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唑来膦酸在犬拔牙创中的早期抑制作用被重组人骨形态发生蛋白抵消。

Early inhibitory effects of zoledronic acid in tooth extraction sockets in dogs are negated by recombinant human bone morphogenetic protein.

作者信息

Gerard David A, Carlson Eric R, Gotcher Jack E, Pickett David O

机构信息

Professor, Department of Oral and Maxillofacial Surgery, University of Tennessee Medical Center, Knoxville, TN.

Professor and Chairman, Department of Oral and Maxillofacial Surgery, University of Tennessee Medical Center, Knoxville, TN.

出版信息

J Oral Maxillofac Surg. 2014 Jan;72(1):61-6. doi: 10.1016/j.joms.2013.06.192. Epub 2013 Jul 25.

Abstract

PURPOSE

This study was conducted with 2 purposes. The first was to determine the effect of a single dose of zoledronic acid (ZA) on the healing of a tooth extraction socket in dogs. The second was to determine if placement of recombinant human bone morphogenetic protein-2 (rhBMP-2)/absorbable collagen sponge (ACS) - INFUSE, (Medtronic, Memphis, TN) into these extraction sockets would inhibit the inhibition on bone healing and remodeling by ZA.

MATERIALS AND METHODS

Nine adult female beagle dogs (2 to 3 yr old) were placed into 3 groups of 3 dogs each. Group I received 15 mL of sterile saline intravenously; group II received 2.5 mg of ZA intravenously; and group III received 5 mg of ZA intravenously. Forty-five days after treatment, all dogs underwent extraction of noncontiguous right and left mandibular first molars and second premolars. In group I, the right mandibular extraction sockets had nothing placed in them, whereas the left mandibular sockets had only ACS placed in them. In groups II and III, the right mandibular sockets had rhBMP-2/ACS placed in them, whereas the left mandibular sockets had only ACS placed. All extraction sockets were surgically closed. Tetracycline was given intravenously 5 and 12 days later, and all animals were euthanized 15 days after tooth extraction. The extraction sockets and rib and femur samples were harvested immediately after euthanasia, processed, and studied microscopically.

RESULTS

A single dose of ZA significantly inhibited healing and bone remodeling in the area of the tooth extractions. The combination of rhBMP-2/ACS appeared to over-ride some of the bone remodeling inhibition of the ZA and increased bone fill in the extraction sites, and remodeling activity in the area was noted. The effects of rhBMP-2/ACS were confined to the area of the extraction sockets because bone activity at distant sites was not influenced.

CONCLUSIONS

A single dose of ZA administered intravenously inhibits early healing of tooth extraction sockets and bone remodeling in this animal model. The combination of rhBMP-2/ACS significantly increased bone fill and bone remodeling in these areas, negating much of the effect of the ZA.

摘要

目的

本研究有两个目的。第一个目的是确定单剂量唑来膦酸(ZA)对犬拔牙创愈合的影响。第二个目的是确定将重组人骨形态发生蛋白-2(rhBMP-2)/可吸收胶原海绵(ACS)-INFUSE(美敦力公司,田纳西州孟菲斯)植入这些拔牙创是否会抑制ZA对骨愈合和重塑的抑制作用。

材料与方法

9只成年雌性比格犬(2至3岁)被分为3组,每组3只。第一组静脉注射15 mL无菌生理盐水;第二组静脉注射2.5 mg ZA;第三组静脉注射5 mg ZA。治疗45天后,所有犬均拔除非相邻的右侧和左侧下颌第一磨牙及第二前磨牙。在第一组中,右侧下颌拔牙创未放置任何东西,而左侧下颌拔牙创仅放置了ACS。在第二组和第三组中,右侧下颌拔牙创放置了rhBMP-2/ACS,而左侧下颌拔牙创仅放置了ACS。所有拔牙创均通过手术关闭。在拔牙后5天和12天静脉注射四环素,所有动物在拔牙后15天安乐死。安乐死后立即采集拔牙创以及肋骨和股骨样本,进行处理并进行显微镜检查。

结果

单剂量ZA显著抑制拔牙区域的愈合和骨重塑。rhBMP-2/ACS的联合应用似乎克服了ZA对骨重塑的一些抑制作用,并增加了拔牙部位的骨填充,且该区域有重塑活动。rhBMP-2/ACS的作用局限于拔牙创区域,因为远处部位的骨活性未受影响。

结论

在该动物模型中,静脉注射单剂量ZA可抑制拔牙创的早期愈合和骨重塑。rhBMP-2/ACS的联合应用显著增加了这些区域的骨填充和骨重塑,抵消了ZA的大部分作用。

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