Morphological assessment of the biological effects of eldecalcitol.
Morphological assessment of the biological effects of eldecalcitol.
复制标题
艾德骨化醇生物效应的形态学评估。
DOI：
10.1007/978-981-16-5613-2_27
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Amizuka N.
中科院分区：
文献类型：
--
作者：
Hasegawa T.;Hongo H.;Yamamoto T.;Amizuka N.
用于骨质疏松患者的治疗药物可分为抗吸收或合成代谢试剂。艾地骨化醇是一种活性维生素D3的类似物，已在日本开发，与艾地骨化醇的前药阿法骨化醇相比，具有更好的抗吸收作用。据报道，艾地骨化醇的抗吸收作用与支持破骨细胞生成的前成骨细胞数量减少、RANKL表达减少和循环破骨细胞前体中鞘氨醇-1-磷酸受体2受抑制有关。相反，在过去的十年中，艾地骨化醇已被证明可诱导骨小梁中基于建模的骨形成，即，Frost先前提出的“微型模型”，除了对骨质疏松治疗发挥抗吸收作用之外。基于微型建模/建模的骨形成不依赖于前述成骨细胞骨吸收;静息成骨细胞（也称为骨衬里细胞）将被激活以在现有骨上沉积存款新骨。艾地骨化醇驱动的基于微型建模/建模的骨形成不仅可以在啮齿动物中看到，而且可以在灵长类动物和人类患者中看到。由于基于微建模/建模的骨形成与骨吸收无关，艾地骨化醇可能能够诱导双向功能-抗吸收作用和基于微建模/建模的骨形成介导的合成代谢作用。本章主要介绍艾地骨化醇的生物学效应研究。
Therapeutic drugs for osteoporotic patients can be divided into anti-resorptive or anabolic reagents. Eldecalcitol, an analog of active vitamin D3, has been developed in Japan and provides more anti-resorptive effects compared to alfacalcidol—a predrug of eldecalcitol. The anti-resorptive effects of eldecalcitol are reportedly related to the reduced population of preosteoblasts that support osteoclastogenesis, diminished expression of RANKL, and suppressed sphingosine-1-phosphate receptor 2 in circulating osteoclast precursors. Conversely, during the last decade, eldecalcitol has been shown to induce the modeling-based bone formation in trabeculae, i.e.,“minimodeling” previously proposed by Frost, in addition to exerting anti-resorptive effects for the osteoporotic treatment. Minimodeling-/modeling-based bone formation is not dependent on foregoing osteoclastic bone resorption; resting osteoblasts, also referred to as bone lining cells, would be activated to deposit new bone on the existing bone. Eldecalcitol-driven minimodeling-/modeling-based bone formation can be seen not only in rodents but also in primates and human patients. Since minimodeling-/modeling-based bone formation is not coupled with osteoclastic bone resorption, eldecalcitol may be able to induce bidirectional function—anti-resorptive effects and anabolic effects mediated by minimodeling-/modeling-based bone formation. In this chapter, studies on the biological effects of eldecalcitol will be introduced.