Changes in proximal tibia fracture strength as a function of time elapsed since s

描述（由申请人提供）：脊髓损伤（SCI）的特征是神经病变以下区域明显的骨质流失。这种骨质减少的临床后果是由于轻微创伤导致下肢骨折的终生风险增加，是普通人群的两倍。一般公众的骨折风险评估工具对于脊髓损伤患者来说是不够的；常规骨折的位置在这两组之间不一致，骨密度阈值定义骨折风险升高是脊髓损伤患者的典型特征。准确量化脊髓损伤患者骨折强度的能力可以作为评估骨折风险的重要临床工具，并客观地确定可以安全参与积极治疗的个体。本应用的目标是：目标1)开发一种基于定量计算机断层扫描（CT）的数值方法，能够预测胫骨近端（脊髓损伤后常见骨折的位置）的骨折强度；目标2)量化自脊髓损伤后骨折强度随时间的变化。目标1将通过数值与实验相结合的研究来完成。尸体胫骨近端将被机械加载直到失效。将从CT数据中导出特定样本的有限元模型，并通过对数值和实验断裂载荷的回归分析确定其预测断裂强度的能力。有限元模型的预测值将与基于CT导出的骨量、密度和结构测量的统计模型进行比较。目的2将通过横断面研究设计来完成，在横断面研究设计中，将从CT数据估计运动性完全性脊髓损伤患者以及健全对照组的骨折强度。损伤后骨折强度和骨参数随时间的变化将被量化。本研究的长期目标是通过减少脊髓损伤患者骨折的发生率来提高他们的生活质量。这项研究将为脊髓损伤后观察到的骨适应性变化带来生物力学相关性，并有助于描述这一人群中骨折强度的最关键决定因素。这将提供重要的信息，可用于指导针对与全骨骨折强度最相关的参数的适应性变化的药物和运动干预。此外，由于脊髓损伤人群作为废用性骨质疏松症的模型系统，这项工作将增加我们对其他慢性骨质流失人群骨骼骨折的理解，并有助于指导针对这些个体的骨强化干预措施的发展。

DESCRIPTION (provided by applicant): Spinal cord injury (SCI) is characterized by marked bone loss at regions below the neurological lesion. The clinical consequence of this reduction in bone is an increased lifetime risk for lower-extremity fracture due to minor trauma that is two times greater than the general population. Fracture risk assessment tools for the general public are inadequate for people living with SCI; the locations of routine fracture do not correspond between these two groups and bone density thresholds defining elevated fracture risk are typical of individuals with SCI. The ability to accurately quantify fracture strength in people with SCI could serve as an important clinical tool to assess fracture risk and objectively identify individuals that could safely participate in active treatment. The objectives of this application are to: Aim 1) develop a numerical method based on quantitative computed tomography (CT) capable of predicting fracture strength at the proximal tibia (a location commonly fractured following SCI), and Aim 2) quantify the change in fracture strength that occurs as a function of time elapsed since SCI. Aim 1 will be accomplished using a combined numerical-experimental study. Cadaveric proximal tibiae will be mechanically loaded until failure. Specimen-specific finite element models will be derived from CT data, and their ability to predict fracture strength determined from a regression analysis of numerical and experimental fracture loads. The predictive value of the finite element models will be compared to statistical models based on CT derived measures of bone mass, density, and structure. Aim 2 will be accomplished using a cross-sectional study design in which the fracture strength of individuals with motor complete SCI, as well as able-bodied controls, will be estimated from CT data. Reductions in fracture strength and bone parameters as a function of time since SCI will be quantified. The long-term goal of this research is to increase the quality of life for people living with SCI by minimizing the incidence of bone fracture in this population. This study will bring biomechanical relevance to the observed bone adaptive changes following SCI and help delineate the most critical determinants of bone fracture strength in this population. This will provide important information that can be used to help guide pharmacologic and exercise interventions that target adaptive changes in parameters most relevant to whole-bone fracture strength. In addition, because the SCI population serves as a model system for disuse osteoporosis, this work will increase our understanding of skeletal fracture in other populations having chronic bone loss and help guide the development of bone strengthening interventions for these individuals. PUBLIC HEALTH RELEVANCE: We propose to 1) develop new methods to quantify whole-bone fracture strength in people living with spinal cord injury, and 2) determine the changes in fracture strength that occur as a function of time elapsed since spinal cord injury. This work will increase our understanding of skeletal fracture in people having chronic bone loss and will facilitate the development of countermeasures to minimize the occurrence of skeletal fracture in this population.