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香叶基香叶醇对双膦酸盐相关性颌骨坏死发展的体内影响。

In vivo effects of geranylgeraniol on the development of bisphosphonate-related osteonecrosis of the jaws.

机构信息

Faculty of Dental Medicine, Ss. Cyril and Methodius University in Skopje, Macedonia.

Faculty of Dental Medicine, Ss. Cyril and Methodius University in Skopje, Macedonia.

出版信息

J Craniomaxillofac Surg. 2018 Feb;46(2):230-236. doi: 10.1016/j.jcms.2017.11.007. Epub 2017 Nov 20.

DOI:10.1016/j.jcms.2017.11.007
PMID:29233701
Abstract

BACKGROUND

Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is a complication of the bisphosphonate (BP) treatment and its pathopysiology is still not fully understood. The existing preventive and treatment options require updates and more attention. Geranylgeraniol (GGOH) so far demonstrated an increased activity and viability of the cells previously treated with zoledronic acid (ZA). The aim of this study was to evaluate the in vivo effects of GGOH on the development of BRONJ.

MATERIALS AND METHODS

A total of 30 male Wistar rats were included in the study, divided into three groups: two experimental groups (EG1 and EG2) and a control group (CG). Rats from EG1 and EG2 were treated with 0,06 mg/kg ZA ip weekly in a duration of five weeks, while CG received saline ip. On the third week all animals underwent extraction of the lower right first molars. The rats from EG2 received a local solution of GGOH in concentration of 5 mM in the socket every day after the tooth extraction. The analyses included clinical evaluation on the wound healing and pathohistological evaluation for presence and level of osteonecrosis.

RESULTS

EG2 showed significantly improved wound healing and tissue proliferation, when compared to EG1. EG2 significantly differed from EG1 and CG (p<0,05) for the presence of microscopical osteonecrosis (80% vs 22,2% vs 0%). Regarding to the number of empty lacunes without osteocytes and the level of necrosis, all groups demonstrated significant differences.

CONCLUSION

Geranylgeraniol in a form of local solution may be a promising option for prevention and treatment of BRONJ.

摘要

背景

双膦酸盐相关性颌骨骨坏死(BRONJ)是双膦酸盐(BP)治疗的一种并发症,其病理生理学仍不完全清楚。现有的预防和治疗选择需要更新和更多关注。香叶基香叶醇(GGOH)迄今为止已证明对先前用唑来膦酸(ZA)治疗的细胞的活性和活力有增加作用。本研究旨在评估 GGOH 对 BRONJ 发展的体内影响。

材料和方法

总共纳入 30 只雄性 Wistar 大鼠进行研究,分为三组:两组实验组(EG1 和 EG2)和一组对照组(CG)。EG1 和 EG2 组大鼠每周腹腔注射 0.06mg/kg ZA 一次,持续五周,而 CG 组大鼠腹腔注射生理盐水。在第三周,所有动物均行右下第一磨牙拔除术。EG2 组大鼠在拔牙后每天接受浓度为 5mM 的 GGOH 局部溶液。分析包括伤口愈合的临床评估和组织学评估以评估是否存在和骨坏死的程度。

结果

与 EG1 相比,EG2 的伤口愈合和组织增生明显改善。EG2 在存在显微镜下骨坏死方面与 EG1 和 CG 明显不同(80%比 22.2%比 0%)。关于无成骨细胞的空陷窝数和坏死程度,所有组均有显著差异。

结论

局部溶液形式的香叶基香叶醇可能是预防和治疗 BRONJ 的一种有前途的选择。

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