Risk Factors for Age Related Bone Loss

年龄相关骨质流失的危险因素

• 批准号: 9539088
• 负责人: DOUGLAS P. KIEL
• 金额: $ 4.25万
• 依托单位: HEBREW REHABILITATION CENTER FOR AGED
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-19 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9539088
• 关键词: Adipocytes; Adipose tissue; Adrenal Glands; Adverse effects; Affect; Age-Related Bone Loss; Ancillary Study; Androstenedione; Attenuated; Bone Density; Central obesity; Clinic Visits; Conflict (Psychology); Data; Degenerative polyarthritis; Development; Disease; Distal; Dual-Energy X-Ray Absorptiometry; Epidemic; Estradiol; Fatty acid glycerol esters; Fracture; Framingham Heart Study; Generations; Genetic; Genetic Risk; Goals; Gonadal Steroid Hormones; Grant; Health; Image; Incidence; Individual; Inflammation; Inflammatory; Intervention; Investigation; Measurement; Measures; Meta-Analysis; Morbidity - disease rate; Muscle; Musculoskeletal; Musculoskeletal System; Obesity; Osteoporosis; Outcome; Peripheral; Physical activity; Porosity; Public Health; Radial; Randomized; Reporting; Research; Research Project Grants; Resolution; Risk; Risk Factors; Role; Scanning; Site; Skeleton; Steroids; Testosterone; Thick; United States; Visceral; Weight; Woman; Work; X-Ray Computed Tomography; adipokines; age related; aged; base; bone; bone strength; cohort; cortical bone; cytokine; density; disability; falls; follow-up; fracture risk; fragility fracture; genetic variant; genome wide association study; imaging approach; lifestyle factors; men; protective effect; public health relevance; sarcopenia; skeletal; steroid metabolism; tibia; trend

 DESCRIPTION (provided by applicant): The Framingham Osteoporosis Study (R01 AR41398 "Risk Factors for Age Related Bone Loss"), an ancillary study of the Framingham Heart Study, has contributed significantly over the past 25 years to the understanding of genetic and lifestyle factors contributing to osteoporosis, sarcopenia, and fractures. Based on the growing epidemic of obesity, and conflicting data regarding the role of visceral adiposity on musculoskeletal health, in this continuation of the Framingham Osteoporosis Study, we will determine the role of visceral adipose tissue (VAT) on bone density, microarchitecture, and strength, as well as on muscle density, and fracture. We are proposing three aims. In Aim 1, to determine the association between VAT and bone density, microarchitecture, and strength, we will measure VAT using longitudinal whole body DXA scans (a baseline previously obtained, and a follow up to be acquired as part of this project) and perform High Resolution Peripheral Quantitative Computed Tomography (HR-pQCT) measurements of the distal radius and tibia, and during a clinic visit of the Framingham Study 3rd Generation Cohort (Gen3). In Aim 2 we will determine the association of VAT and muscle density using longitudinal QCT scans already obtained in the Gen3 Cohort. For both Aim 1 and Aim 2, we will also determine if the effects of VAT on bone density, microarchitecture and strength (Aim 1), and on muscle density (Aim 2), are partly attributable to physical activity levels, inflammation, adipokines, or sex steroid metabolism. In Aim 3, we will perform a Mendelian randomization analysis to obtain an unbiased estimate of the VAT-fracture association by using a genetic risk score ("instrumental variable") to predict incident fracture. The proposed study will be the largest investigation of the potentially deleterious effects of visceral adiposity on the musculoskeletal system. Each of our hypotheses is based on preliminary data from our past grant cycle or from other research grants involving the Framingham Study. The project is significant for several reasons. First, obesity has become one of the most important health problems in the U.S. Second, the precise role of visceral adiposity on the musculoskeletal system has not been previously investigated, and the proposed work will fill this gap, especially with longitudinal data on VAT and to be obtained longitudinal measures of muscle density using existing CT scans. Third, we will investigate potential underlying mechanisms for the effects of VAT on the musculoskeletal system. Finally we will obtain an unbiased estimate of the VAT-fracture association using Mendelian randomization analysis. Overall, the results of this study will provide the best available data on the effects of visceral adiposity on the musculoskeletal system.

 描述（由申请人提供）：Frachial骨质疏松症研究（R 01 AR 41398“年龄相关骨丢失的风险因素”）是Frachial心脏研究的辅助研究，在过去25年中为了解导致骨质疏松症、肌肉减少症和骨折的遗传和生活方式因素做出了重大贡献。基于肥胖症的日益流行，以及内脏脂肪对肌肉骨骼健康的作用的相互矛盾的数据，在本研究的继续中，我们将确定内脏脂肪组织（VAT）对骨密度、微结构和强度以及肌肉密度和骨折的作用。我们提出三个目标。在目标1中，为了确定VAT与骨密度、微结构和强度之间的关系，我们将使用纵向全身DXA扫描测量VAT（之前获得的基线，以及作为本项目的一部分采集的随访），并对桡骨远端和胫骨进行高分辨率外周定量计算机断层扫描（HR-pQCT）测量，以及在Frachial Study第三代队列（Gen 3）的临床访视期间。在目标2中，我们将使用已在Gen 3队列中获得的纵向QCT扫描确定VAT与肌肉密度的关联。对于目标1和目标2，我们还将确定VAT对骨密度、微结构和强度（目标1）以及对肌肉密度（目标2）的影响是否部分归因于体力活动水平、炎症、脂肪因子或性类固醇代谢。在目标3中，我们将进行孟德尔随机化分析，通过使用遗传风险评分（“工具变量”）来预测偶发骨折，以获得无偏估计的增值税-骨折关联。这项拟议的研究将是内脏肥胖对肌肉骨骼系统潜在有害影响的最大调查。我们的每一个假设都是基于我们过去的资助周期或其他涉及Fragrance研究的研究赠款的初步数据。该项目的重要性有几个原因。首先，肥胖已成为美国最重要的健康问题之一。其次，内脏肥胖对肌肉骨骼系统的确切作用以前没有研究过，拟议的工作将填补这一空白，特别是关于VAT的纵向数据，以及使用现有CT扫描获得肌肉密度的纵向测量。第三，我们将研究增值税对肌肉骨骼系统的影响的潜在机制。最后，我们将获得一个无偏估计的增值税骨折的关联使用孟德尔随机化分析。总体而言，本研究的结果将提供内脏肥胖对肌肉骨骼系统影响的最佳可用数据。