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.
OBJECTIVE
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 (muCT) 3-dimensional bone parameters could provide useful information on the mechanism of action of antiosteoporotic agents.


METHODS
Mice were ovariectomized (OVX) or sham-operated, and the OVX mice were treated daily with 17beta-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 muCT 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 muCT 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.
Xiang
Anbo
A
Pharmacology Department, Tsukuba Research Laboratories, GlaxoSmithKline K.K., 43 Wadai, Tsukuba, Ibaraki 300-4247, Japan. anbo.xiang@gsk.com
Kanematsu
Masahiro
M
Mitamura
Mana
M
Kikkawa
Hideo
H
Asano
Satoshi
S
Kinoshita
Mine
M
D000818:Animals; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001862:Bone Resorption / Q000175:diagnosis / Q000188:drug therapy; D004195:Disease Models, Animal; D042241:Early Diagnosis; D004958:Estradiol / Q000627:therapeutic use; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D021621:Imaging, Three-Dimensional; D051379:Mice; D010012:Osteogenesis / Q000187:drug effects; D010024:Osteoporosis / Q000175:diagnosis* / Q000517:prevention & control*; D010052:Ovariectomy; D010281:Parathyroid Hormone / Q000627:therapeutic use; D010446:Peptide Fragments / Q000627:therapeutic use; D020849:Raloxifene Hydrochloride / Q000627:therapeutic use; D020889:Rolipram / Q000627:therapeutic use; D014057:Tomography, X-Ray Computed
D050071:Bone Density Conservation Agents; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D020889:Rolipram