Conservative Approaches to Managing Medication-Related Osteonecrosis of the Jaw (MRONJ): A Narrative Review

Amany Hany Mohamed Kamel; Fatma AlKindi; Rawan Alharrasi; Nadiya AlKindi

doi:10.15517/6bm9sw81

Authors

Amany Hany Mohamed Kamel Dental Unit, Medical Specialities Department, Sultan Qaboos Cancer Care and Research Center, University Medical City, Muscat, Oman. Assistant Professor, Faculty of Dentistry, Cairo University, Cairo, Egypt. Author https://orcid.org/0000-0002-3562-1099
Fatma AlKindi Dental Unit, Medical Specialities Department, Sultan Qaboos Cancer Care and Research Center, University Medical City, Muscat, Oman. Author https://orcid.org/0009-0006-4993-5802
Rawan Alharrasi Dental Unit, Medical Specialities Department, Sultan Qaboos Cancer Care and Research Center, University Medical City, Muscat, Oman. Author https://orcid.org/0000-0002-9739-0425
Nadiya AlKindi Dental Unit, Medical Specialities Department, Sultan Qaboos Cancer Care and Research Center, University Medical City, Muscat, Oman. Author https://orcid.org/0009-0001-9499-2703

DOI:

https://doi.org/10.15517/6bm9sw81

Keywords:

Osteonecrosis; Zoledronic acid; Denosumab; Cancer patients; Conservative treatment; Patient care; Bone turnover.

Abstract

Medication-Related Osteonecrosis of the Jaw (MRONJ) is a severe complication associated with the use of bone-modifying agents, such as Zoledronic Acid and Denosumab, in cancer patients. It poses significant challenges in prevention, diagnosis, and treatment, highlighting the urgent need for effective and evidence-based management strategies to optimize patient outcomes. Conservative approaches have gained attention as viable alternatives to surgical intervention, particularly in early-stage MRONJ. These strategies include antimicrobial therapy, pain management, local wound care, and adjunctive therapies such as low-level laser therapy and photodynamic therapy. Hyperbaric oxygen therapy has also been investigated; however, current literature doesn’t provide strong evidence to support its routine use. Additionally, several inflammatory and bone turnover markers, including CTX, P1NP and RANKL in addition to regulatory cytokines like OPG have been studied for their potential to reflect disease progression and treatment response. While non-surgical management has shown promising results in symptom control and healing, the lack of standardized treatment protocols remains a limitation. Further research is needed to refine conservative treatment guidelines to explore reliable biomarkers and innovative therapeutic strategies to improve clinical outcomes and quality of life for affected patients.

References

Di Fede, O. et al. The dental management of patients at risk of medication-related osteonecrosis of the jaw: New paradigm of primary prevention. BioMed Research International vol. 2018 Preprint at https://doi.org/10.1155/2018/2684924 (2018).

Akashi, M. et al. A literature review of perioperative antibiotic administration in surgery for medication-related osteonecrosis of the jaw. Oral and Maxillofacial Surgery vol. 22: 369-378 Preprint at https://doi.org/10.1007/s10006-018-0732-8 (2018).

Ruggiero, S. L. et al. American association of oral and maxillofacial surgeons position paper on medication-related osteonecrosis of the jaw - 2014 update. Journal of Oral and Maxillofacial Surgery vol. 72: 1938-1956 Preprint at https://doi.org/10.1016/j.joms.2014.04.031 (2014).

AlRowis R., Aldawood A., AlOtaibi M., Alnasser E., AlSaif I., Aljaber A., Natto Z. Medication-Related Osteonecrosis of the Jaw (MRONJ): A Review of Pathophysiology, Risk Factors, Preventive Measures and Treatment Strategies. Saudi Dent J. 34 (3): 202-210. doi: 10.1016/j.sdentj.2022.01.003 (2022).

Lerman, M. A. et al. Conservative management of bisphosphonate-related osteonecrosis of the jaws: Staging and treatment outcomes. Oral Oncol 49: 977-983 (2013).

AlDhalaan, N. A., BaQais, A. & Al-Omar, A. Medication-related Osteonecrosis of the Jaw: A Review. Cureus (2020) doi:10.7759/cureus.6944

On, S. W., Cho, S. W., Byun, S. H. & Yang, B. E. Various therapeutic methods for the treatment of medication-related osteonecrosis of the jaw (Mronj) and their limitations: A narrative review on new molecular and cellular therapeutic approaches. Antioxidants vol. 10 Preprint at https://doi.org/10.3390/antiox10050680 (2021).

Katsarelis, H., Shah, N. P., Dhariwal, D. K. & Pazianas, M. Infection and medication-related osteonecrosis of the jaw. Journal of Dental Research vol. 94: 534-539 Preprint at https://doi.org/10.1177/0022034515572021 (2015).

Ristow, O. et al. Is bone turnover of jawbone and its possible over suppression by bisphosphonates of etiologic importance in pathogenesis of bisphosphonate- related osteonecrosis? Journal of Oral and Maxillofacial Surgery 72: 903-910 (2014).

Zandi, M., Dehghan, A., Janbaz, P., Malekzadeh, H. & Amini, P. The starting point for bisphosphonate-related osteonecrosis of the jaw: Alveolar bone or oral mucosa? A randomized, controlled experimental study. Journal of Cranio-Maxillofacial Surgery 45: 157-161 (2017).

Khan, A. A. et al. Case-Based Review of Osteonecrosis of the Jaw (ONJ) and Application of the International Recommendations for Management From the International Task Force on ONJ. Journal of Clinical Densitometry vol. 20: 8-24 Preprint at https://doi.org/10.1016/j.jocd.2016.09.005 (2017).

McGowan, K., McGowan, T. & Ivanovski, S. Risk factors for medication-related osteonecrosis of the jaws: A systematic review. Oral Diseases vol. 24: 527-536 Preprint at https://doi.org/10.1111/odi.12708 (2018).

Hansen, T., Kunkel, M., Weber, A. & Kirkpatrick, J. Osteonecrosis of the jaws in patients treated with bisphosphonates-histomorphologic analysis in comparison with infected osteoradionecrosis. J Oral Pathol Med 35: 155-160 (2006).

Wood, J. et al. Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid. Journal of Pharmacology and Experimental Therapeutics 302: 1055-1061 (2002).

Allen, M. R. & Burr, D. B. Mandible Matrix Necrosis in Beagle Dogs After 3 Years of Daily Oral Bisphosphonate Treatment. Journal of Oral and Maxillofacial Surgery 66: 987-994 (2008).

Estilo, C. L. et al. Osteonecrosis of the Maxilla and Mandible in Patients with Advanced Cancer Treated with Bisphosphonate Therapy. Oncologist 13: 911-920 (2008).

Naik, N. H. & Russo, T. A. Bisphosphonate-related osteonecrosis of the jaw: The role of actinomyces. Clinical Infectious Diseases 49: 1729-1732 (2009).

Sedghizadeh, P. P. et al. Identification of Microbial Biofilms in Osteonecrosis of the Jaws Secondary to Bisphosphonate Therapy. Journal of Oral and Maxillofacial Surgery 66: 767-775 (2008).

Katsarelis, H., Shah, N. P., Dhariwal, D. K. & Pazianas, M. Infection and medication-related osteonecrosis of the jaw. Journal of Dental Research vol. 94: 534-539 Preprint at https://doi.org/10.1177/0022034515572021 (2015).

Geissmann, F. et al. Development of monocytes, macrophages, and dendritic cells. Science vol. 327: 656-661 Preprint at https://doi.org/10.1126/science.1178331 (2010).

Roelofs, A. J. et al. Fluorescent risedronate analogues reveal bisphosphonate uptake by bone marrow monocytes and localization around osteocytes in vivo. Journal of Bone and Mineral Research 25: 606-616 (2010).

Murray, C. E. & Coleman, C. M. Impact of diabetes mellitus on bone health. International Journal of Molecular Sciences vol. 20 Preprint at https://doi.org/10.3390/ijms20194873 (2019).

Rahimi-Nedjat, R. K., Sagheb, K., Pabst, A., Olk, L. & Walter, C. Diabetes mellitus and its association to the occurrence of medication-related osteonecrosis of the jaw. Dent J (Basel) 4, (2016).

Leite, F. R. M., Nascimento, G. G., Scheutz, F. & López, R. Effect of Smoking on Periodontitis: A Systematic Review and Meta-regression. American Journal of Preventive Medicine vol. 54: 831-841 Preprint at https://doi.org/10.1016/j.amepre.2018.02.014 (2018).

McGowan, K., McGowan, T. & Ivanovski, S. Risk factors for medication-related osteonecrosis of the jaws: A systematic review. Oral Diseases vol. 24: 527-536 Preprint at https://doi.org/10.1111/odi.12708 (2018).

Kuroshima, S., Sasaki, M., Murata, H. & Sawase, T. Medication-related osteonecrosis of the jaw-like lesions in rodents: A comprehensive systematic review and meta-analysis. Gerodontology vol. 36: 313-324 Preprint at https://doi.org/10.1111/ger.12416 (2019).

Kuroshima, S., Sasaki, M. & Sawase, T. Medication-related osteonecrosis of the jaw: A literature review. Journal of Oral Biosciences vol. 61: 99-104 Preprint at https://doi.org/10.1016/j.job.2019.03.005 (2019).

Hoefert, S., Schmitz, I., Tannapfel, A. & Eufinger, H. Importance of microcracks in etiology of bisphosphonate-related osteonecrosis of the jaw: A possible pathogenetic model of symptomatic and non-symptomatic osteonecrosis of the jaw based on scanning electron microscopy findings. Clin Oral Investig 14: 271-284 (2010).

Yarom, N. et al. Medication-Related Osteonecrosis of the Jaw: MASCC/ISOO/ASCO Clinical Practice Guideline. J Clin Oncol 37: (2019).

Voss, P. J., Poxleitner, P., Schmelzeisen, R., Stricker, A. & Semper-Hogg, W. Update MRONJ and perspectives of its treatment. Journal of Stomatology, Oral and Maxillofacial Surgery vol. 118: 232-235 Preprint at https://doi.org/10.1016/j.jormas.2017.06.012 (2017).

Rosella, D. et al. Medication-related osteonecrosis of the jaw: Clinical and practical guidelines. Journal of International Society of Preventive and Community Dentistry vol. 6: 97-104 Preprint at https://doi.org/10.4103/2231-0762.178742 (2016).

Bermúdez-Bejarano, E. B. et al. Prophylaxis and antibiotic therapy in management protocols of patients treated with oral and intravenous bisphosphonates. J Clin Exp Dent 9: e141-e149 (2017).

Pardo-Zamora, G., Martínez, Y., Moreno, J. A. & Ortiz-Ruíz, A. J. Treatment of stage 2 medication-induced osteonecrosis of the jaw: A case series. Int J Environ Res Public Health 18: 1-18 (2021).

Marx, R. E., Sawatari, Y., Fortin, M. & Broumand, V. Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: Risk factors, recognition, prevention, and treatment. Journal of Oral and Maxillofacial Surgery 63: 1567-1575 (2005).

Barrientos Lezcano, F. J. et al. Osteonecrosis de Los Maxilares Inducida Por Bifosfonatos: Prevención y Actitud Terapéutica Bisphosphonate Induced Osteonecrosis of the Jaws: Prevention and Therapeutic Approach. (2007).

Campisi, G., Bedogni, A. & Fusco, V. Giuseppina Campisi. Medication-Related Osteonecrosis of Jaws (MRONJ) Prevention and Diagnosis: Italian Consensus Update 2020 International Journal of Environmental Research and Public Health (2020) doi:https://doi.org/10.3390/ijerph17165998

Hinson, A. M., Smith, C. W., Siegel, E. R. & Stack, B. C. Is bisphosphonate-related osteonecrosis of the jaw an infection? A histological and microbiological ten-year summary. International Journal of Dentistry vol. 2014 Preprint at https://doi.org/10.1155/2014/452737 (2014).

Alons, K., Kuijpers, S. C. C., Jong, E. de & van Merkesteyn, J. P. R. Treating low- and medium-potency bisphosphonate-related osteonecrosis of the jaws with a protocol for the treatment of chronic suppurative osteomyelitis: report of 7 cases. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontology 107, (2009).

Junquera, L. M. & 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) * Diagnosis, Prevention, and Treatment of Bisphosphonate-Associated Osteonecrosis of the Jaw. Recommendations of the Spanish Society of Oral and Maxillofacial Surgery (SECOM). Rev Esp Cir Oral y Maxilofac vol. 30 (2008).

Heifetz-Li, J. J. et al. Systematic review of the use of pentoxifylline and tocopherol for the treatment of medication-related osteonecrosis of the jaw. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology vol. 128: 491-497.e2 Preprint at https://doi.org/10.1016/j.oooo.2019.08.004 (2019).

Ferlito, S., Puzzo, S., Palermo, F. & Verzì, P. Treatment of bisphosphonate-related osteonecrosis of the jaws: Presentation of a protocol and an observational longitudinal study of an Italian series of cases. British Journal of Oral and Maxillofacial Surgery 50: 425-429 (2012).

Bermúdez-Bejarano, E. B. et al. Prophylaxis and antibiotic therapy in management protocols of patients treated with oral and intravenous bisphosphonates. J Clin Exp Dent 9: e141-e149 (2017).

Fleiter, N. et al. Clinical use and safety of a novel gentamicin-releasing resorbable bone graft substitute in the treatment of osteomyelitis/osteitis. Bone Joint Res 3: 223-229 (2014).

Chia, C. L. K., Shelat, V. G., Low, W., George, S. & Rao, J. The use of Collatamp G, local gentamicincollagen sponge, in reducing wound infection. Int Surg 99: 565-570 (2014).

Bagán, J. et al. Hospital (4) Head of the Medical Oncology Service in the Pontevedra ‘Montecelo’ Hospital (5) Hematology Registrar. Hematology Service, Salamanca University Hospital (2007).

Wutzl, A. et al. Factors influencing surgical treatment of bisphosphonate-related osteonecrosis of the jaws. Head Neck 34: 194-200 (2012).

Hinson, A. M., Siegel, E. R. & Stack, B. C. Temporal correlation between bisphosphonate termination and symptom resolution in osteonecrosis of the jaw: A pooled case report analysis. Journal of Oral and Maxillofacial Surgery 73: 53-62 (2015).

Ruggiero SL, D. T. A. T. C. E. W. B. K. D. American Association of Oral and Maxillofacial Surgeons’ Position Paper on Medication-Related Osteonecrosis of the Jaws-2022 Update. J Oral Maxillofac Surg. 80: 920-940 (2022).

Aboalela, A. A. et al. The Effect of Antiresorptive Drug Holidays on Medication-Related Osteonecrosis of the Jaw: A Systematic Review and Meta-Analysis. Cureus (2022) doi:10.7759/cureus.30485

Lorenzo-pouso, A. I. et al. Medication-related osteonecrosis of the jaw: A critical narrative review. Journal of Clinical Medicine vol. 10 Preprint at https://doi.org/10.3390/jcm10194367 (2021).

Terpos, E. et al. The use of bisphosphonates in multiple myeloma: Recommendations of an expert panel on behalf of the European Myeloma Network. Annals of Oncology vol. 20: 1303-1317 Preprint at https://doi.org/10.1093/annonc/mdn796 (2009).

Khan, A. A. et al. Canadian Consensus Practice Guidelines for Bisphosphonate Associated Osteonecrosis of the Jaw. (2008).

D’Amato, S. et al. Resective surgery versus debridement in stage 2 medication-related osteonecrosis of the jaw. Applied Sciences (Switzerland) 11: (2021).

Cicco, D. et al. Citation: Medication-Related Osteonecrosis of the Jaws: A Comparison of SICMF-SIPMO and AAOMS Guidelines. (2023) doi:10.3390/diagnostics

Varoni, E. M. et al. Conservative management of medication-related osteonecrosis of the jaws (Mronj): A retrospective cohort study. Antibiotics 10: 1-16 (2021).

Nicolatou-Galitis, O. 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 vol. 127: 117-135 Preprint at https://doi.org/10.1016/j.oooo.2018.09.008 (2019)

Mozzati, M., Arata, V. & Gallesio, G. Tooth extraction in patients on zoledronic acid therapy. Oral Oncol 48: 817-821 (2012).

Beth-Tasdogan, N. H., Mayer, B., Hussein, H. & Zolk, O. Interventions for managing medication-related osteonecrosis of the jaw. Cochrane Database of Systematic Reviews vol. 2017 Preprint at https://doi.org/10.1002/14651858.CD012432.pub2 (2017).

Hadad, H. et al. Beta tricalcium phosphate, either alone or in combination with antimicrobial photodynamic therapy or doxycycline, prevents medication-related osteonecrosis of the jaw. Sci Rep 12, (2022).

Udagawa, N., Koide, M., Nakamura, M. & Takahashi, N. Minocycline to be used a potential anti-bone resorption agents due to the suppression of osteoclastic bone resorption. in Journal of Oral Biosciences vol. 55: 16-22 (Japanese Association for Oral Biology, 2013).

Sacco R., Sartoretto S.C., de Brito Resende R.F., de Albuquerque Calasans-Maia J., Rossi A.M., de Souza Lima V.H., de Almeida Barros Mourão C.F., Granjeiro J.M., Yates J., Calasans-Maia M.D. The Use of Hydroxyapatite Loaded with Doxycycline (HADOX) in Dentoalveolar Surgery as a Risk-Reduction Therapeutic Protocol in Subjects Treated with Different Bisphosphonate Dosages. Medicina (Kaunas). 2022 Dec 27; 59 (1): 46. doi: 10.3390/medicina59010046

Shakeri, F., Tebyanian, H., Karami, A., Babavalian, H. & Tahmasbi, M. H. Effect of topical phenytoin on wound healing. Trauma Mon 22: (2017).

Tabrizi, R., Arabi, A. M., Arabion, H. R. & Gholami, M. Jaw osteomyelitis as a complication in osteopetrosis. Journal of Craniofacial Surgery 21: 136-141 (2010).

Shaw, J., Hughes, C. M., Lagan, K. M. & Bell, P. M. The clinical effect of topical phenytoin on wound healing: A systematic review. British Journal of Dermatology vol. 157: 997-1004 Preprint at https://doi.org/10.1111/j.1365-2133.2007.08160.x (2007).

Er, N., Kasaboǧlu, O. ǧuzcan, Atabek, A., Öktemer, K. & Akkocaoǧlu, M. Topical Phenytoin Treatment in Bimaxillary Osteomyelitis Secondary to Infantile Osteopetrosis: Report of a Case. Journal of Oral and Maxillofacial Surgery 64: 1160-1164 (2006).

Karasneh, J. A., Al-Eryani, K., Clark, G. T. & Sedghizadeh, P. P. Modified protocol including topical minocycline in orabase to manage medication-related osteonecrosis of the jaw cases. Journal of Oral Pathology and Medicine 45: 718-720 (2016).

Melichercik, P. et al. The effect of Vancomycin degradation products in the topical treatment of osteomyelitis. Bratislava Medical Journal 115: 796-799 (2014).

Svejda, B. et al. Positionspapier zur medikamentenassoziierten Osteonekrose des Kiefers (MRONJ). Stomatologie 112: 241-246 (2015).

Atalay, B. et al. Bisphosphonate-related osteonecrosis: Laser-assisted surgical treatment or conventional surgery? Lasers Med Sci 26: 815-823 (2011).

Altay, M. A., Tasar, F., Tosun, E. & Kan, B. Low-level laser therapy supported surgical treatment of bisphosphonate related osteonecrosis of jaws: A retrospective analysis of 11 cases. Photomed Laser Surg 32: 468-475 (2014).

Weber, J. B. B., Camilotti, R. S. & Ponte, M. E. Efficacy of laser therapy in the management of bisphosphonate-related osteonecrosis of the jaw (BRONJ): a systematic review. Lasers in Medical Science vol. 31: 1261-1272 Preprint at https://doi.org/10.1007/s10103-016-1929-4 (2016).

Latifyan, S., Genot, M. T. & Klastersky, J. Bisphosphonate-related osteonecrosis of the jaw: a review of the potential efficacy of low-level laser therapy. Supportive Care in Cancer 24: 3687-3693 (2016).

Woo, S.-B., Hellstein, J. W. & Kalmar, J. R. Systematic Review: Bisphosphonates and Osteonecrosis of the Jaws. www.annals.org (2006).

Freiberger, J. J. et al. Hyperbaric Oxygen Treatment and Bisphosphonate-Induced Osteonecrosis of the Jaw: A Case Series. Journal of Oral and Maxillofacial Surgery 65: 1321-1327 (2007).

Rollason, V. et al. Interventions for treating bisphosphonate-related osteonecrosis of the jaw (BRONJ). Cochrane Database of Systematic Reviews vol. 2016 Preprint at https://doi.org/10.1002/14651858.CD008455.pub2 (2016).

Ripamonti, C. I., Cislaghi, E., Mariani, L. & Maniezzo, M. Efficacy and safety of medical ozone (O3) delivered in oil suspension applications for the treatment of osteonecrosis of the jaw in patients with bone metastases treated with bisphosphonates: Preliminary results of a phase I-II study. Oral Oncol 47: 185-190 (2011).

Agrillo, A. et al. Ozone Therapy in the Treatment of Avascular Bisphosphonate-Related Jaw Osteonecrosis. (2007) DOI:10.1097/scs.0b013e31857261f

Sim, I.-W. et al. Teriparatide Promotes Bone Healing in Medication-Related Osteonecrosis of the Jaw: A Placebo-Controlled, Randomized Trial. J Clin Oncol vol. 38 https://doi.org/10. (2020).

Morishita, K. et al. Treatment outcomes of adjunctive teriparatide therapy for medication-related osteonecrosis of the jaw (MRONJ): A multicenter retrospective analysis in Japan. Journal of Orthopaedic Science 25: 1079-1083 (2020).

dos Santos Ferreira, L. et al. Is teriparatide therapy effective for medication-related osteonecrosis of the jaw? A systematic review and meta-analysis. Osteoporosis International vol. 32: 2449-2459 Preprint at https://doi.org/10.1007/s00198-021-06078-z (2021).

Cheung, A. & Seeman, E. Teriparatide Therapy for Alendronate-Associated Osteonecrosis of the Jaw. New England Journal of Medicine 363: 2473-2474 (2010).

Epstein, M. S., Wicknick, F. W., Epstein, J. B., Berenson, J. R. & Gorsky, M. Management of bisphosphonate-associated osteonecrosis: Pentoxifylline and tocopherol in addition to antimicrobial therapy. An initial case series. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontology 110: 593-596 (2010).

Cavalcante, R. C. & Tomasetti, G. Pentoxifylline and tocopherol protocol to treat medication-related osteonecrosis of the jaw: A systematic literature review. Journal of Cranio-Maxillofacial Surgery vol. 48: 1080-1086 Preprint at https://doi.org/10.1016/j.jcms.2020.09.008 (2020).

Colapinto, G. et al. Outcomes of a Pharmacological Protocol with Pentoxifylline and Tocopherol for the Management of Medication-Related Osteonecrosis of the Jaws (MRONJ): A Randomized Study on 202 Osteoporosis Patients. J Clin Med 12, (2023).

Sun, X. K., Li, R., Yang, X. L. & Yuan, L. Efficacy and safety of topical oxygen therapy for diabetic foot ulcers: An updated systematic review and meta-analysis. Int Wound J 19: 2200-2209 (2022).

Deliberador, T. M., Stutz, C., Sartori, E., Kluppel, L. & de Freitas, R. M. Treatment of Medication-Related Osteonecrosis of the Jaws (MRONJ) with Topical Therapy Using Active Oxygen Gel. Clin Cosmet Investig Dent 16: 249-254 (2024).

Baumhoer, D. Bone-Related Lesions of the Jaws. Surgical Pathology Clinics vol. 10: 693-704 Preprint at https://doi.org/10.1016/j.path.2017.04.007 (2017).

Santos, G. N. M. et al. Radiomics in bone pathology of the jaws. Dentomaxillofacial Radiology vol. 52 Preprint at https://doi.org/10.1259/dmfr.20220225 (2023).

Parekh, V. & Jacobs, M. A. Radiomics: a new application from established techniques. Expert Review of Precision Medicine and Drug Development vol. 1: 207-226 Preprint at https://doi.org/10.1080/23808993.2016.1164013 (2016).

Park, J. E. et al. Quality of science and reporting of radiomics in oncologic studies: room for improvement according to radiomics quality score and TRIPOD statement. Eur Radiol 30: 523-536 (2020).

Di Ianni, M. et al. Mesenchymal cells recruit and regulate T regulatory cells. Exp Hematol 36: 309-318 (2008).

Kikuiri, T. et al. Cell-based immunotherapy with mesenchymal stem cells cures bisphosphonate-related osteonecrosis of the jaw-like disease in mice. Journal of Bone and Mineral Research 25: 1668-1679 (2010).

Bouland, C. L. et al. Treatment of medication-related osteonecrosis of the jaw with cell therapy. Front Cell Dev Biol 12, (2024).

Anderson, K. et al. JOURNAL OF CLINICAL ONCOLOGY Role of Bone-Modifying Agents in Multiple Myeloma: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol 36: 812-818 (2018).

Bertoldo, F. et al. Medication related osteonecrosis (MRONJ) in the management of CTIBL in breast and prostate cancer patients. Joint report by SIPMO AND SIOMMMS. J Bone Oncol 50, (2025).

Cicco, D. et al. Citation: Medication-Related Osteonecrosis of the Jaws: A Comparison of SICMF-SIPMO and AAOMS Guidelines. (2023) doi:10.3390/diagnostics.

Mücke, T. et al. Prevention of bisphosphonate-related osteonecrosis of the jaws in patients with prostate cancer treated with zoledronic acid – A prospective study over 6 years. Journal of Cranio-Maxillofacial Surgery 44: 1689-1693 (2016).

Bedogni, A. et al. Italian position paper (SIPMO-SICMF) on medication-related osteonecrosis of the jaw (MRONJ). Oral Diseases vol. 30: 3679-3709 Preprint at https://doi.org/10.1111/odi.14887 (2024).

Ristow, O. et al. Wound closure and alveoplasty after preventive tooth extractions in patients with antiresorptive intake-A randomized pilot trial. Oral Dis 27: 532-546 (2021).

Liu, C. et al. Management of Tooth Extraction in Patients Taking Antiresorptive Drugs: An Evidence Mapping Review and Meta-Analysis. Journal of Clinical Medicine vol. 12 Preprint at https://doi.org/10.3390/jcm12010239 (2023).

Kyrgidis, A., Arora, A., Lyroudia, K. & Antoniades, K. Root canal therapy for the prevention of osteonecrosis of the jaws: An evidence-based clinical update. Australian Endodontic Journal 36: 130-133 (2010).

AAE Position Statement. https://www.aae.org/specialty/wp-content/uploads/sites/2/2017/07/bisphosonatesstatement.pdf (2010).

Colleagues for Excellence ENDODONTICS. www.aae.org/colleagues (2012)