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)

Osteonecrosis de los maxilares asociada a medicamentos: revisión de la literatura y propuesta para la prevención y manejo / Osteonecrosis of the jaws

Medication-related osteonecrosis of the jaw is a disease where there is necrotic bone exposed or that can be explored by means of a fistula in the maxillofacial region. It has been associated with the use Biphosphonates and denosumab for osteoporosis. Although its etiology is unclear, it may be related to a decrease in bone turnover produced by these drugs, rendering the bone more prone to generate cell necrosis during invasive dental procedures, especially in the posterior region of the jaw. There is no consensus about the prevention and treatment of this condition. The aim of this paper is to present a review of the literature with the main characteristics of osteonecrosis of the jaws associated with drugs, together with a proposal for prevention and treatment for these patients.

Risk profile for antiangiogenic agent-related osteonecrosis of the jaws / Perfil de risco para osteonecrose dos maxilares associada a agentes antiangiogênicos

ABSTRACT To establish the profile of patients who developed antiangiogenic agent-related osteonecrosis of the jaws, and identify the treatments currently used in dental management. We searched the PubMed®/Medline® and Scopus databases using the words "osteonecrosis AND antiangiogenic therapy", with the following inclusion criteria: articles published in English, case reports, available online, and for an unlimited period. Of the 209 articles retrieved, 18 were selected, for a total of 19 case reports, since one article included two cases that met the inclusion criteria for this study. Medication-related osteonecrosis of the jaws is characterized by exposure of necrotic bone in the oral cavity that does not heal over a period of 8 weeks in patients with no previous history of radiation therapy. Antiangiogenic drugs are indicated in the treatment of certain tumors, since they stop the formation of new blood vessels, controlling tumor growth and the chance of metastasis. Dental prevention is essential in patients who will be put on antiangiogenic agents, to minimize the risk for osteonecrosis.

RESUMO Traçar o perfil dos pacientes que desenvolveram osteonecrose dos maxilares associada a agentes antiangiogênicos e identificar os tratamentos realizados atualmente no manejo odontológico. Foi realizada busca nas bases de dados PubMed®/Medline® e Scopus por meio dos descritores "osteonecrosis AND antiangiogenic therapy", sendo utilizados os critérios de inclusão: artigos publicados em inglês, relato de caso, disponíveis on-line e por período ilimitado. Após análise dos 209 artigos encontrados, foram selecionados 18 artigos para este estudo, resultando em 19 relatos de caso, visto que um dos artigos apresentou dois casos que se enquadravam nos critérios de inclusão. A osteonecrose dos maxilares associada a medicamentos é caracterizada pela exposição de osso necrótico na cavidade oral que não cicatriza em um período de 8 semanas em pacientes que não foram submetidos à radioterapia. Os medicamentos antiangiogênicos são indicados no tratamento de alguns tumores, pois impedem o crescimento de novos vasos sanguíneos, controlando o crescimento do tumor e a chance de metastização. Torna-se imprescindível a realização de prevenção odontológica do paciente a ser submetido a uso de antiangiogênicos visando a minimizar as chances de desenvolvimento da osteonecrose.

The use of bisphosphonates does not contraindicate orthodontic and other types of treatment!

Bisphosphonates have been increasingly used not only to treat bone diseases as well as conditions such as osteopenia and osteoporosis, but also in oncotherapy. The use of bisphosphonates induces clinicians to fear and care. These reactions are associated with controversy resulting from lack of in-depth knowledge on the mechanisms of action as well as lack of a more accurate assessment of side effects. Scientific and clinical knowledge disclosure greatly contributes to professionals' discernment and inner balance, especially orthodontists. Fear does not lead to awareness. For these reasons, we present an article that focuses on that matter. This article was adapted from different journals of different dental specialties, as mentioned on footnote. There is no scientific evidence demonstrating that bisphosphonates are directly involved with etiopathogenic mechanisms of osteonecrosis and jaw osteomyelitis. Their use is contraindicated and limited in cases of dental treatment involving bone tissue. Nevertheless, such fact is based on professional opinion, case reports, and personal experience or experiment trials with failing methods. Additional studies will always be necessary; however, in-depth knowledge on bone biology is of paramount importance to offer an opinion about the clinical use of bisphosphonates and their further implications. Based on bone biopathology, this article aims at contributing to lay the groundwork for this matter.

Cada vez mais se usa os bisfosfonatos nos tratamentos de doenças e de estados ósseos, como a osteopenia e osteoporose, assim como nos protocolos oncoterápicos. O uso dos bisfosfonatos induz muitas reações de medo e cuidado, associadas a polêmicas e controvérsias quase sempre resultantes de uma falta de conhecimento mais profundo dos mecanismos de ação e da falta de uma avaliação mais criteriosa de seus efeitos colaterais. A divulgação e o conhecimento dos aspectos científicos e clínicos contribuem, em muito, para o discernimento e tranquilidade dos profissionais, especialmente dos ortodontistas. O medo não resulta em conscientização. Por essas razões, apresentamos alguns artigos sobre o mesmo assunto, semelhantes e adaptados, em revistas voltadas para as diferentes especialidades odontológicas, entre os quais o citado na nota de rodapé. Nos mecanismos etiopatogênicos da osteonecrose e nas osteomielites, nos maxilares, os bisfosfonatos não se encaixam como um dos fatores diretamente envolvidos e com base em evidências científicas. Suas contraindicações e limitações na prática odontológica como fator limitante de alguns tratamentos envolvendo o tecido ósseo estão baseadas, principalmente, em opiniões, casos clínicos e na experiência pessoal ou trabalhos experimentais com algumas falhas nos métodos experimentais. Sempre serão necessários mais estudos, mas um cuidado importante é se aprofundar no conhecimento da biologia óssea para, quando necessário, emitir-se opiniões sobre protocolos de conduta na clínica odontológica quanto ao uso bisfosfonatos e suas implicações. Esse artigo objetiva contribuir na fundamentação de abordagens sobre esse assunto a partir da biopatologia óssea.

Osteonecrosis de los maxilares asociada al uso de bifosfonatos / Biphosphonate-related osteonecrosis of the jaws

Los bifosfonatos son drogas utilizadas en el tratamiento de tumores óseos metástasis óseas, y en otras afeccionesóseas como el mieloma múltiple. Se utilizan también para la prevención y tratamiento de la osteoporosis enmujeres posmenopáusicas. El número de pacientes en tratamiento con estas drogas es cada vez mayor y demanera concomitante hay un número creciente de informes sobre la osteonecrosis de mandíbula asociada a su uso. Las lesiones maxilares presentan gran variabilidad clínica. El cuadro se ha relacionado con: tipo de bifosfonatos, tiempo de tratamiento, dosis de tratamiento, vía de administración y antecedente de tratamiento odontológico, generalmente exodoncia. El objetivo de este trabajo es proveer información sobre las lesiones óseas maxilares (osteonecrosis) que aparecen en pacientes que utilizan bifosfonatos y las medidas terapéuticas yprofilácticas a ser empleadas ante la aparición de las mismas para lo cual se realizó una revisión de la literaturacientífica disponible a la fecha. El propósito es alertar a los profesionales y futuros profesionales sobre estapatología, haciendo énfasis también en la importancia de la comunicación entre los médicos generales que prescribenbifosfonatos y los odontólogos, quienes deben estar preparados para enfrentar el desafío de su diagnóstico, tratamiento y sobre todo la prevención de su aparición.

Osteonecrosis maxilar postextracción dentaria en pacientes bajo tratamiento con bifosfonatos: presentación de 2 casos clínicos / Postextraction jaw osteonecrosis in patients undergoing biphosphonate treatment: report of 2 clinical cases

Los bisfosfonatos son usados en el tratamiento de pacientes donde es necesario disminuir la reabsorción ósea, principalmente osteoporosis, mieloma múltiple y en metástasis óseas de tumores sólidos, como cáncer de pulmón, mama y próstata. Pero con el advenimiento de los de alto poder, como el zoledronato, pamidronato, administrados por vía endovenosa, aparecen las complicaciones secundarias. En el año 2003 se publicó el primer caso de osteonecrosis de los huesos maxilares (ONM). Desde entonces, se reportaron numerosos casos de pacientes con ONM, que habían recibido tratamientos con bifosfonatos. El objetivo de este trabajo es presentar dos casos clínicos de pacientes medicados con BF que presentaron ONM posterior a una extracción dental.

Bifosfonates are used in the patients’s treatment where it is necessary to diminish the bony reabsorption, mainly osteoporosis, multiple myeloma and in bone metastasis of solid tumors as lung, breast and prostate cancer. However secondary complications appear withthe incoming of zoledronate and pamidronate, of high power, administered by intravenous way. In 2003 it was published the first case of osteonecrosis of maxillary bones (ONM). Since then there were reported numerous cases of patients with ONM that had received treatments with bifosfonates. The aim of this work was to present two clinical cases of patients treated with BF that showed ONM posterior to a dental extraction.

Osteonecrosis maxilar secundaria al uso de bisfosfonatos por vía oral: Exposición de tres casos clínicos relacionados con alendronato / Osteonecrosis of the jaw secondary to oral alendronate: Report of three cases

Osteonecrosis of the jaw associated to biphosphonate use is more common in cancer patients with bone metastases, that are using intravenous diphosphonates. When these drugs are used orally the risk of the complication is lower. We report 3 diabetic women aged 69, 76 and 82 years, receiving alendronate 70 mg every one week. The unveiling event was the extraction of several teeth without the use of antibiotics. All had bone pain, purulent discharge, loss of bone and halitosis. All improved five months after discontinuing alendronate.

Histometric study of alveolar bone in rats submitted to ethanol during lactation

The present work studied the adverse effects of maternal exposure of rats to alcohol during lactation, on the development of their off spring. Histometric evaluation by karyometry and of the alveolar bone at the level of the first upper molar of the sucking was perfomed. Two groups of animals, one coming from mothers exposed to drinking water containing 20 percent ethanol during the total lactation period and the other of controls coming from mothers receiving only alcohol-free drinking water during this period. On the 21 first day of lactation the young of each group were aleatorily selected and following anesthesia, their heads severed; after histological treatment, serial 6 ìm sections on the frontal plane at the molar level, stained with hematoxilin and eosin, were obtained. The experimental results produced, suggest that sucking from ethanol-treated mothers, show retarded post-natal growth, their alveolar bones presenting scarce, little calcified trabeculae, and a more abundant bone marrow compared to controls.

Considerando que la lactancia es un período importante y vulnerable, y que la exposición materna al alcohol durante esta fase puede provocar efectos adversos en las crías en desarrollo, el propósito del presente trabajo es evaluar histométricamente (mediante cariometría y estereología), el hueso alveolar a nivel del primer molar superior, de ratas lactantes sometidas a los efectos del etanol. Con esa finalidad utilizamos dos grupos, uno que recibió etanol al 20 por ciento en el bebedero, durante todo el período de lactancia (21días), y otro que recibió solo agua. En el 21° día de lactancia, 5 ratas de cada grupo fueron aleatoriamente seleccionadas. Después de sacrificados, los animales fueron fijados en formol al 10 por ciento. Las cabezas, separadas de los cuerpos, fueron incluidas en parafina, y cortadas seriadamente con 6 Lim de grosor, a partir de un plano frontal al nivel de los molares, y teñidas con hematoxilina y eosina. Basados en los resultados presentes, es posible concluir que el etanol al 20 por ciento en el agua de beber, administrado a ratas lactantes, provoca los siguientes efectos: reducción significativa del peso corporal, alteraciones de las trabéculas del hueso alveolar, observadas estereológicamente, evidenciadas por trabéculas delicadas y poco calcificadas, con médula abundante, núcleos menores en osteoblastos y osteocitos y más achatados en los primeros, y con osteocitos de volúmenes citoplasmático y celular menor y densidad numérica mayor.

Bisphosphonate-related osteonecrosis of the jaws: a call for multidisciplinary approaches.

Bisphosphonates have been prescribed for the treatments of oncologic and metabolic bone diseases to inhibit bone resorption of osteoclasts. However, in recent years, the increased numbers of cases diagnosed with exposed and necrotic bone localized in the jawbones associated with bisphosphonate use have been reported, mostly in patients with multiple myeloma or bone metastases who received long-term intravenous bisphosphonate treatments. The strong association between patients receiving dentoalveolar surgery and the incidence of this complication highlights the need for multidisciplinary approaches and necessitates the close attention from a team of health care personnel. The present review summarizes the current knowledge on etiology, risk factors, clinical presentations, and recommended preventive measures and managements for afflicted patients. In light of recent available data and because stanterdized management strategies have not been well established, prevention seems to be of paramount benefit to this group of patients.

La terapia con bifosfonatos como causade osteonecrosis de los maxilares. Reporte de un caso / Biphosphonates therapy as a cause of osteonecrosis of the jaws. Case Report

Describimos un caso clínico en un paciente que ha estado sometido a terapia con bifosfonatos durante dos años y medio para control de una metástasis ósea a partir de un cáncer de próstata. Mostró una exposición ósea extensa en cara lingual de mandíbulay dos meses después en sector anterior de maxilar superior. En ambas localizaciones había antecedentes de maniobras invasivas.Se describen los tratamientos realizados.En este momento existen suficientes comunicaciones científicas como para establecer que este tipo de fármacos son capaces de inducir una osteonecrosis de los maxilares, no existiendo reportes de esta patología en otros huesos del organismo. Se detallanalgunos posibles mecanismos de acción de estas drogas.Se hace hincapié en la responsabilidad del odontólogo en la prevención de esta grave complicación.

Osteonecrosis asociada al uso de bifosfonatos: A propósito de un caso clínico / Osteonecrosis associated with the use of biphosphonates: Case report

Biphosphonates reduce the risk of skeletal events and are currently part of standards of therapy in myeloma. Recently, zoledronate and pamidronate have been linked to osteonecrosis of the jaw, specially after surgical dental procedures. We report a 84 year-old man with multiple myeloma who developed spontaneous osteonecrosis of both jaws, after 36 months of therapy with zoledronate with a cumulative dose of 136 mg. We discuss the pathogenic mechanisms, and review the recommendations on prevention and management of this new complication for neoplastic patients under prolonged therapy with biphosphonates.