Knowledge of Brazilian dentists about bisphosphonate-associated osteonecrosis of the jaw / Conhecimento de dentistas brasileiros sobre a osteonecrose dos maxilares associada ao uso de bisfosfonatos

Osteonecrosis of the jaw associated with bisphosphonate use is a matter of utmost importance in clinical practice for the safe treatment of patients using this medication. Objective: The aim of this study was to evaluate the level of knowledge of dentists who carry out clinical practice about bisphosphonate-associated jaw osteonecrosis. Material and Methods: The methodology used in the present research consisted of a non-probability sampling approach for the selection of participants. To conduct the study, a questionnaire created on the Google Forms platform was sent via Direct on Instagram to the professionals who agreed to participate. The data were sent for analysis, using the frequency for each response, and the professionals were divided into subcategories according to their time of professional practice. Results: Participants were familiar with the purpose of the medication (65%) or had heard of it (34%); regarding the professionals' opinion on their knowledge and practice about bisphosphonate-related osteonecrosis a significant percentage (93.24%) responded positively regarding the existence of side effects resulting from the therapeutic use of bisphosphonates and 48.65% self-evaluated their level of knowledge on the subject as insufficient. Conclusion: The study reveals that almost all participating dentists have good knowledge about the effects caused by bisphosphonates, but some of them still do not feel specifically confident about the management and knowledge of jaw osteonecrosis (AU)

A osteonecrose dos maxilares associada ao uso de bisfosfonatos é um assunto de suma importância na prática clínica para o atendimento seguro dos pacientes que fazem uso terapêutico do medicamento. Objetivo: O objetivo deste trabalho foi avaliar o nível de conhecimento de cirurgiões dentistas que realizam atendimento clínico acerca da osteonecrose dos maxilares associada ao uso dos bisfosfonatos. Material e Métodos: A metodologia utilizada na presente pesquisa consistiu em uma abordagem de amostragem não probabilística para a seleção dos participantes. Para conduzir o estudo, enviamos um questionário criado na plataforma Google Forms via Direct no Instagram para os profissionais que concordaram em participar. Os dados foram enviados para análise, usando a frequência para cada resposta, sendo que os profissionais foram divididos em subcategorias por tempo de formação. Resultados: Os participantes estavam familiarizados com a finalidade do medicamento (65%) ou já haviam ouvido falar deles (34%); em relação à opinião dos profissionais sobre seu conhecimento e prática acerca da osteonecrose relacionada aos bisfosfonatos, observou-se que 48,65% autoavaliaram seu nível de conhecimento sobre o assunto como insuficiente e uma parcela expressiva (93,24%) respondeu positivamente em relação à existência de efeitos colaterais decorrentes ao uso terapêutico dos bisfosfonatos. Conclusão: O estudo revela que quase todos os dentistas participantes possuem um bom conhecimento acerca dos efeitos causados pelos bisfosfonatos, mas que parte deles ainda não se sentem seguros especificamente em relação ao manejo e conhecimento da osteonecrose dos maxilares (AU)

Osteonecrose dos maxilares relacionada ao uso demedicamentos: características patológicas, diagnóstico,prevenção e estratégias terapêuticas / Medication-related osteonecrosis of the jaws: pathological characteristics, diagnosis, prevention and therapeutic strategies

Objetivo: Este trabalho tem como propósito fornecer uma análise abrangente das características clínicas, etiológicas, radiográficas e histopatológicas da osteonecrose dos maxilares relacionada ao uso de medicamentos, além de abordar os métodos de diagnóstico, prevenção e estratégias terapêuticas. Materiais e métodos: foi realizada uma busca por artigos científicos publicados no período de 2015 a 2023, utilizando as bases de dados Scientific Electronic Library Online (SciELO), US National Library of Medicine (PubMed) e ScienceDirect. Conclusão: Embora infrequente, há um considerável potencial de ocorrência de osteonecrose dos maxilares em pacientes submetidos a terapia prolongada com medicamentos antirreabsortivos e antiangiogênicos, especialmente quando não são adotadas medidas preventivas adequadas. A implementação de práticas preventivas, a vigilância das condições bucais e a colaboração de uma equipe multidisciplinar são fundamentais para reduzir os riscos associados a essa condição patológica.(AU)

Objective: This work aims to provide a comprehensive analysis of the clinical, etiological, radiographic and histopathological characteristics of Medication-Related Jaw Osteonecrosis, in addition to addressing diagnostic methods, prevention and therapeutic strategies. Materials and methods: A search was carried out for scientific articles published between 2015 and 2023, using the Scientific Electronic Library Online (SciELO), US National Library of Medicine (PubMed) and ScienceDirect databases. Conclusion: Although infrequent, there is a considerable potential for osteonecrosis of the jaw to occur in patients undergoing prolonged therapy with antiresorptive and antiangiogenic medications, especially when adequate preventive measures are not adopted. The implementation of preventive practices, surveillance of oral conditions and the collaboration of a multidisciplinary team are essential to reduce the risks associated with this pathological condition.(AU)

O papel da infecção e inflamação na etiopatogênese da osteonecrose dos maxilares induzida por medicamentos / The role of infection and inflammation in the etiopathogenesis of medication-related osteonecrosis of the jaw

Objetivo: O objetivo desta revisão de literatura é evidenciar o papel da infecção e inflamação na etiopatogenia da osteonecrose dos maxilares induzida por medicamentos (MRONJ). Revisão da literatura: A MRONJ é uma condição rara e grave que impacta negativamente a vida dos pacientes afetados. Sua etiopatogenia é multifatorial e ainda não foi totalmente compreendida. Uma das hipóteses propostas para explicá-la sugere que, além da inibição do turnover ósseo pelos medicamentos antirreabsortivos, a infecção associada à exodontia e a inflamação local desempenham papel decisivo no desencadeamento da condição. O entendimento da etiopatogenia da MRONJ permite ao cirurgião-dentista a identificação dos pacientes com risco maior para a doença, assim como o auxilia no monitoramento e escolha do manejo mais adequado. No campo da pesquisa, ele pode aprimorar estudos pré-clínicos e aprofundar a investigação de biomarcadores para diagnóstico precoce de MRONJ. Considerações finais: Conhecer a contribuição da infecção e inflamação na etiopatogênese da MRONJ é fundamental para orientar a pesquisa e a adoção de estratégias preventivas para os pacientes em risco, e de manejo e monitoramento adequado para aqueles já acometidos. (AU)

Aim: The aim of this literature review is to highlight the role of infection and inflammation in the etiopathogenesis of drug-induced osteonecrosis of the jaw (MRONJ). Literature review: MRONJ is a rare and serious condition that negatively impacts the lives of affected patients. Its etiopathogenesis is multifactorial and has not yet been fully understood. One of the hypotheses proposed to explain it suggests that, in addition to the inhibition of bone turnover by antiresorptive drugs, the infection associated with tooth extraction and local inflammation play a decisive role in triggering the condition. Understanding the etiopathogenesis of MRONJ allows the dentist to identify patients at higher risk for the disease, as well as assisting in monitoring and choosing the most appropriate management. In research, it can improve preclinical studies and deepen the investigation of biomarkers for early diagnosis of MRONJ. Conclusion: Knowing the contribution of infection and inflammation in the etiopathogenesis of MRONJ is essential to guide research and the adoption of preventive strategies for patients at risk, and adequate management and monitoring for those already affected.(AU)

Osteonecrosis maxilar inferior asociado a bifosfonatos / Lower jaw osteonecrosis associated with bisphosphonates / Osteonecrose do maxilar inferior associada a bisfosfonatos

Introducción: dada la alta prescripción de bifosfonatos, presentamos sus efectos adversos en la esfera odontológica, siendo una complicación poco frecuente, pero de difícil tratamiento. Sin necesidad de suspender el tratamiento, dado el importante beneficio en cuanto a la prevención de fractura por fragilidad. Estas fracturas causan una alta morbimortalidad en contraposición al bajo riesgo que conlleva la Osteonecrosis mandibular asociada a bifosfonatos. Objetivo: orientar al personal de salud que maneja estos fármacos y quien asiste dichas complicaciones a poseer conocimientos para la prevención de osteonecrosis. Identificar y diferenciar los pacientes con mayor riesgo, de acuerdo con la dosis de bifosfonatos y la frecuencia del tratamiento. Materiales y Método: se realizó una revisión bibliográfica en las siguientes fuentes: Scielo, Google académico, Medline/Pubmed, Biblioteca Virtual en Salud (Brasil), desde el año 2005 a la fecha, idiomas español, portugués e inglés. Los descriptores utilizados son bifosfonatos, mandíbula, maxilar, odontología, osteonecrosis, osteonecrosis de los maxilares asociada a bifosfonatos. Resultados: las últimas pautas de tratamiento fueron modificadas en 2014, por consenso de la Asociación Americana de cirugía Oral y Maxilofacial. La patogénesis de la osteonecrosis maxilar asociada a bifosfonatos no está completamente definida, aunque las publicaciones tratan de explicarla. El riesgo de desarrollarla por terapia oral es menor que por su administración vía intravenosa. Discusión: el médico que prescribe el antirresortivo debe conocer el estado de salud dental de su paciente y, en lo posible, remitirlo a examen con el odontólogo antes de iniciar la terapia con bifosfonatos.

Introduction: Given the high prescription of bisphosphonates, we present their adverse effects in the dental sphere, being an infrequent complication, but difficult to treat. There is no need to suspend treatment, given the important benefit in terms of prevention of fragility fractures. These fractures cause high morbimortality as opposed to the low risk associated with bisphosphonate-associated osteonecrosis of the jaw. Objective: To orient the health personnel who handle these drugs and who assist these complications to have knowledge for the prevention of osteonecrosis. To identify and differentiate patients at higher risk, according to the dose of bisphosphonates and frequency of treatment. Materials and Method: A literature review was performed in the following sources: Scielo, Google academic, Medline/Pubmed, Virtual Health Library (Brazil), from 2005 to date, Spanish, Portuguese and English languages. The descriptors used were bisphosphonates, mandible, maxilla, dentistry, osteonecrosis, osteonecrosis of the jaws associated with bisphosphonates. Results: The latest treatment guidelines were modified in 2014, by consensus of the American Association of Oral and Maxillofacial Surgery. The pathogenesis of bisphosphonate-associated maxillary osteonecrosis is not completely defined, although publications try to explain it. The risk of developing it by oral therapy is lower than by intravenous administration. Discussion: The physician who prescribes the antiresorptive drug should know the dental health status of his patient and, if possible, refer him for examination by a dentist before initiating bisphosphonate therapy.

Introdução: dada a alta prescrição de bisfosfonatos, apresentamos seus efeitos adversos na esfera odontológica, uma complicação rara, mas de difícil tratamento. Sem a necessidade de suspender o tratamento, dado o importante benefício em termos de prevenção de fraturas por fragilidade. Essas fraturas causam alta morbidade e mortalidade, em contraste com o baixo risco associado à osteonecrose da mandíbula associada aos bisfosfonatos. Objetivo: orientar a equipe de saúde que manipula esses medicamentos e que atende a essas complicações para que tenham conhecimento sobre a prevenção da osteonecrose. Identificar e diferenciar os pacientes de maior risco, de acordo com a dose de bisfosfonatos e a frequência do tratamento. Materiais e Método: foi realizada uma revisão da literatura nas seguintes fontes: Scielo, Google acadêmico, Medline/Pubmed, Biblioteca Virtual em Saúde (Brasil), de 2005 até a presente data, idiomas espanhol, português e inglês. Os descritores utilizados foram: bisfosfonatos, mandíbula, maxila, odontologia, osteonecrose, osteonecrose dos maxilares associada a bisfosfonatos. Resultados: as diretrizes de tratamento mais recentes foram modificadas em 2014, por consenso da Associação Americana de Cirurgia Oral e Maxilofacial. A patogênese da osteonecrose da mandíbula associada a bisfosfonatos não está totalmente definida, embora a literatura tente explicá-la. O risco de desenvolvê-la com a terapia oral é menor do que com a administração intravenosa. Discussão: o médico que prescreve o medicamento deve estar ciente do estado de saúde bucal do paciente e, se possível, encaminhar o paciente para ser examinado por um dentista antes de iniciar a terapia com bisfosfonatos.

Colocación de implantes en paciente con antecedentes de toma de bifosfonatos / Placement of implants in a patient with a history of bisphosphonates taken

El uso de bifosfonatos es un excelente tratamiento para pacientes con artritis reumatoide y enfermedades óseas, por ejemplo, osteoporosis. Se realiza un reporte de caso de paciente femenino, quien estuvo bajo consumo de este fármaco por prescripción de su médico para la prevención de artritis reumatoide postmenopausia. La paciente acude a consulta para la colocación de implantes en zona desdentada y comenta haber terminado el tratamiento de bifosfonatos hace un año. Se tomaron pruebas de diagnóstico y se realizó la colocación de implantes sin ninguna complicación. Sus citas de control fueron más frecuentes en cuatro meses, sobre todo por el detalle de consumo de bifosfonatos, pero en ninguna cita hubo algún detalle alarmante, la cicatrización iba en forma. Se dio de alta a la paciente después de sus citas periódicas y de asegurar su buena cicatrización a un implante bien situado (AU))

The use of bisphosphonates is an excellent treatment for patients with rheumatoid arthritis and bone diseases such as osteoporosis. Here is a case report of a female patient, who was under consumption of this drug by prescription of her doctor for the prevention of post-menopausal rheumatoid arthritis. The patient went to the consultation for the placement of implants in the edentulous area and comments having finished the bisphosphonate treatment one year ago. The diagnostic tests were taken, and the implant placement was performed well without any complications. The control appointments were more frequent in four months, especially due to the detail of bisphosphonate consumption, but in no appointment, there were any alarming details, the healing was in good shape. The patient discharged after her regular appointments and to ensure that she was healing well and that implant was well placed (AU)

Analysis of the Degree of Information of Dental Surgeons about Antiresorptive Drugs According to the Time Since Graduation in Dentistry

ABSTRACT Objective: To determine the level of scientific information of dental surgeons who carry out their professional activities in Brazil about antiresorptive drugs and indicated pharmacological procedures aiming at the prevention of osteonecrosis of the jaws and the therapy of drug sequelae that may occur, considering the time since graduation in Dentistry. Material and Methods: This is a quantitative cross-sectional study in which 339 dentists were consulted using the virtual questionnaire containing topics of personal nature, elements contained in the anamnesis carried out and knowledge about antiresorptive drugs, including indications, adverse effects and treatments applied. Chi-square and Fisher's exact tests were performed to analyze associations of data described by absolute and relative frequencies with professionals' time since graduation. All analyses were performed using the R software, with a 5% significance level. Results: Those who revealed to have graduated for more than five years with the highest academic degree were those who demonstrated maximum knowledge of antiresorptive drugs or revealed that, somehow, they had information about them (p<0.05). Conclusion: Dental surgeons in Brazil who have more than five years since graduation have more scientific information about antiresorptive drugs and pharmacological procedures, which can positively contribute to the prevention of osteonecrosis of the jaws and treatment of drug sequelae that may occur.

Estudo in vivo do efeito da ozonioterapia como prevenção e/ou tratamento da osteonecrose dos maxilares induzida por medicamentos / In vivo study of the effect of ozone therapy as a prevention and/or treatment of druginduced osteonecrosis of the jaws

O ozônio tem sido utilizado no processo de reparo ósseo em condições desfavoráveis, como na osteonecrose dos maxilares induzida por medicamentos (OMIM). O objetivo deste trabalho foi avaliar a aplicação de ozonioterapia como prevenção e/ou o tratamento da OMIM. Cento e vinte ratos wistar foram distribuídos entre os grupos tratamentos: eles foram induzidos com Zoledronato e receberam ozonioterapia antes da exodontia (prevenção ­ GOP), após exodontia (tratamento ­ GOT), em ambos momentos (prevenção e tratamento ­ GOPT), um grupo não recebeu ozônio (ZOL), e outro recebeu soro fisiológico ao invés da indução (SAL). Após 14 e 28 dias pós-operatórios foram eutanasiados e as peças submetidas as análises histológicas com eosina e hematoxilina, imunoistoquímica, microtomográfica computadorizada (microCT), confocal a LASER e histomorfométrica. Em 14 dias observamos o início do reparo em GOT, assim como um epitélio presente em SAL e GOT, o mesmo ocorre em 28 dias, e uma intensa imunomarcação de osteocalcina (OC) em GOPT em 14 dias. A microCT demostrou maiores médias de BV/TV em todos grupos quando comparados a ZOL (p< 0,001), ZOL apresentou maior porosidade (p=0,03) e o espaçamento trabecular foi maior no grupo GOT quando comparado ao GOP (p< 0,05). A taxa de aposição mineral (MAR) dos grupos GOP foram maiores (21,46±14,12), seguida do grupo GOT (19,66± 13,23). GOT apresentou a maior média de %NBA (68,322±25,296), quando comparado ao grupo ZOL (p < 0,05), seguido pelo grupo SAL (66,039±28,379) e ZOL (60,856±28,425). Diante dos resultados pode-se observar que a ozonioterapia pode modular o reparo alveolar em animais induzidos com ácido zoledrônico(AU)

Ozone has been used in the bone repair process under unfavorable conditions, such as in druginduced osteonecrosis of the jaws (OMIM). The objective of this work was to evaluate the application of ozone therapy as prevention and/or treatment of OMIM. One hundred and twenty wistar rats were distributed among treatment groups: they were induced with Zoledronate and received ozone therapy before tooth extraction (prevention - GOP), after tooth extraction (treatment - GOT), at both times (prevention and treatment - GOPT), one group I did not receive ozone (ZOL), and another received saline instead of induction (SAL). After 14 and 28 days postoperatively, they were euthanized and the pieces submitted to histological analysis with eosin and hematoxylin, immunohistochemistry, computed microtomography (microCT), confocal LASER and histomorphometric analysis. In 14 days we observed the beginning of repair in GOT, as well as an epithelium present in SAL and GOT, the same occurs in 28 days, with intense immunostaining of osteocalcin (OC) in GOPT in 14 days. The microCT showed higher BV/TV means in all groups when compared to the ZOL (p< 0.001), ZOL showed greater porosity (p=0.03) and the trabecular spacing was greater in the GOT group when compared to the GOP (p< 0 .05). The mineral apposition rate (MAR) of the GOP groups were higher (21,46±14,12), followed by the GOT group (19,66± 13,23). GOT had the highest average of %NBA (68.322±25.296), when compared to the ZOL group (p < 0.05), followed by the SAL group (66.039±28.379) and ZOL (60.856±28.425). In view of the results, it can be observed that ozone therapy can modulate alveolar repair in animals induced with zoledronic acid(AU)

Estudo in vivo do efeito da ozonioterapia como prevenção e/ou tratamento da osteonecrose dos maxilares induzida por medicamentos / In vivo study of the effect of ozone therapy as a prevention and/or treatment of druginduced osteonecrosis of the jaws

O ozônio tem sido utilizado no processo de reparo ósseo em condições desfavoráveis, como na osteonecrose dos maxilares induzida por medicamentos (OMIM). O objetivo deste trabalho foi avaliar a aplicação de ozonioterapia como prevenção e/ou o tratamento da OMIM. Cento e vinte ratos wistar foram distribuídos entre os grupos tratamentos: eles foram induzidos com Zoledronato e receberam ozonioterapia antes da exodontia (prevenção ­ GOP), após exodontia (tratamento ­ GOT), em ambos momentos (prevenção e tratamento ­ GOPT), um grupo não recebeu ozônio (ZOL), e outro recebeu soro fisiológico ao invés da indução (SAL). Após 14 e 28 dias pós-operatórios foram eutanasiados e as peças submetidas as análises histológicas com eosina e hematoxilina, imunoistoquímica, microtomográfica computadorizada (microCT), confocal a LASER e histomorfométrica. Em 14 dias observamos o início do reparo em GOT, assim como um epitélio presente em SAL e GOT, o mesmo ocorre em 28 dias, e uma intensa imunomarcação de osteocalcina (OC) em GOPT em 14 dias. A microCT demostrou maiores médias de BV/TV em todos grupos quando comparados a ZOL (p< 0,05), seguido pelo grupo SAL (66,039±28,379) e ZOL (60,856±28,425). Diante dos resultados pode-se observar que a ozonioterapia pode modular o reparo alveolar em animais induzidos com ácido zoledrônico(AU)

Ozone has been used in the bone repair process under unfavorable conditions, such as in druginduced osteonecrosis of the jaws (OMIM). The objective of this work was to evaluate the application of ozone therapy as prevention and/or treatment of OMIM. One hundred and twenty wistar rats were distributed among treatment groups: they were induced with Zoledronate and received ozone therapy before tooth extraction (prevention - GOP), after tooth extraction (treatment - GOT), at both times (prevention and treatment - GOPT), one group I did not receive ozone (ZOL), and another received saline instead of induction (SAL). After 14 and 28 days postoperatively, they were euthanized and the pieces submitted to histological analysis with eosin and hematoxylin, immunohistochemistry, computed microtomography (microCT), confocal LASER and histomorphometric analysis. In 14 days we observed the beginning of repair in GOT, as well as an epithelium present in SAL and GOT, the same occurs in 28 days, with intense immunostaining of osteocalcin (OC) in GOPT in 14 days. The microCT showed higher BV/TV means in all groups when compared to the ZOL (p< 0.05), followed by the SAL group (66.039±28.379) and ZOL (60.856±28.425). In view of the results, it can be observed that ozone therapy can modulate alveolar repair in animals induced with zoledronic acid(AU)

Suspensión de antirresortivos en osteonecrosis asociada a medicamentos: revisión de la literatura / Suspension of antiresorptive drugs in medication-related osteonecrosis of the jaws: a review of the literature

La suspensión de antirresortivos en el contexto de cuadros de osteonecrosis asociada a medicamentos (ONAM) es controversial. Aunque la evidencia de ca-lidad al respecto es insuficiente, múltiples socieda-des profesionales y grupos de trabajo han sugerido emplear este recurso. Recientemente la Sociedad Americana de Cirujanos Orales y Maxilofaciales ha puesto en duda sus beneficios. En el presente estudio abordamos esta temática en dos situaciones clínicas diferentes. Por un lado, analizamos la suspensión de los antirresortivos en pacientes asintomáticos an-tes de llevar a cabo procedimientos invasivos en los maxilares para disminuir el riesgo de desarrollo de ONAM. Por otro lado, evaluamos la suspensión de los antirresortivos en pacientes con ONAM establecida para mejorar el pronóstico de la enfermedad (AU)

The suspension of antiresorptive drugs in the context of medication-related osteonecrosis of the jaws (MRONJ) is controversial. Despite the lack of quality evidence, several professional associations and working groups have made suggestions in using this resource. Recently the American Association of Oral and Maxillofacial Surgeons has questioned its benefits. In the present study we address this issue in two different clinical situations. On the one hand, we analyzed the suspension of antiresorptive agents in asymptomatic patients before carrying out invasive procedures in the jaws to reduce the risk of developing MRONJ. On the other hand, we evaluated the suspension of antiresorptive drugs in patients actually presenting MRONJ to improve the prognosis of the disease (AU)

Osteonecrosis maxilar asociada con altas dosis de antirresortivos en paciente oncolólgico adulto mayor: resolución interdisciplinaria de caso clínico / Osteonecrosis of the jaw associated with high doses of antiresorptive in an elderly cancer patient: interdisciplinary resolution of a clinical case

La osteonecrosis maxilar relacionada con medicamentos (ONMM) es una patología de características clínicas objetivas con signo-sintomatología patogno-mónica. El criterio clínico aceptado es la presencia de hueso necrótico expuesto y visible sobre el reborde óseo maxilar que no ha cicatrizado luego de 8 sema-nas, en pacientes con antecedentes de tratamiento antirresortivo. La denominación relacionada con medicamentos se utiliza por el creciente número de casos asociados con otros fármacos antirresortivos como denosumab y con terapias antiangiogénicas, más allá de la conocida relación con bifosfonatos. Si bien la incidencia de ONMM en pacientes tratados por osteopatías metabólicas es muy baja, la situa-ción se torna más compleja en pacientes oncológicos con altas dosis de antirresortivos para tratamiento de metástasis ósea. Varios informes de casos des-criben cuadros de ONMM en pacientes con cáncer que reciben terapias dirigidas, específicamente TKI (inhibidores de tirosina kinasa) y anticuerpos mo-noclonales-VEGF (anticuerpos dirigidos al factor de crecimiento del endotelio vascular). La ONMM afecta negativamente la calidad de vida del paciente onco-lógico y produce comorbilidad significativa. Resulta imperioso identificar los pacientes en riesgo y dise-ñar un protocolo de atención odontológica específico para estos casos. En este artículo, se presenta un caso de ONMM asociado con altas dosis de Deno-sumab y administración simultánea de anticuerpos monoclonales específicos. El caso sorprende por la magnitud de la necrosis y su cuadro insidioso. El pro-tocolo de tratamiento descripto permitió controlar el cuadro inicial, limitar el avance de la lesión, asegurar el control del dolor y la infección, y finalmente, la cu-ración total de la lesión (AU)

Medication-related osteonecrosis of the jaws (MRONJ) is a pathology with objective clinical characteristics with pathognomonic signs and symp-toms. The accepted clinical criterion is the presence of exposed and visible necrotic bone on the maxillofacial region that has not healed after 8 weeks, in patients with history of antiresorptive treatment. The name medication-related is justified by the growing number of cases associated with other antiresorptive drugs such as denosumab and antiangiogenic therapies, beyond the known relationship with bisphosphonates. Although the incidence of MRONJ in patients treated for metabolic osteopathies is very low, the situation becomes more complex in cancer patients who re-ceive high doses of antiresorptives for the treatment of skeletal metastases. Several case reports describe the presence of MRONJ in cancer patients receiving targeted therapies, specifically TKI (tyrosine kinase inhibitors) and monoclonal antibodies-targeting VEGF (vascular endothelial growth factor). MRONJ nega-tively affects the quality of life in cancer patients and produces significant comorbidity. It is imperative to identify patients at risk and design a specific den-tal care strategy for these cases. In this article, we present a case of MRONJ associated with high doses of Denosumab and simultaneous administration of specific monoclonal antibodies. The case is surpris-ing due to magnitude of the necrosis. The described treatment strategies made it possible to control the initial symptoms, limit the lesion progression, ensure pain and infection control, and finally, the total heal-ing of the lesion (AU)

A systematic review assessing occurrence of medication-related osteonecrosis of the jaw following dental procedures

Aim: This study aimed to systematically review existing literature regarding the association between dental procedures­such as tooth extractions and periodontal therapy­and occurrence of medication-related osteonecrosis of the jaw (MRONJ) in individuals using bone-modifying drugs. Methods: Search strategies were performed in PubMed, Scopus, Web of Science and Cochrane Library for a timeframe ending in December 2021. Study selection, data extraction and risk of bias were analyzed independently by two researchers. Three meta-analyses were performed, estimating the crude risk ratio (RR), the adjusted odds ratio (OR) and the adjusted hazard ratio (HR) for the association between tooth extraction and MRONJ. Results: Of the 1,654 studies initially retrieved, 17 were ultimately included. The majority of patients with MRONJ in these studies were female, with a mean age of 64 years. Zoledronic acid was the most commonly used drug among patients with MRONJ, and cancer was the most frequent underlying health condition. Regarding the performed meta-analyses, crude and adjusted analyses demonstrated that tooth extraction increased the risk for MRONJ by 4.28 (95% confidence interval [95%CI]: 1.73­10.58), the OR for MRONJ by 26.94 (95%CI: 4.17­174.17), and the HR for MRONJ by 9.96 (95%CI: 4.04­24.55). Conclusion: It was concluded that performing dental procedures, especially tooth extraction, in patients using bone-modifying drugs increased the risk of MRONJ occurrence and, therefore, should be avoided. Further studies, using adjusted data, are warranted

Osteonecrosis de los maxilares: reacción medicamentosa / Osteonecrosis of the jaws: drug reaction

La osteonecrosis de los maxilares (ONM) secundaria al consumo de medicamentos antirresortivos y antiangiogénicos es una patología oral que afecta el funcionamiento del organismo de los seres humanos no sólo a nivel bucal, sino que disminuye su calidad de vida y aumenta su morbilidad. La ONM se define como la presencia de hueso necrótico expuesto que puede ser explorado mediante una fístula en el territorio maxilofacial, que se mantiene durante un periodo mínimo de ocho se- manas. Los fármacos antirresortivos y antiangiogénicos son indicados a pacientes que presentan patologías osteometabólicas, cáncer, entre otras, de ahí la importancia de mantener una estrecha relación entre médico tratante-odontólogo-paciente. El propósito de este artículo es establecer un protocolo de cuidado oral básico y definir las funciones del médico tratante, cirujano dentista y cirujano maxilofacial mediante una revisión bibliográfica con el fin de crear una propuesta preventiva para el tratamiento de estos pacientes (AU)

Medication-related osteonecrosis of the jaw (MRONJ), secondary to the consumption of antiresorptive and antiangiogenic drugs is an oral pathology that affects the functioning of the human body, not only at the oral level, but also decreasing their quality of life and increasing their morbidity. MRONJ is defined as the presence of exposed necrotic bone that can be explored through a fistula in the maxillofacial territory, which is maintained for a minimum period of eight weeks. Antiresorptive and antiangiogenic drugs are indicated for patients with osteometabolic pathologies, cancer, among others. For the same reasons, the importance of maintaining a close relationship between the treating physician, dentist and patient. The purpose of this article is to establish a clinical guide for basic oral care and define the functions of the treating physician, dental surgeon and maxillofacial surgeon through a bibliographic review; in order to create a preventive proposal for the treatment of these patients (AU)

Interpretation of medication-related osteonecrosis of the jaw: MASCC/ISOO/ASCO clinical practice guideline / 中华口腔医学杂志

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse event related to administration of antiresorptive or antiangiogenic medications. With the increasing usage of bone-modifying agents in cancer therapy, the incidence of MRONJ enhanced gradually, which affects the life quality of patients and interferes with cancer therapy. In 2019, Multinational Association of Supportive Care in Cancer (MASCC), International Society of Oral Oncology (ISOO) and American Society of Clinical Oncology (ASCO) convened a multidisciplinary Expert Panel to evaluate the evidence and formulate recommendations on practices in the prevention and management of MRONJ in patients with cancer. The present article made an interpretation of Medication-Related Osteonecrosis of the Jaw: MASCC/ISOO/ASCO Clinical Practice Guideline so as to provide clinicians with diagnostic and therapeutic approaches for cancer patients with MRONJ.

Osteonecrosis de los maxilares asociada a drogas antirresortivas en pacientes osteoporóticos: presentación de un caso clínico / Antiresorptive drugs-related jaw osteonecrosis in osteoporotic patients: report of a clinical case

La osteoporosis se caracteriza por una masa ósea baja con deterioro de la microarquitectura del tejido que conduce a la fragilidad, lo que aumenta el riesgo de fracturas. Después de la menopausia, la deficiencia de estrógenos aumenta la exposición del tejido al ligan- do RANK, lo que resulta en un aumento de la reabsorción y pérdida ósea, que pueden provocar osteoporosis. (1) Los bifosfonatos y el denosumab son utilizados para el tratamiento de la osteoporosis debido a su capacidad anticatabólica, que reducen la remodelación previniendo la pérdida de masa ósea, disminuyendo la probabilidad de fracturas y aumentando la densidad mineral del tejido. (2) La osteonecrosis de los maxilares asociadas a drogas antirresortivas es una situación que se presenta en pacientes que consumen de manera crónica antirresortivos para el tratamiento de enfermedades como: osteoporosis, osteogénesis imperfecta, enfermedad de Paget, displasia fi- brosa, hipercalcemia maligna asociada a tratamiento oncológico (AU)

Osteoporosis is characterized by low bone mass with deterioration of the tissue microarchitec- ture leading to fragility, which increases the risk of fractures. After menopause, estrogen deficiency increases tissue exposure to the RANK ligand, resulting in increased bone loss and resorption, which can lead to osteoporosis. (1) Bisphosphonates and denosumab are used for the treatment in low concentration, due to their anticatabolic capacity, which reduce remodeling, preventing loss of bone mass and fractures besides, antiresorptives drugs increase the mineral density of the tissue. (2) Osteonecrosis of the jaw associated with antiresorptives drugs occurs in patients whose chro- nically consume these drugs for the treatment of diseases such as: osteoporosis, imperfect osteogenesis, Paget's disease, fibrous dysplasia, malignant hypercalcemia associated with oncological treatment (AU)

Tetrahedral framework nucleic acid carrying angiogenic peptide prevents bisphosphonate-related osteonecrosis of the jaw by promoting angiogenesis / 国际口腔科学杂志·英文版

The significant clinical feature of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is the exposure of the necrotic jaw. Other clinical manifestations include jaw pain, swelling, abscess, and skin fistula, which seriously affect the patients' life, and there is no radical cure. Thus, new methods need to be found to prevent the occurrence of BRONJ. Here, a novel nanoparticle, tFNA-KLT, was successfully synthesized by us, in which the nanoparticle tetrahedral framework nucleic acid (tFNA) was used for carrying angiogenic peptide, KLT, and then further enhanced angiogenesis. TFNA-KLT possessed the same characteristics as tFNA, such as simple synthesis, stable structure, and good biocompatibility. Meanwhile, tFNA enhanced the stability of KLT and carried more KLT to interact with endothelial cells. First, it was confirmed that tFNA-KLT had the superior angiogenic ability to tFNA and KLT both in vitro and in vivo. Then we apply tFNA-KLT to the prevention of BRONJ. The results showed that tFNA-KLT can effectively prevent the occurrence of BRONJ by accelerating angiogenesis. In summary, the prepared novel nanoparticle, tFNA-KLT, was firstly synthesized by us. It was also firstly confirmed by us that tFNA-KLT significantly enhanced angiogenesis and can effectively prevent the occurrence of BRONJ by accelerating angiogenesis, thus providing a new avenue for the prevention of BRONJ and a new choice for therapeutic angiogenesis.

Indigenous microbiota protects development of medication-related osteonecrosis induced by periapical disease in mice / 国际口腔科学杂志·英文版

Bacterial infection is a common finding in patients, who develop medication-related osteonecrosis of the jaw (MRONJ) by the long-term and/or high-dose use of anti-resorptive agents such as bisphosphonate (BPs). However, pathological role of bacteria in MRONJ development at the early stage remains controversial. Here, we demonstrated that commensal microbiota protects against MRONJ development in the pulp-exposed periapical periodontitis mouse model. C57/BL6 female mice were treated with intragastric broad-spectrum antibiotics for 1 week. Zoledronic acid (ZOL) through intravenous injection and antibiotics in drinking water were administered for throughout the experiment. Pulp was exposed on the left maxillary first molar, then the mice were left for 5 weeks after which bilateral maxillary first molar was extracted and mice were left for additional 3 weeks to heal. All mice were harvested, and cecum, maxilla, and femurs were collected. ONJ development was assessed using μCT and histologic analyses. When antibiotic was treated in mice, these mice had no weight changes, but developed significantly enlarged ceca compared to the control group (CTL mice). Periapical bone resorption prior to the tooth extraction was similarly prevented when treated with antibiotics, which was confirmed by decreased osteoclasts and inflammation. ZOL treatment with pulp exposure significantly increased bone necrosis as determined by empty lacunae and necrotic bone amount. Furthermore, antibiotics treatment could further exacerbate bone necrosis, with increased osteoclast number. Our findings suggest that the commensal microbiome may play protective role, rather than pathological role, in the early stages of MRONJ development.

Caracterización clínico-terapéutica de pacientes diagnosticados con Osteonecrosis en los maxilares relacionada con medicación / Clinical and therapeutic characterization of patients diagnosed with medication-related osteonecrosis of the jaws

Introducción: La osteonecrosis en los maxilares por medicación es una afección asociada al tratamiento con bifosfonatos, antireabsortivos y antiangiogénicos. Objetivo: Caracterizar clínica y terapéuticamente los pacientes diagnosticados de Osteonecrosis en los Maxilares relacionada con medicación. Material y Método: Se realizó una serie de casos de 19 pacientes, la totalidad de los diagnosticados con la entidad en el Servicio de Cirugía Maxilofacial. Facultad de Estomatología Raúl González Sánchez, enero 2018-enero 2019. Se identificó severidad, factores de riesgo y se estandarizó tratamiento que incluyó la curación con aceite ozonizado y la aplicación de láser infrarrojo. Se evaluó el tratamiento a los 90 días. Se operacionalizaron las variables: sexo, tipo de medicación, vía y tiempo de administración, localización y evaluación al tratamiento. Resultados: La edad promedio de los pacientes fue 69±8,5 años, un 52,63 por ciento fueron masculinos, el zolendronato fue el agente mas asociado en el 78,95 por ciento de los casos, la enfermedad periodontal fue el factor local preponderante (57,89 por ciento), la localización mandibular postero lateral y el estadio evolutivo 2 predominaron en el 63,16 por ciento y 52,63 por ciento de las lesiones. El 78,94 por ciento de los casos presentó evolución satisfactoria a los 90 días. Conclusiones: La medicación con bifosfosfonatos parenterales predominantemente con el zolendronato, fue la causa principal de las osteonecrosis, las cuales prevalecieron en el sector postero lateral de mandíbula y con el estadio 2. La variante de tratamiento de curación con aceite ozonizado e irradiación con láser fue la más implementada. Los valores de lesiones resueltas y mejoradas a los 90 días fueron satisfactorios(AU)

Introduction: Medication-related osteonecrosis of the jaws is an affection associated with the treatment with bisphosphonates, antiresorptive agents or antiangiogenic medications. Objective: To perform a clinical and therapeutic characterization of patients with the diagnosis of medication-related osteonecrosis of the jaws. Material and Method: A case series of a total of 19 patients with the diagnosis of medication-related osteonecrosis of the jaws was carried out in the Department of Dental and Maxillofacial Surgery of ¨Raúl González Sánchez¨ Dental School of Havana from January 2018 to January 2019. The severity and risk factors were identified and the treatment including the healing with ozone oil and the application of infrared laser was standardized. The patients were evaluated in the 90 days after treatment. The operationalization of variables included: sex, type of medications, ways and time of administration, localization, and evaluation of treatment. Results: The average age of patients was 69±8,5 years and 52,63 percent of them were male. Zolendronate was the most associated agent in 78,95 percent of cases. Periodontal disease was the most identified local factor (57, 89 percent). The posterolateral area of the mandible and stage 2 disease evolution predominated in 63,16 percent and 52, 63 percent of lesions, respectively. Also 78, 94 percent of cases had a satisfactory evolution in the 90 days after treatment. Conclusions: The administration of intravenous bisphosphonates, particularly Zolendronate, was the main cause of osteonecrosis. These lesions were mainly located in the posterior lateral area of the mandible and presented stage 2 disease evolution. Healing with ozone oil and application of infrared laser was the most implemented alternative treatment. The values of resolved and improved lesions were satisfactory in the 90 days after treatment(AU)

Conocimiento y conciencia de los médicos sobre la osteonecrosis relacionada con bifosfonatos / Knowledge and awareness of physicians about bisphosphonate-related osteonecrosis of the jaws

Objetivo: Determinar el conocimiento y la conciencia que tienen los médicos sobre la osteonecrosis relacionada con bifosfonatos. Material y métodos: Se realizó un estudio transversal, en el cual se encuestó a médicos generales y especialistas con la finalidad de identificar el nivel de conocimientos y conciencia que tienen sobre el tema. Resultados: Se entrevistó a un total de 475 médicos generales y especialistas, de los cuales 210 (44.2%) mencionaron prescribir bifosfonatos, de este grupo 58.1% no envía a los pacientes con el odontólogo para eliminar factores de riesgo, a pesar de que 61.8% de los mismos mencionó conocer las reacciones adversas; 36 médicos (17.4%) han visto a algún paciente con osteonecrosis por bifosfonatos. El 37% de los médicos que prescriben medicamentos consideran que no es necesario remitir a los pacientes al odontólogo. Conclusiones: La prescripción de bifosfonatos en la práctica médica va en aumento, los médicos deben tener el conocimiento adecuado sobre las reacciones adversas de estos medicamentos para así poder referir oportunamente al odontólogo, educar al paciente y poder prevenir complicaciones como la osteonecrosis relacionada con bifosfonatos (AU)

Objectives : To evaluate the knowledge and awareness of physicians about bisphosphonate-related osteonecrosis of the jaws. Material and methods: A cross-sectional survey was carried out among general practitioners and specialized physicians to determine their knowledge and awareness of bisphosphonate-related osteonecrosis of the jaws. Results: Of the 475 interviewed general practitioners and specialized physicians, 210 (44.2%) claimed to prescribe bisphosphonates. A total of 58.1% of these physicians did not refer their patients to the dentist for the elimination of risk factors, despite the fact that 61.8% of them reported knowledge of the adverse reactions of these drugs. Thirty-six physicians (17.4%) had seen some patient with bisphosphonate-related osteonecrosis of the jaws. A total of 37% of the physicians that prescribed drugs considered it not necessary to refer patients to the dentist. Conclusions: Bisphosphonate prescription is increasingly common in medical practice, and physicians must have adequate knowledge of the adverse reactions of these drugs in order to ensure opportune patient referral to the dentist, educate their patients, and avoid complications such as bisphosphonate-related osteonecrosis of the jaws (AU)

Osteonecrosis maxilar relacionada con medicamentos en pacientes oncológicos con metástasis óseas: resolución de dos casos / Medication-related osteonecrosis of the jaw in oncological patients with bone metastases: resolution of two cases

La osteonecrosis maxilar relacionada con medicamentos (ONMM) es una patología de características clínicas objetivas con signo-sintomatología patognomónica. El criterio clínico aceptado es la presencia de hueso necrótico expuesto y visible sobre el reborde óseo maxilar que no ha cicatrizado luego de 8 semanas, en pacientes con antecedentes de tratamiento antirresortivo. La denominación "relacionada con medicamentos" se utiliza por el creciente número de casos asociados con otros fármacos antirresortivos como denosumab y con terapias antiangiogénicas, más allá de la conocida relación con bifosfonatos.Si bien la incidencia de ONMM en pacientes tratados por osteopatías metabólicas es muy baja, la situación se torna más compleja en pacientes oncológicos con altas dosis de antirresortivos para tratamiento de metástasis ósea. Varios in-formes de casos describen cuadros de ONMM en pacientes con cáncer que reciben terapias dirigidas, específicamente TKI (inhibidores de tirosina quinasa) y anticuerpos monoclonales-VEGF (anticuerpos dirigidos al factor de crecimiento del endotelio vascular). La ONMM afecta negativamente la calidad de vida del paciente oncológico y produce comorbilidad significativa. Resulta imperioso identificar a los pacientes en riesgo y diseñar un protocolo de atención odontológica específico para estos casos. En este artículo se presentan dos casos de ONMM asociado con altas dosis de denosumab y administración simultánea de anticuerpos monoclonales específicos para el tratamiento del cáncer. Ambos casos sorprenden por la prematura instalación de la necrosis y su cuadro insidio-so. El protocolo de tratamiento descripto permitió controlar el cuadro inicial, limitar el avance de la lesión, asegurar el control del dolor y la infección, y finalmente, la curación total de la lesión. (AU)

Medication-related osteonecrosis of the jaws (MRONJ) is a pathology with objective clinical characteristics, with pathognomonic signs and symptoms. The accepted clinical criterion is the presence of exposed and visible necrotic bone on the maxillofacial region that has not healed after 8 weeks, in patients with history of antiresorptive treatment.The name "medication-related" is justified by the growing number of cases associated with other antiresorptive drugs such as denosumab and antiangiogenic therapies, beyond the known relationship with bisphosphonates. Although the incidence of MRONJ in patients treated for metabolic osteopathies is very low, the situation becomes more complex in cancer patients who receive high doses of antiresorptives for the treatment of skeletal metastases. Several case reports describe the presence of MRONJ in cancer patients receiving targeted therapies, specifically TKI (tyrosine kinase inhibitors) and monoclonal antibodies-targeting VEGF (vascular endothelial growth factor). MRONJ negatively affects the quality of life in cancer patients and produces significant comorbidity. It is imperative to identify patients at risk and design a specific dental care strategy for these cases.In this article, we present two cases of MRONJ associated with high doses of Denosumab and simultaneous administration of specific monoclonal antibodies. Both cases are surprising due to premature onset of necrosis. The described treatment strategies made it possible to control the initial symptoms, limit the lesion progression, ensure pain and infection control, and finally, the total healing of the lesion. (AU)

Osteonecrosis of the jaw in a patient under treatment of osteoporosis with oral bisphosphonate

Although uncommon in patients under oral therapy, bisphosphonate-related osteonecrosis of the jaw (BRONJ) can be a very severe issue. Early intervention with surgical resection should be the preferable method of treating any stage of the disease, resulting in better outcomes and decreasing the morbidity of this condition. A 77-year-old female patient attended the Special Care Dentistry Centre of the University of São Paulo Faculty of Dentistry (CAPE FOUSP) complaining mainly of "an exposed bone that appeared after tooth extraction performed six months earlier". The patient was diagnosed with osteonecrosis associated with bisphosphonate (sodium ibandronate) and surgically treated with removal of bone sequestration and antibiotic therapy. The patient was followed up for six years (a total of 6 appointments), presenting good general health and no sign of bone exposure. Imaging findings showed no changes related to BRONJ either.