Computationally derived endosteal strain and strain gradients correlate with increased bone formation in an axially loaded murine tibia model

Osteoporosis is a common metabolic bone disorder characterized by low bone mass and microstructural degradation of bone tissue due to a derailed bone remodeling process. A deeper understanding of the mechanobiological phenomena that modulate the bone remodeling response to mechanical loading in a healthy bone is crucial to develop treatments. Rodent models have provided invaluable insight into the mechanobiological mechanisms regulating bone adaptation in response to dynamic mechanic stimuli. This study sheds light on these aspects by means of assessing the mechanical environment of the cortical and cancellous tissue to in vivo dynamic compressive loading within the mouse tibia using microCT-based finite element model in combination with diaphyseal strain gauge measures. Additionally, this work describes the relation between the mid-diaphyseal strains and strain gradients from the finite element analysis and bone formation measures from time-lapse in vivo tibial loading with a fluorochrome-derived histomorphometry analysis. The mouse tibial loading model demonstrated that cancellous strains were lower than those in the midshaft cortical bone. Sensitivity analyses demonstrated that the material property of cortical bone was the most significant model parameter. The computationally-modeled strains and strain gradients correlated significantly to the histologically-measured bone formation thickness at the mid-diaphyseal cross-section of the mouse tibia.