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Influence of Ovariectomy on Bone Turnover and Trabecular Bone Mass in Mature Cynomolgus Monkeys
Authors:Jun Iwamoto   Azusa Seki   Masao Matsuura   Yoshihiro Sato   Tsuyoshi Takeda   Hideo Matsumoto     James K. Yeh
Affiliation:1Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, Japan.;2Hamri Co., Ltd., Tokyo, Japan.;3Safety Research Institute for Chemical Compounds Co., Ltd., Hokkaido, Japan.;4Department of Neurology, Mitate Hospital, Fukuoka, Japan.;5Metabolism Laboratory, Department of Medicine, Winthrop-University Hospital, NY, USA.
Abstract:

Purpose

To examine the influence of ovariectomy (OVX) on bone turnover and trabecular bone mass at the 3 clinically important skeletal sites in mature cynomolgus monkeys.

Materials and Methods

Six female cynomolgus monkeys, aged 17-21 years, were randomized into 2 groups by the stratified weight: the OVX and sham-operation groups (n = 3 in each group). The experimental period was 16 months. Lumbar bone mineral density (BMD) in vivo and serum and urinary bone turnover markers were longitudinally measured, and peripheral quantitative computed tomographic and bone histomorphometric analyses were performed on trabecular bone of the lumbar vertebra, femoral neck, and distal radius at the end of the experiment.

Results

OVX induced in a reduction in lumbar BMD compared with the sham controls and the baseline, as a result of increased serum levels of bone-specific alkaline phosphatase and urinary levels of cross-lined N- and C-terminal telopeptides of type I collagen. Furthermore, OVX induced reductions in trabecular volumetric BMD and trabecular bone mass compared with the sham controls, with increased bone formation rate at the lumbar vertebra, femoral neck, and distal radius.

Conclusion

The results indicated that OVX in mature cynomolgus monkeys (17-21 years of age) increased bone turnover and induced trabecular bone loss at the three skeletal sites compared with the sham controls. Thus, mature cynomolgus monkeys could be utilized for preclinical studies to examine the effects of interventions on bone turnover and trabecular bone mass at the 3 clinically important skeletal sites.
Keywords:Ovariectomy   monkey   bone turnover   trabecular bone   femoral neck   lumbar spine   radius
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