Background: Bone modifying agents are used throughout cancer care and their utilisation can optimise advanced stage cancer cases with bone metastases, by reducing skeletal-related events, treatment-induced bone loss and treatment hypercalcaemia. They are also used in patients with a curative intent such as early breast cancer, reducing recurrence and increasing survival rates. Medication-related osteonecrosis of the jaw (MRONJ) is a potential complication following bone modifying agents (BMAs). It represents exposed bone in the maxillofacial region which significantly compromises the quality of life for these patients. Dental disease is the most common initiating factor of MRONJ. We report a case in which MRONJ has dominated cancer care despite its successful treatment.
Case presentation: A 69-year-old female was diagnosed with a breast cancer (grade 1, infiltrating ductal carcinoma, pT1c pN1mi(sc) Mx), for which she was treated with a wide local excision and axillary lymph-node clearance. Seven years after initial presentation, the patient presented with metastatic disease involving the left supraclavicular fossa, bone, peritoneum, and liver. Her BMA regime included zoledronic acid intravenous (IV) every month for 12 months and switched to oral zoledronic acid for a subsequent year due to poor venous access.
Two years after her diagnosis of metastatic disease, the patient presented with exposed bone in her anterior maxilla, which represented advanced stage MRONJ (AAOMS 3). The exposed bone in the maxilla was treated surgically by sequestrectomy and fistula closure. Three years later (12 years after initial breast cancer diagnosis), the patient was re-admitted with a cervical fascial space infection involving the right mandible. The patient developed another site of advanced- stage MRONJ (AAOMS 3) in the right mandible associated with an orocutaneous fistula. The patient had a marginal resection of her mandible, fistula closure and extraction of the remaining teeth under general anesthetic.
Conclusion: The practicing oncologist needs to be cognisant of the possibility of MRONJ in both the curative and palliative setting. Traditionally, oncology care has required a significant degree of self-reliance on patients to navigate dental treatment pathways. Integration of dental clinics into oncology pathways would help eliminate this need for self-reliance. MRONJ is an inevitable risk for a large cohort of oncology patients and active engagement of dental-oncology specialities will ensure optimal care for patients.
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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. doi: 10.1016/s0278-2391(03)00720-1.
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. J Oral Maxillofac Surg. 2022;80(5):920-943. doi: 10.1016/j.joms.2022.02.008.
Coleman R, Hadji P, Body JJ, Santini D, Chow E, Terpos E, 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.
ESMO. De-escalation of Commonly Used Bone-Treating Agents Is A Reasonable Treatment Option for Patients with Bone Metastases from Breast Cancer. Accessed January 5, 2023. Available from: https://www.esmo.org/oncology-news/de-escalation-of-commonly-used-bone-treating-agents-is-a-reasonable-treatment-option-for-patients-with-bone-metastases-from-breast-cancer
Miglietta F, Bottosso M, Griguolo G, Dieci MV, Guarneri V. Major advancements in metastatic breast cancer treatment: when expanding options means prolonging survival. ESMO Open. 2022;7(2). doi: 10.1016/j.esmoop.2022.100409.
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 surgery, oral medicine, oral pathology and oral radiology. 2020;130(3):252-257.
Henien M, Carey B, Hullah E, Sproat C, Patel V. Methotrexate-associated osteonecrosis of the jaw: A report of two cases. Oral Surg Oral Med Oral Pathol Oral Radiol. 2017;124(6):e283-e287. doi: 10.1016/j.oooo.2017.09.005.
Jung S, Kim J, Park JH, Kim KY, Kim HJ, Park W. A 5-year retrospective cohort study of denosumab induced medication related osteonecrosis of the jaw in osteoporosis patients. Sci Rep. 2022;12(1):8641. doi: 10.1038/s41598-022-11615-9.
Nicolatou-Galitis O, Schiødt M, Mendes RA, Ripamonti C, Hope S, Drudge-Coates L, et al. Medication-related osteonecrosis of the jaw: definition and best practice for prevention, diagnosis, and treatment. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology. 2019;127(2):117-135. doi: 10.1016/j.oooo.2018.09.008.
Vallina C, Ramírez L, Torres J, Casañas E, Hernández G, López-Pintor RM. Osteonecrosis of the jaws produced by sunitinib: A systematic review. Med Oral Patol Oral Cir Bucal. 2019;24(3):e326-e338. doi: 10.4317/medoral.22858.
Yamamoto D, Tsubota Y, Utsunomiya T, Sueoka N, Ueda A, Endo K, et al. Osteonecrosis of the jaw associated with everolimus: A case report. Mol Clin Oncol. 2017;6(2):255-257. doi: 10.3892/mco.2016.1100.
Yarom N, Shapiro CL, Peterson DE, Van Poznak CH, Bohlke K, Ruggiero SL, et al. Medication-Related Osteonecrosis of the Jaw: MASCC/ISOO/ASCO Clinical Practice Guideline. JCO. 2019; 37(25):2270-2290. doi: 10.1200/JCO.19.01186.
Kizub DA, Miao J, Schubert MM, Paterson AHG, Clemons M, Dees EC, et al. Risk factors for bisphosphonate-associated osteonecrosis of the jaw in the prospective randomized trial of adjuvant bisphosphonates for early-stage breast cancer (SWOG 0307). Support Care Cancer. 2021;29(5):2509-2517. doi: 10.1007/s00520-020-05748-8.
Vidula N, Greenberg S, Petrillo L, Hwang J, Melisko M, Goga A, et al. Evaluation of disseminated tumor cells and circulating tumor cells in patients with breast cancer receiving adjuvant zoledronic acid. NPJ Breast Cancer. 2021;7(1):113. doi: 10.1038/s41523-021-00323-8.
Paterson AH, Anderson SJ, Lembersky BC, Fehrenbacher L, Falkson CI, King KM, et al. Oral clodronate for adjuvant treatment of operable breast cancer (National Surgical Adjuvant Breast and Bowel Project protocol B-34): a multicentre, placebo-controlled, randomised trial. Lancet Oncol. 2012;13(7):734-742. doi: 10.1016/S1470-2045(12)70226-7.
Coleman RE, Collinson M, Gregory W, Marshall H, Bell R, Dodwell D, et al. Benefits and risks of adjuvant treatment with zoledronic acid in stage II/III breast cancer. 10 years follow-up of the AZURE randomized clinical trial (BIG 01/04). J Bone Oncol. 2018;13:123-135. doi: 10.1016/j.jbo.2018.09.008.
Gnant M, Pfeiler G, Dubsky PC, Hubalek M, Greil R, Jakesz R, et al. Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2015;386(9992):433-443. doi: 10.1016/S0140-6736(15)60995-3.
Rathbone EJ, Brown JE, Marshall HC, Collinson M, Liversedge V, Murden GA, et al. Osteonecrosis of the Jaw and Oral Health–Related Quality of Life After Adjuvant Zoledronic Acid: An Adjuvant Zoledronic Acid to Reduce Recurrence Trial Subprotocol (BIG01/04). JCO. 2013;31(21):2685-2691. doi: 10.1200/JCO.2012.46.4792.
Coleman R, de Boer R, Eidtmann H, Llombart A, Davidson N, Neven P, et al. Zoledronic acid (zoledronate) for postmenopausal women with early breast cancer receiving adjuvant letrozole (ZO-FAST study): final 60-month results. Ann Oncol. 2013;24(2):398-405. doi: 10.1093/annonc/mds277.
von Minckwitz G, Möbus V, Schneeweiss A, Huober J, Thomssen C, Untch M, et al. German adjuvant intergroup node-positive study: a phase III trial to compare oral ibandronate versus observation in patients with high-risk early breast cancer. J Clin Oncol. 2013;31(28):3531-3539. doi: 10.1200/JCO.2012.47.2167.
Jinih M, Relihan N, Corrigan MA, O’Reilly S, Redmond HP. Extended Adjuvant Endocrine Therapy in Breast Cancer: Evidence and Update - A Review. Breast J. 2017;23(6):694-705. doi: 10.1111/tbj.12783.
Colleoni M, Luo W, Karlsson P, Chirgwin J, Aebi S, Jerusalem G, et al. Extended adjuvant intermittent letrozole versus continuous letrozole in postmenopausal women with breast cancer (SOLE): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2018;19(1):127-138. doi: 10.1016/S1470-2045(17)30715-5.
WHO Discussion Paper: Draft Global Strategy On Oral Health. Accessed February 27, 2023. Available from: https://www.who.int/publications/m/item/who-discussion-paper-draft-global-strategy-on-oral-health
Bolette A, Lecloux G, Rompen E, Albert A, Kerckhofs G, Lambert F. Influence of induced infection in medication-related osteonecrosis of the jaw development after tooth extraction: A study in rats. J Craniomaxillofac Surg. 2019;47(2):349-356. doi: 10.1016/j.jcms.2018.08.011.
Otto S, Aljohani S, Fliefel R, Ecke S, Ristow O, Burian E, et al. Infection as an Important Factor in Medication-Related Osteonecrosis of the Jaw (MRONJ). Medicina (Kaunas). 2021;57(5):463. doi: 10.3390/medicina57050463.
Agrasuta V, Thumbuntu T, Karawekpanyawong R, Panichkriangkrai W, Viriyathorn S, Reeponmaha T, et al. Progressive realisation of universal access to oral health services: what evidence is needed? BMJ Glob Health. 2021;6(7):e006556. doi: 10.1136/bmjgh-2021-006556.
World Health Assembly Resolution paves the way for better oral health care. Accessed February 27, 2023. Available from: https://www.who.int/news/item/27-05-2021-world-health-assembly-resolution-paves-the-way-for-better-oral-health-care
Thumbigere-Math V, Michalowicz BS, Hodges JS, Tsai ML, Swenson KK, Rockwell L, et al. Periodontal Disease as a Risk Factor for Bisphosphonate-Related Osteonecrosis of the Jaw. Journal of Periodontology. 2014;85(2):226-233. doi: 10.1902/jop.2013.130017.
Eke PI, Borgnakke WS, Genco RJ. Recent epidemiologic trends in periodontitis in the USA. Periodontol 2000. 2020;82(1):257-267. doi: 10.1111/prd.12323.
McGowan K, McGowan T, Ivanovski S. Risk factors for medication-related osteonecrosis of the jaws: A systematic review. Oral Diseases. 2018;24(4):527-536. doi: 10.1111/odi.12708.
Saad F, Brown JE, Van Poznak C, Ibrahim T, Stemmer SM, Stopeck AT, et al. 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. Annals of Oncology. 2012;23(5):1341-1347. doi: 10.1093/annonc/mdr435
Kang MH, Lee DK, Kim CW, Song IS, Jun SH. Clinical characteristics and recurrence-related factors of medication-related osteonecrosis of the jaw. J Korean Assoc Oral Maxillofac Surg. 2018;44(5):225-231. doi: 10.5125/jkaoms.2018.44.5.225
Campisi G, Mauceri R, Bertoldo F, Bettini G, Biasotto M, Colella G, et al. Medication-Related Osteonecrosis of Jaws (MRONJ) Prevention and Diagnosis: Italian Consensus Update 2020. Int J Environ Res Public Health. 2020. 18;17(16):5998. doi: 10.3390/ijerph17165998.
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. doi: 10.1016/j.joms.2018.08.010.
Katsarelis H, Shah NP, Dhariwal DK, Pazianas M. Infection and medication-related osteonecrosis of the jaw. J Dent Res. 2015;94(4):534-539. doi: 10.1177/0022034515572021.
Bledsaw K, Prudowsky ZD, Yang E, Harriehausen CX, Robins J, DeJean J, et al. A Novel Oncodental Collaborative Team: Integrating Expertise for Central Line-Associated Bloodstream Infection Prevention in Pediatric Oncology Patients. JCO Oncol Pract. 2023;19(1):e25-e32. doi: 10.1200/OP.22.00302.
Marx RE. Drug-Induced Osteonecrosis of the Jaws: How to Diagnose, Prevent, and Treat It. Quintessence Publishing Company, Incorporated; 2021.
Moretti F, Pelliccioni GA, Montebugnoli L, Marchetti C. A prospective clinical trial for assessing the efficacy of a minimally invasive protocol in patients with bisphosphonate-associated osteonecrosis of the jaws. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;112(6):777-782. doi: 10.1016/j.tripleo.2011.07.004.
Patel V, Gadiwalla Y, Sassoon I, Sproat C, Kwok J, McGurk M. Prophylactic use of pentoxifylline and tocopherol in patients who require dental extractions after radiotherapy for cancer of the head and neck. Br J Oral Maxillofac Surg. 2016;54(5):547-550. doi: 10.1016/j.bjoms.2016.02.024
Wutzl A, Pohl S, Sulzbacher I, Seemann R, Lauer G, Ewers R, et al. Factors influencing surgical treatment of bisphosphonate-related osteonecrosis of the jaws. Head Neck. 2012 Feb;34(2):194-200. doi: 10.1002/hed.21708.
Schubert M, Klatte I, Linek W, et al. The saxon bisphosphonate register - therapy and prevention of bisphosphonate-related osteonecrosis of the jaws. Oral Oncol. 2012;48(4):349-354. doi: 10.1016/j.oraloncology.2011.11.004.
Voss PJ, Joshi Oshero J, Kovalova-Müller A, Veigel Merino EA, Sauerbier S, Al-Jamali J, et al. Surgical treatment of bisphosphonate-associated osteonecrosis of the jaw: technical report and follow up of 21 patients. J Craniomaxillofac Surg. 2012;40(8):719-725. doi: 10.1016/j.jcms.2012.01.005.
Ripamonti CI, Maniezzo M, Campa T, et al. Decreased occurrence of osteonecrosis of the jaw after implementation of dental preventive measures in solid tumour patients with bone metastases treated with bisphosphonates. The experience of the National Cancer Institute of Milan. Ann Oncol. 2009;20(1):137-145. doi: 10.1093/annonc/mdn526.
Campisi G, Russo L, Agrillo A, Vescovi P, Fusco V, Bedogni A. BRONJ expert panel recommendation of the Italian Societies for Maxillofacial Surgery (SICMF) and Oral Pathology and Medicine (SIPMO) on Bisphosphonate-Related Osteonecrosis of the Jaws: Risk assessment, preventive strategies and dental management. It J Maxillofac Surg. 2011;22:103-124.
Mauceri R, Coniglio R, Abbinante A, Carcieri P, Tomassi D, Panzarella V, et al. The preventive care of medication-related osteonecrosis of the jaw (MRONJ): a position paper by Italian experts for dental hygienists. Support Care Cancer. 2022;30(8):6429-6440. doi: 10.1007/s00520-022-06940-8.
Vandone AM, Donadio M, Mozzati M, Ardine M, Polimeni MA, Beatrice S, et al. Impact of dental care in the prevention of bisphosphonate-associated osteonecrosis of the jaw: a single-center clinical experience. Ann Oncol. 2012;23(1):193-200. doi: 10.1093/annonc/mdr039.
Trosman JR, Carlos RC, Simon MA, Madden DL, Gradishar WJ, Benson AB 3rd, et al. Care for a Patient With Cancer As a Project: Management of Complex Task Interdependence in Cancer Care Delivery. J Oncol Pract. 2016;12(11):1101-1113. doi: 10.1200/JOP.2016.013573.
Beth-Tasdogan NH, Mayer B, Hussein H, Zolk O, Peter JU. Interventions for managing medication-related osteonecrosis of the jaw. Cochrane Database Syst Rev. 2022;7(7):CD012432. doi: 10.1002/14651858.CD012432.pub3.
Caminha RDG, Alcantara PL, Carvalho CG, Reia VCB, Capelozza ALA, Santos PS da S. The impact of medication-related osteonecrosis of the jaws on the quality of life in cancer patients. J Clin Exp Dent. 2020;12(8):e725-e729. doi: 10.4317/jced.56307.
Gross J, Méder ZZ, De Dreu CKW, Romano A, Molenmaker WE, Hoenig LC. The evolution of universal cooperation. Sci Adv. 2023;9(7):eadd8289. doi: 10.1126/sciadv.add8289.
Salcinovic B, Drew M, Dijkstra P, Waddington G, Serpell BG. Factors Influencing Team Performance: What Can Support Teams in High-Performance Sport Learn from Other Industries? A Systematic Scoping Review. Sports Medicine - Open. 2022;8(1):25. doi: 10.1186/s40798-021-00406-7.
Agnese. European Code of Cancer Practice. European Cancer Organisation. Published September 3, 2020. Accessed March 8, 2023. Available from: https://www.europeancancer.org/2-standard/66-european-code-of-cancer-practice
Bacci C, Cerrato A, Bardhi E, Frigo AC, Djaballah SA, Sivolella S. A retrospective study on the incidence of medication-related osteonecrosis of the jaws (MRONJ) associated with different preventive dental care modalities. Support Care Cancer. 2022;30(2):1723-1729. doi: 10.1007/s00520-021-06587-x.
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