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口服双膦酸盐和三种静脉用双膦酸盐对几种细胞类型的体外影响。

Effects of an oral bisphosphonate and three intravenous bisphosphonates on several cell types in vitro.

机构信息

Department of Oral and Maxillofacial Surgery, Plastic Surgery, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.

Department of Oral and Maxillofacial Surgery, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.

出版信息

Clin Oral Investig. 2018 Sep;22(7):2527-2534. doi: 10.1007/s00784-018-2349-6. Epub 2018 Feb 1.

Abstract

OBJECTIVE

To analyze the influence of an oral bisphosphonate and compare the potency to intravenous bisphosphonates on various cell types as regards the rarity of bisphosphonate-associated osteonecrosis of the jaw (BP-ONJ) caused by oral bisphosphonate.

MATERIALS AND METHODS

A viability assay (MTT), a migration assay (Boyden chamber), and an apoptosis assay (Caspase-Glo® 3/7) were performed to analyze the effect of bisphosphonates on human fibroblasts, umbilical vein endothelial cells (HUVEC), and osteoblasts.

RESULTS

Alendronate and intravenous bisphosphonates suppressed cell viability and migration, and induced apoptosis in all tested cell types. Alendronate had a greater impact than ibandronate on the characteristics in fibroblasts and osteoblasts but not as strong as zoledronate.

CONCLUSIONS

The incidence of BP-ONJ in oral bisphosphonate treatment is reported to be much lower than that in intravenous bisphosphonates. However, the influences of alendronate on human cells were at least as strong as ibandronate, although it was lower than zoledronate.

CLINICAL RELEVANCE

Alendronate showed strong enough effects to suppress human somatic cells and was comparable to certain intravenous bisphosphonates in potency. This study suggests that the lower incidence of BP-ONJ in alendronate treatment is not originated by its potency, but might be due to the low bioavailability of alendronate, lower dosing on a daily basis, and having no additional therapies.

摘要

目的

分析口服双膦酸盐的影响,并比较其与静脉用双膦酸盐在各种细胞类型上的效力,以探讨口服双膦酸盐引起颌骨骨坏死(BP-ONJ)的罕见性。

材料和方法

采用细胞活力测定(MTT)、迁移测定(Boyden 室)和细胞凋亡测定(Caspase-Glo® 3/7)分析双膦酸盐对人成纤维细胞、脐静脉内皮细胞(HUVEC)和成骨细胞的影响。

结果

阿仑膦酸盐和静脉用双膦酸盐均抑制所有测试细胞类型的细胞活力和迁移,并诱导细胞凋亡。阿仑膦酸盐对成纤维细胞和成骨细胞的影响大于伊班膦酸盐,但不如唑来膦酸盐强。

结论

口服双膦酸盐治疗的 BP-ONJ 发生率明显低于静脉用双膦酸盐。然而,阿仑膦酸盐对人细胞的影响至少与伊班膦酸盐一样强,尽管其效力低于唑来膦酸盐。

临床相关性

阿仑膦酸盐具有足够强的抑制人体细胞的作用,其效力与某些静脉用双膦酸盐相当。本研究表明,阿仑膦酸盐治疗中 BP-ONJ 发生率较低并非源于其效力,而是可能与阿仑膦酸盐的生物利用度低、每日剂量较低以及无额外治疗有关。

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