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Longer survival times for patients, particularly secondary to breast cancer, have increased the need for better understanding the impact of skeletal metastases on structural stability. This study aims to apply image registration to calculate strain distributions in metastatically involved rodent vertebrae utilizing \u00b5CT imaging. Osteolytic vertebral lesions were developed in five rnu\/rnu rats 2\u20133 weeks post intracardiac injection with MT\u20101 human breast cancer cells. An image registration algorithm was used to calculate and compare strain fields due to axial compressive loading in metastatically involved and control vertebrae. Tumor\u2010bearing vertebrae had greatly increased compressive strains, double the magnitude of strain compared to control vertebrae (<jats:italic>p<\/jats:italic>\u2009=\u20090.01). Qualitatively strain concentrated within the growth plates in both tumor bearing and control vertebrae. Most interesting was the presence of strain concentrations at the dorsal wall in metastatically involved vertebrae, suggesting structural instability. Strain distributions, quantified by image registration were consistent with known consequences of lytic involvement. Metastatically involved vertebrae had greater strain magnitude than control vertebrae. Strain concentrations at the dorsal wall in only the metastatic vertebrae, were consistent with higher incidence of burst fracture secondary to this pathology. Future use of image registration of whole vertebrae will allow focused examination of the efficacy of targeted and systemic treatments in reducing strains and the related risk of fracture in pathologic bones under simple and complex loading. \u00a9 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. 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