Analysis of Change Patterns of Microcomputed Tomography 3-Dimensional Bone Parameters as a High-Throughput Tool to Evaluate Antiosteoporotic Effects of Agents at an Early Stage of Ovariectomy-Induced Osteoporosis in Mice

OBJECTIVES:The purposes of this study were to develop an osteoporosis model in a short period of 2 weeks after ovariectomy in mice and to investigate whether analysis of microcomputed tomography (μCT) 3-dimensional bone parameters could provide useful information on the mechanism of action of antiosteoporotic agents. MATERIALS AND METHODS:Mice were ovariectomized (OVX) or sham-operated, and the OVX mice were treated daily with 17β-estradiol (E2), parathyroid hormone (PTH[1-34]), raloxifene, rolipram, or vehicle for 2 weeks. On day 14 post-OVX, the left femur bones were removed and then the distal metaphyseal bone was analyzed by both μCT and histomorphometry. RESULTS:The trabecular bone volume, thickness, number, and connectivity significantly decreased and the number of osteoclasts increased in OVX mice. Treatment of OVX animals with each of the 4 antiosteoporotic agents significantly increased the bone volume and improved the bone architecture. However, the improvement of trabecular thickness in the rolipram-treated group and that of cortical thickness in the PTH(1-34)-treated group were the most marked, whereas the improvement of connectivity in the rolipram-treated group was the least among the drug-treated groups. These different improving effects of agents on the bone parameters reflect the differential effects of these agents on bone formation and bone resorption. CONCLUSIONS:This study demonstrated the feasibility of evaluating the effect of the antiosteoporotic agents within 2 weeks after ovariectomy in mice. The μCT analysis may serve as a valuable tool, specifically in a high-throughput pharmacological screening test, offering useful information regarding the effects of test compounds on both bone resorption and formation.