The structural Young's modulus (i.e. that of the cancellous framework) was determined by non-destructive compressive mechanical testing in the three orthogonal axes of 48 vertebral bone cubes. In addition, the material Young's modulus (i.e. of the trabeculae themselves) was estimated using an ultrasonic technique. Apparent and true density were determined by direct physical measurements. Significant mechanical anisotropy was observed:​ mean structural Young's modulus varied from 165 MPa in the supero-inferior direction to 43 MPa in the lateral direction. Structural Young's modulus correlated with apparent density, with power-law regression models giving the best correlations (r²=0.52–0.88). Mechanical anisotropy increased as a function of decreasing apparent density (p<0.001). Material Young's modulus was 10.0±1.3 GPa, and was negatively correlated with apparent density (p<0.001). In multiple regression models, material Young's modulus was a significant independent predictor of structural Young's modulus only in the supero-inferior direction. The data suggest the presence of two effects in vertebral bone associated with decreasing apparent density and, by implication, bone loss in general:​ (a) increased mechanical anisotropy, such that there is relative conservation of stiffness in the axial direction compared with the transverse directions;​ and (b) increased stiffness of the trabeculae themselves.