Mechanical Function of Trabecular Bone: Bone Loss Assessment Beyond BMD

小梁骨的机械功能：BMD 之外的骨丢失评估

• 批准号: 9044771
• 负责人: Luis Cardoso
• 金额: $ 33.66万
• 依托单位: CITY COLLEGE OF NEW YORK
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9044771
• 关键词: Achievement; Affect; Age; Age-Related Bone Loss; Anisotropy; Bone Density; Bone Tissue; Clinical; Complex; Data; Development; Diagnosis; Diagnostic radiologic examination; Dose; Dual-Energy X-Ray Absorptiometry; Exhibits; Failure; Finite Element Analysis; Fracture; Frequencies; Gold; Healthcare; Human; Image; Imaging technology; Incidence; Liquid substance; Magnetic Resonance Imaging; Measurement; Measures; Mechanics; Minerals; Modeling; Morphology; Neck; Osteoporosis; Patients; Peripheral; Play; Porosity; Property; Resolution; Risk; Roentgen Rays; Role; Sensitivity and Specificity; Skeleton; Son of Sevenless Proteins; Structure; System; Technology; Technology Assessment; Testing; Textiles; Tissues; Ultrasonic wave; Ultrasonography; Vertebral column; Woman; Wrist; X-Ray Computed Tomography; base; bone; bone imaging; bone loss; bone mass; bone quality; bone strength; calcaneum; cost; density; diagnosis standard; improved; mechanical behavior; novel; novel diagnostics; novel strategies; osteoporosis with pathological fracture; pressure; public health relevance; quantitative ultrasound; substantia spongiosa; tomography; tool; vibration

DESCRIPTION (provided by applicant): The current gold standard to diagnose age-related bone loss and osteoporosis is the measurement of the Bone Mineral Density (BMD), which is a measure of the amount of mineral per total bone volume determined by Dual Energy X-ray Absorptiometry (DEXA). BMD is highly correlated to bone mass density when measured in the spine, wrist and femoral neck. However, a significant number of women diagnosed with osteoporosis based on a BMD test do not suffer fractures, whereas many women with normal BMD do. These studies demonstrated that BMD measurements lack both sensitivity and specificity to effectively identify patients with decreased bone strength and at risk of fracture, indicating that other factors besides bone mass density play an important role in osteoporosis: bone microarchitecture, anisotropy and tissue composition. Unfortunately, it is not possible for mass density-based approaches to reveal the architectural aspects of bone that influence the strength and risk of fracture in bone's complex structure. Bone images from peripheral quantitative computed tomography (pQCT) and magnetic resonance imaging (MRI) can provide measurements of trabecular microarchitecture, and produce 3D numerical models that are used in finite element analysis (FEA) to estimate the mechanical properties of bone. However, the wide use of these imaging technologies to assess bone loss is limited by their high cost, the resolution of their images and the X-ray dose associated with pQCT. The incidence of osteoporotic fractures in the ageing skeleton is highly associated with impaired bone mechanical properties. Therefore, the general objective of this proposal is to investigate an alternative approach of bone fragility assessment that is neither based on BMD nor FEA from bone images, but based on measurements of the actual mechanical behavior of bone. We propose testing a novel mechanical-function criterion based on the anisotropic elastic constants of trabecular bone and a means to assess such mechanical properties non-invasively using Poroelastic Ultrasound Tomography (PEUT). Anisotropic changes of bone do result in weak (impaired) and strong (functional) mechanical directions within the same bone volume, leading to compromised mechanical function, or increased fracture risk when bone is loaded in the impaired directions. Because the trabecular stiffness are obtained from PEUT -a high frequency mechanical test- it naturally integrates the effect of both bone quantity (i.e., BMD, BV/TV, or porosity) and bone quality (i.e., microarchitecture, anisotropy, tissue composition) into a measurement of the directional-dependent mechanical properties of bone. Thus, the PEUT approach is expected to provide direct information on bone mechanical function, which should have higher sensitivity and specificity to distinguish patients at risk of fracture than BMD measurements. With the development of this non-invasive poroelastic ultrasound tomography approach, we expect to provide an alternative paradigm for assessment of bone loss and osteoporosis based in actual changes of bone mechanical properties. This approach may be at the origin of a conceptual shift on the way we understand and assess bone loss, advancing our understanding of bone mechanical function as a directional-dependent parameter (tensorial quantity) as opposed to a scalar-valued quantity (BMD).

描述（由申请人提供）：目前诊断年龄相关性骨丢失和骨质疏松症的金标准是测量骨矿物质密度（BMD），这是通过双能X射线吸收测定法（DEXA）测定的每总骨体积的矿物质量的量度。当在脊柱、手腕和股骨颈中测量时，BMD与骨质量密度高度相关。然而，根据BMD测试诊断为骨质疏松症的女性中有相当数量的人不会发生骨折，而许多BMD正常的女性会发生骨折。这些研究表明，BMD测量缺乏敏感性和特异性，无法有效识别骨强度降低和骨折风险的患者，表明除骨密度外的其他因素在骨质疏松症中起重要作用：骨微结构、各向异性和组织组成。不幸的是，它是不可能的质量密度为基础的方法，以揭示建筑方面的骨，影响强度和骨折的风险，在骨的复杂结构。来自外周定量计算机断层扫描（pQCT）和磁共振成像（MRI）的骨图像可以提供骨小梁微结构的测量，并产生用于有限元分析（FEA）以估计骨的机械特性的3D数值模型。然而，这些成像技术评估骨丢失的广泛使用受到其高成本、图像分辨率和与pQCT相关的X射线剂量的限制。 老年骨骼中骨质疏松性骨折的发生率与骨机械性能受损高度相关。因此，本提案的总体目标是研究骨脆性评估的替代方法，该方法既不基于骨密度也不基于骨图像的FEA，而是基于骨的实际力学行为的测量。我们建议测试一种新的力学功能标准的基础上的各向异性的弹性常数的骨小梁和一种手段来评估这种机械性能非侵入性使用多孔弹性超声断层扫描（PEUT）。骨的各向异性变化确实导致相同骨体积内的弱（受损）和强（功能）机械方向，导致机械功能受损，或当骨在受损方向上加载时增加骨折风险。因为骨小梁硬度是从PEUT（一种高频机械测试）获得的，所以它自然地整合了骨量（即，BMD、BV/TV或孔隙度）和骨质量（即，微结构、各向异性、组织组成）转化为骨的方向依赖性机械特性的测量。因此，PEUT方法有望提供有关骨机械功能的直接信息，与BMD测量相比，PEUT方法在区分骨折风险患者方面应具有更高的灵敏度和特异性。随着这种非侵入性多孔弹性超声断层成像方法的发展，我们期望提供一种替代的范式，评估骨丢失和骨质疏松症的基础上，骨力学性能的实际变化。这种方法可能是我们理解和评估骨丢失方式的概念转变的起源，推进了我们对骨力学功能作为方向依赖参数（张量）而不是标量值（BMD）的理解。