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：
6374858
负责人：
B. LAWRENCE RIGGS
金额：
$ 73.79万
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.

此申请用于为 RO1 AR27065“与年龄相关的骨质流失和骨折的流行病学”第 21 至 25 年提供更新资金。在美国，骨质疏松症导致至少 150 万例骨折，每年造成 140 亿美元的损失。我们将使用传统方法和罗切斯特流行病学项目的基础设施，继续对骨质疏松症危险因素进行基于人群的研究。然而，我们还将首次在流行病学研究中采用两种最先进的新技术——脊柱和臀部的螺旋体积定量计算机断层扫描（QCT）（CV 0.7-0.9%）和超-桡骨远端和胫骨的高分辨率、3维外周QCT（CV等于或<0.4%）。这些仪器可以定量测量骨宏观结构，例如形状和大小，单独测定松质骨和皮质体积骨矿物质密度 (BMD)，并评估骨微结构特征，例如皮质孔隙度和小梁连接性（“无创骨活检”）。拟议的研究将扩大对明尼苏达州罗彻斯特居民的两个年龄分层队列的随访（大约1980年注册的304名女性和大约1990年注册的351名女性和348名男性），但大多数研究将在由350名罗彻斯特女性组成的新的年龄分层队列中进行和350名男子。我们的具体目标是：1）验证全国使用的裂缝预测模型； 2）定义骨宏观和微观结构与年龄相关的、性别特异性的变化，并利用这些变化来检验与病理生理学和临床问题相关的许多假设； 3) 检验以下假设：与双能 X 射线骨密度测定法相比，骨宏观结构和微观结构变量的特定测量将大大增强骨折预测； 4) 通过测试以下假设来评估雌激素 (E) 缺乏导致骨质流失的病理生理机制：E 和 E 代谢物水平较低的绝经后女性骨质流失较多，绝经后期女性继发性甲状旁腺功能亢进与 E 缺乏相互作用防止松质骨丢失，但增加皮质骨丢失，并且血清 l,25(OH)2D3 和 IGF-I 水平发生变化导致缺乏维生素E的女性骨质流失； 5）在老年男性中，检验以下假设：E-缺乏是钙质骨流失的主要原因，T-缺乏是皮质骨流失的主要原因。新的骨结构测量应该使我们对与年龄相关的骨质流失和骨折的原因有一个新的认识，并大大改善骨质疏松症风险的评估。