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局部单剂量给予特立帕肽预防药物性颌骨坏死:大鼠模型研究的见解

Local Single-Dose Teriparatide Administration for BRONJ Prevention: Insights from a Rat Model Study.

作者信息

Etemadi Sh Milad, Teimoori Farshad, Sehat MohammadSoroush, Razavi Seyed Mohammad, Tajmiri Golnaz

机构信息

Department of Oral and Maxillofacial Surgery, Dental Implants Research Center, Dental Research Institute, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran.

Department of Oral and Maxillofacial Surgery, School of Dentistry, Kermanshah University of Medical Sciences, Kermanshah, Iran.

出版信息

J Maxillofac Oral Surg. 2024 Dec;23(6):1500-1507. doi: 10.1007/s12663-024-02301-6. Epub 2024 Sep 5.

Abstract

BACKGROUND

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) presents significant clinical challenges with uncertain treatment outcomes. Teriparatide, a fragment of human parathyroid hormone, shows potential in prevention strategies for BRONJ.

OBJECTIVE

This study investigates the impact of a single local dose of teriparatide on BRONJ prevention in an animal model.

METHODS

BRONJ was induced on 26 male Wistar rats via intraperitoneal injections of 0.06 mg/kg Zoledronic acid weekly for four weeks. Following tooth extraction under general anesthesia, rats were divided into two groups: one received teriparatide via Gelatamp in the tooth socket and the other as a local injection in the vestibule. Control groups received the treatment without teriparatide. Histopathological assessments for bone remodeling, osteoclast number, inflammation, angiogenesis, and necrosis were performed after four weeks.

RESULTS

Histopathological analysis indicated a significant improvement in bone remodeling and new bone formation in both treatment groups compared to controls, with notably better outcomes in the injection group ( = 0.01). Necrosis in the Gelatamp group was significantly higher in the control group than in the treatment group ( = 0.01), and bone formation was significantly higher in the injection group compared to the Gelatamp group ( = 0.03).

CONCLUSION

Local administration of teriparatide significantly enhances bone remodeling and reduces necrosis, suggesting a potential role in the prevention of BRONJ. These findings support further clinical investigation into teriparatide as a preventive strategy against BRONJ.

摘要

背景

双膦酸盐相关颌骨坏死(BRONJ)带来了重大临床挑战,治疗结果不确定。特立帕肽,一种人甲状旁腺激素片段,在BRONJ的预防策略中显示出潜力。

目的

本研究调查单次局部剂量特立帕肽对动物模型中BRONJ预防的影响。

方法

通过每周腹腔注射0.06mg/kg唑来膦酸,持续四周,在26只雄性Wistar大鼠中诱导BRONJ。在全身麻醉下拔牙后,大鼠被分为两组:一组通过明胶海绵在牙槽窝内给予特立帕肽,另一组在前庭进行局部注射。对照组接受不含特立帕肽的治疗。四周后进行骨重塑、破骨细胞数量、炎症、血管生成和坏死的组织病理学评估。

结果

组织病理学分析表明,与对照组相比,两个治疗组的骨重塑和新骨形成均有显著改善,注射组的结果明显更好(P = 0.01)。明胶海绵组的坏死在对照组中显著高于治疗组(P = 0.01),且注射组的骨形成明显高于明胶海绵组(P = 0.03)。

结论

局部给予特立帕肽可显著增强骨重塑并减少坏死,表明其在预防BRONJ方面具有潜在作用。这些发现支持对特立帕肽作为BRONJ预防策略进行进一步临床研究。

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