Supplementary Files
Keywords
antiresorptive medicines
bisphosphonates
cancer
denosumab
dental extractions
dentistry
neoplasms
oncology
osteonecrosis
osteoporosis
How to Cite
Abstract
Background: Drug-induced osteonecrosis of the jaw (ONJ) is a serious complication associated with prolonged use of antiresorptive (e.g., bisphosphonates and denosumab) and antiangiogenic drugs (e.g., bevacizumab and sunitinib) in patients with osteoporosis or cancer. With this situation, a progressive infection of the maxillary or mandibular bone and later an avascular necrosis of the bone occurs. The incidence of ONJ is higher in people with cancer who are frequently received high doses of antiresorptive drugs intravenously. Risk factors associated with antiresorptive or antiangiogenic therapy have been identified to possibly contributing to the onset of ONJ. Purpose: To review and analyze the current available therapeutic options to treat at-risk patients or who already have ONJ. Methods: In this integrative review of the literature, publications were searched in the ScienceDirect, PubMed, SciELO, and ResearchGate databases between 2003 and 2020. The search terms were “bisphosphonate-associated maxillary osteonecrosis,” “maxillary osteonecrosis associated with medication,” and “maxillary osteonecrosis.” Results: 64 articles were selected in which extractions are identified as the main risk factor for developing ONJ (52 % to 61 %). A second factor identified was the spontaneous appearance of bone necrosis lesions. Conclusions: It is important to implement preventive measures in medical and dental care before, during, and after antiresorptive and antiangiogenic treatments to minimize the risks of ONJ in patients.
Hughes JP, Baron R, Buckland DH, Cooke MA, Craig JD, Duffield DP, Grosart AW, Parkes PW, Porter A. Phosphorus necrosis of the jaw: a present-day study. Br J Ind Med. 1962 Apr; 19(2): 83-99. http://doi.org/10.1136/oem.19.2.83
Marx RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg. 2003 Sep; 61(9): 1115-1117. http://doi.org/10.1016/s0278-2391(03)00720-1
Regaud C. Sur la necrose des os atteints par un processus cancereux et traites par les radiations. Compt Rend Soc Biol. 1922; 87: 427-629.
Ewing J. Radiation osteitis. Acta Radiol. 1926; 6(1-6): 399-412. https://doi.org/10.3109/00016922609139503
Kanthak FF. X-Ray irradiation and osteonecrosis of the jaws. J Am Dent Assoc. 1941; 28(12): 1925-1929. https://doi.org/10.14219/jada.archive.1941.0301
Marx RE. Osteoradionecrosis: A new concept of its pathophysiology. J Oral Maxillofac Surg. 1983; 41(5): 283-288. https://doi.org/10.1016/0278-2391(83)90294-X
Ruggiero SL, Dodson TB, Fantasia J, Goodday R, Aghaloo T, Mehrotra B, O'Ryan F, American Association of Oral and Maxillofacial Surgeons. American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw-2014 update. J Oral Maxillofac Surg. 2014 Oct; 72(10): 1938-1956. https://doi.org/10.1016/j.joms.2014.04.031
Ng EW, Adamis AP. Targeting angiogenesis, the underlying disorder in neovascular age-related macular degeneration. Can J Ophthalmol. 2005 Jun; 40(3): 352-368. https://doi.org/10.1016/S0008-4182(05)80078-X
llahi M. Long term bisphosphonate use in osteoporotic patients; a step forward, two steps back. J Pharm Pharmaceut Sci. 2012 15(2): 305. https://doi.org/10.18433/J3RK5J
Allen MR, Ruggiero SL. Higher bone matrix density exists in only a subset of patients with bisphosphonate-related osteonecrosis of the jaw. J Oral Maxillofac Surg. 2009 Jul; 67(7): 1373-1377. https://doi.org/10.1016/j.joms.2009.03.048
Migliorati CA, Brennan MT, Peterson DE. Medication-related osteonecrosis of the jaws. J Natl Cancer Inst Monogr. 2019 Aug 1; 2019(53): lgz009. https://doi.org/10.1093/jncimonographs/lgz009
Choi WS, Lee JI, Yoon HJ, Min CK, Lee SH. Medication-related osteonecrosis of the jaw: a preliminary retrospective study of 130 patients with multiple myeloma. Maxillofac Plast Reconstr Surg. 2017 Jan 5; 39(1): 1. https://doi.org/10.1186/s40902-016-0099-4
MedlinePlus. Inyección de Denosumab. Washington, DC: Biblioteca Nacional de Medicina; 2019 ago 18. https://medlineplus.gov/spanish/druginfo/meds/a610023-es.html
Wang Y, Fei D, Vanderlaan M, Song A. Biological activity of bevacizumab, a humanized anti-VEGF antibody in vitro. Angiogénesis. 2004; 7(4): 335-345. https://doi.org/10.1007/s10456-004-8272-2
Fujita K, Sano D, Kimura M, Yamashita Y, Kawakami M, Ishiguro Y, Nishimura G, Matsuda H, Tsukuda M. Anti-tumor effects of bevacizumab in combination with paclitaxel on head and neck squamous cell carcinoma. Oncol Rep. 2007 Jul; 18(1): 47-51.
Chung BL, Toth MJ, Kamaly N, Sei YJ, Becraft J, Mulder WJ, Fayad ZA, Farokhzad OC, Kim Y, Langer R. Nanomedicines for endothelial disorders. Nano Today. 2015 Dec 1; 10(6): 759-776. https://doi.org/10.1016/j.nantod.2015.11.009
Ruggiero SL, Fantasia J, Carlson E. Bisphosphonate-related osteonecrosis of the jaw: background and guidelines for diagnosis, staging and management. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006 Oct; 102(4): 433-441. https://doi.org/10.1016/j.tripleo.2006.06.004
Sarin J, DeRossi SS, Akintoye SO. Updates on bisphosphonates and potential pathobiology of bisphosphonate-induced jaw osteonecrosis. Oral Dis. 2008 Apr; 14(3): 277-285. https://doi.org/10.1111/j.1601-0825.2007.01381.x
Peer A, Khamaisi M. Diabetes as a risk factor for medication-related osteonecrosis of the jaw. J Dent Res. 2015 Feb; 94(2): 252-260. https://doi.org/10.1177/0022034514560768
Chang J, Hakam AE, McCauley LK. Current understanding of the pathophysiology of osteonecrosis of the jaw. Curr Osteoporos Rep. 2018 Oct; 16(5): 584-595. https://doi.org/10.1007/s11914-018-0474-4
Khan AA, Morrison A, Hanley DA, Felsenberg D, McCauley LK, O'Ryan F, Reid IR, Ruggiero SL, Taguchi A, Tetradis S, Watts NB, Brandi ML, Peters E, Guise T, Eastell R, Cheung AM, Morin SN, Masri B, Cooper C, Morgan SL, Obermayer-Pietsch B, Langdahl BL, Al Dabagh R, Davison KS, Kendler DL, Sándor GK, Josse RG, Bhandari M, El Rabbany M, Pierroz DD, Sulimani R, Saunders DP, Brown JP, Compston J; International Task Force on Osteonecrosis of the Jaw. Diagnosis and management of osteonecrosis of the jaw: a systematic review and international consensus. J Bone Miner Res. 2015 Jan; 30(1): 3-23. https://doi.org/10.1002/jbmr.2405
Sedghizadeh PP, Kumar SK, Gorur A, Schaudinn C, Shuler CF, Costerton JW. Identification of microbial biofilms in osteonecrosis of the jaws secondary to bisphosphonate therapy. J Oral Maxillofac Surg. 2008 Apr; 66(4): 767-775. https://doi.org/10.1016/j.joms.2007.11.035
Sedghizadeh PP, Kumar SK, Gorur A, Schaudinn C, Shuler CF, Costerton JW. Microbial biofilms in osteomyelitis of the jaw and osteonecrosis of the jaw secondary to bisphosphonate therapy. J Am Dent Assoc. 2009 Oct; 140(10): 1259-1265. https://doi.org/10.14219/jada.archive.2009.0049
Kumar SK, Gorur A, Schaudinn C, Shuler CF, Costerton JW, Sedghizadeh PP. The role of microbial biofilms in osteonecrosis of the jaw associated with bisphosphonate therapy. Curr Osteoporos Rep. 2010 Mar; 8(1):40-8. https://doi.org/10.1007/s11914-010-0008-1
Kalyan S, Wang J, Quabius ES, Huck J, Wiltfang J, Baines JF, Kabelitz D. Systemic immunity shapes the oral microbiome and susceptibility to bisphosphonate-associated osteonecrosis of the jaw. J Transl Med. 2015 Jul 4; 13: 212. https://doi.org/10.1186/s12967-015-0568-z
Krimmel M, Ripperger J, Hairass M, Hoefert S, Kluba S, Reinert S. Does dental and oral health influence the development and course of bisphosphonate-related osteonecrosis of the jaws (BRONJ)? Oral Maxillofac Surg. 2014 Jun; 18(2): 213-218. https://doi.org/10.1007/s10006-013-0408-3
Khosla S, Burr D, Cauley J, Dempster DW, Ebeling PR, Felsenberg D, Gagel RF, Gilsanz V, Guise T, Koka S, McCauley LK, McGowan J, McKee MD, Mohla S, Pendrys DG, Raisz LG, Ruggiero SL, Shafer DM, Shum L, Silverman SL, Van Poznak CH, Watts N, Woo SB, Shane E; American Society for Bone and Mineral Research. Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2007 Oct; 22(10): 1479-1491. https://doi.org/10.1359/jbmr.0707onj
Khan A, Morrison A, Cheung A, Hashem W, Compston J. Osteonecrosis of the jaw (ONJ): diagnosis and management in 2015. Osteoporos Int. 2016 Mar; 27(3): 853-859. https://doi.org/10.1007/s00198-015-3335-3
Ruggiero SL. Diagnosis and staging of medication-related osteonecrosis of the jaw. Oral Maxillofac Surg Clin North Am. 2015 Nov; 27(4): 479-487. https://doi.org/10.1016/j.coms.2015.06.008
Marx RE, Sawatari Y, Fortin M, Broumand V. Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg. 2005 Nov; 63(11): 1567-1575. https://doi.org/10.1016/j.joms.2005.07.010
Khamaisi M, Regev E, Yarom N, Avni B, Leitersdorf E, Raz I, Elad S. Possible association between diabetes and bisphosphonate-related jaw osteonecrosis. J Clin Endocrinol Metab. 2007 Mar; 92(3): 1172-1175. https://doi.org/10.1210/jc.2006-2036
Junquera LM, Martín-Granizo R. Diagnóstico, prevención y tratamiento de la osteonecrosis de los maxilares por bisfosfonatos: Recomendaciones de la Sociedad Española de Cirugía Oral y Maxilofacial (SECOM). Rev Esp Cirug Oral Maxilofac. 2008 jun; 30(3): 145-156.
Kuroshima S, Sasaki M, Sawase T. Medication-related osteonecrosis of the jaw: A literature review. J Oral Biosci. 2019 Jun; 61(2): 99-104. https://doi.org/10.1016/j.job.2019.03.005
Yamazaki T, Yamori M, Ishizaki T, Asai K, Goto K, Takahashi K, Nakayama T, Bessho K. Increased incidence of osteonecrosis of the jaw after tooth extraction in patients treated with bisphosphonates: a cohort study. Int J Oral Maxillofac Surg. 2012 Nov; 41(11): 1397-1403. https://doi.org/10.1016/j.ijom.2012.06.020
Thumbigere-Math V, Michalowicz BS, Hodges JS, Tsai ML, Swenson KK, Rockwell L, Gopalakrishnan R. Periodontal disease as a risk factor for bisphosphonate-related osteonecrosis of the jaw. J Periodontol. 2014 Feb; 85(2): 226-233. https://doi.org/10.1902/jop.2013.130017
Choi WS, Lee JI, Yoon HJ, Min CK, Lee SH. Medication-related osteonecrosis of the jaw: a preliminary retrospective study of 130 patients with multiple myeloma. Maxillofac Plast Reconstr Surg. 2017 Jan 5; 39(1): 1. https://doi.org/10.1186/s40902-016-0099-4
Saad F, Brown JE, Van Poznak C, Ibrahim T, Stemmer SM, Stopeck AT, Diel IJ, Takahashi S, Shore N, Henry DH, Barrios CH, Facon T, Senecal F, Fizazi K, Zhou L, Daniels A, Carrière P, Dansey R. Incidence, risk factors, and outcomes of osteonecrosis of the jaw: integrated analysis from three blinded active-controlled phase III trials in cancer patients with bone metastases. Ann Oncol. 2012 May; 23(5): 1341-1347. https://doi.org/10.1093/annonc/mdr435
Saad F, Brown JE, Van Poznak C, Ibrahim T, Stemmer SM, Stopeck AT, Diel IJ, Takahashi S, Shore N, Henry DH, Barrios CH, Facon T, Senecal F, Fizazi K, Zhou L, Daniels A, Carrière P, Dansey R. Incidence, risk factors, and outcomes of osteonecrosis of the jaw: integrated analysis from three blinded active-controlled phase III trials in cancer patients with bone metastases. Ann Oncol. 2012 May; 23(5): 1341-1347. https://doi.org/10.1093/annonc/mdr435
Dodson TB. The Frequency of medication-related osteonecrosis of the jaw and its associated risk factors. Oral Maxillofac Surg Clin North Am. 2015 Nov; 27(4): 509-516. https://doi.org/10.1016/j.coms.2015.06.003
Boquete-Castro A, Gómez-Moreno G, Calvo-Guirado JL, Aguilar-Salvatierra A, Delgado-Ruiz RA. Denosumab and osteonecrosis of the jaw. A systematic analysis of events reported in clinical trials. Clin Oral Implants Res. 2016 Mar; 27(3): 367-375. https://doi.org/10.1111/clr.12556
Nicolatou-Galitis O, Schiødt M, Mendes RA, Ripamonti C, Hope S, Drudge-Coates L, Niepel D, Van den Wyngaert T. Medication-related osteonecrosis of the jaw: definition and best practice for prevention, diagnosis, and treatment. Oral Surg Oral Med Oral Pathol Oral Radiol. 2019 Feb; 127(2): 117-135. https://doi.org/10.1016/j.oooo.2018.09.008
Ünsal G, Orhan K, What do we expect to visualize on the radiographs of mronj patients? J Exp Clin Med 2021; 38(S2): 98-103 https://doi.org/10.52142/omujecm.38.si.dent.4
Advisory Task Force on Bisphosphonate-Related Osteonecrosis of the Jaws. American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg. 2007; 65:369-376. https://doi.org/10.1016/j.joms.2006.11.003
Ripamonti CI, Maniezzo M, Campa T, et al. Decreased occurrence of osteonecrosis of the jaw after implementation of dental preventive measures in solid tumor patients with bone metastases treated with bisphosphonates. The experience of the National Cancer Institute of Milan. Ann Oncol. 2009; 20(1): 137-145. https://doi.org/10.1093/annonc/mdn526
Dimopoulos MA, Kastritis E, Bamia C, et al. Reduction of osteonecrosis of the jaw (ONJ) after implementation of preventive measures in patients with multiple myeloma treated with zoledronic acid. Ann Oncol. 2008 20(1): 117-120. https://doi.org/10.1093/annonc/mdn554
Bonacina R, Mariani U, Villa F, et al. Preventive strategies and clinical implications for bisphosphonate-related osteonecrosis of the jaw: a review of 282 patients. J Can Dent Assoc. 2011; 77: b147.
American Dental Association Council on Scientific Affairs. Dental management of patients receiving oral bisphosphonate therapy. Expert panel recommendations. J Am Dent Assoc. 2006; 137: 1144-1150. https://doi.org/10.14219/jada.archive.2006.0355
National Health Service Education for Scotland. Oral health management of patients at risk of medication-related osteonecrosis of the jaw: Dental clinical guidance. Scotland: SDCEP; 2017. https://www.sdcep.org.uk/published-guidance/medication-related-osteonecrosis-of-the-jaw/
Beth-Tasdogan NH, Mayer B, Hussein H, Zolk O. Interventions for managing medication-related osteonecrosis of the jaw. Cochrane Database Syst. Rev. 2017; 10. https://doi.org/10.1002/14651858.cd012432.pub2
Wan JT, Sheeley DM, Somerman MJ, Lee JS. Mitigating osteonecrosis of the jaw (ONJ) through preventive dental care and understanding of risk factors. Bone Res. 2020; 8(1). https://doi.org/10.1038/s41413-020-0088-1
Song M. Dental care for patients taking antiresorptive drugs: a literature review. Rest Dent Endod. 2019; 1:44(4): e42. https://doi.org/10.5395/rde.2019.44.e42
Dhesy-Thind S, Fletcher G, Blanchette P, Clemons M, Dillmon M, Frank E, et al. Use of adjuvant bisphosphonates and other bone-modifying agents in breast cancer: a Cancer Care Ontario and American Society of Clinical Oncology Clinical Practice Guideline. J Clin Onc. 2017; 35(18): 2062-2081. https://doi.org/10.1200/jco.2016.70.7257
Yoshiga D, Yoshioka I, Habu M, Sasaguri M, Tominaga K. Effective ancillary role and long-term course of daily or weekly teriparatide treatment on refractory medication-related osteonecrosis of the jaw (MRONJ): a clinical case series. Brit J Oral Maxillofac Surg. 2021. https://doi.org/10.1016/j.bjoms.2021.10.004
Anabtawi, M, Tweedale, H, Mahmood, H. The role, efficacy, and outcome measures for teriparatide use in the management of medication-related osteonecrosis of the jaw. Int J Oral Maxillofac Surg. 2020; https://doi.org/10.1016/j.ijom.2020.07.021
Javelot M-J, et al. Rituximab as a trigger factor of medication-related osteonecrosis of the jaw. A case report. J Stomatol Oral Maxillofac Surg. 2019. https://doi.org/10.1016/j.jormas. 2019.06.009
Sacco R, Shah S, Leeson R, Moraschini V, et al. Osteonecrosis and osteomyelitis of the jaw associated with tumour necrosis factor-alpha (TNF-α) inhibitors: a systematic review. Br J Oral Maxillofac Surg. 2020; 58: 25-33. https://doi.org/10.1016/j.bjoms.2019.09.023
Brijs K, Miclotte I, Vermeire S, Darche V, Politis C. Osteonecrosis of the jaw in patients with inflammatory bowel disease treated with tumour necrosis factor alpha inhibitors. Int J Oral Maxillofac Surg. 2020; 49: 317-324. https://doi.org/10.1016/j.ijom.2019.08.007
Fleissig Y, Regev E, Lehman H. Sunitinib related osteonecrosis of jaw: a case report. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012; 113: e1-e3. https://doi.org/10.1016/j.tripleo.2011.06.023
Mauceri R, Panzarella V, Morreale I, Campisi G. Medication-related osteonecrosis of the jaw in a cancer patient receiving lenvatinib, Case Report. Int J Oral Maxillofac Surg. 2019; 48: 1530-1532. https://doi.org/10.1016/j.ijom.2019.07.010
Zarringhalam P, Brizman E, Shakib K. Medication-related osteonecrosis of the jaw associated with aflibercept. Br J Oral Maxillofac Surg. 2017; 55: 314-315. https://doi.org/10.1016/j.bjoms.2016.11.315
Kim DW, Jung YS, Park HS, Jung HD. Osteonecrosis of the jaw related to everolimus: a case report. Br J Oral Maxillofac Surg. 2013; 51: 302-304. https://doi.org/10.1016/j.bjoms.2013.09.008
Akkach S, Shukla L, Morgan D. Everolimus-induced osteonecrosis of the jaw in the absence of bisphosphonates: a case report. Br J Oral Maxillofac Surg. 2019; 57: 688-690. https://doi.org/10.1016/j.bjoms.2019.05.017
Komatani T, Sonobe J, et al. Methotrexate-related osteonecrosis of the jaw: Report of two cases. J Oral Maxillofac Surg Med Pathol. 2017; 29: 546-549.
Sato T, et al. Osteonecrosis of the jaw with pancytopenia in a patient receiving methotrexate for rheumatoid arthritis without antiresorptive or antiangiogenic agents: Report of a case. J Oral Maxillofac Surg Med Pathol. 2018; 30: 418-421.
King R, et al. Medication-related osteonecrosis of the jaw unrelated to bisphosphonates and denosumab-a review. Oral Surg Oral Med Oral Pathol Oral Radiol. 2019; 127: 289-299. https://doi.org/10.1016/j.oooo.2018.11.012
This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright (c) 2022 Odel Chediak-Barbur