title: Effects of suppressed bone remodeling by minodronic acid and alendronate on bone mass, microdamage accumulation, collagen crosslinks and bone mechanical properties in the lumbar vertebra of ovariectomized cynomolgus monkeys.
abstract: Collagen crosslinking is an important determinant of the quality of bone material. We have previously shown that suppressed bone turnover by high doses of minodronic acid and alendronate increases compressive strength of vertebra, but also increases microdamage accumulation, in monkey bone. The aim of this study is to examine the effects of these bisphosphonates on collagen crosslinks and intrinsic material properties, in addition to microdamage accumulation, in vertebral cancellous bone in ovariectomized cynomolgus monkeys. Sixty female monkeys aged 9-17years were divided into five groups: sham and ovariectomized groups were treated daily for 17months with lactose vehicle, and the other three groups were given minodronic acid daily at 0.015 or 0.15mg/kg or alendronate daily at 0.5mg/kg orally. After sacrifice, lumbar vertebrae were subjected to histomorphometry, microdamage measurement, analysis of collagen crosslinking and compressive mechanical tests. Minodronic acid caused dose-dependent suppression of increased bone remodeling due to ovariectomy, and low-dose minodronic acid suppressed remodeling same level as alendronate. However, low-dose minodronic acid did not change microdamage accumulation, collagen maturity and the pentosidine level, whereas high-dose minodronic acid and alendronate increased these parameters. Compressive ultimate load was increased following high-dose minodronic acid and alendronate, but no treatment altered the reduction in intrinsic material properties caused by ovariectomy. These findings suggest that deterioration of bone material and formation of pentosidine and microdamage induced by minodronic acid is less than that expected based on the extent of remodeling suppression, in comparison with alendronate, but this was not reflected in any significant change of mechanical properties.
authors.affiliation: Department of Orthopedic Surgery, Kagawa University Faculty of Medicine, Kagawa, Japan. Electronic address: task@kms.ac.jp.
authors.forename: Tasuku
authors.initials: T
authors.lastname: Mashiba
authors.affiliation: Department of Orthopedic Surgery, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Saito
authors.affiliation: Department of Orthopedic Surgery, Kagawa University Faculty of Medicine, Kagawa, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Yamagami
authors.affiliation: Research Promotion, Ono Pharmaceutical Co., Ltd., Osaka, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Orthopedic Surgery, Kagawa University Faculty of Medicine, Kagawa, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Iwata
authors.affiliation: Department of Orthopedic Surgery, Kagawa University Faculty of Medicine, Kagawa, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D019386:Alendronate / Q000494:pharmacology*; D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects*; D003094:Collagen / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000378:metabolism; D004164:Diphosphonates / Q000494:pharmacology*; D005260:Female; D007093:Imidazoles / Q000494:pharmacology*; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D008252:Macaca fascicularis; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D013314:Stress, Mechanical
chemical_list: D003432:Cross-Linking Reagents; D004164:Diphosphonates; D007093:Imidazoles; C087958:YM 529; D003094:Collagen; D019386:Alendronate
keywords: Alendronate; Bone microdamage; Collagen crosslink; Mechanical property; Minodronic acid; Remodeling