Osteonecrose Induzida por Bifosfonatos Aspectos Farmacológicos e Fisiopatológicos
DOI:
https://doi.org/10.36557/2674-8169.2025v7n5p1297-1316Palavras-chave:
Osteonecrose, bifosfonatos, fatores de risco, antirreabsortivos ósseosResumo
A osteonecrose dos maxilares induzida por bifosfonatos (ONMB) é uma complicação grave associada ao uso prolongado de agentes antirreabsortivos como bifosfonatos, empregados no tratamento de doenças ósseas metastáticas, osteoporose e outras condições. Este estudo teve como objetivo analisar os mecanismos farmacológicos, fatores de risco e estratégias de manejo da ONMB, com base em evidências científicas recentes. Realizou-se uma revisão de literatura nas bases PubMed e Scielo, incluindo 22 artigos publicados entre 2020 e 2025, que abordaram incidência, fisiopatologia, prevenção e tratamento. Em conclusão, a osteonecrose induzida por bifosfonatos (ONMB) apresenta incidência variável (0,8–16,3%) conforme tipo, dose e duração do agente, associada a fatores como extrações dentárias, comorbidades e saúde periodontal. Seus mecanismos incluem supressão osteoclástica prolongada, toxicidade aos osteócitos e efeitos antiangiogênicos, com denosumabe exigindo monitoramento específico. Estratégias preventivas combinam intervenções locais (fibrina rica em plaquetas, laser) e sistêmicas (ômega-3, pentoxifilina/tocoferol), eficazes em estágios iniciais, enquanto protocolos multidisciplinares e pesquisas em modelos preditivos por IA são necessários para otimizar o manejo.
Downloads
Referências
Drake MT, Clarke BL, Khosla S. Bisphosphonates: mechanism of action and role in clinical practice. Mayo Clin Proc. 2008 Sep;83(9):1032-45. doi: 10.4065/83.9.1032. PMID: 18775204; PMCID: PMC2667901.
Maciel AP, Quispe RA, Martins LJO, Caldas RJ, Santos PS da S. Clinical profile of individuals with bisphosphonate-related osteonecrosis of the jaw: an integrative review. Sao Paulo Med J [Internet]. 2020Jul;138(4):326–35. Available from: https://doi.org/10.1590/1516-3180.2019.0352.R2.15052020
Gupta M, Gupta N. Osteonecrose mandibular relacionada a bifosfonatos. [Atualizado em 24 de julho de 2023]. Em: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; jan. de 2025. Disponível em: https://www.ncbi.nlm.nih.gov/books/NBK534771/
Singh M, Gonegandla GS. Bisphosphonate-Induced Osteonecrosis of the Jaws (BIONJ). J Maxillofac Oral Surg. 2020 Jun;19(2):162-167. doi: 10.1007/s12663-019-01211-2. Epub 2019 Apr 8. PMID: 32346224; PMCID: PMC7176749.
Ruggiero SL, Dodson TB, Assael LA, Landesberg R, Marx RE, Mehrotra B, American Association of Oral and Maxillofacial Surgeons American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws—2009 update. J Oral Maxillofac Surg. 2009;67(5 Suppl):2–12. doi: 10.1016/j.joms.2009.01.009.
Marx RE, Stern DS. Oral and maxillofacial pathology: a rationale for diagnosis and treatment. Chicago: Quintessence; 2002.
Marx RE. Reconstruction of defects caused by bisphosphonate-induced osteonecrosis of jaws. J Oral Maxillofac Surg. 2009;67:107–119. doi: 10.1016/j.joms.2008.12.007.
Marx RE, Sawatari Y, Fortin M, Broumand V. Biphosphonate induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention and treatment. J Oral Maxillofac Surg. 2005;63:1567–1575. doi: 10.1016/j.joms.2005.07.010.
Okawa H, Kondo T, Hokugo A, Cherian P, Campagna JJ, Lentini NA, Sung EC, Chiang S, Lin YL, Ebetino FH, John V, Sun S, McKenna CE, Nishimura I. Mechanism of bisphosphonate-related osteonecrosis of the jaw (BRONJ) revealed by targeted removal of legacy bisphosphonate from jawbone using competing inert hydroxymethylene diphosphonate. Elife. 2022 Aug 26;11:e76207. doi: 10.7554/eLife.76207. PMID: 36017995; PMCID: PMC9489207.
Lin L, Ren Y, Wang X, Yao Q. Effects of Bisphosphonates and Denosumab on Dental Implants: A Systematic Review With Meta-Analysis. Oral Dis. 2025 May 6. doi: 10.1111/odi.15373. Epub ahead of print. PMID: 40326505.
Ruksakiet K, Jarusriwanna A, Sadaeng W, Laoruengthana A, Sang-Ngoen T, Dhippayom T. Effects of discontinuing different antiresorptive regimens on medication-related osteonecrosis of the jaw in patients undergoing dental procedures: a systematic review and network meta-analysis. EFORT Open Rev. 2025 May 5;10(5):258-266. doi: 10.1530/EOR-2024-0133. PMID: 40326547; PMCID: PMC12061011.
Ghio C, Gravier-Dumonceau R, Lafforgue P, Giorgi R, Pham T. Identifying a predictive level of serum C-terminal telopeptide associated with a low risk of medication-related osteonecrosis of the jaw secondary to oral surgery: A systematic review and meta-analysis. PLoS One. 2025 May 5;20(5):e0318260. doi: 10.1371/journal.pone.0318260. PMID: 40323917; PMCID: PMC12052178.
Ali DS et al. Antiresorptive Therapy to Reduce Fracture Risk and Effects on Dental Implant Outcomes in Patients With Osteoporosis: A Systematic Review and Osteonecrosis of the Jaw Taskforce Consensus Statement. Endocr Pract. 2025 May;31(5):686-698. doi: 10.1016/j.eprac.2025.02.016. PMID: 40335186.
Tenore G, et al.. Surgical extraction with photobiomodulation as an adjunctive modality in patients at-risk for medication-related osteonecrosis of the jaw: retrospective study. BMC Oral Health. 2025 Apr 24;25(1):627. doi: 10.1186/s12903-025-05776-y. PMID: 40275275; PMCID: PMC12023369.
Schubert A, Brockmeyer P, Kauffmann P, Wiegel J, Lautenbacher F, Miosge N, Schminke B. Alterations of bone proteins in medication-related osteonecrosis of the jaw. Eur J Oral Sci. 2025 Apr;133(2):e70003. doi: 10.1111/eos.70003. Epub 2025 Feb 19. PMID: 39972547; PMCID: PMC11919809.
Maracineanu R, Tudor A, Hum I, Urtila F, Streian F, Talpos-Niculescu S, Motoc M. Platelet-Rich Fibrin in MRONJ Management: A Prospective Comparative Study on Its Effectiveness in Prevention and Treatment. Medicina (Kaunas). 2025 Mar 28;61(4):625. doi: 10.3390/medicina61040625. PMID: 40282916; PMCID: PMC12028908.
de Almeida JM, Turini HD, Matheus HR, Vitória OAP, Piovezan BR, Dalmonica RHB, de Abreu Furquim EM, Ervolino E. Omega-3 attenuates the severity of medication-related osteonecrosis of the jaws in rats treated with zoledronate. PLoS One. 2025 Mar 26;20(3):e0320413. doi: 10.1371/journal.pone.0320413. PMID: 40138277; PMCID: PMC11940605.
Toriumi S, Shimokawa K, Yamamoto M, Uesawa Y. Development of a Medication-Related Osteonecrosis of the Jaw Prediction Model Using the FDA Adverse Event Reporting System Database and Machine Learning. Pharmaceuticals (Basel). 2025 Mar 17;18(3):423. doi: 10.3390/ph18030423. PMID: 40143199; PMCID: PMC11945420.
Słowik Ł, Totoń E, Nowak A, Wysocka-Słowik A, Okła M, Ślebioda Z. Pharmacological Treatment of Medication-Related Osteonecrosis of the Jaw (MRONJ) with Pentoxifylline and Tocopherol. J Clin Med. 2025 Feb 3;14(3):974. doi: 10.3390/jcm14030974. PMID: 39941644; PMCID: PMC11818125.
Brunner C, et al. Incidence of Medication-Related Osteonecrosis of the Jaw in Patients With Breast Cancer During a 20-Year Follow-Up: A Population-Based Multicenter Retrospective Study. J Clin Oncol. 2025 Jan 10;43(2):180-188. doi: 10.1200/JCO.24.00171. Epub 2024 Aug 20. PMID: 39163561; PMCID: PMC11708989.
Gonzaga AKG, Morais HGF, Oliveira CDM, Campos MLR, Diaz CRLDM, Custódio M, Andrade NS, Santana T. Imaging aspects of maxillomandibular bone alterations in patients with multiple myeloma treated with bisphosphonates: A systematic review. Imaging Sci Dent. 2024 Sep;54(3):221-231. doi: 10.5624/isd.20240032. Epub 2024 Jul 17. PMID: 39371309; PMCID: PMC11450414.
Chavarry NGM, et al. Efeitos do alendronato de sódio na cicatrização alveolar após extração dentária: uma revisão sistemática de estudos em animais. Braz oral res [Internet]. 2024;38:e038. Disponível em: https://doi.org/10.1590/1807-3107bor-2024.vol38.0038
Seluki R, Seluki M, Vaitkeviciene I, Jagelaviciene E. Comparison of the Effectiveness of Conservative and Surgical Treatment of Medication-Related Osteonecrosis of the Jaw: a Systematic Review. J Oral Maxillofac Res. 2023 Dec 31;14(4):e1. doi: 10.5037/jomr.2023.14401. PMID: 38222882; PMCID: PMC10783881.
Bracchi P, Zecca E, Brunelli C, Miceli R, Tinè G, Maniezzo M, Lo Dico S, Caputo M, Shkodra M, Caraceni AT. A real-world study on the prevalence and risk factors of medication related osteonecrosis of the jaw in cancer patients with bone metastases treated with Denosumab. Cancer Med. 2023 Sep;12(17):18317-18326. doi: 10.1002/cam4.6429. Epub 2023 Aug 9. PMID: 37559413; PMCID: PMC10523953.
Carlos ACAM, et al. Risk factors for bisphosphonate-related osteonecrosis of the jaws in bone metastatic breast and prostate cancer under zoledronate treatment: a retrospective analysis from 10 years of evaluation. Asian Pac J Cancer Prev. 2023 Aug 1;24(8):2681–2689. doi: 10.31557/APJCP.2023.24.8.2681. PMID: 37642054; PMCID: PMC10685221.
Guirguis RH, Tan LP, Hicks RM, Hasan A, Duong TD, Hu X, Hng JYS, Hadi MH, Owuama HC, Matthyssen T, McCullough M, Canfora F, Paolini R, Celentano A. In Vitro Cytotoxicity of Antiresorptive and Antiangiogenic Compounds on Oral Tissues Contributing to MRONJ: Systematic Review. Biomolecules. 2023 Jun 10;13(6):973. doi: 10.3390/biom13060973. PMID: 37371553; PMCID: PMC10296421.
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 (Kaunas). 2023 May 18;59(5):972. doi: 10.3390/medicina59050972. PMID: 37241204; PMCID: PMC10221057.
Kemp APT, Ferreira VHC, Mobile RZ, Brandão TB, Sassi LM, Zarpellon A, et al.. Risk factors for medication-related osteonecrosis of the jaw and salivary IL-6 IN cancer patients. Braz j otorhinolaryngol [Internet]. 2022Sep;88(5):683–90.
Soutome S, Otsuru M, Hayashida S, Murata M, Yanamoto S, Sawada S, Kojima Y, Funahara M, Iwai H, Umeda M, Saito T. Relationship between tooth extraction and development of medication-related osteonecrosis of the jaw in cancer patients. Sci Rep. 2021 Aug 26;11(1):17226. doi: 10.1038/s41598-021-96480-8. PMID: 34446755; PMCID: PMC8390686.
Kizub DA, Miao J, Schubert MM, Paterson AHG, Clemons M, Dees EC, Ingle JN, Falkson CI, Barlow WE, Hortobagyi GN, Gralow JR. 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 May;29(5):2509-2517. doi: 10.1007/s00520-020-05748-8. Epub 2020 Sep 15. PMID: 32929540; PMCID: PMC7956914.
Govaerts D, Piccart F, Ockerman A, Coropciuc R, Politis C, Jacobs R. Adjuvant therapies for MRONJ: A systematic review. Bone. 2020 Dec;141:115676. doi: 10.1016/j.bone.2020.115676. Epub 2020 Oct 3. PMID: 33022455.
Downloads
Publicado
Como Citar
Edição
Seção
Licença
Copyright (c) 2025 Marco Antônio Franco Cançado, Francielle Nunes de Lira Cunha, Gabriela Cristina Baccaro, Mauricio Santos Souza, Tatiana Santos Rebouças, Carla Cristine Vieira Araújo Machado, Isabela Maria Gontijo Machado, Damián Marco Bertiz Loza, Maria Thaynara Lopes da Silva , Vitória Ribeiro de de Araújo, Gabriella Peres Cabral, Raimunda Rodrigues da Silva Brito, Karen Pollyana Corrêa Ferreira, Alice Angélica de Souza Pereira, Rodolfo Medeiros Gonçalves de Paiva, Amanda Cypriano Alves
Este trabalho está licenciado sob uma licença Creative Commons Attribution 4.0 International License.
Os autores são detentores dos direitos autorais mediante uma licença CCBY 4.0.
