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.

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

Awareness of patients receiving bisphosphonates: a cross-sectional study

Abstract The aim of this study was to evaluate the awareness of patients using bisphosphonates (BP) regarding their risks and benefits. Sixty-five patients using BP were included. Each participant completed a self-administered questionnaire consisting of 13 questions, including sociodemographic and general information on BP. Data were analyzed using descriptive statistics, and a binomial test was used to assess patient knowledge about BP, considering a 5% significance level. Fifty-nine (90.2%) patients were unaware or had never heard of BP drugs and only 3 (4.6%) knew their indications. Only 6 patients (9.2%) said they knew about the oral complications caused by BP. Sixty-three patients (96.9%) said they were not referred to the dentist before starting BP treatment. Patients using BP do not have satisfactory knowledge regarding the risks and benefits of BP. Physicians and dentists must be prepared to inform and counsel BP users about their adverse effects and possible risk factors. Our results emphasize the importance of public policies, whether individual or collective, to be taken to increase knowledge about BP to avoid medication-related osteonecrosis of the jaw.

Absence of medication-related jaw osteonecrosis after treatment with strontium ranelate in ovariectomized rats

Abstract This study aimed to evaluate the potential of strontium ranelate (SR) in medication-related jaw osteonecrosis (MRONJ) after tooth extraction in ovariectomized rats. Thirty ovariectomized rats were divided into three groups (n = 10): bisphophonate (BP) group (zoledronic acid; 0.4 mg/kg/week), SR group (625 mg/kg/day), and control group (saline solution). The lower first molars were extracted after 60 days of drug therapy. Drug administration was continued for another 30 days after tooth extraction. The mandibles were subjected to clinical, histological, radiographic, and microtomographic evaluations. Only the BP group showed clinical changes, characterized by the presence of 70% (n = 7) and 20% (n = 2) of ulcers and extraoral fistulas. Radiographic evaluation demonstrated bone sequestration only in the BP group (n = 7, 70%). Microtomographic analysis revealed increased bone porosity after ovariectomy, particularly in the the control group (p < 0.05). The BP group showed a higher bone surface density, bone volume, and trabecular number than SR and control groups, but with less trabecular separation (p < 0.05). All the animals in the BP group demonstrated histological osteonecrosis. There was no evidence of osteonecrosis in the control and SR groups, which was characterized by the absence of empty osteocyte gaps and associated with the gradual healing of the extraction area. Also, an increased number of blood vessels and a reduced number of osteoclasts were observed in the SR group (p < 0.05). Therefore, SR treatment increased angiogenesis and osteoclastogenesis in the healing socket and was not associated with MRONJ development after tooth extraction in ovariectomized rats.

Impact of Antiresorptive Agents on Maxillary Bones: a Narrative Literature Review / Impacto dos Agentes Antirreabsortivos nos Ossos Maxilares: uma Revisão de Literatura narrativa

Abstract Antiresorptive drugs operate in the bone metabolism modulation and are widely used in the treatment of bone metastases and bone losses related to hormonal deficiency. Although this therapy shows satisfactory results, there are adverse effects associated with its use, such as osteonecrosis of the jaws. Medication-related osteonecrosis of the jaws (MRONJ) is, therefore, a serious and challenging condition with important implications in dentistry. The aim was to conduct a narrative literature review on anti-resorptive drugs and their latest repercussions on the maxillary bones. The review was carried out through a bibliographic search using Decs/Mesh descriptors of interest, in Portuguese and English, in the PubMed, Virtual Health Library (VHL) and Scielo databases. After applying the inclusion and exclusion criteria, a total of 33 studies were selected for analysis. It can be noticed that therapy with anti-resorptive agents is complex, especially in dental practice, since MRONJ is a complication that is difficult to manage. Regarding the therapeutic options, these are divided into conservative, surgical or adjuvant therapy, however, there are no protocols in the literature, and there is no consistency regarding the indication of the suspension of the drug administration - "Drug Holiday". Thus, it is important that the multidisciplinary team seeks strategies that minimize complications and promote control over the use of these drugs. In addition, there is a need for investigations that contribute with guidelines for the management and control of adverse effects resulting from therapy with antiresorptive drugs. (AU)

Resumo As drogas antirreabsortivas atuam na modulação do metabolismo ósseo e são indicadas para o tratamento de metástases ósseas e perdas ósseas relacionadas à deficiência hormonal. Ainda que esta terapia apresente resultados satisfatórios, observam-se efeitos adversos associados ao seu uso, como a osteonecrose dos maxilares. A osteonecrose dos maxilares associada ao uso de medicamentos (OMAM) é, portanto, uma condição séria e desafiadora com implicações importantes na Odontologia. O objetivo foi realizar uma revisão narrativa de literatura sobre as drogas antirreabsortivas e suas respectivas repercussões nos ossos maxilares. A revisão foi realizada através de busca bibliográfica utilizando descritores Decs/Mesh de interesse, em português e inglês, nas bases de dados PubMed, Biblioteca Virtual de Saúde (BVS) e Scielo. Após aplicação dos critérios de inclusão e exclusão, um total de 33 trabalhos foram selecionados para análise. Pode-se constatar que a terapia com agentes antirreabsortivos é complexa, sobretudo na prática odontológica, visto que a OMAM é uma complicação de difícil manejo. Em relação às condutas terapêuticas para esta condição, divide-se em terapia conservadora, cirúrgica ou adjuvante, todavia, não existem protocolos validados na literatura, bem como não há consistência quanto à indicação do intervalo de suspensão da administração da droga - "Drug Holiday". Desse modo, é importante que a equipe multidisciplinar busque estratégias que minimizem as complicações e promovam o controle no uso dessas drogas. Além disso, nota-se a necessidade de realizar investigações que contribuam com diretrizes para o manejo e controle dos efeitos adversos decorrentes da terapia com medicamentos antirreabsortivos. (AU)

Ozonotherapy for Treatment of Radiation Therapy-induced Jaw Osteonecrosis and Bisphosphonates: Case Report / Ozonioterapia para o Tratamento de Osteonecrose em Mandíbula Induzida pela Radioterapia Associada com Bisfosfonato: Relato de Caso / Ozonoterapia para el Tratamiento de la Osteonecrosis de la Mordaza Inducida por Terapia de Radiación y Bisfosfonatos: Relato de Caso

Introduction: The inhibition of osteoclastic activity, associated with different treatment modalities in patients with head and neck cancer, make bones unable to respond to repair processes related to physiological traumas or infection and may result in bone necrosis. The present study aims to report a clinical case of osteoradionecrosis in mandible, and how its sequels were controlled by ozonotherapy. Case report: A 73-year-old female patient with infiltrative ductal breast carcinoma with mandibular metastasis was submitted to chemo and radiotherapy at head and neck region associated with bisphosphonate. Three years later, she was diagnosed with hemimandibular osteoradionecrosis that exhibited communication with oral cavity and with a chronic, suppurative and persistent associated infection. It was applied adjuvant therapy with ozone through the cutaneous fistula and the exposed and necrotic bone. Additionally, non-vital bone debridement was proceeded in two surgical steps. The patient is after a 1-year follow-up non-symptomatic. Conclusion: It is supposed that ozonotherapy, due to its antibacterial and immunoregulatory mechanism of action, was an important therapeutic agent for improving the patient's quality of life.

Introdução: A inibição da atividade osteoclástica, associada a diversas modalidades de tratamento utilizadas em pacientes com câncer de cabeça e pescoço, torna o osso incapaz de responder aos processos de reparo relacionados a traumas fisiológicos ou à infecção, e pode resultar em necrose óssea. O presente estudo tem como objetivo relatar um caso clínico de osteonecrose em mandíbula como consequência do uso de bisfosfonato associado à quimioterapia e à radioterapia para tratamento de câncer de mama com metástase para mandíbula, tendo suas sequelas controladas por meio do uso da ozonioterapia. Relato do caso: Paciente do sexo feminino, 73 anos, com história de carcinoma ductal infiltrante de mama com metástase óssea em mandíbula, a qual foi submetida ao tratamento de quimioterapia e radioterapia em região de cabeça e pescoço; três anos depois, foi diagnosticada com osteonecrose da hemimandíbula direita com exposição completa para a cavidade bucal e infecção crônica, supurativa e persistente. Foi realizada terapia adjuvante com aplicação de ozônio nas fístulas cutâneas e no remanescente ósseo exposto e necrosado, além do desbridamento dos sequestros ósseos em duas etapas cirúrgicas. Paciente encontra-se em acompanhamento há 1 ano, sem sintomatologia associada. Conclusão: Observou-se que a ozonioterapia, em razão da sua ação antibacteriana e cicatrizante, foi um importante agente terapêutico para a melhora da qualidade de vida da paciente.

Introducción: La inhibición de la actividad osteoclástica, asociada con las diversas modalidades de tratamiento utilizadas por los pacientes con cáncer de cabeza y cuello, hace que el hueso no pueda responder a los procesos de reparación relacionados con traumas o infecciones fisiológicas y puede provocar necrosis ósea. El presente estudio tiene como objetivo informar un caso clínico de osteonecrosis mandibular como consecuencia del uso de bisfosfonato asociado con quimioterapia y radioterapia para tartar el cáncer de mama con mandíbula metastásica, controlando sus secuelas mediante el uso de la terapia con ozono. Relato del caso: Paciente de 73 años con antecedentes de carcinoma ductal mamario infiltrante con metástasis en la mandíbula ósea fue sometida a quimioterapia y radioterapia en la región de la cabeza y el cuello. Tres años después, le diagnostica con osteonecrosis hemimandibular derecha con exposición completa a la cavidad oral e infección crónica, supurativa y persistente. La terapia adyuvante se realizó con la aplicación de ozono en las fístulas cutáneas y en el remanente óseo expuesto y necrótico, además del desbridamiento de los secuestros óseos en dos etapas quirúrgicas. El paciente ha estado bajo seguimiento durante 1 años in síntomas asociados. Conclusión: Debido a su acción antibacteriana y curativa, la ozonioterapia fue un importante agente terapéutico para mejorar la calidad de vida del paciente.

Clinical profile of individuals with bisphosphonate-related osteonecrosis of the jaw: an integrative review

ABSTRACT BACKGROUND: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is still the most prevalent type of osteonecrosis with clinical relevance. In Brazil, bisphosphonate use is high but there is a lack of epidemiological studies on BRONJ. OBJECTIVE: To determine the clinical profile of BRONJ in a Brazilian population through an integrative review. DESIGN AND SETTING: Integrative review of BRONJ in a Brazilian population. METHODS: Cases and clinical research on Brazilians with BRONJ between 2010 and 2019, indexed in PubMed/MEDLINE, Scopus, Web of Science and LILACS were reviewed. Age, sex, type and time of bisphosphonate intake, administration route, related diseases, region of the BRONJ, diagnostic criteria, staging, triggering factor and type of treatment were analyzed. RESULTS: Fifteen articles on 128 subjects were included. Most patients were women (82.03%); the mean age was 63 years. Intravenous zoledronic acid was mostly used (62.50%), for breast cancer treatment (46.87%). The main localization of BRONJ was the mandible (54.68%), associated mainly with tooth extractions (45.98%). The diagnostic criteria were clinical (100%) and radiographic (89.06%), mostly in stage II (68.08%). The surgical treatments were sequestrectomy (37.50%) and platelet-rich plasma (PRP) (36.71%). Microbial control was done using chlorhexidine (93.75%) and infection control using clindamycin (53.90%). CONCLUSIONS: BRONJ had higher prevalence in Brazilian women receiving treatment for breast cancer and osteoporosis. The mandible was the region most affected with a moderate stage of BRONJ, particularly when there were histories of tooth extraction and peri-implant surgery. Sequestrectomy with additional drugs and surgical therapy was the treatment most accomplished.

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.

Delayed alveolar bone repair and osteonecrosis associated with Zoledronic Acid therapy in rats: macroscopic, microscopic and molecular analysis

Abstract Objective This study aims to evaluate bone repair and the development of the medication related osteonecrosis of the jaw (MRONJ) associated with the use of zoledronic acid in Wistar rats. Methodology 48 male Wistar rats were divided into four groups: ZA, treated with intraperitoneal zoledronic acid, 0.6 mg/kg every 28 days, totaling five doses; control (C), treated with 0.9% sodium chloride; ZA-surgical (SZA) and C-surgical (SC), submitted to extraction of the right upper molars 45 days after the first application. Alveolar bone repair was evaluated by macroscopic and histological analysis. Protein expression evaluations were performed by qPCR. Results Macroscopic evaluation showed that 91.66% (11) of the animals in the SZA group and 41.66% (5) from the SC group presented solution of epithelium continuity (P<0.05). All animals in the SZA group and none in the SC group had bone sequestration. The area of osteonecrosis was higher in the SZA group than in the SC group (P<0.05). In molecular evaluation, the SZA group presented changes in the expression of markers for osteoclasts, with increased RANK and RANKL, and a decrease in OPG. Conclusion The results highlighted strong and evident interference of zoledronic acid in bone repair of the socket, causing osteonecrosis and delayed bone remodeling.

Osteonecrosis of the jaw associated to biphosponates in Cali - Colombia / Osteonecrosis Maxilar asociada a bifosfonatos en Cali, Colombia

Antecedentes: Después de más de 15 años del primer reporte de osteonecrosis asociada a bifosfonato (BP), siguen reportándose casos relacionados con este y con otros medicamentos, dándose el aumento en el número de prescripciones. Objetivo: Caracterizar pacientes con osteonecrosis de maxilar asociada a bifosfonatos (BRONJ), atendidos en la ciudad de Cali, Colombia. Materiales y Métodos: Se realizó una encuesta estructurada a 32 cirujanos maxilofaciales de la ciudad de Cali, Colombia, donde se preguntó sobre diferentes tópicos relacionados con pacientes afectados y desarrollo de la patología como edad y genero de los pacientes, tipo de medicamento, tiempo de administración, hueso expuesto, etc. Resultados: Treinta y dos cirujanos maxilofaciales respondieron la encuesta con un total de 8 casos. Se encontró 6 casos correspondieron a mujeres y 2 a hombres, la edad fue superior a 44 años; 4 de los tratamientos con bifosfonatos fueron de prescripción oral y 4 intravenoso. La mayor parte de los casos de osteonecrósis se presentaron en mandíbula (88%) y 6 casos (75%) presentaron exposición de hueso. Conclusiones: La osteonecrosis asociada a bifosfonatos es una situación que todavía se presenta, es necesario que la comunidad de pacientes y el personal de salud conozcan más sobre esta situación.

Background: After more than 15 years of the first report of osteonecrosis associated with bisphosphonate (BP), still cases related to BP and other medications continue to be reported and there is an alert about the increase in the number of prescriptions. The need for both patients and students and health professionals to be familiar with medications, pathology, prevention and treatment measures has been highlighted. Aim: To characterize patients with osteonecrosis in the maxilla associated to bisphosphonate (BRONJ), from Cali, Colombia. Materials and Methods: A structured survey was conducted of 32 maxillofacial surgeons from the city of Cali, Colombia, where different topics related to affected patients and the development of the pathology such as age and gender of patients, type of medication, time of study were asked. administration, exposed bone, etc. Results: Thirty-two maxillofacial surgeons answered the survey with a total of 8 cases, it was found that 6 corresponded to women and 2 to men and the age was over 44 years; 4 of the treatments were oral prescription and 4 intravenous; the majority of cases were presented in the jaw (88%) and 6 cases (75%) presented bone exposure. Conclusions: Osteonecrosis associated with bisphosphonates is a situation that still occurs and could increase its incidence due to the increase in the number of prescriptions for osteoporosis medications, it is necessary that the patient community and health staff know More about this situation.

Osteonecrosis mandibular secundaria al uso de bisfosfonatos. Reporte de un caso / Jaw secondary osteonecrosis to bisphosphonates. Case report

RESUMEN Fundamento: La osteonecrosis de los maxilares secundaria a la administración de bisfosfonatos es una patología que se ha ido incrementando a partir del aumento del uso de esta droga, ya sea por vía oral o endovenosa. Objetivo: Ofrecer una enseñanza clínico-quirúrgica y crear conciencia entre los profesionales de la salud sobre la osteonecrosis mandibular por bisfosfonatos. Presentación de caso: Se reportó un caso de una paciente de 74 años de edad, con osteonecrosis mandibular secundaria al uso de bifosfonatos, localizada en cuerpo mandibular derecho; se le realizó mandibulectomía segmentaria intraoral. Conclusiones: La osteonecrosis de los maxilares asociada al uso de bisfosfonatos es una complicación que repercute en la calidad de vida de estos pacientes. La paciente de este caso, un mes después del tratamiento, se encontraba bien clínicamente y con buenos resultados en los exámenes imaginológicos.

ABSTRACT Background: Osteonecrosis of the jaws, secondary to the administration of bisphosphonates is a pathology that has been increasing from the use of this drug, either orally or intravenously. Objective: To offer clinical-surgical education and raise awareness among health professionals concerning jaw osteonecrosis to bisphosphonate. Case report: A 74-year-old patient with jaw secondary Osteonecrosis to bisphosphonates, located in the right mandibular body was reported; and intraoral segmental mandibulectomy performed. Conclusions: Osteonecrosis of the jaws associated with the use of bisphosphonates is a complication that affects the life quality of these patients. The patient in this case, one month after the treatment, was well clinically and with good results in the imaging tests.

Risk factors of medication-related osteonecrosis of the jaw: a retrospective study in a Turkish subpopulation

OBJECTIVES: Medication-related osteonecrosis of the jaw (MRONJ) is a well-known side effect of certain drugs that are used to influence bone metabolism to treat osteometabolic disease or cancers. The purpose of our study was to investigate how high-concentration and low-concentration bisphosphonate (BP) intake affects the disease severity. MATERIALS AND METHODS: Data collected from the medical records of 52 patients treated with BPs, antiresorptive, antiangiogenic drugs and diagnosed with MRONJ were included in this study. Age, sex, type of systemic disease, type of drug, duration of drug treatment, jaw area with MRONJ, drug administration protocol, and MRONJ clinical and radiological findings were obtained. Patients were divided into two groups: anti-neoplastic (Group I, n=23) and anti-osteoporotic (Group II, n=29). Statistical evaluations were performed using the IBM SPSS ver. 21.0 program. RESULTS: In both groups, more females had MRONJ. MRONJ was found in the mandibles of 30 patients (Group I, n=14; Group II, n=16). When we classified patients according to the American Association of Oral and Maxillofacial Surgeons staging system, significant differences were seen between groups (χ2=12.23, P<0.01). More patients with advanced stage (stage 2–3) MRONJ were found in Group I (60.9%). CONCLUSION: According to our results, high-concentration BP intake, age and duration of drug intake increased disease severity.

Computer programme to assess mandibular cortex morphology in cases of medication-related osteonecrosis of the jaw with osteoporosis or bone metastases

PURPOSE: The purpose of this study was to evaluate the morphology of the mandibular cortex in cases of medication-related osteonecrosis of the jaw (MRONJ) in patients with osteoporosis or bone metastases using a computer programme.MATERIALS AND METHODS: Fifty-four patients with MRONJ (35 with osteoporosis and 19 with bone metastases) were examined using panoramic radiography. The morphology of the mandibular cortex was evaluated using a computer programme that scanned the mandibular inferior cortex and automatically assessed the mandibular cortical index (MCI) according to the thickness and roughness of the mandibular cortex, as follows: normal (class 1), mildly to moderately eroded (class 2), or severely eroded (class 3). The MCI classifications of MRONJ patients with osteoporosis or bone metastases were evaluated with the Pearson chi-square test. In these analyses, a 5% significance level was used.RESULTS: The MCI of MRONJ patients with osteoporosis (class 1: 6, class 2: 15, class 3: 14) tended to be higher than that of patients with bone metastases (class 1: 14, class 2: 5, class 3: 0) (P=0.000).CONCLUSION: The use of a computer programme to assess mandibular cortex morphology may be an effective technique for the objective and quantitative evaluation of the MCI in MRONJ patients with osteoporosis or bone metastases.

Prognostic factors for outcome of surgical treatment in medication-related osteonecrosis of the jaw

OBJECTIVES: The number of patients with medication-related osteonecrosis of the jaw (MRONJ) is increasing, but treatment remains controversial. Published papers and systematic reviews have suggested that surgical treatment is effective in patients with MRONJ. The purpose of this study was to determine whether preoperative University of Connecticut Osteonecrosis Numerical Scale (UCONNS), other serologic biomarkers, and size of necrosis are prognostic factors for outcome of surgical treatment in MRONJ. MATERIALS AND METHODS: From January 2008 to December 2016, 65 patients diagnosed with MRONJ at the Department of Oral and Maxillofacial Surgery in College of Dentistry, Dankook University who required hospitalization and surgical treatment were investigated. Patient information, systemic factors, and UCONNS were investigated. In addition, several serologic values were examined through blood tests one week before surgery. The size of osteolysis was measured by panoramic view and cone-beam computed tomography in all patients. With this information, multivariate logistic regression analysis with backward elimination was used to examine factors affecting postoperative outcome. RESULTS: In multivariate logistic analysis, higher UCONNS, higher C-reactive protein (CRP), larger size of osteolysis, and lower serum alkaline phosphate were associated with higher incidence of incomplete recovery after operation. This shows that UCONNS, CRP, serum alkaline phosphate, and size of osteolysis were statistically significant as factors for predicting postoperative prognosis. CONCLUSION: This study demonstrated that CRP, UCONNS, serum alkaline phosphate, and size of osteolysis were statistically significant factors in predicting the prognosis of surgical outcome of MRONJ. Among these factors, UCONNS can predict the prognosis of MRONJ surgery as a scale that includes various influencing factors, and UCONNS should be used first as a predictor. More aggressive surgical treatment and more definite surgical margins are needed when the prognosis is poor.

Efeito da terapia de longa duração com ácido zoledrônico no osso esponjoso da mandíbula e fêmur de ratos Wistar / Effect of long-term zoledronic acid treatment on cancellous bone in the mandible and femur of Wistar rats

Os bisfosfonatos (BF) são amplamente utilizados no tratamento de doenças osteolíticas como metástases ósseas e osteoporose. A osteonecrose dos maxilares associada ao uso de BF (OMAB) é caracterizada pela presença de osso exposto ou que pode ser sondado através de uma fístula que persiste por mais de oito semanas em pacientes com história de terapia de BF e sem história de radioterapia na região de cabeça e pescoço e/ou sem doença metastática nos maxilares. A incidência de OMAB aumenta com a potência, duração do tratamento e dose de BF recebida. Até o presente momento, a fisiopatologia da OMAB não está clara, dificultando a prevenção e o tratamento. O objetivo deste estudo foi avaliar o efeito da administração de altas doses Ácido Zoledrônico (AZ) por período prolongado no osso esponjoso da mandíbula e da metáfise proximal do fêmur de ratos Wistar. Para relacionar as descobertas à fisiopatologia da OMAB, o regime de administração de BF de um modelo animal relevante desta lesão foi reproduzido. Seis animais receberam AZ (0,6 mg / kg) e seis receberam solução salina no mesmo volume (Controles). Os compostos foram administrados por via intraperitoneal em cinco doses a cada 28 dias. A eutanásia dos animais ocorreu após 150 dias de início da terapia. As hemimandíbulas e fêmures direitos foram escaneados usando Micro-tomografia computadorizada (Micro-CT) de alta resolução (14 m). Para a primeira análise realizada neste estudo, os dados morfométricos do osso esponjoso foram calculados na região do segundo e primeiro molar na mandíbula e na metáfise do fêmur usando CTAnalyzer (Bruker, Bélgica). Para a segunda análise, cinco amostras de hemimandíbulas de cada grupo foram cortadas em lâminas histológicas (5 m) e coradas com Hematoxilina e Eosina. Para comparar os parâmetros morfométricos na Micro-CT e histologia, as imagens de Micro-CT foram espacialmente alinhadas à histologia. Os dados morfométricos do osso alveolar foram calculados usando o software CTAnalyzer (Bruker, Bélgica) na região entre as raízes mesial e distal do primeiro molar. A densidade da área vascular (área vascular/área total; VA/TA) e os dados histomorfométricos ósseos foram estimados usando Axiovision na mesma região (entre as raízes mesial e distal do primeiro molar). Foi adotada significância estatística de 5% ( = 0,05). Os animais tratados com AZ apresentaram aumento significativo na porcentagem de volume ósseo (p <0,05) com trabéculas mais espessas, osso mais compacto com menor separação trabecular na mandíbula e no fêmur. Na mandíbula, o aumento da densidade óssea e diminuição da separação trabecular foram fortemente correlacionados com a diminuição da área vascular observada no grupo AZ (p <0,05). Em conclusão, o tratamento de longa duração com altas doses de AZ foi significativamente associado ao aumento na densidade óssea e à diminuição dos espaços medulares, canais nutritivos e vasculatura do osso alveolar. A análise com Micro-CT revelou alterações semelhantes na estrutura óssea tanto na mandíbula quanto no fêmur do grupo AZ.(AU)

Bisphosphonates (BFs) are widely used in the treatment of osteolytic diseases such as bone metastases and osteoporosis. The osteonecrosis of the jaws related to BF (ONB) is characterized by the presence of exposed bone or bone that can be probed through a fistula that persists for more than eight weeks in patients with a history of BF therapy and without history of head and neck radiotherapy and / or without metastatic disease in the jaws. The incidence of ONB increases with potency, duration of treatment and dose of BF received. Thus far, the pathophysiology of ONB is unclear, hampering prevention and treatment. The aim of this study was to objectively assess the effect of long-term high-dose Zoledronic Acid (ZA) on cancellous bone in the jaw and femur of Wistar rats. In order to link our findings to the physiopathology of ONB, the therapeutic regiment of a relevant ONB animal model was reproduced. Twelve Wistar rats were randomly divided in two groups: six received Zoledronic acid (ZA; 0.6 mg / kg) and six (Controls) received saline solution in the same volume. The compounds were administrated intraperitoneally in five doses each 28 days. The rats were killed after 150 days of the therapy onset. Mandibles and femurs were scanned using a high-resolution (14m) micro-computerized tomography (Micro-CT). For the first analysis carried in this study, cancellous bone morphometric data were calculates in the region of the second and first molar in the mandible and in the proximal femur using CTAnalyzer (Bruker, Belgium). For the second analysis five samples were cut into histological slices (5m) and stained with Hematoxylin and Eosin. In order to compare the same morphological structures in Micro-CT and histology, the Micro-CT images were aligned to histology. Alveolar bone morphometric data (Micro-CT) was calculated using CTAnalyzer (Bruker, Belgium) in the region between the mesial and distal roots of the first molar. Blood vessels density and bone histomorphometric data were calculated using Axiovision (Carl Zeiss, Germany) in the same region used for Micro-CT evaluation. Statistical significance of 5% (=0.05) was adopted. ZA treated rats presented significant increase in the percentage of bone volume (p<0.05) with thicker trabeculae and more compact bone with smaller marrow spaces in the mandible and femur. In the mandible, the increase in bone density and decrease of marrow spaces size was strongly correlated with the decrease in the vascular area noticed in the ZA group (p<0.05). In conclusion, long-term high-dose ZA treatment was significant associated with the increase of bone density and the diminution of medullary spaces and nutritive canals size as well as decrease in vascularity of the alveolar bone. Micro-CT investigation showed similar changes in bone structure in the mandible and femur in the ZA group.(AU)

A Case of Pentastomiasis at the Left Maxilla Bone in a Patient with Thyroid Cancer

Pentastomiasis, a zoonotic parasite infection, is typically found in the respiratory tract and viscera of the host, including humans. Here, we report for the first time an extremely rare case of intraosseous pentastomiasis in the human maxilla suffering from medication related osteonecrosis of the jaw (MRONJ). A 55-year-old male had continuously visited the hospital for MRONJ which had primarily developed after bisphosphonate and anti-neoplastic administration for previous bone metastasis of medullary thyroid cancer. Pain, bone exposure, and pus discharge in the right mandible and left maxilla were seen. Osteolysis with maxillary cortical bone perforation at the left buccal vestibule, palate, nasal cavity, and maxillary sinus was observed by radiologic images. A biopsy was done at the left maxilla and through pathological evaluation, a parasite with features of pentastome was revealed within the necrotic bone tissue. Further history taking and laboratory evaluation was done. The parasite was suspected to be infected through maxillary open wounds caused by MRONJ. Awareness of intraosseous pentastomiasis should be emphasized not to be missed behind the MRONJ. Proper evaluation and interpretation for past medical history may lead to correct differential diagnosis and therapeutic intervention for parasite infections.

A case of bisphosphonate-related osteonecrosis of the jaw with a particularly unfavourable course: a case report

Bisphosphonates are drugs used to treat osteoclast-mediated bone resorption, including osteoporosis, Paget disease, multiple myeloma, cancer-related osteolysis, and malignant hypercalcemia. The use of these drugs has increased in recent years as have their complications, especially bisphosphonate-related osteonecrosis of the jaw (BRONJ), which more frequently affects the mandible. Here we report a case of BRONJ with a particularly unfavorable course due to cervical inflammation that developed into necrotizing fasciitis, followed by multiorgan involvement leading to septic shock and death.

Risk factors of osteonecrosis of the jaw after tooth extraction in osteoporotic patients on oral bisphosphonates

PURPOSE: The aim of this study was to investigate the incidence of bisphosphonate-related osteonecrosis of the jaw (BRONJ) after tooth extraction in patients with osteoporosis on oral bisphosphonates in Korea and to evaluate local factors affecting the development of BRONJ. MATERIALS AND METHODS: The clinical records of 320 patients who underwent dental extraction while receiving oral bisphosphonates were reviewed. All patients had a healing period of more than 6 months following the extractions. Each patient's clinical record was used to assess the incidence of BRONJ; if BRONJ occurred, a further radiographic investigation was carried out to obtain a more definitive diagnosis. Various local factors including age, gender, extraction site, drug type, duration of administration, and C-terminal telopeptide (CTx) level were retrieved from the patients' clinical records for evaluating their effect on the incidence of BRONJ. RESULTS: Among the 320 osteoporotic patients who underwent tooth extraction, 11 developed BRONJ, reflecting an incidence rate of 3.44%. Out of the local factors that may affect the incidence of BRONJ, gender, drug type, and CTx level showed no statistically significant effects, while statistically significant associations were found for age, extraction site, and duration of administration. The incidence of BRONJ increased with age, was greater in the mandible than the maxilla, and was associated with a duration of administration of more than 3 years. CONCLUSION: Tooth extraction in patients on oral bisphosphonates requires careful consideration of their age, the extraction site, and the duration of administration, and close postoperative follow-up should be carried out to facilitate effective early management.

Relationship between disease stage and renal function in bisphosphonate-related osteonecrosis of the jaw

OBJECTIVES: Bisphosphonate is the primary cause of bisphosphonate-related osteonecrosis of the jaw (BRONJ). Bisphosphonates are eliminated from the human body by the kidneys. It is anticipated that bisphosphonate levels in the body will increase if the kidney is in a weak state or if there is systemic disease that affects kidney function. The aim of this study was to analyze the relevance of renal function in the severity of BRONJ. MATERIALS AND METHODS: Ninety-three patients diagnosed with BRONJ in Pusan National University Dental Hospital from January 2012 to December 2014 were included in this study. All patients underwent a clinical exam, radiographs, and serologic lab test, including urine analysis. The patient's medical history was also taken, including the type of bisphosphonate drug, the duration of administration and drug holiday, route of administration, and other systemic diseases. In accordance with the guidelines of the 2009 position paper of American Association of Oral and Maxillofacial Surgeons, the BRONJ stage was divided into 4 groups, from stage 0 to 3, according to the severity of disease. IBM SPSS Statistics version 21.0 (IBM Co., USA) was used to perform regression analysis with a 0.05% significance level. RESULTS: BRONJ stage and renal factor (estimated glomerular filtration rate) showed a moderate statistically significant correlation. In the group with higher BRONJ stage, the creatinine level was higher, but the increase was not statistically significant. Other factors showed no significant correlation with BRONJ stage. There was a high statistically significant correlation between BRONJ stage and ‘responder group’ and ‘non-responder group,’ but there was no significant difference with the ‘worsened group.’ In addition, the age of the patients was a relative factor with BRONJ stage. CONCLUSION: With older age and lower renal function, BRONJ is more severe, and there may be a decrease in patient response to treatment.

Medication-related osteonecrosis of the jaw. Introduction of a new modified experimental model

ABSTRACT PURPOSE : To evaluate a modified experimental model for medication-related osteonecrosis of the jaw (MRONJ) through the upper right central incisor extraction followed by intravenous bisphosphonate administration. METHODS: Forty five rats underwent the upper right central incisor tooth extraction were divided in 2 groups: Group I - experimental group, 30 rats received an intravenous administration protocol of zoledronic acid 35μg/kg into the tail vein every two weeks, totalizing four administrations, during eight weeks of administration, previously the extraction, and Group II - control group, 15 rats didn't received any medication before extraction. The groups were subdivided in postoperative periods: 14/28/42 days. Clinical analysis and microtomography were performed to verify the presence of osteonecrosis. In addition, descritive histological analysis of hematoxylin-eosin stained sections was performed to evaluate the presence of osteonecrosis or necrotic foci. RESULTS: Twelve (40%) rats, from experimental group, showed clinical signs of MRONJ (p=0.005), however, all samples showed imaginologic findings like osteolysis and loss of integrity of the cellular walls (p≤0.001). Microscopic evaluation revealed osteonecrosis areas with microbial colonies and inflammatory infiltrate (p≤0.001). In the control group, all animals presented the chronology of a normal wound healing. CONCLUSIONS: The presence of medication-related osteonecrosis of the jaw after maxillary central incisor extraction in rats. This new experimental model may be considered an option for the study of MRONJ.