Biomechanics of Vertebral Fracture: The Framingham QCT Study

描述（申请人提供）：椎体骨折是最常见的骨质疏松性骨折，发生在1/3的女性和1/6的50岁以上男性。它们引起显著的发病率和死亡率增加，是未来骨折的最大危险因素之一。尽管椎体骨折的发生率高且在不断增加，而且对个人和社会都造成了巨大的损失，但椎体骨折背后的生物力学机制仍然不清楚，特别是为什么它们优先发生在脊柱的中胸和胸腰椎区域。最近，我们发现骨骼负荷与骨骼强度之比解释了许多年龄和性别特异性骨折模式。因此，我们建议通过生物力学方法，将施加在脊柱上的载荷与脊柱特定区域的椎体强度联系起来，更好地了解椎体骨折的机制。我们的总体假设是，年龄、性别和位置特定的椎体骨折模式可以通过评估椎体强度和脊柱负荷之间的比率来解释。为此，我们提出两个具体目标。在Aim 1中，我们将使用年龄和性别分层的872个样本，这些样本来自3529名男性和女性（31 - 83岁）的胸椎和腰椎的3D定量计算机断层扫描（QCT），他们参加了“Framingham心脏研究后代和第三代多探测器CT研究”，以比较男性和女性在整个生命周期和脊柱上脊柱负荷与椎体强度的比例（即风险因素）。在Aim 2中，我们将使用Aim 1中的队列进行病例对照研究，比较无普遍椎体骨折的风险因素。此外，我们将“比较”椎体强度估计。两个JQCT——!基于方法：基于有限的。因此，一项研究将提供关于椎体骨折的新信息，因为尽管胸椎骨折的发生率很高，但没有基于人群的研究评估了胸椎区域椎体强度和/或脊柱负荷的年龄和性别相关变化。总之，通过利用最先进的3D定量计算机断层扫描（QCT）扫描和在弗雷明汉心脏研究队列的子研究中已经获得的高质量临床数据，拟议的项目将具有创新性和高成本效益。这项以人群为基础的研究将通过采用生物力学方法进行骨折风险评估，并首次研究大年龄段男女胸椎和腰椎的骨密度、几何形状和躯干肌肉形态，为椎体骨折的病理生理学提供新的见解。这一发现将具有重要的公共卫生意义，因为更好地了解骨密度、几何形状和脊柱负荷之间的相互作用，可能会改善对骨折风险个体的诊断，并为预防和治疗椎体骨折提供有针对性的治疗干预。

DESCRIPTION (provided by applicant): Vertebral fractures are the most common osteoporotic fracture, occurring in 1/3 of women and 1/6 of men over age 50. They cause significant morbidity and increased mortality, and are among the strongest risk factors for future fractures. Despite the high and growing occurrence, personal and societal costs, the biomechanical mechanisms that underlie vertebral fractures remain obscure, in particular why they occur preferentially at the mid-thoracic and thoraco-lumbar regions of the spine. Recently, we showed that the ratio of skeletal loading to bone strength explains much of the age- and sex-specific patterns of fractures. Thus, we propose that a better understanding of the mechanisms underlying vertebral fracture can be gained by a biomechanical approach that relates the loads applied to the spine to vertebral strength at specific regions along the spine. Our overall hypothesis is that the age-, sex- and location-specific patterns of vertebral fracture can be explained by assessing the ratio between vertebral strength and spinal loading. To address this, we propose two specific aims. In Aim 1 we will use age- and sex-stratified sample of 872 previously acquired 3D quantitative computed tomography (QCT) scans of the thoracic and lumbar spine from 3529, men and women (aged 31 - 83), enrolled in the "Framingham Heart Study Offspring and Third Generation Multidetector CT Study" to compare the ratio of spine load to vertebral strength (i.e., the factor-of-risk), in men and women, across the lifespan, and along the spine. In Aim 2 we will use the cohort from Aim 1 to conduct a case-control study comparing the factor-qf-risk m without prevalent vertebral fractures. Also, we will'compare vertebral'Strength estimates from .two JQCT-! based methods:'yoxelrbased ^finite .ejem^ent, a^ study will provide novel information about vertebral fractures, because despite the high occurrence of fractures in the thoracic spine, no population-based studies have assessed age- and sex-related variation in vertebral strength and/or spine loading in the thoracic region. In summary, by drawing on state-of-the-art 3D quantitative computed tomography (QCT) scans and high quality clinical data already obtained within a sub-study of the well-characterized Framingham Heart Study cohorts, the proposed project will be innovative and highly cost effective. This population-based study will provide new insights into the pathophysiology of vertebral fractures by employing a biomechanical approach to fracture risk assessment, and by studying, for the first time, bone density and geometry and trunk muscle morphology in both the thoracic and lumbar spine in men and women over a wide age range. The findings will have important public health implications, as a better understanding of the interaction between bone density, geometry and spinal loading may lead to improved diagnosis of individuals at risk for fracture and to targeted therapeutic interventions for prevention and treatment of vertebral fractures.