Mashiba Tasuku, Saito Mitsuru, Yamagami Yoshiki, Tanaka Makoto, Iwata Ken, Yamamoto Tetsuji
Department of Orthopedic Surgery, Kagawa University Faculty of Medicine, Kagawa, Japan.
Department of Orthopedic Surgery, Jikei University School of Medicine, Tokyo, Japan.
Bone. 2017 Apr;97:184-191. doi: 10.1016/j.bone.2017.01.008. Epub 2017 Jan 7.
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.
胶原蛋白交联是骨材料质量的一个重要决定因素。我们之前已经表明，高剂量的米诺膦酸和阿仑膦酸钠抑制骨转换会增加猴骨中椎骨的抗压强度，但也会增加微损伤的积累。本研究的目的是研究这些双膦酸盐对去卵巢食蟹猴椎体松质骨中胶原蛋白交联、内在材料特性以及微损伤积累的影响。60只9 - 17岁的雌性猴子被分为五组：假手术组和去卵巢组每天用乳糖载体治疗17个月，另外三组分别每天口服0.015mg/kg或0.15mg/kg的米诺膦酸或0.5mg/kg的阿仑膦酸钠。处死后，对腰椎进行组织形态计量学分析、微损伤测量、胶原蛋白交联分析和压缩力学测试。米诺膦酸导致去卵巢引起的骨重塑增加呈剂量依赖性抑制，低剂量米诺膦酸抑制重塑的水平与阿仑膦酸钠相同。然而，低剂量米诺膦酸并未改变微损伤积累、胶原蛋白成熟度和戊糖苷水平，而高剂量米诺膦酸和阿仑膦酸钠增加了这些参数。高剂量米诺膦酸和阿仑膦酸钠后压缩极限载荷增加，但没有治疗改变去卵巢引起的内在材料特性的降低。这些发现表明，与阿仑膦酸钠相比，米诺膦酸引起的骨材料劣化、戊糖苷形成和微损伤小于基于重塑抑制程度所预期的情况，但这并未反映在力学性能的任何显著变化中。
