Voss Pit Jacob, Stoddart Martin, Ziebart Thomas, Zeiter Stephan, Nelson Katja, Bittermann Gido, Schmelzeisen Rainer, Poxleitner Philipp
Department of Oral and Maxillofacial Surgery, University Medical Center Freiburg, (Head: Prof. Dr. R. Schmelzeisen), Hugstetter Str. 55, 79106 Freiburg im Breisgau, Germany.
AO Research Institute Davos, (Head: Prof. Dr. G. Richards), Clavadeler Str. 8, 7270 Davos Platz, Switzerland.
J Craniomaxillofac Surg. 2015 Sep;43(7):1133-8. doi: 10.1016/j.jcms.2015.04.020. Epub 2015 Apr 30.
The treatment of bisphosphonate-related osteonecrosis of the jaw has become routine in maxillofacial hospitals. However, the etiopathology has not yet been fully understood. The aim of this study was to develop a large animal model for medication-related osteonecrosis of the jaw (MRONJ).
Eight Swiss mountain sheep were randomly assigned into two groups. Group I received 0.075 mg/kg zoledronate (ZOL) intravenously every third week for 16 weeks. After 16 weeks, extraction of the first and second lower left premolar was performed. Group II underwent surgery and no ZOL was administered. After surgery, Group I continued to receive ZOL infusions; after 16 weeks, all animals were euthanized. The jaw bones were investigated macroscopically, radiographically (computed tomography) and histologically.
Osteonecrosis of the jaw was observed at all extraction sites in all the animals receiving ZOL, and at none of the sites in animals without ZOL. All ZOL-treated animals spontaneously developed exposed bone lesions in the oral cavity at sites where no surgical intervention was performed. CT imaging shows persistent alveolar extraction sockets 16 weeks after surgery in all animals of the ZOL-group, and healed alveolar extraction sockets in non-ZOL-treated animals.
Sheep treated with ZOL reproducibly demonstrated osteonecrosis of the jaw after tooth extraction, and spontaneous development of exposed bone in the oral cavity at sites where no manipulation was performed. This animal model can be used for further research in the fields of BP-ONJ etiopathology, oral implantology, bone and fracture healing and periodontology.
双膦酸盐相关颌骨坏死的治疗在颌面医院已成为常规操作。然而，其病因病理尚未完全明确。本研究的目的是建立一种用于药物相关性颌骨坏死（MRONJ）的大型动物模型。
将八只瑞士山地绵羊随机分为两组。第一组每三周静脉注射0.075mg/kg唑来膦酸（ZOL），共16周。16周后，拔除左下第一和第二前磨牙。第二组进行手术但未给予ZOL。手术后，第一组继续接受ZOL输注；16周后，所有动物实施安乐死。对颌骨进行宏观、影像学（计算机断层扫描）和组织学检查。
在所有接受ZOL的动物的所有拔牙部位均观察到颌骨坏死，而未接受ZOL的动物的所有部位均未出现坏死。所有接受ZOL治疗的动物在未进行手术干预的部位自发出现口腔内骨质暴露病变。CT成像显示，ZOL组所有动物在手术后16周牙槽拔牙窝持续存在，而未接受ZOL治疗的动物牙槽拔牙窝已愈合。
用ZOL治疗的绵羊在拔牙后可重复性地出现颌骨坏死，并在未进行操作的部位自发出现口腔内骨质暴露。该动物模型可用于BP-ONJ病因病理、口腔种植学、骨与骨折愈合以及牙周病学等领域的进一步研究。
