To characterize an experimental model of osteoporosis in rabbits induced either by ovariectomy (OVX), glucocorticoids, or by a combination of both. Thirty-five rabbits were randomly allocated into five groups: bilateral OVX, daily methylprednisolone hemisuccinate (MPH) injections at a 1.5 mg/kg/day dose for 4 consecutive weeks (MPH group), or variable dose of MPH between 0.5 and 2 mg/kg/day in combination with OVX (OVX + MPH at low, medium, and high dose). Twenty-two animals were killed 6 weeks after OVX, and 13 were killed 16 weeks later. Dual-energy X-ray absorptiometry was obtained at baseline and 6 and 16 weeks after OVX. High-resolution magnetic resonance imaging (MRI) was carried out at 0 and 6 weeks after OVX. Glucose, total cholesterol, triglyceride, and oestradiol blood levels before and 16 weeks after OVX were determined. Bone mineral density (BMD) decreased significantly at lumbar spine in MPH and OVX + MPH medium-dose groups, and at global knee and subchondral bone of the knee in MPH, OVX + MPH low- and medium-dosage groups (P < 0.05). BMD variations in OVX rabbits were not significant in any of the three anatomical locations analyzed. BMD variation 16 weeks after OVX was significant at lumbar spine and global knee in the OVX + MPH medium-dose group and only at global knee in the OVX + MPH low-dose group (P < 0.05). MRI did not show bone or cartilage changes. Osteoporosis can be induced experimentally in rabbits through isolated MPH or by a combination of OVX and medium dose corticosteroid for 4 weeks. OVX alone was not sufficient to induce osteoporosis.