Collaborative Research: Uncovering the Multiscale Determinants of Atypical Femoral Fracture using MRI and CT-Based Modeling

该奖项支持揭示导致非典型股骨骨折的因素的基础研究。非典型股骨骨折是长期使用某些治疗骨质疏松药物的罕见副作用。骨质疏松症，或骨质强度下降，是美国每年超过200万例骨折的原因。这增加了死亡率，降低了生活质量。本项目将根据真实患者的图像制作非典型股骨骨折的计算机模型。然后，它将被用于研究骨骼几何形状和材料特性（例如，骨头的硬或软）如何影响骨折风险。该项目对非典型股骨骨折的新认识将最终提高识别高危人群的能力，也可能使新药开发成为可能，以避免所有类型的骨折。这些长期结果将改善患者的生活质量并降低医疗保健费用。该项目还将包括通过拓展科学和工程领域代表性不足的群体，改善科学和工程领域长期教师多样性的活动。目前还没有系统的实验或计算研究来确定哪些因素是非典型股骨骨折的最重要决定因素，也没有合适的计算模型来评估这类骨折。因此，该项目的总体目标是通过一种新型、多模态、基于图像和多尺度的计算骨模型来确定导致非典型股骨骨折的基本机制。该项目将开发和验证基于磁共振成像和高分辨率微计算机断层扫描的多尺度全股骨计算模型。这个新模型将用于确定宏观和微观尺度特性对非典型股骨骨折的个体和耦合影响，以及这些因素导致非典型股骨骨折的临界水平。因此，这种新颖的计算建模方法将为非典型股骨骨折最重要的决定因素提供独特的信息，这些决定因素无法通过实验直接确定。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This award supports fundamental research to uncover the factors that contribute to atypical femoral fracture. Atypical femoral fracture is a rare side effect of long-term use of some drugs to treat osteoporosis. Osteoporosis, or a decrease in bone strength, is responsible for over two million bone fractures annually in the United States. This increases mortality and decreases quality-of-life. This project will make a computer model of atypical femoral fracture, based on images from real patients. It will then be used to study how the effects of bone geometry and material properties (for example, how hard or soft a bone is) combine to determine fracture risk. This new understanding of atypical femoral fracture made possible by this project will ultimately improve the ability to identify those at risk and may also enable new drug discovery to avoid all types of bone fracture. These longer-term outcomes will result in improved quality of life for patients and reduced health care costs. This project will also include activities to improve long term faculty diversity in science and engineering through outreach to groups underrepresented in science and engineering. There is currently neither a systematic experimental or computational study that has identified which factors are the most important determinants of atypical femoral fracture, nor a suitable computational model for assessing such types of fracture. Thus, the overall goal of this project is to identify the fundamental mechanisms that lead to atypical femoral fracture using a novel, multimodal, image-based, and multiscale computational bone model. The project will develop and validate multiscale whole femur computational models based on magnetic resonance imaging and high resolution micro-computed tomography. This new model will be used to determine the individual and coupled effects of macro- and microscale properties on atypical femoral fracture, as well as the critical levels of these factors that would lead to atypical femoral fracture. As a result, this novel computational modeling approach will provide unique information on the most important determinants of atypical femoral fracture that cannot be directly identified by experiments.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.