{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T09:49:33Z","timestamp":1762508973413,"version":"build-2065373602"},"reference-count":42,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T00:00:00Z","timestamp":1681344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Dentistry Journal"],"abstract":"<jats:p>A 60-year-old woman suffering from multiple myeloma (MM) was treated with zoledronic acid (bisphosphonate), dexamethasone (corticosteroid), bortezomib (a chemotherapeutic agent), and lenalidomide (thalidomide analog) for about a year and with lenalidomide alone as maintenance therapy for almost two years and developed stage three medication-related osteonecrosis of the jaws (MRONJ) in the upper left dental arch approximately two weeks after tooth extraction, which was treated with a medical nonoperative conservative approach until reversion to stage one. The present case report describing the development of multi-drug-related osteonecrosis of the jaws during the pharmacologic MM maintenance phase draws attention to the complex multidisciplinary and multistage management of MM subjects and also that during disease remission, crucially involving oral healthcare providers for MRONJ prevention and pharmacovigilance. To prevent similar cases, cancer patient management should ensure proper dental care not only before starting but also throughout therapy duration and ensure continuous interdisciplinary consensus between oncologists and dentists. Moreover, also considering the independent negative and potentially synergistic effect on bone metabolism and mucosal healing processes of employed medicaments, additionally combined with the cumulative one of previous intravenous bisphosphonates, further studies should highlight the polypharmacy effect and hopefully aid in patient-specific MRONJ risk assessment in cancer patients.<\/jats:p>","DOI":"10.3390\/dj11040104","type":"journal-article","created":{"date-parts":[[2023,4,14]],"date-time":"2023-04-14T01:32:03Z","timestamp":1681435923000},"page":"104","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Multiple-Drugs-Related Osteonecrosis of the Jaw in a Patient Affected by Multiple Myeloma: A Case Report"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3163-7170","authenticated-orcid":false,"given":"Mario","family":"Caggiano","sequence":"first","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry \u201cScuola Medica Salernitana\u201d, University of Salerno, Via Allende, 84081 Baronissi, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5458-6559","authenticated-orcid":false,"given":"Federica","family":"Di Spirito","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry \u201cScuola Medica Salernitana\u201d, University of Salerno, Via Allende, 84081 Baronissi, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfonso","family":"Acerra","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry \u201cScuola Medica Salernitana\u201d, University of Salerno, Via Allende, 84081 Baronissi, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3744-891X","authenticated-orcid":false,"given":"Marzio","family":"Galdi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry \u201cScuola Medica Salernitana\u201d, University of Salerno, Via Allende, 84081 Baronissi, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Sisalli","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry \u201cScuola Medica Salernitana\u201d, University of Salerno, Via Allende, 84081 Baronissi, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Campisi, G., Mauceri, R., Bertoldo, F., Bettini, G., Biasotto, M., Colella, G., Consolo, U., di Fede, O., Favia, G., and Fusco, V. (2020). Medication-Related Osteonecrosis of Jaws (MRONJ) Prevention and Diagnosis: Italian Consensus Update 2020. Int. J. Environ. Res. Public. Health, 17.","DOI":"10.3390\/ijerph17165998"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6945","DOI":"10.1002\/cam4.2591","article-title":"Use of Bone-Modifying Agents and Clinical Outcomes in Older Adults with Multiple Myeloma","volume":"8","author":"Olszewski","year":"2019","journal-title":"Cancer Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s40729-021-00323-0","article-title":"Clinical Considerations for Medication-Related Osteonecrosis of the Jaw: A Comprehensive Literature Review","volume":"7","author":"Kawahara","year":"2021","journal-title":"Int. J. Implant. Dent."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.annonc.2020.11.014","article-title":"Multiple Myeloma: EHA-ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-Up","volume":"32","author":"Dimopoulos","year":"2021","journal-title":"Ann. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.6004\/jnccn.2015.0167","article-title":"Multiple Myeloma, Version 2.2016: Clinical Practice Guidelines in Oncology","volume":"13","author":"Anderson","year":"2015","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S13","DOI":"10.6004\/jnccn.2010.0112","article-title":"Complications of Multiple Myeloma Therapy, Part 2: Risk Reduction and Management of Venous Thromboembolism, Osteonecrosis of the Jaw, Renal Complications, and Anemia","volume":"8","author":"Niesvizky","year":"2010","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.2165\/00003495-200767130-00005","article-title":"Lenalidomide in Myelodysplastic Syndrome and Multiple Myeloma","volume":"67","author":"Shah","year":"2007","journal-title":"Drugs"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"866871","DOI":"10.3389\/froh.2022.866871","article-title":"Oral Complications in Cancer Patients-Medication-Related Osteonecrosis of the Jaw (MRONJ)","volume":"3","author":"Migliorati","year":"2022","journal-title":"Front. Oral Health"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.jcms.2018.12.014","article-title":"Is the Conservative Non-Surgical Management of Medication-Related Osteonecrosis of the Jaw an Appropriate Treatment Option for Early Stages? A Long-Term Single-Center Cohort Study","volume":"47","author":"Ristow","year":"2019","journal-title":"J. Craniomaxillofac. Surg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/jbmr.2405","article-title":"Diagnosis and Management of Osteonecrosis of the Jaw: A Systematic Review and International Consensus","volume":"30","author":"Khan","year":"2015","journal-title":"J. Bone Miner. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.tripleo.2006.06.004","article-title":"Bisphosphonate-Related Osteonecrosis of the Jaw: Background and Guidelines for Diagnosis, Staging and Management","volume":"102","author":"Ruggiero","year":"2006","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endodontology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1016\/j.ijom.2012.06.020","article-title":"Increased Incidence of Osteonecrosis of the Jaw after Tooth Extraction in Patients Treated with Bisphosphonates: A Cohort Study","volume":"41","author":"Yamazaki","year":"2012","journal-title":"Int. J. Oral Maxillofac. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2269","DOI":"10.1007\/s00784-021-04331-7","article-title":"Non-Antiresorptive Drugs Associated with the Development of Medication-Related Osteonecrosis of the Jaw: A Systematic Review and Meta-Analysis","volume":"26","author":"Suryani","year":"2022","journal-title":"Clin. Oral Investig."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1016\/S0140-6736(20)32381-3","article-title":"Breast Cancer","volume":"397","author":"Loibl","year":"2021","journal-title":"Lancet"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"a030361","DOI":"10.1101\/cshperspect.a030361","article-title":"The Epidemiology of Prostate Cancer","volume":"8","author":"Pernar","year":"2018","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.jcms.2011.05.003","article-title":"Bisphosphonate-Related Osteonecrosis of the Jaws\u2014Characteristics, Risk Factors, Clinical Features, Localization and Impact on Oncological Treatment","volume":"40","author":"Otto","year":"2012","journal-title":"J. Craniomaxillofac. Surg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1016\/j.joms.2022.02.008","article-title":"American Association of Oral and Maxillofacial Surgeons\u2019 Position Paper on Medication-Related Osteonecrosis of the Jaws-2022 Update","volume":"80","author":"Ruggiero","year":"2022","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1016\/j.joms.2014.04.031","article-title":"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","volume":"72","author":"Ruggiero","year":"2014","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.bjoms.2014.04.009","article-title":"Staging of Osteonecrosis of the Jaw Requires Computed Tomography for Accurate Definition of the Extent of Bony Disease","volume":"52","author":"Bedogni","year":"2014","journal-title":"Br. J. Oral Maxillofac. Surg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.jcms.2014.11.014","article-title":"Treatment Perspectives for Medication-Related Osteonecrosis of the Jaw (MRONJ)","volume":"43","author":"Ristow","year":"2015","journal-title":"J. Craniomaxillofac. Surg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s10006-020-00831-0","article-title":"Laser Surgery in Management of Medication-Related Osteonecrosis of the Jaws: A Meta-Analysis","volume":"24","author":"Momesso","year":"2020","journal-title":"Oral Maxillofac. Surg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"S94","DOI":"10.1016\/j.joms.2015.09.024","article-title":"Disease Stage and Mode of Therapy Are Important Determinants of Treatment Outcomes for Medication-Related Osteonecrosis of the Jaw","volume":"73","author":"Ruggiero","year":"2015","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.1016\/j.joms.2020.05.037","article-title":"Can Surgical Management Improve Resolution of Medication-Related Osteonecrosis of the Jaw at Early Stages? A Prospective Cohort Study","volume":"78","author":"Giudice","year":"2020","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e28","DOI":"10.1016\/j.jormas.2021.09.011","article-title":"Surgical Management of Stage-2 Medication-Related Osteonecrosis of the Jaw with Transplantation of Human Amniotic Membrane: Preliminary Results","volume":"123","author":"Er","year":"2022","journal-title":"J. Stomatol. Oral Maxillofac. Surg."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"115676","DOI":"10.1016\/j.bone.2020.115676","article-title":"Adjuvant Therapies for MRONJ: A Systematic Review","volume":"141","author":"Govaerts","year":"2020","journal-title":"Bone"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.oooo.2018.02.004","article-title":"Pentoxifylline, Tocopherol, and Clodronate for the Treatment of Mandibular Osteoradionecrosis: A Systematic Review","volume":"125","year":"2018","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Giudice, A., Antonelli, A., Chiarella, E., Baudi, F., Barni, T., and Di Vito, A. (2020). The Case of Medication-Related Osteonecrosis of the Jaw Addressed from a Pathogenic Point of View. Innovative Therapeutic Strategies: Focus on the Most Recent Discoveries on Oral Mesenchymal Stem Cell-Derived Exosomes. Pharmaceuticals, 13.","DOI":"10.3390\/ph13120423"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"S9","DOI":"10.1016\/j.ijsu.2016.05.057","article-title":"Zygomatic Fractures: Technical Modifications for Better Aesthetic and Functional Results in Older Patients","volume":"33","author":"Cortese","year":"2016","journal-title":"Int. J. Surg."},{"key":"ref_29","first-page":"259","article-title":"Computed Tomography Evaluation of Jaw a Trophies before and after Surgical Bone Augmentation","volume":"12","author":"Toti","year":"2019","journal-title":"Int. J. Clin. Dent."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"253","DOI":"10.3390\/prosthesis4020025","article-title":"Prosthodontic Treatment in Patients with Temporomandibular Disorders and Orofacial Pain and\/or Bruxism: A Review of the Literature","volume":"4","author":"Minervini","year":"2022","journal-title":"Prosthesis"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.rcl.2017.08.006","article-title":"Imaging of Radiation- and Medication-Related Osteonecrosis","volume":"56","author":"Mallya","year":"2018","journal-title":"Radiol. Clin. N. Am."},{"key":"ref_32","first-page":"131","article-title":"Telescopic Overdenture on Natural Teeth: Prosthetic Rehabilitation on (OFD) Syndromic Patient and a Review on Available Literature","volume":"32","author":"Minervini","year":"2018","journal-title":"J. Biol. Regul. Homeost. Agents"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1111\/odi.12708","article-title":"Risk Factors for Medication-Related Osteonecrosis of the Jaws: A Systematic Review","volume":"24","author":"McGowan","year":"2018","journal-title":"Oral Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/j.oraloncology.2007.11.012","article-title":"Bisphosphonate-Induced Osteonecrosis of the Jaws: Prospective Study of 80 Patients with Multiple Myeloma and Other Malignancies","volume":"44","author":"Boonyapakorn","year":"2008","journal-title":"Oral Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"575","DOI":"10.2217\/14796694.1.5.575","article-title":"Lenalidomide: An Immunomodulatory Drug","volume":"1","author":"Crane","year":"2005","journal-title":"Future Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.jormas.2018.04.006","article-title":"Numb Chin Syndrome: A Reflection of Malignancy or a Harbinger of MRONJ? A Multicenter Experience","volume":"119","author":"Fortunato","year":"2018","journal-title":"J. Stomatol. Oral Maxillofac. Surg."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.oooo.2018.08.015","article-title":"Prevalence, Initiating Factor, and Treatment Outcome of Medication-Related Osteonecrosis of the Jaw-a 4-Year Prospective Study","volume":"126","author":"Hallmer","year":"2018","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.oraloncology.2012.03.009","article-title":"Tooth Extraction in Patients on Zoledronic Acid Therapy","volume":"48","author":"Mozzati","year":"2012","journal-title":"Oral Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1016\/j.joms.2013.01.006","article-title":"Tooth Extractions in Intravenous Bisphosphonate-Treated Patients: A Refined Protocol","volume":"71","author":"Scoletta","year":"2013","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_40","first-page":"105","article-title":"Mronj Incidence After Multiple Teeth Extractions in Patients Taking Oral Bisphosphonates Without \u201cDrug Holiday\u201d: A Retrospective Chart Review","volume":"12","author":"Argentino","year":"2019","journal-title":"Oral Implantol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1186\/2193-1801-3-123","article-title":"Necrotizing Fasciitis as a Rare Complication of Osteonecrosis of the Jaw in a Patient with Multiple Myeloma Treated with Lenalidomide: Case Report and Review of the Literature","volume":"3","author":"Mondello","year":"2014","journal-title":"Springerplus"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Al-Mahalawy, H., El-Mahallawy, Y., Dessoky, N.Y., Ibrahim, S., Amer, H., Ayad, H.M., El Sherif, H.M., and Shabaan, A.A. (2022). Post-COVID-19 Related Osteonecrosis of the Jaw (PC-RONJ): An Alarming Morbidity in COVID-19 Surviving Patients. BMC Infect. Dis., 22.","DOI":"10.1186\/s12879-022-07518-9"}],"container-title":["Dentistry Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2304-6767\/11\/4\/104\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:15:39Z","timestamp":1760123739000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2304-6767\/11\/4\/104"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,13]]},"references-count":42,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["dj11040104"],"URL":"https:\/\/doi.org\/10.3390\/dj11040104","relation":{},"ISSN":["2304-6767"],"issn-type":[{"type":"electronic","value":"2304-6767"}],"subject":[],"published":{"date-parts":[[2023,4,13]]}}}