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

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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.