Whereas the structural implications of drug intervention are well established, there are few data on the possible mechanical consequences of treatment. In this work we examined the changes in elastic and shear moduli (EM and SM) in a region of trabecular bone in the distal radius and distal tibia of early postmenopausal women on the basis of MRI-based micro-finite-element (Β΅FE) analysis. Whole-section axial stiffness (AS) encompassing both trabecular and cortical compartments was evaluated as well. The study was conducted on previously acquired high-resolution images at the two anatomic sites. Images were processed to yield a 3D voxel array of bone-volume fraction (BVF), which was converted to a Β΅FE model of hexahedral elements in which tissue modulus was set proportional to voxel BVF. The study comprised 65 early postmenopausal women (age range 45 to 55 years), of whom 32 had chosen estrogen supplementation (estradiol group); the remainder had not (control group). Subjects had been scanned at baseline and 12 and 24 months thereafter. At the distal tibia, EM and SM were reduced by 2.9% to 5.5% in the control group (p < .05 to <.005), but there was no change in the estradiol subjects. AS decreased 3.9% (4.0%) in controls (p < .005) and increased by 5.8% (6.2%) in estradiol group subjects (p < .05) at 12 (24) months. At the distal radius, EM and SM changes from baseline were not significant, but at both time points AS was increased in estradiol group subjects and decreased in controls (p < .005 to <.05), albeit by a smaller margin than at the tibia. EM and SM were strongly correlated with BV/TV (r^2^ = 0.44 to 0.92) as well as with topologic parameters expressing the ratio of plates to rods (r^2^ = 0.45 to 0.82), jointly explaining up to 96% of the variation in the mechanical parameters. Finally, baseline AS was strongly correlated between the two anatomic sites (r^2^ = 0.58), suggesting that intersubject variations in the bone's mechanical competence follows similar mechanisms. In conclusion, the results demonstrate that micro-MRI-based Β΅FE models are suited for the study of the mechanical implications of antiresorptive treatment. The data further highlight the anabolic effect of short-term estrogen supplementation. Β© 2010 American Society for Bone and Mineral Research.