Characterization of a rabbit osteoporosis model induced by ovariectomy and glucocorticoid

Abstract

BACKGROUND AND PURPOSE: Experimental models of osteoporosis in rabbits are useful to investigate anabolic agents because rabbits have an active Haversian remodeling and achieve skeletal maturity quickly. In this study, an experimental model of osteoporosis in rabbits induced by a combination of ovariectomy and glucocorticoid was characterized to provide a useful model for prevention and therapy of osteoporosis. METHODS: 32 skeletally mature female rabbits were divided randomly into 4 groups: sham control, bilateral ovariectomy (OVX), 1mg/kg/day methylprednisolone (MP) for 8 weeks, and OVX in combination with MP. All rabbits were killed 10 weeks after surgery. Bone mineral density (BMD) of lumbar spine was measured by dual-energy X-ray absorptiometry at baseline, and at 6 and 10 weeks postoperatively. Bone microarchitecture and mechanical properties of lumbar vertebrae were investigated by high-resolution micro-computed tomography and compression test, respectively, after killing. RESULTS: Mean BMD of the OVX+MP group at 10 weeks was reduced by about 36% from baseline (p < 0.001). Bone microarchitecture of lumbar vertebrae in the OVX+MP group indicated osteoporosis-associated deterioration. There was a statistically significant reduction in maximum load, stiffness, and energy absorption capacity of lumbar vertebrae in the OVX+MP group, but not in the OVX group, compared to the sham control. In the MP group, BMD and some microarchitecture parameters such as trabecular thickness and bone volume fraction were reduced. The mechanical properties were not statistically significantly different from those in the sham control group, however, although a negative trend was observed. INTERPRETATION: Osteopenia can be induced experimentally in rabbits through a combination of OVX and MP, and can be evaluated by BMD, bone microstructure, and mechanical parameters.