DXA-BASED BONE GEOMETRY AND OSTEOPOROTIC FRACTURE RISK

美国每年发生超过130万例与年龄相关的骨折。 包括大约25万例髋关节骨折，55万例 脊椎和250,000的手腕 每年的治疗费用被认为是 超过100亿美元，预计将增长到300多亿美元， 未来30年 按其频率衡量，对质量的影响 生活和经济成本，老年人与年龄有关的骨折是 一个危机程度的公共卫生问题 在成功 旨在减少其发生率的倡议， 本世纪卫生资源的分配是 令人震惊 采取干预措施，减少与年龄有关的 骨折必须基于对骨折病因的正确理解， 关于已证明有效性和成本效益的药剂和方法， 以及诊断、筛查和治疗监测程序。的 适当的准确度、精密度和灵敏度。 本研究 计划，我们继续解决新的密度测量的发展 提高诊断灵敏度和预测准确性的工具。 我们 前三年的目标是描述 骨几何学和密度学特性之间的关系 通过新的多扫描双能X射线吸收测定法（DXA）测定 技术和桡骨远端和近端的骨折载荷 股骨 我们发现：1）多扫描DXA参数高度预测 桡骨远端骨折载荷（r2 = 0.67，p，0.0001），而传统 桡骨远端的BMD测量值不是（r2 = 0.07，p 0.0.1）; 2） 多扫描DXA参数和股骨颈BMD是良好的预测因子 股骨近端的骨折载荷（r2 = 0.740，但常规BMD 转子间部位的测量值不存在（r2 = 0.12，p = 0.10）;以及 3)桡骨远端的骨折载荷是骨折的不良预测因子 臀部负重 这些发现对使用 以及对传统密度测定的解释， 对DXA技术的发展进行了展望。 在这次竞争激烈的续约中 我们建议从两个重要方面扩展我们的研究结果。 一是在 具体目标1和2，我们计划测试DXA的区分能力 两项病例对照临床研究（一项回顾性研究）中的几何变量 审查来自单独资助的福尔斯监测的可用DXA扫描 自发性髋部骨折患者的研究和一项新的观察性研究 以及他们的年龄和性别匹配的对照）。 第二，具体目标 3和4，我们将我们的DXA方法扩展到脊柱，从而 允许常规和几何DXA和断裂载荷比较， 这是三个高骨折风险地区之间的首次合作 在同一具尸体上 我们期待自发性的研究 骨折产生更强的密度分离之间髋关节 骨折患者和对照组，因为数据不会受到 与跌倒严重程度和创伤负荷相关的问题。 我们希望 提供（甚至对于常规密度测定）更现实的估计， 与日常生活活动相关的骨折风险阈值 从而更好地针对真正脆弱的风险候选人 髋部骨折

Over 1.3 million age-related fractures occur annually in the U.S. including approximately 250,000 fractures of the hip, 550,000 of the spine and 250,000 of the wrist. Annual costs for treatment are thought to exceed $10 billion are expected to grow to more than $30 billion in the next 30 years. As measured by their frequency, influence on quality of life and economic cost, age-related fractures among the elderly are a public health problem of crisis proportions. Within successful initiatives aimed at reducing their incidence, the implications for the allocation of health resources in this and the next century are staggering. Interventions to reduce the prevalence of age-related fractures must be based on a sound understanding of fracture etiology, on agents and approaches of demonstrated efficacy and cost effectiveness, and on diagnostic, screening and therapeutic monitoring procedures. of appropriate accuracy, precision and sensitivity. In this research program, we continue to address the development of new densitometric tools of increased diagnostic sensitivity and predictive accuracy. Our objectives in the first three years were to characterize the relationships between bone geometric and densitometric properties determined by a new multiscan Dual Energy X-Ray Absorptiometry (DXA) technique and bone fracture loads at the distal radius and proximal femur. We showed: 1) multiscan DXA parameters are highly predictive of distal radius fracture loads (r2=0.67,p,0.0001) whereas conventional measures of BMD at the distal radius are not (r2= 0.07, p .0.1);2) multiscan DXA parameters and BMD at the femoral neck are good predictors of fracture load in the proximal femur (r2=0.740 but conventional BMD measures at intertrochanteric sites are not (r2=0.12, p=0.10); and 3)fracture loads at the distal radius are poor predictors of fracture load at the hip. These findings have important implications for the use and interpretation of conventional densitometry an suggest athe further development of DXA techniques are warmed. In this competitive renewal we propose to extend our findings in two significant ways. First, in Specific Aims 1 and 2, we plan to test the discriminatory power of DXA geometric variables in two case-control clinical studies (a retrospective review of available DXA scans from a separately funded falls surveillance study and a new observational study of spontaneous hip fracture patients and their age- and gender-matched controls). Second, in Specific Aims 3 and 4, we will extend our DXA methodology to the spine and thereby allow conventional and geometric DXA and fracture load comparisons to be made for the first time between all three high fracture risk regions within the same cadaveric specimen. We expect the study of spontaneous fracture to yield a much stronger densitometric separation between hip fracture patients and controls since the data will not be confounded by issues related to fall severity and traumatic loading. We hope to provide (even for conventional densitometry) more realistic estimates of the fracture risk threshold associated with activities of daily living and thus better targeting of candidates at risk for true fragility fractures of the hip.