Ultra-high Resolution pQCT as a Biomarker of Bone Strength in Osteoporosis Trials

描述(申请人提供)：骨质疏松症，一种NIAMS感兴趣的疾病，是一种非常常见的衰老障碍。用双能X射线骨密度仪(DXA)测量骨密度(BMD)在诊断骨质疏松症、预测骨折和评估降低骨折风险的治疗反应方面具有重要的局限性。由于骨质疏松症也以微结构恶化为特征，在体内评估骨小梁和皮质骨的微结构，可能会在这些功能上优于DXA。为响应NIAMS临床试验结果仪器开发资助计划，我们将评估一种新的非侵入性成像技术--超高分辨率外周定量计算机断层扫描(HR-pQCT)，作为骨折和非骨折患者骨强度的生物标志物。Xtreme CT(瑞士巴塞多夫的Sanco Medical AG)分辨率为80-100 nm，可以单独测量皮质和骨小梁间隔，区分骨小梁微结构的超微结构细节，并产生可接受有限元分析(FEA)建模以评估骨强度的数据集。我们假设HR-pQCT将比DXA更准确地评估骨折状态和骨强度。我们将在一项横断面研究中验证这一假设，该研究比较了DXA和HR-pQCT在对60岁以上女性的骨折状况进行分类时的有效性。由于肾功能下降通常伴随着年龄增长，并可能导致骨折风险，我们还将评估其对HR-pQCT和DXA对骨折状态进行分类的能力的影响。一个子集将进行髂骨顶骨活检，以比较HR-pQCT对微观结构和强度的测量与活检标本的Micro-CT评估的类似测量。具体目的有：1.评价HR-pQCT骨量和微结构测量在骨折分类中的应用价值。2.评价HR-pQCT图像的有限元分析在骨折状态分类中的作用。3.在一组受试者中，将HR-pQCT进行的骨量、微结构和强度的测量与对活检标本进行的类似测量相关联。这项研究可能支持未来将HR-pQCT作为测试骨质疏松治疗方法的临床试验的注册结果。由于骨折与相当高的发病率和过高的死亡率有关，这项研究与公共卫生具有很高的相关性。

DESCRIPTION (provided by applicant): Osteoporosis, a disease of interest to NIAMS, is a very common disorder of aging. Measurement of bone mineral density (BMD) by dual energy x-ray absorptiometry (DXA) has important limitations in diagnosis of osteoporosis, prediction of fracture, and assessment of response to therapies to reduce fracture risk. As osteoporosis is also characterized by microarchitectural deterioration, in vivo assessment of trabecular and cortical bone microarchitecture, may improve upon DXA in these functions. In response to the NIAMS Clinical Trial Outcomes Instrument Development Grant Program, we will evaluate a new noninvasive imaging technology, ultra high-resolution peripheral quantitative computed tomography (HR-pQCT), as a biomarker of bone strength in patients with and without fracture. The Xtreme CT (Scanco Medical AG, Basserdorf, Switzerland), with a resolution of 80-100 urn, permits separate measurements of cortical and trabecular compartments, distinguishes ultra-structural details of trabecular microarchitecture, and yields datasets that can be subjected to finite element analysis (FEA) modeling to assess bone strength. We hypothesize that HR-pQCT will assess fracture status and bone strength more accurately than DXA. We will test this hypothesis in a cross sectional study that compares the utility of DXA and HR-pQCT to classify fracture status in women over age 60. As declining kidney function commonly accompanies aging and could contribute to fracture risk, we will also assess its impact on the ability of HR-pQCT and DXA to classify fracture status. A subset will have iliac crest bone biopsies to compare measures of microarchitecture and strength from HR-pQCT to similar measures assessed by micro-CT of biopsy specimens. The 3 Specific Aims are: 1. To evaluate the utility of HR-pQCT measurements of bone mass and microarchitecture for classification of fracture status. 2. To evaluate the utility of FEA of HR-pQCT images, a computational approach to assess mechanical competence, for classification of fracture status. 3. In a subset of participants, to correlate measures of bone mass, microarchitecture, and strength performed by HR-pQCT to similar measures performed on biopsy specimens. This research may support the future use of HR-pQCT as a registrable outcome in clinical trials that test therapies for osteoporosis. As fractures are associated with considerable morbidity and excess mortality, this research has high relevance to public health.