In this study, we attempt to predict cortical and trabecular bone adaptation in the mouse caudal vertebrae loading model using knowledge of bone’s local mechanical environment at the onset of loading. In a previous study, we demonstrated appreciable 25.9 and 11% increases in both trabecular and cortical bone volume density, respectively, when subjecting the fifth caudal vertebrae (C5) of C57BL/6 (B6) mice to an acute loading regime (amplitude of 8N, 3000 cycles, 10 Hz, 3 times a week for 4 weeks). We have also established a validated finite element (FE) model of the C5 vertebra using micro-computed tomography (micro-CT), which characterizes, in 3D, the micro-mechanical strains present in both cortical and trabecular compartments due to the applied loads. To investigate the relationship between load-induced bone adaptation and mechanical strains in-vivo and in-silico data sets were compared. Using data from the previous cross-sectional study, we divided cortical and trabecular compartments into 15 subregions and determined, for each region, a bone formation parameter ΔBV/BS (a cross-sectional measure of the bone volume added to cortical and trabecular surfaces following the described loading regime). Linear regression was then used to correlate mean regional values of ΔBV/BS with mean values of mechanical strains derived from the FE models which were similarly regionalized. The mechanical parameters investigated were strain energy density (SED), the orthogonal strains (e x , e y , e z ) and the three shear strains (e xy , e yz , e zx ). For cortical regions, regression analysis showed SED to correlate extremely well with ΔBV/BS (R² = 0.82) and e z (R² = 0.89). Furthermore, SED was found to predict expansion of the cortical shell correlating significantly with the regional percentage increases in cortical tissue volume (R² = 0.92), cortical marrow volume (R² = 0.91) and cortical thickness (R² = 0.56). For trabecular regions, FE parameters were found not to correlate with load-induced trabecular bone morphology. These results indicate that load-induced cortical morphology can be predicted from population data, whereas the prediction of trabecular morphology requires subject-specific micro-architecture.