Epidemiology of Age-Related Bone Loss and Fractures

描述（由申请人提供）：在这个更新申请中，我们已经从双能x射线吸收测定法（DXA）转移到通过椎骨和股骨近端定量计算机断层扫描（QCT）和桡骨远端超高分辨率外周QCT对体积骨矿物质密度（vBMD）、结构和骨强度指标进行新的评估。此外，与博士的新合作。Tony Keaveny（加州大学伯克利分校）和Ralph Muller（瑞士联邦理工学院）将允许我们在人口研究中首次使用QCT进行基于体素的有限元（FE）模型来评估骨骼“强度”。此外，在与博士合作。Mary Bouxsein（哈佛大学）和Kenton Kaufman（梅奥），我们将结合骨骼强度评估和骨骼负荷评估来阐明骨骼结构和负荷之间的关系。我们的中心假设是：(1)骨量/结构的年龄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)临床可获得的骨强度估计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中得到验证：(1)继续对我们已建立的罗切斯特市居民队列（年龄分层样本，375名女性和325名男性，年龄20-97岁）进行横断面和纵向（至6年的随访）分析，以更好地了解骨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；并确定日常载荷力与vBMD、骨几何形状和微观结构变化的关系（AIM 1c）；(2)在以人群为基础的病例对照研究中，对患有椎体和前臂远端骨折的绝经后罗切斯特女性进行研究，使用FE模型量化脊柱和桡骨远端骨强度，并确定每个部位强度的关键结构决定因素（AIM 2a）；使用来自FE模型的骨衰竭强度测量来改善目前对各种活动中椎骨的“风险因素”（phi，所施加的载荷与已知导致骨衰竭的载荷的比率，即骨折）的估计，并对有跌倒的桡骨远端进行开发（AIM 2b）；并与使用DXA （AIM 2c）的传统风险评估相比，确定我们的新方法在区分骨折病例和对照组方面的实用性。

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).