Biomechanics of Vertebral Fracture: The Framingham QCT Study

描述(申请人提供)：脊椎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岁以上的男性。它们会导致严重的发病率和死亡率增加，并且是未来骨折的最大风险因素之一。尽管脊柱骨折的发生率、个人和社会成本越来越高，但其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胸中和胸腰椎区域。最近，我们发现骨骼负荷与骨强度的比率可以解释骨折的年龄和性别特征。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沿线特定区域的脊柱强度联系起来，可以更好地了解脊柱骨折的机制。我们的总体假设是，脊椎骨折的年龄、性别和位置的特定模式可以通过评估脊柱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，我们将使用年龄和性别分层的872个先前获得的胸腰椎3D定量计算机断层扫描(QCT)样本，这些样本来自3529名男性和女性(年龄31-83岁)，这些患者参加了“Framingham心脏研究后代和第三代多探测器CT研究”，以比较脊柱负荷与脊柱强度(即风险因素)的比率，在男性和女性中，跨越整个寿命，并沿着脊柱。在目标2中，我们将使用来自目标1的队列来进行病例对照研究，比较不存在普遍的椎体骨折的因素QF风险m。此外，我们还将比较来自两个JQCT的椎体强度估计-！基于方法：一项有限的研究将提供有关脊柱骨折的新信息，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脊柱强度和/或脊柱负荷与年龄和性别相关的差异。总而言之，通过利用最先进的3D定量计算机断层扫描(QCT)扫描和在具有良好特征的弗雷明翰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极高的成本效益。这项以人群为基础的研究将通过使用生物力学方法评估骨折风险，并首次研究广泛年龄范围的男性和女性胸椎和腰椎的骨密度、几何形状和躯干肌肉形态，为脊柱骨折的病理生理学提供新的见解。这些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有骨折风险的个人的诊断，并为预防和治疗脊柱骨折提供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.