A combined in vivo/ex vivo experimental platform for the thorough 3D investigation of bone fatigue related microdamage

骨质疏松症是一种主要的公共卫生疾病，影响全球2亿多人，包括200万加拿大人，在老龄人口中患病率很高。这种骨代谢紊乱与脆性骨折有关，脆性骨折的发生率随着疲劳而增加，疲劳是重复载荷损害骨基质并引发微裂纹的过程。超过80%的50岁以上的骨折是由骨质疏松症引起的。2010年，这种情况给加拿大医疗保健系统造成了2.3圭元的开支。毫无疑问，有必要进行新的基础研究和科学举措，以解决这一健康问题。** 与普通工程材料不同，骨组织具有内在的重塑或自我修复能力。骨结构完整性取决于骨微损伤、骨重建、骨应变和骨力学性能等关键过程之间的复杂相互作用。健康骨可以承受微损伤，有效地控制其传播，并诱导适当的重塑反应，以减少损伤，而不是病理性骨。实验研究提供了有限的调查如何2D或3D微损伤转化为受损的机械性能，它如何发展相对于骨应变，或它是如何与2D骨重建。然而，严重缺乏对疲劳微损伤及其关键过程之间这种复杂相互作用的全面并行3D评估，无法为评估与年龄相关的疲劳微损伤和骨折风险提供全面的科学依据。** 拟议的研究计划直接针对年龄相关的疲劳微损伤和随之而来的骨折，通过实施一种新的体内/体外实验平台，以3D方式研究骨微损伤，骨重建，骨应变和骨机械性能之间的时空复杂相互作用，这将克服与2D方法或假设相关的建模工具的局限性。利用该实验平台的科学研究将为年龄相关疲劳微损伤的病因学和病理机制提供关键见解，这将进一步有助于改善疲劳断裂风险预测和管理。获得的知识将非常重视与年龄相关的疲劳微损伤管理，但也为儿童骨质疏松症或运动疲劳损伤。

Osteoporosis is a major public health condition affecting more than 200 million people worldwide, including 2 million Canadians, with a high prevalence in the aging population. This bone metabolic disorder is associated with fragility fractures, whose occurrence increases with fatigue, a process by which repetitive loading impairs bone matrix and initiates microcracks. Over 80% of all fractures in people older than 50 years old are caused by osteoporosis. In 2010, this situation incurred G$2.3 in expenses to the Canadian healthcare system. There is definitively a need for novel fundamental research and scientific initiatives to address this health problem. ******Unlike common engineering materials, bone tissue has the inherent ability to remodel or self-repair. Bone structural integrity depends on complex interactions between key processes, namely bone microdamage, bone remodeling, bone strains and bone mechanical properties. Healthy bones can sustain microdamage, efficiently control its propagation and induce appropriate remodeling response to reduce damage, as opposed to pathological bones. Experimental studies provide limited investigations on how 2D or 3D microdamage translates into impaired mechanical properties, how it develops with respect to bone strains, or how it is associated with 2D bone remodeling. Yet, a thorough concurrent 3D assessment of this complex interplay between fatigue microdamage and its key processes is critically lacking to provide a comprehensive scientific basis for assessing age related fatigue microdamage and fracture risks. ******The proposed research program directly targets age related fatigue microdamage and consequent fractures by implementing a novel in vivo/ex vivo experimental platform to investigate, in 3D, the space-time complex interplay between bone microdamage, bone remodeling, bone strains and bone mechanical properties that will overcome limitations associated to 2D approaches or to hypotheses dependant modeling tools. Scientific researches leveraging this experimental platform will provide key insight into the etiology and pathomechanisms of age-related fatigue microdamage, which will further contribute to improving fatigue fracture risk prediction and management. Acquired knowledge will be greatly valued for age related fatigue microdamage management, but also for pediatric osteoporosis or athletic fatigue damage.**