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.

项目概要 健康的骨骼对于长期健康至关重要，不仅可以最大限度地降低骨折风险，而且可以作为活跃的内分泌器官 影响能量稳态、矿物质代谢和身体成分。重大公共卫生 骨骼健康状况不佳的后果包括骨折相关发病率和死亡率的风险增加、胰岛素 抵抗力和心血管疾病。然而，普遍存在的内分泌干扰化学物质的潜力 影响骨骼健康尚不清楚。邻苯二甲酸盐是塑料和个人护理产品中使用的化学物质， 与可能影响骨骼健康的生物途径有关，包括破坏激素 对于骨稳态和 PPARg 激活至关重要，指导间充质干细胞的分化 从成骨细胞到脂肪细胞。最近，尿邻苯二甲酸酯代谢物与 NHANES 中绝经后妇女的骨矿物质密度 (BMD) 较低，骨质疏松症风险较高，但 尚未探讨暴露在不同生命阶段或对骨代谢功能的影响。一些 重金属还与骨密度下降以及骨质疏松和骨折风险增加有关。 例如，铅积聚在骨基质中，损害骨完整性。怀孕和 围绝经期是对骨骼健康的暴露相关变化可能敏感的生命阶段，因为它们 其特点是强烈的骨重塑以及代谢和激素稳态的变化。所以， 我们的目标是调查妊娠期和围绝经期邻苯二甲酸盐和金属暴露的关系 中年时期骨骼健康的衡量标准。拟议的研究利用了墨西哥的早期生活暴露 作为参与环境毒物 (ELEMENT) 出生队列的母亲，她们现在年龄为 40-65 岁 年龄，提供了广泛的人口统计、人体测量和健康信息，以及重复的邻苯二甲酸盐和 怀孕期间的金属接触措施。在本研究中，参与者将提供有关邻苯二甲酸盐的信息 围绝经期随访中的金属暴露、骨结构、骨代谢和身体成分 访问 (n=400)。将探索 BMI 和更年期状态作为潜在的影响调节剂，以及邻苯二甲酸盐 代谢物和金属将被单独和作为混合物考虑。我们的目标是调查 1) 怀孕期间的 BMI 以及怀孕期间和围产期的 BMI 轨迹与 BMD 的关联， 使用双能 X 射线评估骨骼肌指数以及雌性和机器人脂肪组织分布 中年时期的骨吸收测定法（iDXA）和定量超声评估骨微结构； 2）协会 怀孕和围绝经期期间邻苯二甲酸盐和金属暴露与骨微结构、BMD 和 肌肉和脂肪组织的分布； 3) 怀孕期间邻苯二甲酸盐和金属暴露的关联 和围绝经期，具有中年骨代谢的生物标志物。这项工作的发现将提供见解 研究与暴露相关的骨骼健康变化机制，对骨质疏松症具有重要影响， 骨折风险以及长期代谢和心血管健康。