Relating phthalate and metals exposure during pregnancy and perimenopause to bone health and body composition in midlife

怀孕和围绝经期期间邻苯二甲酸盐和金属暴露与中年骨骼健康和身体成分的关系

• 批准号: 10260609
• 负责人: Marcela Tamayo-Ortiz
• 金额: $ 31.82万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-10 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10260609
• 关键词: Adipocytes; Adipose tissue; Affect; Age-Years; Alkaline Phosphatase; Biological; Biological Markers; Birth; Body Composition; Body mass index; Bone Density; Bone Matrix; Bone remodeling; Bone structure; Cadmium; Cardiovascular Diseases; Cells; Chemicals; Collaborations; Drug or chemical Tissue Distribution; Dual-Energy X-Ray Absorptiometry; Elderly; Endocrine; Endocrine Disruptors; Endocrine Glands; Environmental Epidemiology; Environmental Pollution; Exposure to; Femur; Fracture; Future; Goals; Gonadal Steroid Hormones; Health; Health Policy; Heavy Metals; Hip region structure; Homeostasis; Hormones; Human; Individual; Insulin Resistance; Lead; Life; Long-Term Effects; Longitudinal Studies; Measures; Menopausal Status; Mesenchymal Differentiation; Mesenchymal Stem Cells; Metabolic; Metabolic hormone; Metabolism; Metal exposure; Metals; Mexico; Minerals; Morbidity - disease rate; Mothers; Mus; Muscle; National Health and Nutrition Examination Survey; Nutrient; Obesity; Osteoblasts; Osteogenesis; Osteoporosis; Outcome; PPAR gamma; Participant; Pathway interactions; Perimenopause; Plastics; Population; Postmenopause; Postpartum Period; Pregnancy; Public Health; Recording of previous events; Recovery; Reporting; Research; Risk; Risk Factors; Sampling; Serum; Skeletal Muscle; Speed; Spinal; Statistical Methods; Time; Toxic Environmental Substances; Vertebral column; Visit; Vitamin D; Woman; Work; blood Pb concentration; blood lead; bone; bone health; bone loss; bone metabolism; calcium supplementation; cardiovascular health; cohort; early life exposure; fibroblast growth factor 23; follow-up; fracture risk; indexing; insight; lead exposure; middle age; modifiable risk; mortality; perinatal period; personal care products; phthalates; postnatal; prenatal; prenatal exposure; preventive intervention; quantitative ultrasound; randomized trial; recruit; sound; urinary

PROJECT SUMMARY Healthy bone is critical for long term health not only to minimize fracture risk, but as an active endocrine organ with influence on energy homeostasis, mineral metabolism, and body composition. Significant public health consequences of poor bone health include increased risk of fracture-related morbidity and mortality, insulin resistance, and cardiovascular disease. However, the potential for ubiquitous endocrine-disrupting chemicals to affect bone health is unknown. Phthalates, chemicals used in plastics and personal care products, have been associated with biological pathways that may affect bone health, including disruption of hormones essential to bone homeostasis and activation of PPARg, directing differentiation of mesenchymal stem cells from osteoblasts to adipocytes. Recently, urinary phthalate metabolites were cross-sectionally associated with lower bone mineral density (BMD) and higher osteoporosis risk in post-menopausal women in NHANES, but the effects of exposure at different life stages or on bone metabolic function have not been explored. Some heavy metals have also been associated with decreased BMD and increased risk of osteoporosis and fracture. For example, lead accumulates in the bone matrix, compromising bone integrity. Pregnancy and perimenopause are life stages potentially sensitive to exposure related changes in bone health, as they are characterized by intense bone remodeling and changes in metabolic and hormone homeostasis. Therefore, our goal is to investigate relationships of phthalate and metals exposure across pregnancy and perimenopause with measures of bone health in midlife. The proposed research leverages the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) birth cohort, as participating mothers, who are now 40-65 years of age, provided extensive demographic, anthropometric, and health information, and repeated phthalate and metal exposure measures, during pregnancy. In this study, participants will provide information on phthalate and metal exposure, bone structure, bone metabolism, and body composition at a perimenopausal follow-up visit (n=400). BMI and menopausal status will be explored as potential effect modifiers, and phthalate metabolites and metals will be considered individually and as mixtures. Our aims are to investigate 1) associations of BMI during pregnancy and BMI trajectory through pregnancy and perinatal periods with BMD, skeletal muscle index, and gynoid and android adipose tissue distribution assessed using dual energy x-ray absorptiometry (iDXA), and bone microstructure assessed by quantitative ultrasound, in midlife; 2) associations of phthalate and metals exposure during pregnancy and perimenopause with bone microstructure, BMD, and muscle and adipose tissue distribution; 3) associations of phthalate and metals exposure during pregnancy and perimenopause with biomarkers of bone metabolism in midlife. Findings from this work will provide insight into mechanisms of exposure-related changes in bone health, with important implications for osteoporosis, fracture risk, and long-term metabolic and cardiovascular health.

项目摘要 健康的骨头对于长期健康至关重要，不仅可以最大程度地减少骨折风险，而且是活跃的内分泌器官 对能量稳态，矿物质代谢和身体成分的影响。重要的公共卫生 骨骼健康不良的后果包括增加与骨折相关的发病率和死亡率的风险增加，胰岛素 抗药性和心血管疾病。但是，无处不在的内分泌化学物质的潜力 影响骨骼健康是未知的。邻苯二甲酸盐，塑料和个人护理产品中使用的化学物质，具有 与可能影响骨骼健康的生物学途径有关，包括激素的破坏 对骨稳态和PPARG的激活必不可少的，指导间充质干细胞的分化 从成骨细胞到脂肪细胞。最近，尿邻苯二甲酸盐代谢物在横截面上与 NHANES绝经后妇女中较低的骨矿物质密度（BMD）和较高的骨质疏松症风险，但 尚未探索不同生命阶段的暴露或对骨代谢功能的影响。一些 重金属也与BMD降低以及骨质疏松和骨折的风险增加有关。 例如，铅积累在骨基质中，损害骨完整性。怀孕和 围绝经期是生命阶段可能对暴露与骨骼健康相关的变化敏感，因为它们是 以强烈的骨骼重塑以及代谢和激素稳态的变化为特征。所以， 我们的目标是调查邻苯二甲酸酯和金属在怀孕和围绝经期之间的关系 与中年的骨骼健康措施。拟议的研究利用了墨西哥的早期生活暴露 作为参与母亲的环境有毒物质（元素）出生队列，现在已经40 - 65年了 年龄提供了广泛的人口，人体测量和健康信息，并重复邻苯二甲酸盐和 怀孕期间的金属暴露措施。在这项研究中，参与者将提供有关邻苯二甲酸盐的信息 以及金属暴露，骨骼结构，骨骼代谢和身体成分 访问（n = 400）。 BMI和更年期状态将作为潜在效应修饰剂探索，邻苯二甲酸盐 代谢物和金属将被视为单独和混合物。我们的目的是调查1） 怀孕期间BMI与BMD期间与BMD期间的BMI轨迹的关联， 使用双能X射线评估的骨骼肌指数以及脊髓和Android脂肪组织分布 中年的吸收法（IDXA）和通过定量超声评估的骨微结构； 2）协会 怀孕期间邻苯二甲酸酯和金属暴露于骨微结构，BMD和 肌肉和脂肪组织分布； 3）怀孕期间邻苯二甲酸酯和金属暴露的关联 和中期生物标志物的骨骼代谢。这项工作的发现将提供洞察力 进入与暴露相关的骨骼健康变化的机制，对骨质疏松症具有重要意义 断裂风险以及长期代谢和心血管健康。