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

描述（由申请人提供）：骨质疏松症是NIAMS关注的一种疾病，是一种非常常见的衰老疾病。双能X线骨密度仪（DXA）测量骨密度（BMD）在诊断骨质疏松症、预测骨折和评估对降低骨折风险的治疗反应方面具有重要的局限性。由于骨质疏松症的特征还在于微结构恶化，因此对骨小梁和皮质骨微结构的体内评估可能会改善DXA的这些功能。为了响应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。分辨率为80-100 μ m的Xtreme CT（瑞士Basserdorf的Scorio Medical AG）允许分别测量皮质和小梁间室，区分小梁微结构的超微结构细节，并产生可进行有限元分析（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检验这一假设，该研究比较了DXA和HR-pQCT在60岁以上女性骨折状态分类中的效用。由于肾功能下降通常伴随着衰老，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。一个子集将进行髂嵴骨活检，以比较HR-pQCT的微结构和强度测量值与活检标本的micro-CT评估的类似测量值。三个具体目标是：1。评价HR-pQCT测量骨量和微结构对骨折状态分类的实用性。2.评价HR-pQCT图像FEA的效用，这是一种评估机械能力的计算方法，用于骨折状态分类。3.在一个参与者子集中，将HR-pQCT进行的骨量、微结构和强度测量与活检标本上进行的类似测量相关联。这项研究可能支持未来使用HR-pQCT作为临床试验中的可注册结果，测试骨质疏松症的治疗。由于骨折与相当高的发病率和死亡率相关，因此这项研究与公共卫生具有高度相关性。

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.