Age-dependent variations of cancellous bone in response to ovariectomy in C57BL/6J mice.

Abstract

The ovariectomized (OVX) mouse model has been widely accepted to be suitable for the study of postmenopausal osteoporosis. However, whether C57BL/6J mice, a commonly used genetic background mouse strain, is an appropriate model for postmenopausal osteoporosis remains controversial. The present study investigated the effect of the OVX model on alterations in bone density and microarchitecture in C57BL/6J female mice of different ages. C57BL/6J mice were divided into 8-, 12- and 16-week-old groups (OVX8, OVX12 and OVX16) from the beginning of OVX. At 8 weeks post-surgery, the mice were anesthetized and micro-computed tomography was used to analyze the bone density and microarchitecture. The results revealed that OVX-induced loss of cancellous bone was greatest in OVX8, moderate in OVX12, and only a weak bone loss was observed in the OVX16 group when compared with the SHAM16 control group. In addition, the effect of genetic backgrounds in response to the OVX model were examined. Several other strains of mice, including inbred (BALB/c) and outbred (ICR and Kunming), were used in the present study, all of which were subjected to OVX at 8 weeks of age. The present findings revealed that the highest rate of bone loss was detected in C57BL/6J female mice. In addition, treatment with estrogen (17β-estradiol, 30 µg/kg five times per week) led to a significant increase in bone density in C57BL/6J mice compared with the other strains of mice. Therefore, these results may provide novel insights into the age- and strain-associated effect of OVX on regulating turnover of bone in female mice. The present findings also suggest 8-week-old C57BL/6J mice as an animal model for postmenopausal osteoporosis and preclinical testing of potential therapies for this disease.