Urine cadmium and risk of fracture and bone loss

尿镉与骨折和骨质流失的风险

• 批准号: 10612697
• 负责人: Jaymie R Meliker
• 金额: $ 11.22万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-20 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10612697
• 关键词: Affect; Bone Density; Bone structure; Cadmium; Cohort Studies; Cotinine; Creatinine; Cross-Sectional Studies; Cyclophosphamide; Data; Epidemiologist; Epidemiology; Fracture; Investigation; Link; Longterm Follow-up; Measures; Metals; Methods; Modeling; Muscular Atrophy; Musculoskeletal; Nutrient; Osmolalities; Osteoporosis; Parents; Persons; Policies; Public Health; Reporting; Research; Research Design; Risk; Sampling; Sum; Testing; Urine; Woman; bone; bone loss; bone metabolism; cohort; cost effective; epidemiology study; experimental study; follow-up; fracture risk; hip bone; insight; learning strategy; men; muscle form; novel; osteoporosis with pathological fracture; parent grant; parent project; prospective; sex; statistical learning

Diversity Supplement: Urine cadmium and risk of fracture and bone loss Abstract We propose to leverage the parent grant, which uses existing samples and data from the two largest prospective US osteoporosis cohort studies to perform an in depth study of urine cadmium (U-Cd), bone loss, and fractures that will include long-term follow-up of up to 20 years using: 1) The Osteoporotic Fractures in Men (MrOS) Study and 2) the Study of Osteoporotic Fractures (SOF). The parent grant uses an efficient case-cohort study design to investigate the prospective association between U-Cd and incident fractures in 1,321 MrOS men and 1,578 SOF women who will be sex matched with 1500 randomly selected persons from each respective cohort. Cd, creatinine, osmolality, and cotinine are being analyzed in urine. The parent grant also evaluates the prospective association between U-Cd and rate of loss of total hip bone mineral density (BMD) in men and women from the subcohorts, and in incident fracture cases; and will utilize markers of bone metabolism and structure (PINP, CTX, and HR-pQCT) to provide novel insights into the cellular and structural mechanisms by which Cd may adversely affect bone. To this parent project, we are adding two Aims in this Supplement. Aim 1. Evaluate the prospective association between U-Cd and muscle mass in men and women from the subcohorts, and in fracture cases. This will be a follow-up to a recent cross-sectional study which reported an association between U-Cd and muscle loss. Aim 2. Explore whether mixtures of metals and nutrients are associated with fracture in the parent case- cohort study, and whether these mixtures are associated with bone loss, and muscle loss in the subcohorts. Shedding insights on risks from mixtures has been a desire of epidemiologists for decades; we will be using cutting edge statistical learning methods to analyze associations between mixtures and risk of incident fractures, bone loss, and muscle loss. These methods, including Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) regression, have the advantages over standard regression models containing interaction terms of avoiding problems associated with multiple testing, interpretation of higher-order interaction terms, and limited statistical power. A large fraction of older US men and women have documented Cd exposure. Highly accurate measures of Cd exposure linked to powerful epidemiological cohorts provide a unique, cost effective approach to this important public health issue. These studies will transform the field of Cd-musculoskeletal research and have high potential to impact policy decisions in the US and globally.

多样性补充：尿镉与骨折和骨丢失的风险 摘要 我们建议利用母公司赠款，它使用现有的样本和数据，从两个最大的前景 美国骨质疏松症队列研究，对尿镉（U-Cd）、骨丢失和骨折进行深入研究 这将包括长达20年的长期随访：1）男性骨质疏松性骨折（MrOS） 研究和2）骨质疏松性骨折（SOF）的研究。父母补助金使用了一种有效的病例队列研究 研究设计旨在调查1,321名MrOS男性中U-Cd与新发骨折之间的前瞻性相关性， 1，578名SOF女性将与每个队列中随机选择的1500人进行性别匹配。 正在分析尿液中的镉、肌酐、渗透压摩尔浓度和可替宁。父母补助金还评估 U-Cd与男性总髋部骨矿物质密度（BMD）丢失率之间的前瞻性关联， 来自亚组群的女性，以及发生骨折的病例;并将利用骨代谢标志物， 结构（PINP，CTX和HR-pQCT），以提供对细胞和结构机制的新见解， Cd可能对骨骼产生不利影响。 对于这个父项目，我们在本补充中添加了两个目标。目标1.评估前景 U-Cd和肌肉质量之间的关联，在男性和女性的亚组，并在骨折的情况下。 这将是最近一项横断面研究的后续研究，该研究报告了U-Cd和肌肉之间的联系 损失目标2.探索金属和营养物质的混合物是否与母病例中的骨折有关- 队列研究，以及这些混合物是否与亚队列中的骨丢失和肌肉丢失相关。 几十年来，流行病学家一直希望从混合物中摆脱风险;我们将使用 尖端的统计学习方法来分析混合物和事故骨折风险之间的关联， 骨质流失和肌肉萎缩这些方法，包括贝叶斯核机器回归（BKMR）和 加权分位数和（WQS）回归，具有优于标准回归模型的优点， 避免与多重测试相关的问题的交互作用术语，高阶交互作用的解释 有限的统计能力。 大部分美国老年男性和女性都记录了镉暴露。高精度测量Cd 与强大的流行病学队列相关的暴露提供了一种独特的、具有成本效益的方法， 公共卫生问题。这些研究将改变镉-肌肉骨骼研究领域，具有很高的潜力 影响美国和全球的政策决定。