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Evaluation of crystallographic orientation of biological apatite in vertebral cortical bone in ovariectomized cynomolgus monkeys treated with minodronic acid and alendronate

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Abstract

Quantitative analysis of the orientational distribution of biological apatite (BAp) crystals is proposed as a new index of bone quality. This study aimed to analyze BAp c-axis orientation in ovariectomized (OVX) monkeys treated with amino-bisphosphonates minodronic acid and alendronate as reference. Sixty female monkeys aged 9–17 years were divided into five groups: one sham group and four OVX groups. The sham group and one OVX group were treated daily with vehicle for 17 months. The other three groups were treated daily with minodronic acid at doses of 0.015 and 0.15 mg/kg, and alendronate at 0.5 mg/kg orally, respectively. The seventh lumbar vertebrae were subjected to analysis of the preferential BAp c-axis orientation in the ventral cortical bone. The BAp c-axis orientation along the craniocaudal axis was significantly increased in the OVX monkeys. The high dose of minodronic acid suppressed the OVX-induced increase in the BAp c-axis orientation, whereas alendronate showed a non-significant tendency to suppress the increase in the orientation. In analysis with other parameters, the BAp c-axis orientation was positively correlated with bone formation indices in biochemical markers and bone histomorphometry and negatively correlated with the increase in lumbar bone mineral density. On the other hand, the BAp c-axis orientation was not correlated with bone resorption indices, except for the eroded surface. These results indicate that the increase in BAp c-axis orientation was ameliorated by minodronic acid treatment in OVX monkeys, mainly by suppression of bone formation increase.

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Acknowledgments

The authors thank Satoshi Nishikawa and Hiroshi Mori for their technical assistance in this study.

Conflict of interest

M Tanaka is a research scientist at Ono Pharmaceutical Co., Ltd. All other authors state no conflict of interest, except that measurement of the BAp c-axis orientation was funded by Ono Pharmaceutical Co., Ltd. Minodronic acid was launched by Ono Pharmaceutical Co., Ltd. and Astellas Pharma Inc. in Japan.

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Correspondence to Makoto Tanaka.

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Tanaka, M., Matsugaki, A., Ishimoto, T. et al. Evaluation of crystallographic orientation of biological apatite in vertebral cortical bone in ovariectomized cynomolgus monkeys treated with minodronic acid and alendronate. J Bone Miner Metab 34, 234–241 (2016). https://doi.org/10.1007/s00774-015-0658-2

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  • DOI: https://doi.org/10.1007/s00774-015-0658-2

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