e hypothesized that osteoporosis due to estrogen deficiency progresses faster than due to disuse and that at the same amount of bone loss, disuse leads to less favorable bone structure and mechanical properties than estrogen deficiency. Adult rats were either ovariectomized (OVX) (n = 9) or neurectomized (NX) (n = 8). At week 0, 1, 2, 3, and 4, in vivo micro-CT scans were made of the proximal tibia. Segmented CT-scans at weeks 0 and 4 were used to build a 3D voxel-based micro finite element model (FEM). Displacement in the longitudinal direction was prescribed at the proximal end leading to a compression step of 1%. The severe reduction in metaphyseal bone volume fraction was not significantly different between OVX and NX. Epiphyseal bone loss was less severe in both groups, and BV/TV was significantly lower after NX. Trabecular separation and degree of anisotropy in the metaphysis and connectivity and trabecular number in the epiphysis were significantly more deteriorated after NX. FEM-derived stiffness decreased in both groups, but more after NX. Osteoporosis due to estrogen-deficiency progressed overall at a rate similar to osteoporosis due to disuse. At the same amount of induced bone loss, disuse led to more deteriorated bone structure and mechanical properties than estrogen deficiency.