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）的特征是神经病变下方区域的明显骨丢失。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SCI患者来说是不够的;常规骨折的位置在这两组之间并不对应，定义骨折风险升高的骨密度阈值是SCI患者的典型特征。准确量化SCI患者骨折强度的能力可以作为评估骨折风险和客观识别可以安全参与积极治疗的个体的重要临床工具。本申请的目的是：目的1）开发一种基于定量计算机断层扫描（CT）的数值方法，该方法能够预测胫骨近端（SCI后通常发生骨折的位置）的骨折强度，目的2）量化自SCI以来随时间推移而发生的骨折强度变化。目标1将通过数值-实验相结合的研究来实现。对尸体近端胫骨进行机械加载，直至失效。特定于样本的有限元模型将从CT数据中推导出来，其预测断裂强度的能力由数值和实验断裂载荷的回归分析确定。将有限元模型的预测值与基于CT导出的骨量、密度和结构测量值的统计模型进行比较。目标2将采用横断面研究设计完成，其中运动完全性SCI患者以及健全对照组的骨折强度将根据CT数据进行估计。将量化骨折强度和骨参数随SCI后时间的变化。这项研究的长期目标是通过最大限度地减少这一人群的骨折发生率来提高SCI患者的生活质量。这项研究将带来生物力学相关性观察到的骨适应性变化后，脊髓损伤，并帮助划定最重要的决定因素，骨折强度在这一人群。这将提供重要的信息，可用于帮助指导药理学和运动干预，目标是适应性变化的参数最相关的全骨骨折强度。此外，由于SCI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丢失人群骨折的理解，并有助于指导这些个体骨强化干预措施的发展。 公共卫生相关性：我们建议1）开发新的方法来量化脊髓损伤患者的全骨骨折强度，2）确定脊髓损伤后骨折强度随时间的变化。这项工作将增加我们对慢性骨丢失人群骨折的了解，并将促进制定对策，以尽量减少这一人群骨折的发生。

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.