Tanaka Makoto, Matsugaki Aira, Ishimoto Takuya, Nakano Takayoshi
Research Promotion, Ono Pharmaceutical Co., Ltd., 3-1-1 Sakurai, Shimamoto, Osaka, 618-8585, Japan.
Division of Materials and Manufacturing Science, Graduate School of Engineering, Osaka University, Suita, Osaka, 565-0871, Japan.
J Bone Miner Metab. 2016 Mar;34(2):234-41. doi: 10.1007/s00774-015-0658-2. Epub 2015 Apr 3.
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.
生物磷灰石(BAp)晶体取向分布的定量分析被提议作为一种新的骨质量指标。本研究旨在分析用氨基双膦酸盐米诺膦酸和阿仑膦酸钠治疗的去卵巢(OVX)猴子的BAp c轴取向,作为对照。60只9 - 17岁的雌性猴子被分为五组:一组假手术组和四组OVX组。假手术组和一组OVX组每天给予赋形剂,持续17个月。其他三组分别每天口服0.015和0.15 mg/kg的米诺膦酸以及0.5 mg/kg的阿仑膦酸钠。对第七腰椎腹侧皮质骨中BAp c轴的优先取向进行分析。OVX猴子中沿头尾轴的BAp c轴取向显著增加。高剂量的米诺膦酸抑制了OVX诱导的BAp c轴取向增加,而阿仑膦酸钠显示出抑制取向增加的趋势,但不显著。在与其他参数的分析中,BAp c轴取向与生化标志物和骨组织形态计量学中的骨形成指标呈正相关,与腰椎骨密度的增加呈负相关。另一方面,除了侵蚀表面外,BAp c轴取向与骨吸收指标无关。这些结果表明,米诺膦酸治疗改善了OVX猴子中BAp c轴取向的增加,主要是通过抑制骨形成的增加。