Vertebrae provide essential biomechanical stability to the skeleton. In this work novel morphing techniques were used to parameterize three aspects of the geometry of a specimen-specific finite element (FE) model of a rat caudal vertebra (process size, neck size, and end-plate offset). Material properties and loading were also parameterized using standard techniques. These parameterizations were then integrated within an RSM framework and used to produce a family of FE models. The mechanical behavior of each model was characterized by predictions of stress and strain. A metamodel was fit to each of the responses to yield the relative influences of the factors and their interactions. The direction of loading, offset, and neck size had the largest influences on the levels of vertebral stress and strain. Material type was influential on the strains, but not the stress. Process size was substantially less influential. A strong interaction was identified between dorsal-ventral offset and dorsal-ventral off-axis loading. The demonstrated approach has several advantages for spinal biomechanical analysis by enabling the examination of the sensitivity of a specimen to multiple variations in shape, and of the interactions between shape, material properties, and loading
