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，影响着全球2亿多人，其中包括200万加拿大人，在老龄化人口中患病率很高。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的增加而增加，重复加载会损害骨基质并引发微裂纹。在50岁以上的人群中，超过80%的骨折是由骨质疏松引起的。2010年，这种情况给加拿大医疗系统带来了2.3加元的费用。确实需要新的基础研究和科学倡议来解决这一健康问题。 与普通工程材料不同，骨组织具有固有的重塑或自我修复能力。骨结构的完整性依赖于关键过程之间的复杂相互作用，即骨微损伤、骨重塑、骨应变和骨力学特性。健康的骨骼可以承受微小的损伤，有效地控制其传播，并诱导适当的重塑反应来减少损伤，而不是病理性的骨骼。实验研究对2D或3D微损伤如何转化为力学性能受损，它如何与骨应变相关，或它与2D骨重塑的关系进行了有限的研究。然而，对疲劳微损伤及其关键过程之间的这种复杂相互作用的全面同时3D评估严重缺乏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基础。 建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，通过实施一个新的体内/体外实验平台，在3D中研究骨微损伤、骨重塑、骨应变和骨力学特性之间的时空复杂相互作用，将克服与2D方法或假设依赖的建模工具相关的限制。利用这一实验平台进行的科学研究将为揭示与年龄相关的疲劳微损伤的病因和病理机制提供关键的见解，这将进一步有助于提高疲劳断裂风险的预测和管理。所获得的知识将对年龄相关的疲劳微损伤管理，也对儿童骨质疏松症或运动性疲劳损伤具有极大的价值。

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.