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

早期接触铅对非裔美国女性晚年骨骼健康构成风险

• 批准号: 9036387
• 负责人: AMIT BHATTACHARYA
• 金额: $ 58.22万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-09 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9036387
• 关键词: Address; Adult; Affect; African American; Age; Biological; Birth; Blood specimen; Body Burden; Bone Density; Bone Growth; Bone Mineral Contents; Caucasians; Childhood; Chondrocytes; Cohort Studies; Data; Development; Diagnosis; Dietary Calcium; Epiphysial cartilage; Equilibrium; Fracture; Gasoline; General Population; Geometry; Health; Hip region structure; Hormonal; Injury; Knowledge; Lactose; Lead; Lead levels; Life; Literature; Low Birth Weight Infant; Measurement; Measures; Methods; Minority; Minority Groups; Muscle; Musculoskeletal Equilibrium; Nutritional status; Organ; Osteoporosis; Outcome; Population; Predisposition; Process; Prospective Studies; Public Health; Recording of previous events; Research; Resistance; Resources; Risk; Role; Shock; Signal Pathway; Skeleton; Source; System; Techniques; Time; Venipunctures; Vertebral column; Vitamin D; Weight-Bearing state; Woman; absorption; base; blood Pb concentration; bone; bone health; bone mass; cohort; design; early life exposure; environmental Pb exposure; experience; fall risk; falls; gender disparity; innovation; interest; lead concentration; lead exposure; meetings; postnatal; racial disparity; sound; tibia; tool

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.

描述（由申请人提供）：拟议的研究旨在首次提供变革性知识，了解童年环境铅 (Pb) 暴露史如何影响非裔美国女性日后的骨骼和肌肉组织 (CBAM) 健康。虽然自不再使用铅作为汽油添加剂以来，美国普通人群的血铅浓度 (PbB) 有所下降，但骨骼中的铅仍然是数百万女性体内暴露的来源，尤其是在她们的成长时期接触中度至高水平铅的少数群体。非裔美国女性的膳食钙含量较低，更有可能出现乳糖不耐症、维生素 D 缺乏，并且环境中的铅暴露与出生体重较低、姿势平衡不良和跌倒有关。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。其中包括骨矿物质含量 (BMC)、骨矿物质密度 (BMD)、影响出生后骨骼生长的较低出生体重以及 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，从而增加了骨折的可能性。 CBAM 系统的能量吸收或阻尼 (ζ) 能力是使用我们小组最近开发的非侵入性骨减震 (BSA) 工具来测量的。与未接触或接触较低铅的人相比，这些与铅相关的骨和肌肉参数的有害变化可能共同导致早期骨质疏松症的发生，并容易发生骨折。此外，铅还会影响破骨细胞和成骨细胞过程、激素信号传导途径以及生长板软骨细胞的成熟速率，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。这些研究构成了我们长期核心假设的基础：“生命早期接触铅会对骨骼健康产生不利影响，其特征是骨量、骨骼的宏观结构和CBAM维持动态载荷的结构完整性能力，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牵头研究 (CLS) 队列一起进行；因此，我们能够利用 CLS 前瞻性研究的广泛数据资源，该研究在早年（20 世纪 70 年代末和 1980 年代）经历了中度至高水平的铅暴露，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所提出的骨宏观结构、BMD、FPS 和 ze 测量方法的能力，集体和单独评估 识别符合或接近文献中跌倒、骨质疏松相关骨折和无骨折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。