We have previously indicated that a single injection of alendronate, one of the nitrogen-containing bisphosphonates (NBPs), affects murine hematopoietic processes, such as the shift of erythropoiesis from bone marrow (BM) to spleen, disappearance of BM-resident macrophages, the increase of granulopoiesis in BM and an increase in the number of osteoclasts. NBPs induce apoptosis and the formation of giant osteoclasts in vitro and/or in patients undergoing long-term NBP treatment. Therefore, the time-kinetic effect of NBPs on osteoclasts needs to be clarified. In this study, we examined the effect of alendronate on mouse osteoclasts and osteoclastogenesis. One day after the treatment, osteoclasts lost the clear zone and ruffled borders, and the cell size decreased. After 2 days, the cytoplasm of osteoclasts became electron dense and the nuclei became pyknotic. Some of the cells had fragmented nuclei. After 4 days, osteoclasts had euchromatic nuclei attached to the bone surface. Osteoclasts had no clear zones or ruffled borders. After 7 days, osteoclasts formed giant osteoclasts via the fusion of multinuclear and mononuclear osteoclasts. These results indicate that NBPs affect osteoclasts and osteoclastogenesis via two different mechanisms.

中文翻译：

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含氮双膦酸盐对破骨细胞和破骨细胞生成的影响：超微结构研究

我们之前已经指出，单次注射阿仑膦酸盐，一种含氮双膦酸盐 (NBPs)，会影响小鼠的造血过程，例如红细胞生成从骨髓 (BM) 转移到脾脏，BM 驻留巨噬细胞的消失， BM 中的粒细胞生成增加和破骨细胞数量增加。NBP 在体外和/或在接受长期 NBP 治疗的患者中诱导细胞凋亡和巨大破骨细胞的形成。因此，需要阐明NBPs对破骨细胞的时间-动力学效应。在这项研究中，我们检查了阿仑膦酸钠对小鼠破骨细胞和破骨细胞生成的影响。治疗后一天，破骨细胞失去了清晰的区域和褶皱的边界，细胞大小减少。2天后，破骨细胞的细胞质变得电子致密，细胞核变得固缩。一些细胞具有破碎的细胞核。4 天后，破骨细胞具有附着在骨表面的常染色质细胞核。破骨细胞没有清晰的区域或褶皱的边界。7天后，破骨细胞通过多核和单核破骨细胞融合形成巨大的破骨细胞。这些结果表明，NBPs 通过两种不同的机制影响破骨细胞和破骨细胞生成。