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: 10907998
• 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/10907998
• 关键词: Affect; Age; Aging; Agreement; Behavioral; Biological Markers; Bone Density; Bone Resorption; Bone structure; Cadmium; Cell Culture System; Clinic Visits; Clinical Data; Cohort Studies; Complement; Cotinine; Creatinine; Cross-Sectional Studies; Cyclophosphamide; Data; Diet; Dual-Energy X-Ray Absorptiometry; Elements; Environment; Environmental sludge; Epidemiology; Etiology; Excretory function; Female; Femur; Fertilizers; Foundations; Fracture; Half-Life; Health; Heavy Metals; Human; Individual; Industrialization; Intake; International; Investigation; Kidney; Link; Longterm Follow-up; Measures; Mediating; Mediation; Minerals; Morbidity - disease rate; National Health and Nutrition Examination Survey; Neck; Odds Ratio; Organ Culture Techniques; Osmolalities; Osteogenesis; Osteoporosis; Persons; Policies; Population; Population Attributable Risks; Prevalence; Prospective Studies; Public Health; Random Allocation; Reporting; Research; Research Design; Sampling; Scanning; Serum; Sewage; Smoking; Smoking History; Soil; Source; Time; Toxic effect; United States; Urine; Vertebral column; Visit; Woman; adjudication; aged; bone; bone loss; bone metabolism; bone turnover; clinical research site; cohort; cost; cost effective; dietary; epidemiology study; experimental study; fracture risk; hip bone; human old age (65+); inorganic phosphate; insight; male; men; mortality; never smoker; novel; osteoporosis with pathological fracture; prospective; recruit; sex; skeletal; skeletal tissue; urinary; working group

Urine cadmium and risk of fracture and bone loss Abstract Osteoporosis and related fractures are a major cause of morbidity and mortality in the United States and globally. Mechanistic studies from bone organ and cell culture systems suggest cadmium (Cd) mobilizes bone minerals from skeletal tissue. Cd is a heavy metal and natural element found in soil, with increasing concentrations linked to phosphate fertilizers and sewage sludge found in croplands. As a result, human dietary exposures have increased over time by 26% dating from 1990 through 2003. In addition, Cd has increased in human bones ten- fold since pre-industrial times. Following intake, Cd is stored in the kidney, where it remains for decades (half- life: 10-30 years). A small portion of Cd is slowly excreted in the urine, making urinary Cd (U-Cd) a well- established biomarker of long-term exposure. Cross-sectional studies have linked Cd to low bone mineral density, osteoporosis, and fracture, suggesting a potential population attributable fraction of 30% assuming there is a causal relationship. However, currently lacking are large prospective studies. We propose to leverage existing samples and data from the two largest prospective US osteoporosis cohort studies to perform an in depth study of 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). Aim 1: Using efficient case-cohort study designs we will 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 will be analyzed in urine. Aim 2: Evaluate 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. Aim 3: Utilize markers of bone metabolism and structure to provide novel insights into the cellular and structural mechanisms by which Cd may adversely affect bone. Evaluate the association between U-Cd and markers of bone formation (PINP) and bone resorption (CTX) in men and women. In a substudy using data already available in men, evaluate the association between U-Cd and bone structure (HR-pQCT). Also, in an exploratory subAim, apply mediation analyses using a counterfactual framework based approach to estimate the extent to which Cd’s influence on bone loss might be mediated via biomarkers of bone metabolism (serum PINP, CTX). 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-bone research and have high potential to impact policy decisions in the US and globally.

尿镉与骨折和骨质流失的风险 抽象的 骨质疏松症和相关骨折是美国和全球发病和死亡的主要原因。 骨器官和细胞培养系统的机制研究表明镉 (Cd) 可以动员骨矿物质 来自骨骼组织。镉是土壤中发现的一种重金属和天然元素，其浓度不断增加 农田中发现的磷肥和污水污泥。因此，人类饮食暴露 从 1990 年到 2003 年，镉的含量随时间增加了 26%。此外，人体骨骼中的镉含量也增加了 10- 自前工业时代以来就开始折叠。摄入后，镉会储存在肾脏中，并在其中保留数十年（半数） 寿命：10-30年）。一小部分镉慢慢随尿液排出，使尿镉（U-Cd）成为良好的 建立了长期暴露的生物标志物。横断面研究已将镉与低骨矿物质联系起来 密度、骨质疏松症和骨折，表明假设存在 30% 的潜在人群归因分数 是一种因果关系。然而，目前缺乏大规模的前瞻性研究。 我们建议利用来自美国两个最大的前瞻性骨质疏松症队列的现有样本和数据 对 U-Cd、骨质流失和骨折进行深入研究的研究，其中包括长期随访 使用以下长达 20 年的时间：1) 男性骨质疏松性骨折 (MrOS) 研究和 2) 骨质疏松性骨折研究 骨折（SOF）。目标 1：使用有效的病例队列研究设计，我们将调查前瞻性研究 U-Cd 与 1,321 名 MrOS 男性和 1,578 名 SOF 女性发生性骨折之间的关联 与从每个队列中随机选择的 1500 人进行匹配。 Cd、肌酐、渗透压和 将在尿液中分析可替宁。目标 2：评估 U-Cd 与损失率之间的前瞻性关联 亚组中男性和女性以及骨折病例中的总髋骨矿物质密度 (BMD)。 目标 3：利用骨代谢和结构标记物为细胞和结构提供新的见解 镉可能对骨骼产生不利影响的机制。评估 U-Cd 和标记物之间的关联 男性和女性的骨形成（PINP）和骨吸收（CTX）。在使用现有数据的子研究中 在男性中，评估 U-Cd 与骨结构之间的关联 (HR-pQCT)。此外，在探索性子目标中， 使用基于反事实框架的方法应用中介分析来估计 Cd 的程度 对骨丢失的影响可能是通过骨代谢生物标志物（血清PINP、CTX）介导的。 很大一部分美国老年男性和女性都曾接触过镉。高精度 Cd 测量 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来解决这一重要问题 公共卫生问题。这些研究将改变镉骨研究领域，并具有巨大的影响潜力 美国和全球的政策决定。