队列一起进行；因此，我们可以利用CLS前瞻性研究的广泛数据资源，这些研究对象在其早期生活（20世纪70年代末和80年代）经历了中等至高水平的铅暴露，现在正接近骨骼成熟年龄（28-32岁）。解决长期核心假说的第一步是评估拟议的骨宏观结构、骨密度、FPS和？在CLS年龄范围内的健康受试者中，确定符合或接近文献中跌倒、骨质疏松相关骨折和无骨折的独立阈值的铅暴露受试者。

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.