Skeletal metastasis leads to changes in bone architecture, quality and strength, including microdamage accumulation. This dissertation aims to combine image-based computational and experimental techniques to study trabecular bone microdamage in healthy and metastatic whole bones. Deformable image registration was used to demonstrate proof of concept that post-euthanasia strain analysis of µCT images represents in vivo quasi static mechanical behavior of whole rat vertebrae. The ability to concurrently identify microdamage in whole vertebrae using histologic techniques (calcein and fuschin) and contrast enhanced BaSO4 µCT imaging was demonstrated and compared to stresses and strains calculated through micro finite element analysis. Significantly higher stresses and strains were found in regions of trabecular microdamage compared to undamaged regions, and in metastatic compared to healthy vertebrae. The techniques and knowledge developed through this work improve understanding of trabecular bone microdamage and form a solid platform for modeling the material and structural behaviour of skeletal tissue.