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用米诺膦酸和阿仑膦酸盐治疗的去卵巢食蟹猴椎体皮质骨中生物磷灰石晶体取向的评估。

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

作者信息

Tanaka Makoto, Matsugaki Aira, Ishimoto Takuya, Nakano Takayoshi

机构信息

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.

出版信息

J Bone Miner Metab. 2016 Mar;34(2):234-41. doi: 10.1007/s00774-015-0658-2. Epub 2015 Apr 3.

DOI:10.1007/s00774-015-0658-2
PMID:25837430
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.

摘要

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。

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Bone. 2013 May;54(1):1-7. doi: 10.1016/j.bone.2013.01.016. Epub 2013 Jan 26.
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Degree of biological apatite c-axis orientation rather than bone mineral density controls mechanical function in bone regenerated using recombinant bone morphogenetic protein-2.使用重组骨形态发生蛋白-2 再生的骨中,生物性磷灰石 c 轴取向的程度而非骨矿物质密度控制着力学功能。
J Bone Miner Res. 2013 May;28(5):1170-9. doi: 10.1002/jbmr.1825.
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一种优化具有球形孔的支架微观几何尺寸的算法。
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A Novel Role of Interleukin-6 as a Regulatory Factor of Inflammation-Associated Deterioration in Osteoblast Arrangement.白细胞介素-6 在调节破骨细胞排列炎症相关恶化中的新作用
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Minodronic acid induces morphological changes in osteoclasts at bone resorption sites and reaches a level required for antagonism of purinergic P2X2/3 receptors.米诺膦酸在骨吸收部位诱导破骨细胞发生形态变化,并达到拮抗嘌呤能P2X2/3受体所需的水平。
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Decreased bone remodeling and porosity are associated with improved bone strength in ovariectomized cynomolgus monkeys treated with denosumab, a fully human RANKL antibody.在去卵巢食蟹猴中,使用完全人源化 RANKL 抗体地舒单抗治疗可减少骨重建和孔隙率,从而改善骨强度。
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Balicatib, a cathepsin K inhibitor, stimulates periosteal bone formation in monkeys.巴利昔替尼,一种组织蛋白酶 K 抑制剂,可刺激猴子的骨膜骨形成。
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