3-D Visualization and Prediction of Vertebral Fractures

脊椎骨折(VF)困扰着超过25%的50岁以上的人，而且他们的负担还在增加。当前 评估VF风险的方法，在很大程度上依赖于平均骨密度的测量 (BMD)在脊椎，已知是不够的，但对更好的诊断的搜索受到较差的阻碍 对室性心动过速发病机制的认识。越来越多的证据表明，风险、机制和 VF的结局关键取决于椎骨和椎骨交界处附近组织的相互作用 腰间盘。该终板区域被定义为软骨终板(CEP)，骨终板(BEP)， 软骨下骨小梁(STB)。椎间盘调节给定椎骨所承受的净力是多少。 分布在端板表面上(“端板加载”)，端板区域如何调节这一点 力的分布被传递到椎骨的其余部分。圆盘和端板的力学性能 因此，该区域预计会影响脊椎何时以及如何发生故障。事实上，我们已经发现VF在 老年人的椎骨通常起始于终板区域，该区域的失效方式受到影响 不仅取决于该区域的微结构，而且还取决于相邻盘中的退化程度。此外， 最近的数据表明，终板区域的力学行为可能会随着年龄和椎间盘的变化而改变 脊椎的平均骨密度不能很好地预测退变的方式。这些集体发现 揭示了描述终板区域和椎间盘之间的生物力学相互作用的范例 对于确定VF的危险因素，从而减少VF的发生率和 VF的负担。因此，该项目的总体目标是定义光盘的退化和老化 端板区域影响VF的发生机制。目标1将量化终板载荷的依赖关系 并将使用非侵入性获得的终板载荷估计来开发准确的， 患者特定的VF的有限元(FE)模拟。这一目标将利用磁力技术的最新进展。 基于磁共振成像(MRI)的椎间盘评估，实现了最先进的新集成 在临床可行的椎间盘和椎体有限元模型中。目标2将解决当前数据匮乏的问题 终板区域的生物力学。使用机械测试、µFE建模和生化分析，我们将 确定性能的程度，如BEP的脆性、STB的强度和刚性 CEP随年龄和椎间盘退变而变化。目标3将重点放在终板区域 在VF期间失败。受临床和临床前观察的推动，椎间盘健康状况下降得更快 在涉及BEP骨折的VFS之后，与仅涉及STB故障的VFS相反，我们将 使用实验和大型µFE模型来确定圆盘和端板区域的特征， 与BEP骨折有关。综上所述，这三个目标构成了机械性、创新性和 跨学科的方法，将使对室性心动过速的理解、预防和治疗有一个步骤的改变。

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.