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磷酸二酯酶抑制剂己酮可可碱对药物相关性颌骨坏死的预防作用:一项动物研究。

Preventive Effect of Phosphodiesterase Inhibitor Pentoxifylline Against Medication-Related Osteonecrosis of the Jaw: An Animal Study.

作者信息

Yalcin-Ulker Gül Merve, Cumbul Alev, Duygu-Capar Gonca, Uslu Ünal, Sencift Kemal

机构信息

Assistant Professor, Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Okan University, Istanbul, Turkey.

Assistant Professor, Department of Histology and Embryology, Faculty of Medicine, Yeditepe University, Istanbul, Turkey.

出版信息

J Oral Maxillofac Surg. 2017 Nov;75(11):2354-2368. doi: 10.1016/j.joms.2017.04.017. Epub 2017 Apr 26.

Abstract

PURPOSE

The aim of this experimental study was to investigate the prophylactic effect of pentoxifylline (PTX) on medication-related osteonecrosis of the jaw (MRONJ).

MATERIALS AND METHODS

Female Sprague-Dawley rats (n = 33) received zoledronic acid (ZA) for 8 weeks to create an osteonecrosis model. The left mandibular second molars were extracted and the recovery period lasted 8 weeks before sacrifice. PTX was intraperitoneally administered to prevent MRONJ. The specimens were histopathologically and histomorphometrically evaluated.

RESULTS

Histomorphometrically, between the control and ZA groups, there was no statistically significant difference in total bone volume (P = .999), but there was a statistically significant difference in bone ratio in the extraction sockets (P < .001). A comparison of the bone ratio of the ZA group with the ZA/PTX group (PTX administered after extraction) showed no statistically significant difference (P = .69), but there was a statistically significant difference with the ZA/PTX/PTX group (PTX administered before and after extraction; P = .008). Histopathologically, between the control and ZA groups, there were statistically significant differences for inflammation (P = .013), vascularization (P = .022), hemorrhage (P = .025), and regeneration (P = .008). Between the ZA and ZA/PTX groups, there were no statistically significant differences for inflammation (P = .536), vascularization (P = .642), hemorrhage (P = .765), and regeneration (P = .127). Between the ZA and ZA/PTX/PTX groups, there were statistically significant differences for inflammation (P = .017), vascularization (P = .04), hemorrhage (P = .044), and regeneration (P = .04).

CONCLUSION

In this experimental model of MRONJ, it might be concluded that although PTX, given after tooth extraction, improves new bone formation that positively affects bone healing, it is not prophylactic. However, PTX given before tooth extraction is prophylactic. Therefore, PTX might affect healing in a positive way by optimizing the inflammatory response.

摘要

目的

本实验研究旨在探讨己酮可可碱(PTX)对药物性颌骨坏死(MRONJ)的预防作用。

材料与方法

33只雌性Sprague-Dawley大鼠接受唑来膦酸(ZA)治疗8周以建立骨坏死模型。拔除左侧下颌第二磨牙,恢复期持续8周后处死大鼠。腹腔注射PTX以预防MRONJ。对标本进行组织病理学和组织形态计量学评估。

结果

组织形态计量学方面,对照组与ZA组之间,总骨体积无统计学显著差异(P = 0.999),但拔牙窝骨比例有统计学显著差异(P < 0.001)。ZA组与ZA/PTX组(拔牙后给予PTX)的骨比例比较无统计学显著差异(P = 0.69),但与ZA/PTX/PTX组(拔牙前后均给予PTX)有统计学显著差异(P = 0.008)。组织病理学方面,对照组与ZA组之间,炎症(P = 0.013)、血管化(P = 0.022)、出血(P = 0.025)和再生(P = 0.008)有统计学显著差异。ZA组与ZA/PTX组之间,炎症(P = 0.536)、血管化(P = 0.642)、出血(P = 0.765)和再生(P = 0.127)无统计学显著差异。ZA组与ZA/PTX/PTX组之间,炎症(P = 0.017)、血管化(P = 0.04)、出血(P = 0.044)和再生(P = 0.04)有统计学显著差异。

结论

在本MRONJ实验模型中,可以得出结论,虽然拔牙后给予PTX可改善新骨形成,对骨愈合有积极影响,但它并无预防作用。然而,拔牙前给予PTX具有预防作用。因此,PTX可能通过优化炎症反应以积极方式影响愈合。

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