Epidemiology of Age-Related Bone Loss and Fractures

与年龄相关的骨质流失和骨折的流行病学

• 批准号: 7929382
• 负责人: Sundeep Khosla
• 金额: $ 18.04万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-18 至 2010-12-17
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7929382
• 关键词: 3-Dimensional; Accounting; Address; Age; Age-Related Bone Loss; Aging; Aromatase; Bioavailable; Biochemical; Biomechanics; Biopsy; Body Weight; Bone Density; Caliber; California; Case-Control Studies; Clinical; Collaborations; Communities; Data; Distal; Elements; Epidemiologic Methods; Epidemiology; Estrogen Receptors; Estrogens; Failure; Femur; Forearm; Forearm Fracture; Fracture; Funding; Genes; Genetic Polymorphism; Gonadal Steroid Hormones; Hip Fractures; Hormonal; Image Analysis; Institutes; Insulin-Like Growth-Factor-Binding Proteins; Measurement; Measures; Methods; Modeling; Osteoporosis; Parathyroid Hormones; Peripheral; Population; Population Study; Postmenopause; Production; Progress Reports; Protocols documentation; Public Health; Radial; Research Infrastructure; Research Personnel; Risk; Risk Assessment; Risk Factors; Sampling; Serum; Site; Somatomedins; Spinal Fractures; Structure; Technology; Testing; Time; Universities; Upper arm; Variant; Vertebral column; Vitamin D; Width; Woman; X-Ray Computed Tomography; age related; base; bone; bone geometry; bone mass; bone strength; bone turnover; case control; cohort; experience; falls; follow-up; human PTH protein; improved; in vivo; indexing; men; muscle form; novel; novel strategies; population based; programs; response; sex; skeletal; spine bone structure; substantia spongiosa; ultra high resolution

DESCRIPTION (provided by applicant): In this renewal application, we have moved from dual-energy x-ray absorptiometry (DXA) to novel assessments of volumetric bone mineral density (vBMD), structure, and indices of bone strength by quantitative computed tomography (QCT) of the vertebrae and proximal femur and ultra-high resolution, peripheral QCT of the distal radius. In addition, new collaborations with Drs. Tony Keaveny (UC-Berkeley) and Ralph Muller (Swiss Federal Institute of Technology) will allow us to use QCT for voxel-based finite element (FE) models to assess bone "strength" for the first time in population studies. Moreover, in collaborations with Drs. Mary Bouxsein (Harvard) and Kenton Kaufman (Mayo), we will combine estimates of bone strength with assessments of skeletal loading to elucidate the relationship between bone structure and loads. Our central hypotheses are: (1) Age-related changes in bone mass/structure can be accounted for, in large part, by specific hormonal/biochemical parameters, loading forces, and the interactions between them; and (2) Bone strength estimates that can now be obtained clinically will enhance the ability to identify subjects at increased fracture risk. These hypotheses will be tested in our Specific Aims: (1) To continue the cross-sectional and longitudinal (to 6 yrs of follow-up) analysis of our established cohort of Rochester, MN residents (age-stratified sample of 375 women and 325 men, age 20-97 yrs), to better understand bone structural changes with aging (AIM 1a); to relate these changes to sex steroid/biochemical parameters and to estrogen receptor and aromatase polymorphisms (AIM 1b); and to determine the relationship of everyday loading forces to changes in vBMD, bone geometry, and microstructure (AIM 1c); (2) In population-based, case-control studies of postmenopausal Rochester women with vertebral and distal forearm fractures, to use the FE models to quantify bone strength at the spine and distal radius and define the key structural determinants of strength at each site (AIM 2a); to use measures of bone failure strength from FE models to improve current estimates of the "factor-of-risk" (phi, the ratio of applied load to that known to cause bone failure, i.e., fracture) for the vertebrae during various activities and to develop them for the distal radius with falls (AIM 2b); and to determine the utility of our new approaches in differentiating fracture cases from controls in comparison with conventional risk assessment using DXA (AIM 2c).

描述（由申请人提供）：在本次更新申请中，我们已从双能X线吸收测定法（DXA）转移到通过椎骨和股骨近端的定量计算机断层扫描（QCT）以及桡骨远端的超高分辨率外周QCT对体积骨矿物质密度（vBMD）、结构和骨强度指数进行的新型评估。此外，与Tony Keaveny博士（加州大学伯克利分校）和Ralph Muller博士（瑞士联邦理工学院）的新合作将使我们能够将QCT用于基于体素的有限元（FE）模型，以首次在人口研究中评估骨“强度”。此外，在与玛丽Bouxsein博士（哈佛）和Dr. J.考夫曼（马约）的合作中，我们将结合联合收割机对骨强度的估计和对骨骼负荷的评估，以阐明骨结构和负荷之间的关系。我们的主要假设是：（1）骨量/结构的骨密度相关变化在很大程度上可以通过特定的激素/生化参数、载荷力以及它们之间的相互作用来解释;（2）现在可以在临床上获得的骨强度估计值将增强识别骨折风险增加的受试者的能力。这些假设将在我们的具体目标进行检验：（1）继续横向和纵向研究，（至6年随访）对我们已建立的明尼苏达州罗切斯特居民队列的分析（年龄分层样本，375名女性和325名男性，年龄20-97岁），以更好地了解骨骼结构随年龄增长的变化（AIM 1a）;将这些变化与性类固醇/生化参数以及雌激素受体和芳香化酶多态性（AIM 1b）联系起来;并确定日常负荷力与vBMD、骨几何形状和微观结构变化的关系（AIM 1c）;（2）在绝经后罗切斯特妇女椎体和前臂远端骨折的人群病例对照研究中，使用有限元模型量化脊柱和桡骨远端的骨强度，并定义每个部位强度的关键结构决定因素（AIM 2a）;使用来自FE模型的骨失效强度的测量来改进“风险因子”（phi，施加的载荷与已知引起骨失效的载荷的比率，即，骨折）的椎骨在各种活动中，并制定他们的桡骨远端福尔斯（AIM 2b）;并确定我们的新方法的效用，区分骨折的情况下，对照组相比，传统的风险评估使用DXA（AIM 2c）。