Medication-related osteonecrosis of the jaw: an emerging adverse effect of rituximab therapy – a case report

Barbara Bruno Fagundes Marques; Raquel Richelieu Lima de Andrade Pontes; Renato Liess Krebs; Brenda Xavier dos Santos; Eduardo Muniz Barretto Tinoco

doi:10.5327/2525-5711.465

Autores

Barbara Bruno Fagundes Marques Rio de Janeiro State University, Department of Periodontology – Rio de Janeiro (RJ), Brazil. https://orcid.org/0000-0003-0876-8607
Raquel Richelieu Lima de Andrade Pontes Rio de Janeiro State University, Pedro Ernesto University Hospital – Rio de Janeiro (RJ), Brazil. https://orcid.org/0009-0002-7139-5639
Renato Liess Krebs Rio de Janeiro State University, Department of endodontics – Rio de Janeiro, Brazil. https://orcid.org/0000-0002-6428-4992
Brenda Xavier dos Santos Rio de Janeiro State University, Department of endodontics – Rio de Janeiro, Brazil. https://orcid.org/0000-0003-1132-9509
Eduardo Muniz Barretto Tinoco Rio de Janeiro State University, Department of Periodontology – Rio de Janeiro (RJ), Brazil. https://orcid.org/0000-0003-4798-7175

DOI:

https://doi.org/10.5327/2525-5711.465%20

Palavras-chave:

Osteonecrosis, Rituximab, Lymphoma, Monoclonal antibodies, Photobiomodulation therapy

Resumo

Medication-related osteonecrosis of the jaw (MRONJ) is traditionally linked to antiresorptive and antiangiogenic therapies. However, recent evidence suggests that biologic agents, including monoclonal antibodies (mAbs), may also be associated with osteonecrosis. This study reports a case of MRONJ following Rituximab therapy in a patient after treating a non-Hodgkin lymphoma, emphasizing the emergence of this adverse effect in non-antiresorptive protocols. A female patient, following R-CHOP therapy, presented with a painless lesion characterized by bone exposure and suppuration in the periapical region of teeth 43 and 44. Initial management combined professional prophylaxis, antiseptic therapy, debridement, and endodontic treatment under antibiotic coverage. However, the lesion proved refractory, resulting in persistent suppuration and spontaneous bone sequestration after 5 months, which was subsequently treated surgically with adjuvant antibiotic therapy and photobiomodulation. Histopathological examination successfully ruled out malignancy. This clinical outcome highlights the increased susceptibility to bone necrosis in patients undergoing this specific immunotherapy regimen. Ultimately, the early identification of this non-antiresorptive-induced bone necrosis pathobiology is essential to facilitate conservative management and minimize the requirement for extensive surgical interventions.

Referências

1. Assouline-Dayan Y, Chang C, Greenspan A, Shoenfeld Y, Gershwin ME. Pathogenesis and natural history of osteonecrosis. Semin Arthritis Rheum. 2002;32(2):94-124. PMID: 12430099.

2. 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):920-43. https://doi.org/10.1016/J.JOMS.2022.02.008

3. Javelot MJ, Sergheraert J, Agbo-Godeau S, Levy-Weil F, Laurence S, Goudot P, et al. Rituximab as a trigger factor of medication-related osteonecrosis of the jaw. A case report. J Stomatol Oral Maxillofac Surg. 2020;121(3):300-4. https://doi.org/10.1016/j.jormas.2019.06.009

4. Ahdi HS, Wichelmann TA, Pandravada S, Ehrenpreis ED. Medication-induced osteonecrosis of the jaw: a review of cases from the Food and Drug Administration Adverse Event Reporting System (FAERS). BMC Pharmacol Toxicol. 2023;24(1):15. https://doi.org/10.1186/S40360-023-00657-y

5. Sisalli L, Giordano F, Chiacchio A, Acerra A, Caggiano M. Medication-related osteonecrosis of the jaw: a case report of an unusual side effect of adalimumab. Case Rep Dent. 2023;2023:5544285. https://doi.org/10.1155/2023/5544285

6. Maloney DG, Smith B, Rose A. Rituximab: mechanism of action and resistance. Semin Oncol. 2002;29(1 Suppl 2):2-9. PMID: 11842383.

7. Pfreundschuh M, Trümper L, Österborg A, Pettengell R, Trneny M, Imrie K, et al. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006;7(5):379-91. https://doi.org/10.1016/S1470-2045(06)70664-7

8. Baur DA, Weber JM, Collette DC, Dhaliwal H, Quereshy F. Osteonecrosis of the jaws unrelated to bisphosphonate exposure: a series of 4 cases. J Oral Maxillofac Surg. 2012;70(12):2802-8. https://doi.org/10.1016/j.joms.2012.02.019

9. Weigert KL, Lewgoy J, Mazzoleni DS, Franco FR, Enriconi L, Sasso JH. Rituximab and osteonecrosis of the jaws: case study. Oral Surg Oral Med Oral Pathol Oral Radiol. 2014;117(2):e188-9. https://doi.org/10.1016/J.OOOO.2013.12.203

10. Allegra A, Oteri G, Alonci A, Bacci F, Penna G, Minardi V, et al. Association of osteonecrosis of the jaws and POEMS syndrome in a patient assuming rituximab. J Craniomaxillofac Surg. 2014;42(4):279-82. https://doi.org/10.1016/j.jcms.2013.05.014

11. Keribin P, Guerrot D, Jardin F, Moizan H. Osteonecrosis of the jaw in a patient presenting with post-transplantation lymphoproliferative disorder treated with rituximab: a case report. J Oral Maxillofac Surg. 2017;75(12):2599-605. https://doi.org/10.1016/j.joms.2017.05.016

12. Gonzalez-Lugo JD, Kabarriti R, Mantzaris I. Osteoradionecrosis of the jaw in a patient with lymphoma treated with rituximab and concomitant involved field radiation therapy. Adv Radiat Oncol. 2018;3(4):701-4. https://doi.org/10.1016/J.ADRO.2018.05.008

13. Aghaloo TL, Tetradis S. Osteonecrosis of the jaw in the absence of antiresorptive or antiangiogenic exposure: a series of 6 cases. J Oral Maxillofac Surg. 2017;75(1):129-42. https://doi.org/10.1016/J.JOMS.2016.07.019

14. Saran S, Rauniyar A, Madhuri BV, Kundu P. Multilevel vertebral body osteonecrosis in an adult patient: a rare case with review of literature. J Assoc Physicians India. 2024;72(10):96-8. https://doi.org/10.59556/JAPI.72.0640

15. Ashtari F, Hakamifard A, Hariri A, Gholipour-shahraki T. Rituximab associated necrosis: a case report. Mult Scler Relat Disord. 2020;37:101429. https://doi.org/10.1016/j.msard.2019.101429

16. Kasi PM, Tawbi HA, Oddis CV, Kulkarni HS. Clinical review: serious adverse events associated with the use of rituximab – a critical care perspective. Crit Care. 2012;16(4):231. https://doi.org/10.1186/CC11304

17. Li Y, Toraldo G, Li A, Yang X, Zhang H, Qian WP, et al. B cells and T cells are critical for the preservation of bone homeostasis and attainment of peak bone mass in vivo. Blood. 2007;109(9):3839-48. https://doi.org/10.1182/BLOOD-2006-07-037994

18. Athni TS, Barmettler S. Hypogammaglobulinemia, late-onset neutropenia, and infections following rituximab. Ann Allergy Asthma Immunol. 2023;130(6):699-712. https://doi.org/10.1016/J.ANAI.2023.01.018

19. Di Fede O, Panzarella V, Mauceri R, Fusco V, Bedogni A, Lo Muzio L, 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;2018:2684924. https://doi.org/10.1155/2018/2684924

20. Weinstein RS, Nicholas RW, Manolagas SC. Apoptosis of osteocytes in glucocorticoid-induced osteonecrosis of the hip. J Clin Endocrinol Metab. 2000;85(8):2907-12. https://doi.org/10.1210/JCEM.85.8.6714

21. Favia G, Tempesta A, Limongelli L, Crincoli V, Maiorano E. Medication-related osteonecrosis of the jaw: surgical or non-surgical treatment? Oral Dis. 2018;24(1-2):238-42. https://doi.org/10.1111/ODI.12764

22. Vescovi P, Merigo E, Meleti M, Manfredi M, Guidotti R, Nammour S. Bisphosphonates-related osteonecrosis of the jaws: a concise review of the literature and a report of a single-centre experience with 151 patients. J Oral Pathol Med. 2012;41(3):214-21. https://doi.org/10.1111/J.1600-0714.2011.01091.x

23. Şahin O, Akan E, Tatar B, Ekmekcioğlu C, Ünal N, Odabaşı O. Combined approach to treatment of advanced stages of medication-related osteonecrosis of the jaw patients. Braz J Otorhinolaryngol. 2022;88(4):613-20. https://doi.org/10.1016/j.bjorl.2021.04.004

24. Bermúdez-Bejarano EB, Serrera-Figallo MA, Gutiérrez-Corrales A, Romero-Ruiz MM, Castillo-de-Oyagüe R, Gutiérrez-Pérez JL, et al. Prophylaxis and antibiotic therapy in management protocols of patients treated with oral and intravenous bisphosphonates. J Clin Exp Dent. 2017;9(1):e141-9. https://doi.org/10.4317/JCED.53372

25. Romeo U, Galanakis A, Marias C, Del Vecchio A, Tenore G, Palaia G, et al. Observation of pain control in patients with bisphosphonate-induced osteonecrosis using low level laser therapy: preliminary results. Photomed Laser Surg. 2011;29(7):447-52. https://doi.org/10.1089/PHO.2010.2835

26. Peplow PV, Chung TY, Baxter GD. Laser photobiomodulation of proliferation of cells in culture: a review of human and animal studies. Photomed Laser Surg. 2010;28 Suppl 1:S3-40. https://doi.org/10.1089/pho.2010.2771

27. Corazza AV, Jorge J, Kurachi C, Bagnato VS. Photobiomodulation on the angiogenesis of skin wounds in rats using different light sources. Photomed Laser Surg. 2007;25(2):102-6. https://doi.org/10.1089/PHO.2006.2011

28. Hanna R, Miron IC, Dalvi S, Arany P, Bensadoun RJ, Benedicenti S. A systematic review of laser photobiomodulation dosimetry and treatment protocols in the management of medications-related osteonecrosis of the jaws: a rationalised consensus for future randomised controlled clinical trials. Pharmaceuticals (Basel). 2024;17(8):1011. https://doi.org/10.3390/PH17081011

29. Razavi P, Jafari A, Vescovi P, Fekrazad R. Efficacy of adjunctive photobiomodulation in the management of medication-related osteonecrosis of the jaw: a systematic review. Photobiomodul Photomed Laser Surg. 2022;40(12):777-91. https://doi.org/10.1089/photob.2022.0084

30. Marx RE, Sawatari Y, Fortin M, Broumand V. Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg. 2005;63(11):1567-75. https://doi.org/10.1016/j.joms.2005.07.010