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

基本信息

批准号：
9236194
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
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-01 至 2019-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9236194
关键词：
Achievement Affect Age-Related Bone Loss Aging Anisotropy Architecture Bone Density Bone Tissue Clinical Complex Data Development Diagnosis Dose Dual-Energy X-Ray Absorptiometry Exhibits Failure Finite Element Analysis Fracture Frequencies Gold Healthcare Human Image Imaging technology Impairment Incidence Liquid substance Magnetic Resonance Imaging Measurement Measures Mechanics Minerals Modeling Modulus Morphology Neck Osteoporosis Patients Peripheral Play Porosity Resolution 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 fragility bone imaging bone loss bone mass bone quality bone strength calcaneum cost density diagnosis standard fracture risk improved mechanical behavior mechanical properties novel novel diagnostics novel strategies osteoporosis with pathological fracture pressure public health relevance quantitative ultrasound substantia spongiosa tomography tool vibration

项目摘要

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）：目前诊断与年龄相关的骨质流失和骨质疏松症的黄金标准是骨矿物质密度（BMD）的测量，它是通过 Dual Energy X 确定的每总骨体积的矿物质含量的量度射线吸收测定法（DEXA）。在脊柱、腕部和股骨颈中测量时，BMD 与骨量密度高度相关。然而，大量根据 BMD 测试诊断为骨质疏松症的女性并未发生骨折，而许多 BMD 正常的女性却发生了骨折。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下降和有骨折风险的患者，这表明除骨量密度外的其他因素在骨质疏松症中也发挥着重要作用：骨微结构、各向异性和组织成分。不幸的是，基于质量密度的方法不可能揭示影响骨骼复杂结构的强度和骨折风险的骨骼结构方面。来自外周定量计算机断层扫描 (pQCT) 和磁共振成像 (MRI) 的骨图像可以提供小梁微结构的测量，并生成用于有限元分析 (FEA) 的 3D 数值模型，以估计骨的机械特性。然而，这些成像技术在评估骨质流失方面的广泛使用受到其高成本、图像分辨率以及与 pQCT 相关的 X 射线剂量的限制。衰老骨骼中骨质疏松性骨折的发生率与骨机械性能受损密切相关。因此，本提案的总体目标是研究一种骨脆性评估的替代方法，该方法既不基于骨密度，也不基于骨图像的有限元分析，而是基于骨实际机械行为的测量。我们建议测试一种基于骨小梁各向异性弹性常数的新型机械功能标准，以及一种使用多孔弹性超声断层扫描（PEUT）非侵入性评估此类机械性能的方法。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）机械方向，从而导致机械功能受损，或者当骨骼在受损方向上加载时增加骨折风险。由于小梁刚度是通过 PEUT（一种高频机械测试）获得的，因此它自然地将骨量（即 BMD、BV/TV 或孔隙率）和骨质量（即微结构、各向异性、组织成分）的影响整合到骨的方向相关机械特性的测量。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，该方法应具有更高的敏感性和特异性来区分有骨折风险的患者。随着这种非侵入性多孔弹性超声断层扫描方法的发展，我们期望为基于骨机械性能的实际变化评估骨丢失和骨质疏松症提供替代范例。这种方法可能是我们理解和评估骨质流失方式概念转变的根源，促进了我们对骨机械功能作为方向相关参数（张量）而不是标量值量（BMD）的理解。