Biomechanics of Vertebral Fracture: The Framingham QCT Study

描述（由申请人提供）：椎骨骨折是最常见的骨质疏松性骨折，发生在 50 岁以上的 1/3 女性和 1/6 男性中。它们会导致显着的发病率和死亡率增加，并且是未来骨折的最强危险因素之一。尽管发生率很高且不断增加，个人和社会成本也很高，但椎骨骨折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胸椎中部和胸腰椎区域。最近，我们发现骨骼负荷与骨强度的比率可以解释大部分年龄和性别特异性的骨折模式。因此，我们建议通过生物力学方法更好地理解椎骨骨折的机制，该方法将施加到脊柱的载荷与脊柱特定区域的椎骨强度联系起来。我们的总体假设是，椎骨骨折的年龄、性别和位置特定模式可以通过评估椎骨强度和脊柱负荷之间的比率来解释。为了解决这个问题，我们提出了两个具体目标。在目标 1 中，我们将使用参加“弗雷明汉心脏研究后代和第三代多探测器 CT 研究”的 872 名先前获得的 3529 名男性和女性（31 - 83 岁）的胸椎和腰椎 3D 定量计算机断层扫描 (QCT) 扫描的年龄和性别分层样本来比较脊柱负荷与椎骨强度的比率（即风险因素），对于男性和女性，贯穿一生，沿着脊柱。在目标 2 中，我们将使用目标 1 中的队列进行病例对照研究，比较没有普遍椎体骨折的情况下的因子-qf-风险 m。另外，我们将“比较椎骨”强度估计值。两个 JQCT-！基于yoxelr的^有限.ejem^ent，研究将提供有关椎体骨折的新信息，因为尽管胸椎骨折发生率很高，但没有基于人群的研究评估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) 扫描和在充分表征的弗雷明汉心脏研究队列的子研究中获得的高质量临床数据，拟议的项目将具有创新性和高度成本效益。这项基于人群的研究将通过采用生物力学方法进行骨折风险评估，并首次研究不同年龄段男性和女性胸椎和腰椎的骨密度和几何形状以及躯干肌肉形态，为椎骨骨折的病理生理学提供新的见解。这些发现将对公共健康产生重要影响，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有骨折风险的个体的诊断，并有助于预防和治疗椎骨骨折的有针对性的治疗干预措施。

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.