Abstract
Objective
To propose a modified protocol of mandibular osteoradionecrosis induction in rats with external beam radiation therapy.
Material and methods
A total of 45 male Wistar rats were used in this study. Firstly, 25 rats were divided into 5 groups (n = 5) according to the radiation dose protocol: without irradiation and irradiated with 15 Gy, 20 Gy, 25 Gy, or 30 Gy using a linear accelerator. Secondly, 15 other rats were divided into 3 groups (n = 5) according to the time of extraction of the three right mandibular molars: 7, 10, or 14 days after irradiation of 20 Gy. Lastly, dental extractions were performed in 5 other rats without irradiation (C-E10) for comparison with those of the group of dental extractions 10 days after irradiation (I-E10).
Results
The irradiated animals survived throughout the study period only at single doses of 15 Gy and 20 Gy. The suitable time for dental extractions after irradiation to induce mandibular osteoradionecrosis was defined as 10 days. Macroscopic evaluation of the right hemimandibles showed presence of osteoradionecrosis in I-E10 group and complete gingival healing in C-E10 group.
Conclusion
A single radiation dose of 20 Gy focused on head and neck region combined with the extraction of the three mandibular molars 10 days after irradiation constitutes a feasible protocol of mandibular osteoradionecrosis induction in rats with external beam radiation therapy.
Clinical relevance
Establishing a solid and widely available protocol of mandibular osteoradionecrosis induction is essential in the search for methods to prevent this complex disease.
Similar content being viewed by others
References
Chrcanovic BR, Reher P, Sousa AA, Harris M (2010) Osteoradionecrosis of the jaws - a current overview - part 1: physiopathology and risk and predisposing factors. Oral Maxillofac Surg 14:3–16. https://doi.org/10.1007/s10006-009-0198-9
Chronopoulos A, Zarra T, Ehrenfeld M, Otto S (2018) Osteoradionecrosis of the jaws: definition, epidemiology, staging and clinical and radiological findings. A concise review. Int Dent J 68:22–30. https://doi.org/10.1111/idj.12318
Sathasivam HP, Davies GR, Boyd NM (2018) Predictive factors for osteoradionecrosis of the jaws: a retrospective study. Head Neck 40:46–54. https://doi.org/10.1002/hed.24907
Kurihashi T, Iwata H, Nasu M, Yosue T (2002) Experimental study on wound healing of alveolar bone sockets in the rat maxilla after X-ray irradiation. Odontology 90:35–42. https://doi.org/10.1007/s102660200005
Niehoff P, Springer IN, Açil Y, Lange A, Marget M, Roldán JC, Köppe K, Warnke PH, Kimmig B, Wiltfang J (2008) HDR brachytherapy irradiation of the jaw - as a new experimental model of radiogenic bone damage. J Craniomaxillofac Surg 36:203–209. https://doi.org/10.1016/j.jcms.2008.01.003
Fenner M, Park J, Schulz N, Amann K, Grabenbauer GG, Fahrig A, Karg J, Wiltfang J, Neukam FW, Nkenke E (2010) Validation of histologic changes induced by external irradiation in mandibular bone. An experimental animal model. J Craniomaxillofac Surg 38:47–53. https://doi.org/10.1016/j.jcms.2009.07.011
Cohen M, Nishimura I, Tamplen M, Hokugo A, Beumer J, Steinberg ML, Suh JD, Abemayor E, Nabili V (2011) Animal model of radiogenic bone damage to study mandibular osteoradionecrosis. Am J Otolaryngol 32:291–300. https://doi.org/10.1016/j.amjoto.2010.06.001
Tamplen M, Trapp K, Nishimura I, Armin B, Steinberg M, Beumer J, Abemayor E, Nabili V (2011) Standardized analysis of mandibular osteoradionecrosis in a rat model. Otolaryngol Head Neck Surg 145:404–410. https://doi.org/10.1177/0194599811400576
Damek-Poprawa M, Both S, Wright AC, Maity A, Akintoye SO (2013) Onset of mandible and tibia osteoradionecrosis: a comparative pilot study in the rat. Oral Surg Oral Med Oral Pathol Oral Radiol 115:201–211. https://doi.org/10.1016/j.oooo.2012.09.008
Bléry P, Espitalier F, Hays A, Crauste E, Demarquay C, Pilet P, Sourice S, Guicheux J, Malard O, Benderitter M, Weiss P, Mathieu N (2015) Development of mandibular osteoradionecrosis in rats: importance of dental extraction. J Craniomaxillofac Surg 43:1829–1836. https://doi.org/10.1016/j.jcms.2015.08.016
Lerouxel E, Moreau A, Bouler JM, Giumelli B, Daculsi G, Weiss P, Malard O (2009) Effects of high doses of ionising radiation on bone in rats: a new model for evaluation of bone engineering. Br J Oral Maxillofac Surg 47:602–607. https://doi.org/10.1016/j.bjoms.2008.12.011
Yamasaki MC, Nejaim Y, Roque-Torres GD, Freitas DQ (2017) Meloxicam as a radiation-protective agent on mandibles of irradiated rats. Braz Dent J 28:249–255. https://doi.org/10.1590/0103-6440201701271
Cabrera AR, Yoo DS, Brizel DM (2013) Contemporary radiotherapy in head and neck cancer: balancing chance for cure with risk for complication. Surg Oncol Clin N Am 22:579–598. https://doi.org/10.1016/j.soc.2013.02.001
Liu L, Bassano DA, Prasad SC, Hahn SS, Chung CT (2003) The linear-quadratic model and fractionated stereotactic radiotherapy. Int J Radiat Oncol 57:827–832. https://doi.org/10.1016/S0360-3016(03)00634-5
Acknowledgments
The authors would like to thank the Oncology Center of the Hospital Fornecedores de Cana for the assistance during the experimental phase of the study.
Funding
This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior–Brasil (CAPES)-Finance Code 001.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The author Mayra Cristina Yamasaki has received research grants from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior–Brasil (CAPES) during the conduct of the study.
Ethical approval
All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted (Comissão de Ética no Uso de Animais da Universidade Estadual de Campinas-CEUA/UNICAMP-Protocol #3385-1).
Informed consent
For this study, informal consent was not required.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Yamasaki, M.C., Roque-Torres, G.D., Peroni, L.V. et al. A modified protocol of mandibular osteoradionecrosis induction in rats with external beam radiation therapy. Clin Oral Invest 24, 1561–1567 (2020). https://doi.org/10.1007/s00784-019-03054-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00784-019-03054-0