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

描述(由申请人提供)：这项拟议的研究旨在首次提供变革性的知识，即儿童时期的环境铅暴露史如何影响非裔美国女性日后的骨骼和肌肉系统(CBAM)健康。虽然自铅作为汽油添加剂停止使用以来，美国普通人群的血铅浓度(PBB)有所下降，但骨中隔离的铅仍然是数百万女性内部暴露的来源，特别是在成长过程中暴露于中到高水平铅的少数族裔。非洲裔美国女性饮食中的钙含量较低，更有可能患有乳糖不耐受、维生素D缺乏，以及环境铅暴露，这与出生体重较低、姿势平衡不良和摔倒有关。因此，营养状况和铅暴露的联合风险可能会损害几个骨骼和肌肉参数。这些指标包括骨矿含量(BMC)、骨密度(BMD)、出生体重降低对出生后骨生长和CBAM结构完整性的影响。较低的结构完整性表明CBAM吸收外部动态载荷的能力降低，从而增加了骨折的易感性。使用本课题组最近开发的非侵入性骨吸收(ζ)工具来测量CBAM系统的能量吸收或衰减(BSA)能力。这些与铅相关的骨骼和肌肉参数的有害变化，与无铅暴露或铅暴露较少的人群相比，共同易于发生早期骨质疏松相关的骨折易感性。此外，铅影响破骨和成骨过程、激素信号通路和生长板软骨细胞成熟速度，并导致功能性姿势不稳定(FPS)，增加与跌倒相关的骨折和损伤的风险。这些研究构成了我们长期核心假说的基础：“早年接触铅会损害骨骼健康，其特征是骨量、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/平衡，从而使受试者在晚年容易发生骨折风险增加”。拟议的研究将与我们现有的辛辛那提领先研究(CLS)队列一起进行；因此，我们可以利用CLS前瞻性研究的大量数据资源，该研究在他们的早期(20世纪70年代末和80年代‘S)经历了中到高度的铅暴露，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拟议的骨宏观结构指标、骨密度、FPS和ζ的能力，以集体和单独地识别铅暴露对象达到或接近文献中关于跌倒、骨质疏松相关骨折和无骨折的独立阈值的能力，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 (ζ) 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 ζ, 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.