The role of infection and inflammation in the etiopathogenesis of medication-related osteonecrosis of the jaw
DOI:
https://doi.org/10.5335/rfo.v28i1.15099Keywords:
Bisphosphonate-Associated Osteonecrosis of the Jaw, Infections, InflammationAbstract
Aim: The aim of this literature review is to highlight the role of infection and inflammation in the etiopathogenesis of drug-induced osteonecrosis of the jaw (MRONJ). Literature review: MRONJ is a rare and serious condition that negatively impacts the lives of affected patients. Its etiopathogenesis is multifactorial and has not yet been fully understood. One of the hypotheses proposed to explain it suggests that, in addition to the inhibition of bone turnover by antiresorptive drugs, the infection associated with tooth extraction and local inflammation play a decisive role in triggering the condition. Understanding the etiopathogenesis of MRONJ allows the dentist to identify patients at higher risk for the disease, as well as assisting in monitoring and choosing the most appropriate management. In research, it can improve preclinical studies and deepen the investigation of biomarkers for early diagnosis of MRONJ. Conclusion: Knowing the contribution of infection and inflammation in the etiopathogenesis of MRONJ is essential to guide research and the adoption of preventive strategies for patients at risk, and adequate management and monitoring for those already affected.
Downloads
References
Ruggiero SL, Dodson TB, Aghaloo T, Carlson ER, War BB, Kademani D. American Association of Oral and Maxillofacial Surgeons’ Position Paper on Medication-Related Osteonecrosis of the Jaws—2022 Update. J Oral Maxillofac Surg 2022;80(5):920–43. Disponível em:https://doi.org/10.1016/j.joms.2022.02.008
Soares AL, Simon S, Gebrim LH, Nazário ACP, Lazaretti-Castro M. Prevalence and risk factors of medication-related osteonecrosis of the jaw in osteoporotic and breast cancer patients: a cross-sectional study. Support Care Cancer 2020;28(5):2265–71. Disponível em:https://doi.org/10.1007/s00520-019-05044-0
Kim R, Kim SW, Kim H, Ku SY. The impact of sex steroids on osteonecrosis of the jaw. Osteoporosis and Sarcopenia 2022;8(2):58–67. Disponível em: https://doi.org/10.1016/j.afos.2022.05.003
Lee D et al. Inhibition of Osteoclast Differentiation and Bone Resorption by Bisphosphonate-conjugated Gold Nanoparticles. Scientific Reports 2016; 6:1–11. Disponível em:https://doi.org/10.1038/srep27336
Katsarelis H, Shah NP, Dhariwal DK, Pazianas M. Infection and medication-related osteonecrosis of the jaw. J Dent Res 2015;94(4):534-9. Disponível em: https://doi.org/10.1177/0022034515572021
Soutome S et al. Factors affecting development of medication-related osteonecrosis of the jaw in cancer patients receiving high-dose bisphosphonate or denosumab therapy: Is tooth extraction a risk factor? PLoS ONE 2018;13(7):e0201343. Disponível em:https://doi.org/10.1371/journal.pone.0201343
Marx RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg. 2003;61(9):1115-1117. https://doi.org/10.1016/S0278-2391(03)00720-1
Eguia A, Bagán-Debón L, Cardona F. Review and update on drugs related to the development of osteonecrosis of the jaw. Med Oral Patol Oral Cir Bucal. 2020;25(1):e71-e83. Disponível em:http://dx.doi.org/doi:10.4317/medoral.23191
Kawahara M, Kuroshima S, Sawase T. Clinical considerations for medication-related osteonecrosis of the jaw: a comprehensive literature review. Int J Implant Dent 2021;7(47). Disponível em:https://doi.org/10.1186/s40729-021-00323-0
AlDhalaan NA, BaQais A, Al-Omar A. Medication-related Osteonecrosis of the Jaw: A Review. Cureus 2020;12(2):e6944. Disponível em:doi:10.7759/cureus.6944
Kuroshima S, Al-Omari FA, Sasaki M, Sawase T. Medication-related osteonecrosis of the jaw: A literature review and update. Genesis (United States), 2022;60(8–9):1–18. Disponível em: https://doi.org/10.1002/dvg.23500
Fliefel R, Tröltzsch M, Kühnisch J, Ehrenfeld M, Otto S. Treatment strategies and outcomes of bisphosphonate-related osteonecrosis of the jaw (BRONJ) with characterization of patients: a systematic review. Int. J. Oral Maxillofac Surg 44(5):568-585 Disponível em:https://doi.org/10.1016/j.ijom.2015.01.026
Avishai G, Muchnik D, Masri D, Zlotogorski-Hurvitz A, Chaushu L. Minimizing MRONJ after Tooth Extraction in Cancer Patients Receiving Bone-Modifying Agents. J. Clin. Med 2022; 11(7). Disponível em:https://doi.org/10.3390/jcm11071807
Ozyurtseven TB et al. Medication-related osteonecrosis of the jaw (MRONJ) and eNOS Polymorphisms in multiple myeloma patients: a single center experience. BMC Oral Health 2021;21(272). Disponível em:https://doi.org/10.1186/s12903-021-01634-9
Maciel GBM, Maciel RM, Danesi CC. Bone cells and their role in physiological remodeling. Mol Biol Rep 2023;50:2857–63. Disponível em: https://doi.org/10.1007/s11033-022-08190-7
He L, Sun X, Liu Z, Qiu Y, Niu Y. Pathogenesis and multidisciplinary management of medication-related osteonecrosis of the jaw. Int J Oral Sci 2020; 12(1):1–11. Disponível em:https://doi.org/10.1038/s41368-020-00093-2
Abtahi J, Agholme F, Aspenberg P. Prevention of osteonecrosis of the jaw by mucoperiosteal coverage in a rat model. Int. J. Oral Maxillofac. Surg 2013;42(5):632–636. Disponível em:https://doi.org/10.1016/j.ijom.2013.02.007
Singh M, Gonegandla GS. Bisphosphonate-Induced Osteonecrosis of the Jaws (BIONJ). J. Maxillofac. Oral Surg 2019; 19(2):162–167. Disponível em:https://doi.org/10.1007/s12663-019-01211-2
Soares MQS, Van Dessel J, Jacobs R, da Silva Santos PS, Cestari TM, Garlet GP, Duarte MAH, Imada TSN, Lambrichts I, Rubira-Bullen IRF. Zoledronic Acid Induces Site-Specific Structural Changes and Decreases Vascular Area in the Alveolar Bone. J Oral Maxillofac Surg 2018;76(9):1893-1901. Disponível em:https://doi.org/10.1016/j.joms.2018.03.007
Moreno-Rabié C, Lapauw L, Gaêta-Araujo H, Ferreira-Leite A, Couck W, van den Wyngaert T, Jacobs R. Radiographic predictors for MRONJ in oncologic patients undergoing tooth extraction. Sci Rep 2022; 12(1):1–11. Disponível em:https://doi.org/10.1038/s41598-022-15254-y
Otto S. Tooth extraction in patients receiving oral or intravenous bisphosphonate administration: A trigger for BRONJ development? J Craniomaxillofac Surg 2015;43(6):847-854. Disponível em:https://doi.org/10.1016/j.jcms.2015.03.039
Soutome S et al. Relationship between tooth extraction and development of medication-related osteonecrosis of the jaw in cancer patients. Sci. Rep 2021;11(1):1–8. Disponível em:https://doi.org/10.1038/s41598-021-96480-8
Schwech N, Nilsson J, Gabre P. Incidence and risk factors for medication-related osteonecrosis after tooth extraction in cancer patients—A systematic review. Clin. Exp. Dent 2023;9(1):55–65. Disponível em:https://doi.org/10.1002/cre2.698
Hallmer F. Prevalence, initiating factor, and treatment outcome of medication-related osteonecrosis of the jaw—a 4-year prospective study. Oral Surg Oral Med Oral Pathol Oral Radiol 2018;126(6):477-85. Disponível em:https://doi.org/10.1016/j.oooo.2018.08.015
Nicolatou-Galitis O et al. Periodontal disease preceding osteonecrosis of the jaw (ONJ) in cancer patients receiving antiresorptives alone or combined with targeted therapies: Report of 5 cases and literature review. Oral Surgery, Oral Surg Oral Med Oral Pathol Oral Radiol 2015;120(6):699–706. Disponível em:https://doi.org/10.1016/j.oooo.2015.08.007
Hasegawa T et al. Medication-related osteonecrosis of the jaw after tooth extraction in cancer patients: a multicenter retrospective study. Osteoporos Int 2019;30(1):231–239. Disponível em: https://doi.org/10.1007/s00198-018-4746-8
Soutome S et al. Factors affecting development of medication-related osteonecrosis of the jaw in cancer patients receiving high-dose bisphosphonate or denosumab therapy: Is tooth extraction a risk factor? PLoS ONE 2018;13(7): e0201343. Disponível em:https://doi.org/10.1371/journal.pone.0201343
Kuehn S, Scariot R, Elsalanty M. Medication-Related Osteonecrosis: Why the Jawbone?. Dent J (Basel). 2023;11(5):109. Disponível em: https://doi.org/10.3390/dj11050109
Otto S et al. Bisphosphonate-Related Osteonecrosis of the Jaw: Is pH the Missing Part in the Pathogenesis Puzzle? J Oral Maxillofac Surg 2010;68(5):1158–61. Disponível em:https://doi.org/10.1016/j.joms.2009.07.079
Hallmer F, Bjarnadottir O, Götrick B, Malmström P, Andersson G. Incidence of and risk factors for medication-related osteonecrosis of the jaw in women with breast cancer with bone metastasis: a population-based study. Oral Surg Oral Med Oral Pathol Oral Radiol. 2020;130(3):252-257. https://doi.org/10.1016/j.oooo.2020.04.808
Tsurushima H, Kokuryo S, Sakaguchi O, Tanaka J, Tominaga K. Bacterial promotion of bisphosphonate-induced osteonecrosis in Wistar rats. Int. J. Oral Maxillofac. Surg 2013;42(11):1481–1487. Disponível em:https://doi.org/10.1016/j.ijom.2013.06.011
Soundia A et al. Osteonecrosis of the jaws (ONJ) in mice after extraction of teeth with periradicular disease. Bone 2016; 90:133–141. Disponível em:https://doi.org/10.1016/j.bone.2016.06.011
Hadaya D, Soundia A, Gkouveris I, Dry SM, Aghaloo TL, Tetradis S. Development of Medication-Related Osteonecrosis of the Jaw After Extraction of Teeth With Experimental Periapical Disease. J Oral Maxillofac Surg 2019;77(1):71–86. Disponível em:https://doi.org/10.1016/j.joms.2018.08.010
Mozzati M, Arata V, Gallesio G. Tooth extraction in osteoporotic patients taking oral bisphosphonates. Osteoporos Int. 2013;24(5):1707-1712. Disponível em: https://doi.org/10.1007/s00198-012-2239-8
López-Jornet P, Camacho-Alonso F, Martínez-Canovas A, Molina-Miano F, Gómez-García F, Vicente-Ortega V. Perioperative antibiotic regimen in rats treated with pamidronate plus dexamethasone and subjected to dental extraction: A study of the changes in the jaws. J Oral Maxillofac Surg 2011;69(10):2488–93. Disponível em: https://doi.org/10.1016/j.joms.2011.02.059
Minamisako MC, Ribeiro GH, Lisboa ML, Cordeiro MRM, Grando LJ. Medication-Related Osteonecrosis of Jaws: A Low-Level Laser Therapy and Antimicrobial Photodynamic Therapy Case Approach. Case Rep Dent 2016;6267406. Disponível em: https://doi.org/10.1155/2016/6267406
Tartaroti NC, Marques MM, Naclério-Homem MDG, Migliorati CA, Zindel Deboni MC. Antimicrobial photodynamic and photobiomodulation adjuvant therapies for prevention and treatment of medication-related osteonecrosis of the jaws: Case series and long-term follow-up. Photodiagnosis Photodyn Ther. 2020;29:101651. Disponível em:https://doi.org/10.1016/j.pdpdt.2020.101651
Ervolino E et al. Effectiveness of antimicrobial photodynamic therapy mediated by butyl toluidine blue in preventing medication-related osteonecrosis of the jaws in rats. Photodiagnosis Photodyn Ther 2022;40. Disponível em:https://doi.org/10.1016/j.pdpdt.2022.103172
Silva PGB et al. Photodynamic therapy and photobiomodulation therapy in zoledronic acid-induced osteonecrosis in rats. Photodiagnosis Photodyn Ther 2022;38. Disponível em:https://doi.org/10.1016/j.pdpdt.2022.102889
Aghaloo TL et al. Periodontal disease and bisphosphonates induce osteonecrosis of the jaws in the rat. J Bone Miner Res. 2011;26(8):1871-1882. Disponível em:https://doi.org/10.1002/jbmr.379
Hansen T, Kunkel M, Springer E, Walter C, Weber A, Siegel E, Kirkpatrick CJ. Actinomycosis of the jaws - Histopathological study of 45 patients shows significant involvement in bisphosphonate-associated osteonecrosis and infected osteoradionecrosis. Virchows Archiv 2007;451(6):1009–1017. Disponível em:https://doi.org/10.1007/s00428-007-0516-2
Dayisoylu EH, Üngör C, Tosun E, Ersöz S, Duman MK, Taskesen F, Åženel FÇ. Does an alkaline environment prevent the development of bisphosphonate-related osteonecrosis of the jaw? An experimental study in rats. Oral Surgery, Oral Surg Oral Med Oral Pathol Oral Radiol, 2014;117(3):329–334. Disponível em:https://doi.org/10.1016/j.oooo.2013.11.490
Lesclous P et al. Bisphosphonate-associated osteonecrosis of the jaw: A key role of inflammation? Bone 2009; 45(5):843–852. Disponível em:https://doi.org/10.1016/j.bone.2009.07.011
Kobayashi Y et al. Zoledronic acid delays wound healing of the tooth extraction socket, inhibits oral epithelial cell migration, and promotes proliferation and adhesion to hydroxyapatite of oral bacteria, without causing osteonecrosis of the jaw, in mice. J. Bone Miner. Metab 2010;28(2):165–175. Disponível em:https://doi.org/10.1007/s00774-009-0128-9
Pazianas M. Osteonecrosis of the Jaw and the Role of Macrophages, JNCI 2011;103(3):232–240. Disponível em:https://doi.org/10.1093/jnci/djq516
Wolf AM, Rumpold H, Tilg H, Gastl G, Gunsilius E, Wolf D. The effect of zoledronic acid on the function and differentiation of myeloid cells. Haematologica 2006;91(9):1165-1171. Disponível em:https://pubmed.ncbi.nlm.nih.gov/16956814/
Kinane DF, Stathopoulou PG, Papapanou PN. Periodontal diseases. Nat Rev Dis Primers 2017;3:17038. Disponível em:https://doi.org/10.1038/nrdp.2017.38
Kwoen MJ, Park JH, Kim KS, et al. Association between periodontal disease, tooth extraction, and medication-related osteonecrosis of the jaw in women receiving bisphosphonates: A national cohort-based study. J Periodontol 2023;94(1):98-107. Disponível em:https://doi.org/10.1002/JPER.21-0611
Song M, Alshaikh A, Kim T, et al. Preexisting Periapical Inflammatory Condition Exacerbates Tooth Extraction-induced Bisphosphonate-related Osteonecrosis of the Jaw Lesions in Mice. J Endod 2016;42(11):1641-46. Disponível em:https://doi.org/10.1016/j.joen.2016.07.020
Bagan J, Sheth CC, Soria JM, Margaix M, Bagan L. Bisphosphonates-related osteonecrosis of the jaws: a preliminary study of salivary interleukins. J Oral Pathol Med 2012;42(5). Disponível em:https://doi.org/10.1111/jop.12021
Bagan J et al. Interleukin-6 concentration changes in plasma and saliva in bisphosphonate-related osteonecrosis of the jaws. Oral Dis 2014;20:446-52. Disponível em: https://doi.org/10.1111/odi.12150
Soma T, Iwasaki R, Sato Y et al. Tooth extraction in mice administered zoledronate increases inflammatory cytokine levels and promotes osteonecrosis of the jaw. J Bone Miner Metab 2021;39:372. Disponível em:https://doi.org/10.1007/s00774-020-01174-2
Aguirre JI, Castillo EJ, Kimmel DB. Biologic and pathologic aspects of osteocytes in the setting of medication-related osteonecrosis of the jaw (MRONJ). Bone 2021;153(352):1–37. Disponível em:https://doi.org/10.1016/j.bone.2021.116168
Kuroshima S, Nakajima K, Sasaki M et al. Systemic administration of quality- and quantity-controlled PBMNCs reduces bisphosphonate-related osteonecrosis of jaw-like lesions in mice. Stem Cell Res Ther 2019;10(209). Disponível em:https://doi.org/10.1186/s13287-019-1308-8
Hayano H, Kuroshima S, Sasaki M, Tamaki S, Inoue M, Ishisaki A, Sawase T. Distinct immunopathology in the early stages between different antiresorptives-related osteonecrosis of the jaw-like lesions in mice. Bone 2020;135:115308. Disponível em:https://doi.org/10.1016/j.bone.2020.115308
Aghaloo T, Hazboun R, Tetradis S. Pathophysiology of Osteonecrosis of the Jaws. Oral Maxillofacial Surg Clin N Am 2015;27(4): 489–496. https://doi.org/10.1016/j.coms.2015.06.001
Chrysanthakopoulos NA. Reasons for extraction of permanent teeth in Greece: a five-year follow-up study. Int Dent J 2011;61(1):19-24. Disponível em:https://doi.org/10.1111/j.1875-595X.2011.00004.x
Downloads
Published
Issue
Section
License
Copyright (c) 2023 Revista da Faculdade de Odontologia - UPF

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

This work is licensed under aCreative Commons Atribuição-NãoComercial-SemDerivações 4.0 Internacional.
						