Medication-Related Osteonecrosis of the Jaw in Women with Breast Cancer: A Narrative Review
Main Article Content
Abstract
Breast cancer remains a leading cause of premature death in women globally, spurring the adoption of comprehensive treatment approaches. Despite therapeutic progress, significant challenges persist for patients, especially those with advanced breast cancer prone to bone metastases. Bisphosphonates and Denosumab are key bone-modifying agents used to target bone metabolism, reduce metastatic risk, and enhance adjuvant therapy efficacy in early-stage breast cancer. However, using these agents carries risks, including adverse events such as osteonecrosis of the jaw. Due to the impact of these drugs on the jaw bone, this condition is now known as Medication-related osteonecrosis of the jaw (MRONJ). The aim is to provide a comprehensive investigation into MRONJ in the context of breast cancer treatment, with a specific focus on the effects of antiresorptive drugs such as Bisphosphonates and Denosumab. The objective of this article is to review clinical and radiographic manifestations, evaluate the pathophysiology, determine risk factors and incidence and provide guidelines to healthcare professionals for the management and treatment of MRONJ.
Medication-related osteonecrosis of the jaw is a condition that occurs in breast cancer patients due to various risk factors. The treatment of MRONJ depends on the different stages of the condition. Recent research suggests that optimal management of patients prone to MRONJ necessitates a multidisciplinary approach, and the dentist is one of the team members who play a crucial role in patient care by assessing modifiable risk factors, establishing follow-up protocols, and maintaining open communication with oncologists. Preventive measures should be implemented before and during treatment with antiresorptive drugs. However, despite increased awareness, many doctors and dentists still have a limited understanding of MRONJ. Therefore, this research provides practical guidelines for preventing, managing, and treating MRONJ in breast cancer patients based on currently available literature. Dentists should follow specific protocols for patients undergoing antiresorptive therapy. The primary goals are to prevent MRONJ and maintain patients' quality of life. Therefore, dental students and specialists must stay updated and consider this side effect.
Article Details
How to Cite
ČEBATARIŪNIENĖ, Alina; RASEKHI, Niyosha.
Medication-Related Osteonecrosis of the Jaw in Women with Breast Cancer: A Narrative Review.
Medical Research Archives, [S.l.], v. 12, n. 12, dec. 2024.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6194>. Date accessed: 06 jan. 2025.
doi: https://doi.org/10.18103/mra.v12i12.6194.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Slepicka PF, Cyrill SL, dos Santos CO. Pregnancy and Breast Cancer: Pathways to Understand Risk and Prevention. Trends Mol Med. 2019;25(10):866-881. doi:10.1016/j.molmed.2019.06.003
2. Van Acker HH, Anguille S, Willemen Y, Smits EL, Van Tendeloo VF. Bisphosphonates for cancer treatment: Mechanisms of action and lessons from clinical trials. Pharmacol Ther. 2016;158:24-40. doi:10.1016/j.pharmthera.2015.11.008
3. 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. doi:10.1016/j.oooo.2020.04.808
4. Shapiro CL. Bone-modifying Agents (BMAs) in Breast Cancer. Clin Breast Cancer. 2021;21(5):e618-e630. doi:10.1016/j.clbc.2021.04.009
5. Goldvaser H, Amir E. Role of Bisphosphonates in Breast Cancer Therapy. Curr Treat Options Oncol. 2019;20(4). doi:10.1007/s11864-019-0623-8
6. Reyes C, Hitz M, Prieto-Alhambra D, Abrahamsen B. Risks and Benefits of Bisphosphonate Therapies. J Cell Biochem. 2016;117(1):20-28. doi:10.1002/jcb.25266
7. Mirelli C, Marino S, Bovio A, et al. Medication-Related Osteonecrosis of the Jaw in Dental Practice: A Retrospective Analysis of Data from the Milan Cohort. Dent J (Basel). 2022;10(5). doi:10.3390/dj10050089
8. Mauceri R, Coppini M, Attanasio M, et al. MRONJ in breast cancer patients under bone modifying agents for cancer treatment-induced bone loss (CTIBL): a multi-hospital-based case series. BMC Oral Health. 2023;23(1). doi:10.1186/s12903-023-02732-6
9. Boston B, Ipe D, Capitanescu B, et al. Medication-related osteonecrosis of the jaw: A disease of significant importance for older patients. J Am Geriatr Soc. 2023;71(8):2640-2652. doi:10.1111/jgs.18414
10. 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. Supportive Care in Cancer. 2020;28(5):2265-2271. doi:10.1007/s00520-019-05044-0
11. Kashyap D, Pal D, Sharma R, et al. Global Increase in Breast Cancer Incidence: Risk Factors and Preventive Measures. Biomed Res Int. 2022;2022. doi:10.1155/2022/9605439
12. Dall GV, Britt KL. Estrogen effects on the mammary gland in early and late life and breast cancer risk. Front Oncol. 2017;7(MAY). doi:10.3389/fonc.2017.00110
13. Sinn HP, Kreipe H. A brief overview of the WHO classification of breast tumors, 4th edition, focusing on issues and updates from the 3rd edition. Breast Care. 2013;8(2):149-154. doi:10.1159/000350774
14. Barzaman K, Karami J, Zarei Z, et al. Breast cancer: Biology, biomarkers, and treatments. Int Immunopharmacol. 2020;84. doi:10.1016/j.intimp.2020.106535
15. 14. Otto S ASFRESROBETMPCEMM (Kaunas).. Infection as an Important Factor in Medication-Related Osteonecrosis of the Jaw (MRONJ). Published online May 2021.
16. Tsang JYS, Tse GM. Molecular Classification of Breast Cancer.; 2019. http://journals.lww.com/anatomicpathology
17. Trayes KP, Cokenakes SEH. Breast Cancer Treatment. Am Fam Physician. 2021;104(2):171-178.
18. He Z, Chen Z, Tan M, et al. A review on methods for diagnosis of breast cancer cells and tissues. Cell Prolif. 2020;53(7). doi:10.1111/cpr.12822
19. Gradishar WJ, Anderson BO, Abraham J, et al. Breast cancer, version 3.2020. JNCCN Journal of the National Comprehensive Cancer Network. 2020;18(4):452-478. doi:10.6004/jnccn.2020.0016
20. Suarez-Almazor ME, Herrera R, Lei X, Chavez-MacGregor M, Zhao H, Giordano SH. Survival in older women with early stage breast cancer receiving low-dose bisphosphonates or denosumab. Cancer. 2020;126(17):3929-3938. doi:10.1002/cncr.33035
21. Gnant M, Pfeiler G, Dubsky PC, et al. Adjuvant denosumab in breast cancer (ABCSG-18): A multicentre, randomised, double-blind, placebo-controlled trial. The Lancet. 2015;386(9992):433-443. doi:10.1016/S0140-6736(15)60995-3
22. Coleman R, Finkelstein DM, Barrios C, et al. Adjuvant denosumab in early breast cancer (D-CARE): an international, multicentre, randomised, controlled, phase 3 trial. Lancet Oncol. 2020;21(1):60-72. doi:10.1016/S1470-2045(19)30687-4
23. Fu PA, Shen CY, Yang S R, et al. Long-term use of denosumab and its association with skeletal-related events and osteonecrosis of the jaw. Sci Rep. 2023;13(1). doi:10.1038/s41598-023-35308-z
24. O’Carrigan B, Wong MHF, Willson ML, Stockler MR, Pavlakis N, Goodwin A. Bisphosphonates and other bone agents for breast cancer. Cochrane Database of Systematic Reviews. 2017;2017(10). doi:10.1002/14651858.CD003474.pub4
25. Poon M, Zeng L, Zhang L, et al. Incidence of Skeletal-related Events Over Time from Solid Tumour Bone Metastases Reported in Randomised Trials Using Bone-modifying Agents. Clin Oncol. 2013;25(7):435-444. doi:10.1016/j.clon.2013.03.003
26. Coleman R, Hadji P, Body JJ, et al. Bone health in cancer: ESMO Clinical Practice Guidelines †. Annals of Oncology. 2020;31(12):1650-1663. doi:10.1016/j.annonc.2020.07.019
27. Poznak C Van, Somerfield MR, Barlow WE, et al. JOURNAL OF CLINICAL ONCOLOGY Role of Bone-Modifying Agents in Metastatic Breast Cancer: An American Society of Clinical Oncology-Cancer Care Ontario Focused Guideline Update. J Clin Oncol. 2017;35:3978-3986. doi:10.1200/JCO
28. Anastasilakis AD, Pepe J, Napoli N, et al. Osteonecrosis of the Jaw and Antiresorptive Agents in Benign and Malignant Diseases: A Critical Review Organized by the ECTS. Journal of Clinical Endocrinology and Metabolism. 2022;107(5):1441-1460. doi:10.1210/clinem/dgab888
29. Dalle Carbonare L, Mottes M, Valenti MT. Medication-related osteonecrosis of the jaw (MRONJ): Are antiresorptive drugs the main culprits or only accomplices? the triggering role of vitamin d deficiency. Nutrients. 2021;13(2):1-14. doi:10.3390/nu13020561
30. Ruggiero SL, Dodson TB, Aghaloo T, Carlson ER, Ward BB, Kademani D. American Association of Oral and Maxillofacial Surgeons’ Position Paper on Medication-Related Osteonecrosis of the Jaws—2022 Update. Journal of Oral and Maxillofacial Surgery. 2022;80(5):920-943. doi:10.1016/j.joms.2022.02.008
31. Dunphy L, Salzano G, Gerber B, Graystone J. Medication-related osteonecrosis (MRONJ) of the mandible and maxilla. BMJ Case Rep. 2020;13(1). doi:10.1136/bcr-2018-224455
32. Fda. HIGHLIGHTS OF PRESCRIBING INFORMATION. www.fda.gov/medwatch.
33. Lu J, Hu D, Zhang Y, Ma C, Shen L, Shuai B. Current comprehensive understanding of denosumab (the RANKL neutralizing antibody) in the treatment of bone metastasis of malignant tumors, including pharmacological mechanism and clinical trials. Front Oncol. 2023;13. doi:10.3389/fonc.2023.1133828
34. Reid IR, Billington EO. Drug therapy for osteoporosis in older adults. The Lancet. 2022;399(10329):1080-1092. doi:10.1016/S0140-6736(21)02646-5
35. Kuehn S, Scariot R, Elsalanty M. Medication-Related Osteonecrosis: Why the Jawbone? Dent J (Basel). 2023;11(5). doi:10.3390/dj11050109
36. AlDhalaan NA, BaQais A, Al-Omar A. Medication-related Osteonecrosis of the Jaw: A Review. Cureus. Published online February 11, 2020. doi:10.7759/cureus.6944
37. Schiodt M, Otto S, Fedele S, et al. Workshop of European task force on medication-related osteonecrosis of the jaw—Current challenges. In: Oral Diseases. Vol 25. Blackwell Publishing Ltd; 2019:1815-1821. doi:10.1111/odi.13160
38. Hadaya D, Soundia A, Freymiller E, et al. Nonsurgical Management of Medication-Related Osteonecrosis of the Jaws Using Local Wound Care. Journal of Oral and Maxillofacial Surgery. 2018;76(11):2332-2339. doi:10.1016/j.joms.2018.05.025
39. Lončar Brzak B, Horvat Aleksijević L, Vindiš E, et al. Osteonecrosis of the Jaw. Dent J (Basel). 2023;11(1). doi:10.3390/dj11010023
40. Otto S, Pautke C, Van den Wyngaert T, Niepel D, Schiødt M. Medication-related osteonecrosis of the jaw: Prevention, diagnosis and management in patients with cancer and bone metastases. Cancer Treat Rev. 2018;69:177-187. doi:10.1016/j.ctrv.2018.06.007
41. Deepigaa M, Arvind M. Clinical Practice Guidelines in Dental Management of Medication Related Osteonecrosis of Jaw (MRONJ). Journal of Research in Medical and Dental Science 2021. 2021;9(1):128-133. www.jrmds.in
42. Kim JE, Yoo S, Choi SC. Several issues regarding the diagnostic imaging of medication-related osteonecrosis of the jaw. Imaging Sci Dent. 2020;50(4):273-279. doi:10.5624/ISD.2020.50.4.273
43. Kuchuk I, Mazzarello S, Butterfield K, Appleton A, Addison CL, Clemons M. Oral care and the use of bone-targeted agents in patients with metastatic cancers: A practical guide for dental surgeons and oncologists. J Bone Oncol. 2013;2(1):38-46. doi:10.1016/j.jbo.2012.12.001
44. Kün-Darbois JD, Fauvel F. Medication-related osteonecrosis and osteoradionecrosis of the jaws: Update and current management. Morphologie. 2021;105(349):170-187. doi:10.1016/j.morpho.2020.11.008
45. Kuroshima S, Sasaki M, Sawase T. Medication-related osteonecrosis of the jaw: A literature review. J Oral Biosci. 2019;61(2):99-104. doi:10.1016/j.job.2019.03.005
46. Kün-Darbois JD, Libouban H, Mabilleau G, Pascaretti-Grizon F, Chappard D. Bone mineralization and vascularization in bisphosphonate-related osteonecrosis of the jaw: an experimental study in the rat. Clin Oral Investig. 2018;22(9):2997-3006. doi:10.1007/s00784-018-2385-2
47. Lorenzo‐pouso AI, Bagán J, Bagán L, et al. Medication‐related osteonecrosis of the jaw: A critical narrative review. J Clin Med. 2021;10(19). doi:10.3390/jcm10194367
48. Gkouveris I, Hadaya D, Soundia A, et al. Vasculature submucosal changes at early stages of osteonecrosis of the jaw (ONJ). Bone. 2019;123:234-245. doi:10.1016/j.bone.2019.03.031
49. Basso FG, Pansani TN, Soares DG, Cardoso LM, Hebling J, de Souza Costa CA. Influence of bisphosphonates on the adherence and metabolism of epithelial cells and gingival fibroblasts to titanium surfaces. Clin Oral Investig. 2018;22(2):893-900. doi:10.1007/s00784-017-2167-2
50. de Molon RS, Hsu C, Bezouglaia O, et al. Rheumatoid Arthritis Exacerbates the Severity of Osteonecrosis of the Jaws (ONJ) in Mice. A Randomized, Prospective, Controlled Animal Study. Journal of Bone and Mineral Research. 2016;31(8):1596-1607. doi:10.1002/jbmr.2827
51. Wick A, Bankosegger P, Otto S, et al. Risk factors associated with onset of medication-related osteonecrosis of the jaw in patients treated with denosumab. Clin Oral Investig. 2022;26(3):2839-2852. doi:10.1007/s00784-021-04261-4
52. Khan AA, Morrison A, Hanley DA, et al. Diagnosis and management of osteonecrosis of the jaw: A systematic review and international consensus. Journal of Bone and Mineral Research. 2015;30(1):3-23. doi:10.1002/jbmr.2405
53. De Cicco D BCSMCGSSGABGVRDS. Medication-Related Osteonecrosis of the Jaws: A Comparison of SICMF-SIPMO and AAOMS Guidelines. Diagnostics (Basel). Published online June 2023.
54. şahin O, Odabaşı O, Aliyev T, Tatar B. Risk factors of medication-related osteonecrosis of the jaw: A retrospective study in a Turkish subpopulation. J Korean Assoc Oral Maxillofac Surg. 2019;45(2):108-115. doi:10.5125/jkaoms.2019.45.2.108
55. Soutome S, Otsuru M, Hayashida S, et al. Relationship between tooth extraction and development of medication-related osteonecrosis of the jaw in cancer patients. Sci Rep. 2021;11(1). doi:10.1038/s41598-021-96480-8
56. 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). doi:10.3390/jcm11071807
57. Pichardo SEC, van der Hee JG, Fiocco M, Appelman-Dijkstra NM, van Merkesteyn JPR. Dental implants as risk factors for patients with medication-related osteonecrosis of the jaws (MRONJ). British Journal of Oral and Maxillofacial Surgery. 2020;58(7):771-776. doi:10.1016/j.bjoms.2020.03.022
58. 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). doi:10.1038/s41368-020-00093-2
59. Singh N, Surface L. Dental Management of Medication-Related OSTEONECROSIS of the JAW: WHILE RARE, THIS PATHOLOGY HAS DEVASTATING EFFECTS ON PATIENT HEALTH AND QUALITY OF LIFE.
60. Nicolatou-Galitis O, Schiødt M, Mendes RA, et al. Medication-related osteonecrosis of the jaw: definition and best practice for prevention, diagnosis, and treatment. Oral Surg Oral Med Oral Pathol Oral Radiol. 2019;127(2):117-135. doi:10.1016/j.oooo.2018.09.008
61. Scribante A, Ghizzoni M, Pellegrini M, Pulicari F, Spadari F. Laser Devices and Autologous Platelet Concentrates in Prevention and Treatment of Medication-Related Osteonecrosis of the Jaws: A Systematic Review. Medicina (Lithuania). 2023;59(5). doi:10.3390/medicina59050972
62. Ottesen C, Schiodt M, Gotfredsen K. Efficacy of a high-dose antiresorptive drug holiday to reduce the risk of medication-related osteonecrosis of the jaw (MRONJ): A systematic review. Heliyon. 2020;6(4). doi:10.1016/j.heliyon.2020.e03795
63. Di Fede O, Panzarella V, Mauceri R, et al. The dental management of patients at risk of medication-related osteonecrosis of the jaw: New paradigm of primary prevention. Biomed Res Int. 2018;2018. doi:10.1155/2018/2684924
64. Yong CW, Robinson A, Hong C. Dental Evaluation Prior to Cancer Therapy. Frontiers in Oral Health. 2022;3. doi:10.3389/froh.2022.876941
65. Prof. G. Campisi – Professore Straordinario - Dirigente Medico I Livello Dott. O. Di Fede - Ricercatore-. PROMaF protocol: Prevention and research on Medication relate Osteonecrosis of the Jaws, . Published online December 2014.
66. A. Bedogni GCVF and AA. Raccomandazioni clinico-terapeutiche sull’osteonecrosi delle ossamascellari associata a bisfosfonati e sua prevenzione,” SICMF - SIPMO. Published online 2013.
67. Mauceri R, Panzarella V, Pizzo G, et al. Platelet-Rich Plasma (PRP) in dental extraction of patients at risk of bisphosphonate-related osteonecrosis of the jaws: A two-year longitudinal study. Applied Sciences (Switzerland). 2020;10(13). doi:10.3390/app10134487
68. Parise GK, Costa BN, Nogueira ML, Sassi LM, Schussel JL. Efficacy of fibrin-rich platelets and leukocytes (L-PRF) in tissue repair in surgical oral procedures in patients using zoledronic acid—case–control study. Oral Maxillofac Surg. 2023;27(3):507-512. doi:10.1007/s10006-022-01094-7
69. Moinzadeh AT, Shemesh H, Neirynck NAM, Aubert C, Wesselink PR. Bisphosphonates and their clinical implications in endodontic therapy. Int Endod J. 2013;46(5):391-398. doi:10.1111/iej.12018
70. Mosaico G, Casu C. Management and maintenance of oral health: Personalized primary prevention strategies and protocols in patients at risk of developing medication-related osteonecrosis of the jaw. INNOSC Theranostics and Pharmacological Sciences. 2024;0(0):1419. doi:10.36922/itps.1419
71. Ministero della Salute “Dipartimento della sanit`a pubblica e dell’innovazione. Raccomandazioni per la promozione della salute orale, la prevenzione delle patologie orali e la terapia odontostomatologica nei pazienti adulti con malattia neoplastica. Published online January 2014.
72. Hadaya D, Soundia A, Freymiller E, et al. Nonsurgical Management of Medication-Related Osteonecrosis of the Jaws Using Local Wound Care. Journal of Oral and Maxillofacial Surgery. 2018;76(11):2332-2339. doi:10.1016/j.joms.2018.05.025
73. Inchingolo AM, Malcangi G, Ferrara I, et al. MRONJ Treatment Strategies: A Systematic Review and Two Case Reports. Applied Sciences (Switzerland). 2023;13(7). doi:10.3390/app13074370
74. Kaibuchi N, Hoshi K, Yamazaki A, Miyamoto-Sangu N, Akagi Y, Okamoto T. The progress of medication-related osteonecrosis of the jaw with conservative initial treatment: A 12-year retrospective study of 129 patients. Bone Rep. 2021;14. doi:10.1016/j.bonr.2021.101072
2. Van Acker HH, Anguille S, Willemen Y, Smits EL, Van Tendeloo VF. Bisphosphonates for cancer treatment: Mechanisms of action and lessons from clinical trials. Pharmacol Ther. 2016;158:24-40. doi:10.1016/j.pharmthera.2015.11.008
3. 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. doi:10.1016/j.oooo.2020.04.808
4. Shapiro CL. Bone-modifying Agents (BMAs) in Breast Cancer. Clin Breast Cancer. 2021;21(5):e618-e630. doi:10.1016/j.clbc.2021.04.009
5. Goldvaser H, Amir E. Role of Bisphosphonates in Breast Cancer Therapy. Curr Treat Options Oncol. 2019;20(4). doi:10.1007/s11864-019-0623-8
6. Reyes C, Hitz M, Prieto-Alhambra D, Abrahamsen B. Risks and Benefits of Bisphosphonate Therapies. J Cell Biochem. 2016;117(1):20-28. doi:10.1002/jcb.25266
7. Mirelli C, Marino S, Bovio A, et al. Medication-Related Osteonecrosis of the Jaw in Dental Practice: A Retrospective Analysis of Data from the Milan Cohort. Dent J (Basel). 2022;10(5). doi:10.3390/dj10050089
8. Mauceri R, Coppini M, Attanasio M, et al. MRONJ in breast cancer patients under bone modifying agents for cancer treatment-induced bone loss (CTIBL): a multi-hospital-based case series. BMC Oral Health. 2023;23(1). doi:10.1186/s12903-023-02732-6
9. Boston B, Ipe D, Capitanescu B, et al. Medication-related osteonecrosis of the jaw: A disease of significant importance for older patients. J Am Geriatr Soc. 2023;71(8):2640-2652. doi:10.1111/jgs.18414
10. 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. Supportive Care in Cancer. 2020;28(5):2265-2271. doi:10.1007/s00520-019-05044-0
11. Kashyap D, Pal D, Sharma R, et al. Global Increase in Breast Cancer Incidence: Risk Factors and Preventive Measures. Biomed Res Int. 2022;2022. doi:10.1155/2022/9605439
12. Dall GV, Britt KL. Estrogen effects on the mammary gland in early and late life and breast cancer risk. Front Oncol. 2017;7(MAY). doi:10.3389/fonc.2017.00110
13. Sinn HP, Kreipe H. A brief overview of the WHO classification of breast tumors, 4th edition, focusing on issues and updates from the 3rd edition. Breast Care. 2013;8(2):149-154. doi:10.1159/000350774
14. Barzaman K, Karami J, Zarei Z, et al. Breast cancer: Biology, biomarkers, and treatments. Int Immunopharmacol. 2020;84. doi:10.1016/j.intimp.2020.106535
15. 14. Otto S ASFRESROBETMPCEMM (Kaunas).. Infection as an Important Factor in Medication-Related Osteonecrosis of the Jaw (MRONJ). Published online May 2021.
16. Tsang JYS, Tse GM. Molecular Classification of Breast Cancer.; 2019. http://journals.lww.com/anatomicpathology
17. Trayes KP, Cokenakes SEH. Breast Cancer Treatment. Am Fam Physician. 2021;104(2):171-178.
18. He Z, Chen Z, Tan M, et al. A review on methods for diagnosis of breast cancer cells and tissues. Cell Prolif. 2020;53(7). doi:10.1111/cpr.12822
19. Gradishar WJ, Anderson BO, Abraham J, et al. Breast cancer, version 3.2020. JNCCN Journal of the National Comprehensive Cancer Network. 2020;18(4):452-478. doi:10.6004/jnccn.2020.0016
20. Suarez-Almazor ME, Herrera R, Lei X, Chavez-MacGregor M, Zhao H, Giordano SH. Survival in older women with early stage breast cancer receiving low-dose bisphosphonates or denosumab. Cancer. 2020;126(17):3929-3938. doi:10.1002/cncr.33035
21. Gnant M, Pfeiler G, Dubsky PC, et al. Adjuvant denosumab in breast cancer (ABCSG-18): A multicentre, randomised, double-blind, placebo-controlled trial. The Lancet. 2015;386(9992):433-443. doi:10.1016/S0140-6736(15)60995-3
22. Coleman R, Finkelstein DM, Barrios C, et al. Adjuvant denosumab in early breast cancer (D-CARE): an international, multicentre, randomised, controlled, phase 3 trial. Lancet Oncol. 2020;21(1):60-72. doi:10.1016/S1470-2045(19)30687-4
23. Fu PA, Shen CY, Yang S R, et al. Long-term use of denosumab and its association with skeletal-related events and osteonecrosis of the jaw. Sci Rep. 2023;13(1). doi:10.1038/s41598-023-35308-z
24. O’Carrigan B, Wong MHF, Willson ML, Stockler MR, Pavlakis N, Goodwin A. Bisphosphonates and other bone agents for breast cancer. Cochrane Database of Systematic Reviews. 2017;2017(10). doi:10.1002/14651858.CD003474.pub4
25. Poon M, Zeng L, Zhang L, et al. Incidence of Skeletal-related Events Over Time from Solid Tumour Bone Metastases Reported in Randomised Trials Using Bone-modifying Agents. Clin Oncol. 2013;25(7):435-444. doi:10.1016/j.clon.2013.03.003
26. Coleman R, Hadji P, Body JJ, et al. Bone health in cancer: ESMO Clinical Practice Guidelines †. Annals of Oncology. 2020;31(12):1650-1663. doi:10.1016/j.annonc.2020.07.019
27. Poznak C Van, Somerfield MR, Barlow WE, et al. JOURNAL OF CLINICAL ONCOLOGY Role of Bone-Modifying Agents in Metastatic Breast Cancer: An American Society of Clinical Oncology-Cancer Care Ontario Focused Guideline Update. J Clin Oncol. 2017;35:3978-3986. doi:10.1200/JCO
28. Anastasilakis AD, Pepe J, Napoli N, et al. Osteonecrosis of the Jaw and Antiresorptive Agents in Benign and Malignant Diseases: A Critical Review Organized by the ECTS. Journal of Clinical Endocrinology and Metabolism. 2022;107(5):1441-1460. doi:10.1210/clinem/dgab888
29. Dalle Carbonare L, Mottes M, Valenti MT. Medication-related osteonecrosis of the jaw (MRONJ): Are antiresorptive drugs the main culprits or only accomplices? the triggering role of vitamin d deficiency. Nutrients. 2021;13(2):1-14. doi:10.3390/nu13020561
30. Ruggiero SL, Dodson TB, Aghaloo T, Carlson ER, Ward BB, Kademani D. American Association of Oral and Maxillofacial Surgeons’ Position Paper on Medication-Related Osteonecrosis of the Jaws—2022 Update. Journal of Oral and Maxillofacial Surgery. 2022;80(5):920-943. doi:10.1016/j.joms.2022.02.008
31. Dunphy L, Salzano G, Gerber B, Graystone J. Medication-related osteonecrosis (MRONJ) of the mandible and maxilla. BMJ Case Rep. 2020;13(1). doi:10.1136/bcr-2018-224455
32. Fda. HIGHLIGHTS OF PRESCRIBING INFORMATION. www.fda.gov/medwatch.
33. Lu J, Hu D, Zhang Y, Ma C, Shen L, Shuai B. Current comprehensive understanding of denosumab (the RANKL neutralizing antibody) in the treatment of bone metastasis of malignant tumors, including pharmacological mechanism and clinical trials. Front Oncol. 2023;13. doi:10.3389/fonc.2023.1133828
34. Reid IR, Billington EO. Drug therapy for osteoporosis in older adults. The Lancet. 2022;399(10329):1080-1092. doi:10.1016/S0140-6736(21)02646-5
35. Kuehn S, Scariot R, Elsalanty M. Medication-Related Osteonecrosis: Why the Jawbone? Dent J (Basel). 2023;11(5). doi:10.3390/dj11050109
36. AlDhalaan NA, BaQais A, Al-Omar A. Medication-related Osteonecrosis of the Jaw: A Review. Cureus. Published online February 11, 2020. doi:10.7759/cureus.6944
37. Schiodt M, Otto S, Fedele S, et al. Workshop of European task force on medication-related osteonecrosis of the jaw—Current challenges. In: Oral Diseases. Vol 25. Blackwell Publishing Ltd; 2019:1815-1821. doi:10.1111/odi.13160
38. Hadaya D, Soundia A, Freymiller E, et al. Nonsurgical Management of Medication-Related Osteonecrosis of the Jaws Using Local Wound Care. Journal of Oral and Maxillofacial Surgery. 2018;76(11):2332-2339. doi:10.1016/j.joms.2018.05.025
39. Lončar Brzak B, Horvat Aleksijević L, Vindiš E, et al. Osteonecrosis of the Jaw. Dent J (Basel). 2023;11(1). doi:10.3390/dj11010023
40. Otto S, Pautke C, Van den Wyngaert T, Niepel D, Schiødt M. Medication-related osteonecrosis of the jaw: Prevention, diagnosis and management in patients with cancer and bone metastases. Cancer Treat Rev. 2018;69:177-187. doi:10.1016/j.ctrv.2018.06.007
41. Deepigaa M, Arvind M. Clinical Practice Guidelines in Dental Management of Medication Related Osteonecrosis of Jaw (MRONJ). Journal of Research in Medical and Dental Science 2021. 2021;9(1):128-133. www.jrmds.in
42. Kim JE, Yoo S, Choi SC. Several issues regarding the diagnostic imaging of medication-related osteonecrosis of the jaw. Imaging Sci Dent. 2020;50(4):273-279. doi:10.5624/ISD.2020.50.4.273
43. Kuchuk I, Mazzarello S, Butterfield K, Appleton A, Addison CL, Clemons M. Oral care and the use of bone-targeted agents in patients with metastatic cancers: A practical guide for dental surgeons and oncologists. J Bone Oncol. 2013;2(1):38-46. doi:10.1016/j.jbo.2012.12.001
44. Kün-Darbois JD, Fauvel F. Medication-related osteonecrosis and osteoradionecrosis of the jaws: Update and current management. Morphologie. 2021;105(349):170-187. doi:10.1016/j.morpho.2020.11.008
45. Kuroshima S, Sasaki M, Sawase T. Medication-related osteonecrosis of the jaw: A literature review. J Oral Biosci. 2019;61(2):99-104. doi:10.1016/j.job.2019.03.005
46. Kün-Darbois JD, Libouban H, Mabilleau G, Pascaretti-Grizon F, Chappard D. Bone mineralization and vascularization in bisphosphonate-related osteonecrosis of the jaw: an experimental study in the rat. Clin Oral Investig. 2018;22(9):2997-3006. doi:10.1007/s00784-018-2385-2
47. Lorenzo‐pouso AI, Bagán J, Bagán L, et al. Medication‐related osteonecrosis of the jaw: A critical narrative review. J Clin Med. 2021;10(19). doi:10.3390/jcm10194367
48. Gkouveris I, Hadaya D, Soundia A, et al. Vasculature submucosal changes at early stages of osteonecrosis of the jaw (ONJ). Bone. 2019;123:234-245. doi:10.1016/j.bone.2019.03.031
49. Basso FG, Pansani TN, Soares DG, Cardoso LM, Hebling J, de Souza Costa CA. Influence of bisphosphonates on the adherence and metabolism of epithelial cells and gingival fibroblasts to titanium surfaces. Clin Oral Investig. 2018;22(2):893-900. doi:10.1007/s00784-017-2167-2
50. de Molon RS, Hsu C, Bezouglaia O, et al. Rheumatoid Arthritis Exacerbates the Severity of Osteonecrosis of the Jaws (ONJ) in Mice. A Randomized, Prospective, Controlled Animal Study. Journal of Bone and Mineral Research. 2016;31(8):1596-1607. doi:10.1002/jbmr.2827
51. Wick A, Bankosegger P, Otto S, et al. Risk factors associated with onset of medication-related osteonecrosis of the jaw in patients treated with denosumab. Clin Oral Investig. 2022;26(3):2839-2852. doi:10.1007/s00784-021-04261-4
52. Khan AA, Morrison A, Hanley DA, et al. Diagnosis and management of osteonecrosis of the jaw: A systematic review and international consensus. Journal of Bone and Mineral Research. 2015;30(1):3-23. doi:10.1002/jbmr.2405
53. De Cicco D BCSMCGSSGABGVRDS. Medication-Related Osteonecrosis of the Jaws: A Comparison of SICMF-SIPMO and AAOMS Guidelines. Diagnostics (Basel). Published online June 2023.
54. şahin O, Odabaşı O, Aliyev T, Tatar B. Risk factors of medication-related osteonecrosis of the jaw: A retrospective study in a Turkish subpopulation. J Korean Assoc Oral Maxillofac Surg. 2019;45(2):108-115. doi:10.5125/jkaoms.2019.45.2.108
55. Soutome S, Otsuru M, Hayashida S, et al. Relationship between tooth extraction and development of medication-related osteonecrosis of the jaw in cancer patients. Sci Rep. 2021;11(1). doi:10.1038/s41598-021-96480-8
56. 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). doi:10.3390/jcm11071807
57. Pichardo SEC, van der Hee JG, Fiocco M, Appelman-Dijkstra NM, van Merkesteyn JPR. Dental implants as risk factors for patients with medication-related osteonecrosis of the jaws (MRONJ). British Journal of Oral and Maxillofacial Surgery. 2020;58(7):771-776. doi:10.1016/j.bjoms.2020.03.022
58. 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). doi:10.1038/s41368-020-00093-2
59. Singh N, Surface L. Dental Management of Medication-Related OSTEONECROSIS of the JAW: WHILE RARE, THIS PATHOLOGY HAS DEVASTATING EFFECTS ON PATIENT HEALTH AND QUALITY OF LIFE.
60. Nicolatou-Galitis O, Schiødt M, Mendes RA, et al. Medication-related osteonecrosis of the jaw: definition and best practice for prevention, diagnosis, and treatment. Oral Surg Oral Med Oral Pathol Oral Radiol. 2019;127(2):117-135. doi:10.1016/j.oooo.2018.09.008
61. Scribante A, Ghizzoni M, Pellegrini M, Pulicari F, Spadari F. Laser Devices and Autologous Platelet Concentrates in Prevention and Treatment of Medication-Related Osteonecrosis of the Jaws: A Systematic Review. Medicina (Lithuania). 2023;59(5). doi:10.3390/medicina59050972
62. Ottesen C, Schiodt M, Gotfredsen K. Efficacy of a high-dose antiresorptive drug holiday to reduce the risk of medication-related osteonecrosis of the jaw (MRONJ): A systematic review. Heliyon. 2020;6(4). doi:10.1016/j.heliyon.2020.e03795
63. Di Fede O, Panzarella V, Mauceri R, et al. The dental management of patients at risk of medication-related osteonecrosis of the jaw: New paradigm of primary prevention. Biomed Res Int. 2018;2018. doi:10.1155/2018/2684924
64. Yong CW, Robinson A, Hong C. Dental Evaluation Prior to Cancer Therapy. Frontiers in Oral Health. 2022;3. doi:10.3389/froh.2022.876941
65. Prof. G. Campisi – Professore Straordinario - Dirigente Medico I Livello Dott. O. Di Fede - Ricercatore-. PROMaF protocol: Prevention and research on Medication relate Osteonecrosis of the Jaws, . Published online December 2014.
66. A. Bedogni GCVF and AA. Raccomandazioni clinico-terapeutiche sull’osteonecrosi delle ossamascellari associata a bisfosfonati e sua prevenzione,” SICMF - SIPMO. Published online 2013.
67. Mauceri R, Panzarella V, Pizzo G, et al. Platelet-Rich Plasma (PRP) in dental extraction of patients at risk of bisphosphonate-related osteonecrosis of the jaws: A two-year longitudinal study. Applied Sciences (Switzerland). 2020;10(13). doi:10.3390/app10134487
68. Parise GK, Costa BN, Nogueira ML, Sassi LM, Schussel JL. Efficacy of fibrin-rich platelets and leukocytes (L-PRF) in tissue repair in surgical oral procedures in patients using zoledronic acid—case–control study. Oral Maxillofac Surg. 2023;27(3):507-512. doi:10.1007/s10006-022-01094-7
69. Moinzadeh AT, Shemesh H, Neirynck NAM, Aubert C, Wesselink PR. Bisphosphonates and their clinical implications in endodontic therapy. Int Endod J. 2013;46(5):391-398. doi:10.1111/iej.12018
70. Mosaico G, Casu C. Management and maintenance of oral health: Personalized primary prevention strategies and protocols in patients at risk of developing medication-related osteonecrosis of the jaw. INNOSC Theranostics and Pharmacological Sciences. 2024;0(0):1419. doi:10.36922/itps.1419
71. Ministero della Salute “Dipartimento della sanit`a pubblica e dell’innovazione. Raccomandazioni per la promozione della salute orale, la prevenzione delle patologie orali e la terapia odontostomatologica nei pazienti adulti con malattia neoplastica. Published online January 2014.
72. Hadaya D, Soundia A, Freymiller E, et al. Nonsurgical Management of Medication-Related Osteonecrosis of the Jaws Using Local Wound Care. Journal of Oral and Maxillofacial Surgery. 2018;76(11):2332-2339. doi:10.1016/j.joms.2018.05.025
73. Inchingolo AM, Malcangi G, Ferrara I, et al. MRONJ Treatment Strategies: A Systematic Review and Two Case Reports. Applied Sciences (Switzerland). 2023;13(7). doi:10.3390/app13074370
74. Kaibuchi N, Hoshi K, Yamazaki A, Miyamoto-Sangu N, Akagi Y, Okamoto T. The progress of medication-related osteonecrosis of the jaw with conservative initial treatment: A 12-year retrospective study of 129 patients. Bone Rep. 2021;14. doi:10.1016/j.bonr.2021.101072