title: Evaluation of crystallographic orientation of biological apatite in vertebral cortical bone in ovariectomized cynomolgus monkeys treated with minodronic acid and alendronate.
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.
authors.affiliation: Research Promotion, Ono Pharmaceutical Co., Ltd., 3-1-1 Sakurai, Shimamoto, Osaka, 618-8585, Japan. mak.tanaka@ono.co.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Division of Materials and Manufacturing Science, Graduate School of Engineering, Osaka University, Suita, Osaka, 565-0871, Japan.
authors.forename: Aira
authors.initials: A
authors.lastname: Matsugaki
authors.affiliation: Division of Materials and Manufacturing Science, Graduate School of Engineering, Osaka University, Suita, Osaka, 565-0871, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Ishimoto
authors.affiliation: Division of Materials and Manufacturing Science, Graduate School of Engineering, Osaka University, Suita, Osaka, 565-0871, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Nakano
mesh_terms: D019386:Alendronate / Q000494:pharmacology*; D000818:Animals; D001031:Apatites / Q000737:chemistry*; D019540:Area Under Curve; D015415:Biomarkers / Q000378:metabolism; D015519:Bone Density / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects; D000071538:Cortical Bone / Q000187:drug effects*; D003461:Crystallography; D004164:Diphosphonates / Q000494:pharmacology*; D005260:Female; D007093:Imidazoles / Q000494:pharmacology*; D008159:Lumbar Vertebrae / Q000187:drug effects*; D008252:Macaca fascicularis; D015675:Osteocalcin / Q000097:blood; D010052:Ovariectomy; D013977:Tibia / Q000187:drug effects; D014961:X-Ray Diffraction
chemical_list: D001031:Apatites; D015415:Biomarkers; D004164:Diphosphonates; D007093:Imidazoles; D015675:Osteocalcin; C087958:YM 529; D019386:Alendronate
keywords: Alendronate; Bisphosphonate; Minodronic acid; Osteoporosis; Ovariectomy
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