Skeletal fractures, including those resulting from osteoporosis, result in significant healthcare and societal costs on an annual basis. Therefore, it is important to understand the mechanisms by which these fractures occur. Incremental compression testing combined with micro-CT imaging has been used to visualize the progression of failure in trabecular bone samples; however, these studies have ignored the potential contributions of the cortical shell. In the current study, incremental compression testing with simultaneous micro-CT imaging was performed on rat vertebrae from multiple disease states (healthy control, osteoporotic, osteoporotic + treatment). These tests allowed the progression of failure through an entire vertebral body to be visualized for the first time. Three distinct failure modes were observed throughout all specimens, independent of disease state. Two of these failure modes (types I and II), which were observed in 93% of all specimens, were associated with the vascular apertures in the vertebrae's dorsal and ventral surfaces. This behaviour is likely caused by the stress concentrations in the cortical shell resulting from the apertures themselves, coupled with the reduced trabecular bone volume adjacent to them. These results suggest that the combined contributions of both the cortical shell and trabecular bone must be considered when studying the compressive failure behaviour of rat vertebrae.