Objectives: Bone loss induced by ovariectomy (OVX) affects less the mandible than other skeletal sites. The mandible is of membranous origin in contrast to most of the axial and peripheral skeleton, and it is subjected to very heavy abrupt forces during mastication. Whether this modifies its response to bone gain stimuli is not known. Methods: 45 4-month-old female Sprague-Dawley rats underwent transabdominal ovariectomy (OVX) or sham operation (sham). After 9 weeks OVX animals were randomly allocated into 4 groups. Two of them received IGF-I by osmotic mini-pumps implanted subcutaneously. The two other OVX groups and the sham group received the vehicle alone. Then, one group which received IGF-I and one OVX control group received subcutaneous injections of pamidronate (APD). The sham and the other OVX groups received the vehicle. After sixteen weeks the animals were sacrificed, their mandibles were dissected and the left hemi-mandible was thoroughly defleshed. Dual-energy x-ray absorptiometry was used to measure bone mineral density (BMD) of an anatomically and geometrically defined region in the mandibular alveolar process. Three-dimensional evaluation of alveolar bone micro-architecture parameters was also performed using 3D microtomographic histomorphometry. The alveolar process was scanned dorsoventrally with a voxel size of 12µm in all spatial directions. Results: IGF and APD increased BMD in OVX animals (p<0.05 and p<0.01), while OVX did not influence alveolar BMD. Alveolar micro-architecture was not influenced by IGF. However, APD increased BV/TV (p<0.05), and trabecular thickness (p<0.01) and number (p<0.05). OVX decreased trabecular number and spacing (p<0.05 and p<0.05). IGF increased cortical thickness (p<0.05) which may explain the concurrent BMD increase. Conclusions: Mandibular alveolar bone responds favorably after OVX to APD but not to IGF-I. These results seem to confirm the hypothesis that the mandible responds differently than other skeletal sites to osteotropic agents, possibly due to functional, morphological, and embryological differences.