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）：诊断与年龄相关的骨质流失和骨质疏松症的当前黄金标准是骨矿物质密度（BMD）的测量，这是通过双能X射线吸收仪（DEXA）确定的总骨骼体积的矿物质量的量度。当在脊柱，腕部和股骨颈中测量时，BMD与骨质量密度高度相关。但是，许多基于BMD测试的诊断患有骨质疏松症的妇女不会遭受骨折，而许多正常BMD的女性则遭受骨折。这些研究表明，BMD测量值既缺乏灵敏度和特异性，无法有效地识别骨骼强度降低和骨折风险的患者，表明除了骨骼质量密度以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，基于质量密度的方法不可能揭示骨骼的建筑方面，从而影响骨骼复杂结构中骨折的强度和风险。来自外围定量计算机断层扫描（PQCT）和磁共振成像（MRI）的骨图像可以提供小梁微体系结构的测量，并产生用于有限元分析（FEA）（FEA）的3D数值模型，以估算骨骼的机械性能。但是，这些成像技术的广泛使用来评估骨质流失受其高成本，图像的分辨率以及与PQCT相关的X射线剂量的限制。 老化骨骼中骨质疏松骨折的发生率与骨骼机械性能受损高度相关。因此，该提案的一般目标是研究骨骼脆弱性评估的替代方法，该方法既不基于骨骼图像的BMD也不是FEA，而是基于对骨骼实际机械行为的测量。我们提出了基于小梁骨各向异性弹性常数的新型机械功能标准，并使用孔隙弹性超声断层扫描（PEUT）评估这种机械性能的方法。骨骼的各向异性变化确实会导致相同骨体积内的弱（受损）和强（功能性的）机械方向，从而导致机械功能受损，或者当骨骼在受损方向受损时增加骨折风险。由于小梁刚度是从PEUT-A高频机械测试中获得的，因此自然会将骨骼数量（即BMD，BV/TV或孔隙率）和骨质质量（即微结构，各向异性，各向异性，组织组成）的影响整合到骨骼依赖性机械特性的测量中。因此，PEUT方法有望提供有关骨骼机械功能的直接信息，该功能应具有更高的敏感性和特异性，以区分骨折风险的患者，而不是BMD测量。随着这种非侵入性毛弹性超声断层扫描方法的发展，我们希望为基于骨骼机械性能的实际变化而评估骨质流失和骨质疏松症的替代范式。这种方法可能是我们理解和评估骨质流失方式的概念转变的起源，将我们对骨骼机械功能作为方向依赖性参数（张力量）而不是标量值值（BMD）相反。