EPIDEMIOLOGY OF AGE RELATED BONE LOSS AND FRACTURES

年龄相关骨质流失和骨折的流行病学

基本信息

批准号：
6632597
负责人：
Sundeep Khosla
金额：
$ 77.77万
依托单位：
MAYO CLINIC ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
1980
资助国家：
美国
起止时间：
1980-06-01 至 2005-05-31
项目状态：
已结题

项目摘要

This application is for renewed funding for yrs 21 to 25 of RO1 AR27065 "Epidemiology of Age-Related Bone Loss and Fractures." Osteoporosis accounts for at least 1.5 million fractures and costs $14 billion annually in the United States. We will continue our population-based studies on risk factors for osteoporosis using conventional methodologies and the infrastructure of the Rochester Epidemiology Project. However, we will also employ, for the first time in an epidemiologic study, two new state- of-the-art technologies--spiral volumetric quantitative computed tomography (QCT) of the spine and hips (CV 0.7-0.9%) and ultra-high resolution, 3-dimensional peripheral QCT (CV equal to or < 0.4%) of the distal radius and tibia. These instruments allow quantitative measurement of bone macrostructure, such as shape and size, separate determination of cancellous and cortical volumetric bone mineral density (BMD), and assessment of bone microstructural characteristics, such as cortical porosity and trabecular connectivity ("noninvasive bone biopsy"). The proposed research will extend followup on two age-stratified cohorts of Rochester, MN residents (304 women enrolled approximately 1980 and 351 women and 348 men enrolled approximately 1990) but most studies will be made in a new age-stratified cohort of 350 Rochester women and 350 men. Our Specific Aims are: 1) to validate a nationally-employed fracture prediction model; 2) to define the age-related, sex-specific changes of bone macro- and microstructure and to use these to test a number of hypotheses related to pathophysiology and to clinical issues; 3) to test the hypotheses that specific measurements of bone macrostructural and microstructural variables will greatly enhance fracture prediction as compared with BMD by dual-energy x-ray absorptiometry; 4) to assess the pathophysiologic mechanisms by which estrogen (E)-deficiency causes bone loss by testing the hypotheses that postmenopausal women with lower levels of E and E-metabolites have greater bone loss, that secondary hyperparathyroidism in late postmenopausal women interacts with E deficiency to protect against cancellous bone loss but to enhance cortical bone loss, and that alterations in levels of serum l,25(OH)2D3 and IGF-I contribute to bone loss in E deficient women; and 5) in aging men, to test the hypotheses that E-deficiency is the main cause of calcellous bone loss and T- deficiency is the main cause of cortical bone loss. The new bone structure measurements should take us to a new level of understanding of the causes of age-related bone loss and fractures and improve substantially the assessment of risk for osteoporosis.

该应用是用于RO1 AR27065的21至25年的新资金，“与年龄相关的骨质流失和骨折的流行病学”。在美国，骨质疏松症的骨折至少为150万美元，每年占140亿美元。我们将继续使用常规方法和罗切斯特流行病学项目的基础设施进行基于人群的骨质疏松症风险因素的研究。但是，我们还将在一项流行病学研究中首次采用两种新的状态技术 - 脊柱和臀部（CV 0.7-0.9％）（CV 0.7-0.9％）和超高分辨率，三维外围QCT（CV等于cct（CV）和<0.4％）的两种新的状态 - 刺激性数量计算机断层扫描（QCT）。这些仪器允许对骨宏结构（例如形状和大小）进行定量测量，分别确定具有皮质和皮质骨矿物质密度（BMD）的分别确定，以及评估骨微结构特征的评估，例如皮质孔隙率和小线虫连接性（“无侵袭性骨骼活检”）。拟议的研究将扩大对两个年龄分离的罗切斯特群体的随访（304名妇女，约有1980年和351名女性和348名女性和348名男性约为1990年），但大多数研究将以新的年龄分层的350名罗切斯特女性和350名男性和350名男性进行。我们的具体目的是：1）验证一个全国就业的断裂预测模型； 2）定义与年龄相关的，特定于骨骼宏观和微观结构的性别变化，并使用它们来检验许多与病理生理学和临床问题有关的假设； 3）测试假设，与双能量X射线吸收仪相比，与BMD相比，与BMD相比，骨骼宏结构和微结构变量的特定测量将大大增强断裂预测； 4) to assess the pathophysiologic mechanisms by which estrogen (E)-deficiency causes bone loss by testing the hypotheses that postmenopausal women with lower levels of E and E-metabolites have greater bone loss, that secondary hyperparathyroidism in late postmenopausal women interacts with E deficiency to protect against cancellous bone loss but to enhance cortical bone loss, and that alterations in levels of血清L，25（OH）2d3和IGF-I导致E缺乏女性的骨质流失； 5）在衰老的男性中，为了测试假设，即e缺乏症是造成骨质骨丢失和T缺乏的主要原因，这是造成皮质骨质流失的主要原因。新的骨结构测量应使我们对与年龄相关的骨质流失和断裂的原因有了新的了解，并大大改善了骨质疏松症风险的评估。