Tomography-Based Quantification of Regional Differences in Cortical Bone Surface Remodeling and Mechano-Response

Bone has an adaptive capacity to maintain structural integrity. However, there seems to be a heterogeneous cortical (re)modeling response to loading at different regions within the same bone, which may lead to inconsistent findings since most studies analyze only one region. It remains unclear if the local mechanical environment is responsible for this heterogeneous response and whether both formation and resorption are affected. Thus, we compared the formation and resorptive response to in vivo loading and the strain environment at two commonly analyzed regions in the mouse tibia, the mid-diaphysis and proximal metaphysis. We quantified cortical surface (re)modeling by tracking changes between geometrically aligned consecutive in vivo micro-tomography images (time lapse 15 days). We investigated the local mechanical strain environment using finite element analyses. The relationship between mechanical stimuli and surface (re)modeling was examined by sub-dividing the mid-diaphysis and proximal metaphysis into 32 sub-regions. In response to loading, metaphyseal cortical bone (re)modeled predominantly at the periosteal surface, whereas diaphyseal (re)modeling was more pronounced at the endocortical surface. Furthermore, different set points and slopes of the relationship between engendered strains and remodeling response were found for the endosteal and periosteal surfaces at the metaphyseal and diaphyseal regions. Resorption was correlated with strain at the endocortical, but not the periosteal surfaces, whereas, formation correlated with strain at all surfaces, except at the metaphyseal periosteal surface. Therefore, besides mechanical stimuli, other non-mechanical factors are likely driving regional differences in adaptation. Studies investigating adaptation to loading or other treatments should consider region-specific (re)modeling differences.