3-D Visualization and Prediction of Vertebral Fractures

超过25%的50岁以上的人患有椎骨骨折（VF），他们的负担正在增加。电流 估计VF风险的方法，主要依赖于平均骨矿物质密度的测量 (BMD)在椎骨中，已知是不够的，但是对更好的诊断的探索受到了不良的阻碍。 了解VF的发病机制。越来越多的证据表明， VF的结果主要取决于椎骨和椎体之间界面附近组织的相互作用。 椎间盘该终板区域被定义为软骨终板（CEP），骨终板（BEP）， 和软骨下骨小梁（STB）。椎间盘调节给定椎骨所承受的净力如何 分布在终板的表面（“终板负荷”），终板区域介导了这一过程。 力分布被传递到椎骨的其余部分。椎间盘和终板的力学行为 因此，预期区域会影响椎骨何时以及如何失效。我曾发现， 老年人的椎骨通常在终板区域内开始，并且该区域的失效方式受到 这不仅取决于该区域的微观结构，还取决于相邻椎间盘的退变程度。此外，委员会认为， 最近的数据表明，终板区域的力学行为可能会随着年龄的增长而改变， 椎骨的平均BMD不能很好地预测退化的方式。这些集体发现 揭示了终板区域和椎间盘之间生物力学相互作用的描述 是识别VF风险因素的重要关键，从而降低发病率， VF的负担因此，本项目的总体目标是确定椎间盘的退行性变和衰老 终板区影响VF的发生机制。目标1将量化终板载荷的依赖性 并将使用非侵入性获得的终板载荷估计， VF的患者特定有限元（FE）模拟。这一目标将利用最近的进展，磁 基于共振成像（MRI）的椎间盘评估，以实现最新技术水平的新整合 在椎间盘和椎骨的临床可行的FE模型中。目标#2将解决目前缺乏数据的问题， 终板区域的生物力学。通过机械测试、µFE建模和生化分析，我们将 确定诸如BEP的脆性、STB的强度和 CEP随年龄和椎间盘退变而变化。目标3将重点关注终板区域 VF期间失败。受临床和临床前观察结果的启发，椎间盘健康下降更快 在涉及BEP断裂的VF之后，与仅涉及STB故障的VF相反，我们将 使用实验和大规模µFE模型来识别椎间盘和终板区域的特征， 与BEP骨折有关。总而言之，这三个目标构成了一个机械的，创新的， 跨学科的方法，这将使一个步骤的变化，在理解，预防和治疗VF。

Vertebral fractures (VF) afflict more than 25% of people over age 50, and their burden is growing. Current approaches for estimating VF risk, which rely heavily on measurement of the average bone mineral density (BMD) in the vertebra, are known to be insufficient, but the search for better diagnostics is hindered by poor understanding of the pathogenesis of VF. Increasing evidence suggests that the risk, mechanisms, and outcomes of VF depend critically on the interaction of tissues near the interface between the vertebra and the intervertebral disc. This endplate region is defined as the cartilage endplate (CEP), the bony endplate (BEP), and the subchondral trabecular bone (STB). The disc mediates how the net force borne by a given vertebra is distributed over the surface of the endplate (“endplate loading”), and the endplate region mediates how this force distribution is transferred to the rest of the vertebra. The mechanical behaviors of the disc and endplate region are therefore expected to affect when and how the vertebra fails. Indeed, we have found that VF in elderly vertebrae commonly initiate within the endplate region, and that the way this region fails is influenced by not only the microstructure of this region but also the extent of degeneration in the adjacent disc. Moreover, recent data suggest that the mechanical behavior of the endplate region may change with aging and disc degeneration in ways that are not well predicted by the average BMD of the vertebra. These collective findings reveal a paradigm in which delineation of the biomechanical interactions between the endplate region and disc holds an important key to identifying risk factors for VF and, consequently, to reducing the incidence and burden of VF. As such, the overall goal of this project is to define how degeneration and aging of the disc and endplate region influence the mechanisms of VF. Aim #1 will quantify the dependence of endplate loading on disc degeneration and will use non-invasively obtained estimates of endplate loading to develop accurate, patient-specific, finite element (FE) simulations of VF. This Aim will capitalize on recent advances in magnetic resonance imaging (MRI)-based assessments of the disc to achieve a novel integration of the state-of-the-art in clinically feasible FE models of the disc and vertebra. Aim #2 will address the current paucity of data on the biomechanics of the endplate region. Using mechanical testing, µFE modeling and biochemical assays, we will identify the extent to which properties such as the brittleness of the BEP, strength of the STB, and stiffness of the CEP change with age and disc degeneration. Aim #3 will focus on the way in which the endplate region fails during VF. Motivated by clinical and pre-clinical observations that disc health declines more rapidly following VFs that involve fracture of the BEP, as opposed to those that involve failure of only the STB, we will use both experiment and large-scale µFE models to identify characteristics of the disc and endplate region that are associated with BEP fracture. Altogether, these three Aims constitute a mechanistic, innovative, and interdisciplinary approach that will enable a step change in the understanding, prevention, and treatment of VF.