To facilitate the investigation of bone formation, in vivo, in response to mechanical loading a caudal vertebra axial compression device (CVAD) has been developed to deliver precise mechanical loads to the fifth caudal vertebra (C5) of the C57BL/6 female mouse. A combined experimental and computational approach was used to quantify the micro-mechanical strain induced in trabecular and cortical components following static and dynamic loading using the CVAD. Cortical bone strains were recorded using micro-strain gages. Finite element (FE) models based on micro-computed tomography were constructed for all C5 vertebrae. Both theoretical and experimental cortical strains correlated extremely well (R2 > 0.96) for a Young's modulus of 14.8 GPa, thus validating the FE model. In this study, we have successfully applied mechanical loads to the C5 murine vertebrae, demonstrating the potential of this model to be used for in vivo loading studies aimed at stimulating both trabecular and cortical bone adaptation.