3-D Visualization and Prediction of Vertebral Fractures

描述(申请人提供)：脊椎骨折是最常见的骨质疏松性骨折类型，50岁以上的女性和男性中分别有1/3和1/6患病。尽管其发病率很高，但对脊椎骨折风险的敏感和具体估计仍然难以捉摸。目前估计脊柱强度和骨折风险的方法的局限性被广泛认识，这些方法严重依赖于平均骨矿密度(BMD)的测量。然而，在验证和相对于“平均骨密度”方法的明显优势方面，缺乏替代方法。我们最近的数据解决了知识和翻译方面的这一关键差距，通过演示使用定量计算机断层扫描(QCT)所做的临床可行测量来增强对椎体衰竭的预测。使用QCT衍生的骨组织分布测量，我们发现椎体内骨密度异质性的大小可以更好地预测椎体强度，并且在有椎体骨折的女性和没有椎体骨折的女性中更低。这些数据还表明，椎骨内骨密度的多个特征空间分布(“模式”)可以提供高的骨强度，并且这些模式和强度之间的关联可能受相邻间盘(IVD)中退变的严重程度的调节。我们现在建议在基于人群的研究和补充的体外研究中定义椎体内骨密度异质性、椎体衰竭和IVD退变之间的关系。目标1将采用病例对照研究设计，对参加弗雷明翰心脏研究(FHS)多探测器QCT研究的男性和女性进行先前获得的QCT扫描，以验证异质性程度降低与普遍骨折风险增加相关的假设。目标2将使用来自FHS QCT队列的按年龄和性别分层的随机样本来确定BMD的空间分布与IVD健康之间的关联，随后将进行体外研究，确定这些关联如何影响脊椎强度。我们在目标2中的双重假设是，骨密度的空间分布模式与IVD健康相关，而椎体强度取决于空间骨密度分布和静脉畸形提供的负荷分布之间的一致性。目的3将通过一种新的实验方法继续我们的临床重点生物力学研究，该方法为基于QCT的椎体衰竭有限元(FE)模型的准确性提供了亟需的评估。这一目标将检验这样一种假设，即通过结合临床可获得的IVD健康评估，FE预测的准确性得到改善。总而言之，这些目标是朝着减轻脊柱骨折负担迈出的重要一步。这项工作结合了病例对照和对这种异质性的生物力学后果的实验室研究，对社区居住人口的椎体内异质性现象进行了具有成本效益的研究。研究结果将为脊柱健康提供广泛适用的综合评估，并配有可翻译的工具，为骨折风险的评估设定新的标准。

DESCRIPTION (provided by applicant): Vertebral fractures are the most common type of osteoporotic fracture, afflicting one in three women and one in six men over the age of 50. Despite their high prevalence, sensitive and specific estimates of vertebral fracture risk have remained elusive. The limitations of current approaches for estimating vertebral strength and fracture risk, which rely heavily on measurement of the average bone mineral density (BMD), are widely recognized. However, alternative methods have been lacking with respect to validation and clear advantages over the "average BMD" approach. Our recent data address this critical gap in knowledge and translation by demonstrating the use of clinically feasible measurements made from quantitative computed tomography (QCT) scans to enhance predictions of vertebral failure. Using QCT-derived measures of the distribution of bone tissue throughout the vertebra, we have found that the magnitude of the intra-vertebral heterogeneity in BMD provides improved predictions of vertebral strength and is lower in women with vs. without vertebral fracture. These data also indicate that multiple, characteristic spatial distributions ("patterns") of BMD within the vertebra can confer high bone strength, and that the associations between these patterns and strength may be modulated by the severity of degeneration in the adjacent intervertebral discs (IVDs). We now propose to define relationships among intra-vertebral heterogeneity in BMD, vertebral failure, and IVD degeneration in population-based studies and complementary ex vivo studies. Aim 1 will use a case-control study design with previously acquired QCT scans in men and women enrolled in the Framingham Heart Study (FHS) Multidetector QCT study to test the hypothesis that decreased magnitude of heterogeneity is associated with increased risk of prevalent fracture. Aim 2 will use an age- and sex-stratified, random sample from the FHS QCT cohort to determine associations between the spatial distribution of BMD and IVD health, followed by ex vivo studies that define how these associations can influence vertebral strength. Our dual hypotheses in Aim #2 are that the spatial patterns of BMD are associated with IVD health and that vertebral strength depends on the congruence between the spatial BMD pattern and the load distribution supplied by the IVDs. Aim 3 will continue our clinically focused, biomechanical investigations via a novel experimental approach that provides much-needed evaluation of the accuracy of QCT-based finite element (FE) models of vertebral failure. This aim will test the hypothesis that the accurac of the FE predictions is improved by incorporating clinically obtainable assessments of IVD health. Together, these Aims are a major step towards reducing the burden of vertebral fracture. This work partners a cost-effective study of the phenomenon of intra-vertebral heterogeneity in a community-dwelling population with case-control and laboratory studies of the biomechanical consequences of this heterogeneity. The results will provide a widely applicable, integrated assessment of vertebral health, complete with translatable tools to set a new standard for estimation of fracture risk.