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

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.

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.

Viability of dental implants in head and neck irradiated patients: A systematic review.

BACKGROUND: The purpose of this systematic review was to evaluate the safety of dental implants placed in irradiated bone and to discuss their viability when placed post-radiotherapy (RT). METHODS: A systematic review was performed to answer the questions: "Are dental implants in irradiated bone viable?" and "What are the main factors that influence the loss of implants in irradiated patients?" RESULTS: The search strategy resulted in 8 publications. A total of 331 patients received 1237 implants, with an overall failure rate of 9.53%. The osseointegration success rates ranged between 62.5% and 100%. The optimal time interval between irradiation and dental implantation varied from 6 to 15 months. CONCLUSION: The interval time between RT and implant placement and the radiation doses are not associated with significant implant failure rates. The placement of implants in irradiated bone is viable, and head and neck RT should not be considered as a contraindication for dental rehabilitation with implants. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2229-E2240, 2016.

Avaliação da estabilidade de implantes curtos Neodent, tipo Cone Morse, por meio do teste do torque reverso: estudo preliminar em coelhos / Assessing stability of Neodent Morse taper implants through reverse torque technique testing: a preliminary study in rabbits

Introdução: atualmente, vários tipos de implantes estão disponíveis no mercado. Entre esses, pode-se citar os com conexão do tipo hexágono externo, hexágono interno e Cone Morse,sendo que os com Cone Morse fornecem melhor distribuição e transmissão da força ao longo do implante. O grau de osseointegração de um implante pode ser medido e avaliado por meio do valordo torque reverso. Objetivo: com base nisso, o objetivo do presente trabalho é testar, em implantes do tipo Cone Morse, instalados em tíbias de coelhos, a viabilidade de um novo método de avaliação de torque reverso. Métodos: foram instalados implantes (Neodent Cone Morse WS) em tíbias de coelho. Os animais foram eutanasiados em diferentes períodos de tempo. Os blocos ósseos contendo os implantes foram recortados e o montador correspondente ao implante Cone Morse foi acoplado a esse, formando um pilar único e contínuo. O torque reverso foi simulado utilizando a máquina universal de ensaios EMIC DL 1000. Uma força de compressão foi aplicada sobre o braçoda alavanca (Neodent), acoplado ao dispositivo de montagem do implante. Resultados: os valores obtidos com o teste foram os seguintes: Coelho 1 (imediato) = 1,8Kgf, Coelho 2 (7 dias) = 7,6Kgf, Coelho 3 (15 dias) = 17Kgf, Coelho 4 (30 dias) = 27Kgf, Coelho 5 (45 dias) = 36Kgf. Conclusão: os resultados mostraram-se promissores, uma vez que se obteve um aumento do valor do torque reverso com o passar do tempo.

Introduction: Several types of implants are available on the market, including internal or external hexagonal connections and the Morse Taper connection. The latter provides betterdistribution and transmission of forces throughout the implant. Implant osseointegration can be measured and assessed by reverse torque. Objective: The objective of this study is to test, inMorse Taper implants installed in rabbits’ tibia, the feasibility of a new reverse torque assessment method. Methods: Neodent Morse Taper WS implants were installed in rabbits’ tibia. The animals were sacrificed at different periods of time. The bone blocks containing the implants were cut, anda corresponding mounting device was attached to the implant, forming a single pillar. Reverse torque was simulated using a universal testing machine EMIC DL 1000. Compressive force wasapplied to the arm of the ratchet. Results: The values obtained with the test were: Rabbit 1 (immediate)= 1.8 Kgf, Rabbit 2 (7 days) = 7.6 Kgf, Rabbit 3 (15 days) = 17 Kgf, Rabbit 4 (30 days)=27Kgf, and Rabbit 5 (45 days) = 36 Kgf. Conclusion: Results were promising as they indicated an increase in the value of reverse torque over time.

Análise molecular e microscópica do reparo ósseo de alvéolos dentários após exodontia em um modelo de osteonecrose dos maxilares induzida pelo ácido zoledrônico em ratos Wistar / Molecular and microscopic analysis of bone repair of dental sockets after tooth extraction in a model of osteonecrosis of the jaws induced by zoledronic acid in rats

O reparo ósseo de alvéolos após exodontia dos molares superiores em um modelo animal em ratos Wistar (Rattus norvegicus, albinus) de osteonecrose dos maxilares associada ao uso de bisfosfonatos foi avaliado através de analise microscópica e molecular. Foram utilizados 48 ratos (Rattus norvegicus, albinus, Wistar) machos, com 12 semanas de vida e peso aproximado de 300 gramas, que foram dividos em 4 grupos. Cada grupo era composto por 12 animais, sendo 2 grupos experimentais AZ e AZ-Cirúrgico (AZ-C), que foram submetidos a administração de ácido zoledrônico, 0,6 mg/kg a cada 28 dias com um total de 5 doses e 2 grupos controles CO e CO-Cirúrgico (CO-C) com administração de cloreto de sódio 0,9% no mesmo volume e frequencia do ácido zoledrônico. Todas as soluções foram administradas por via intraperitoneal. O grupo AZ-C e o grupo CO-C foram submetidos a exodontia do primeiro, segundo e terceiro molares superiores 45 dias após a primeira aplicação das soluções. Todos os animais foram eutanasiados após 150 dias do início do experimento (105 dias após as exodontias). As maxilas dos animais foram avaliadas macroscopicamente para presença de lesões espontâneas e com uma sonda clinica número 5 as regiões das exodontias dos molares foram avaliadas para presença ou ausência de solução continua do epitélio. Após feita a avaliação macroscópica as regiões das exodontias dos molares superior esquerdo e do lado contralateral de cada animal foram submetidas a análises qualitativa e quantitativa para presença de sequestros ósseos, restos radiculares, área de osteonecrose, área de espaço trabecular, área de reação periosteal, através de estudos por microscopia óptica pela coloração Hematoxilina e Eosina. Análise quantitativa da expressão do RNAm de proteínas envolvidas no processo de reparo ósseo RANK, RANKL, OPG e VEGF, pelo método de reação em cadeia da polimerase em tempo real (RealTimePCR) também foi realizada. A avaliação macroscópica mostrou que 91,66% dos animais...

The alveolar bone repair following extraction of maxillary molars in an animal model of bisphosphonate related osteonecrosis of the jaws in Wistar rats (Rattus norvegicus, Albinus) was assessed through microscopic and molecular analysis. A total of 48 rats (Rattus norvegicus, Albinus, Wistar rats) with 12 weeks old and weighing approximately 300 grams were used, they were divided into 4 groups. Each group consisted of 12 animals, with 2 experimental groups AZ and AZ-Cirúrgico (AZ-C), who underwent the administration of zoledronic acid, 0.6 mg / kg every 28 days with a total of 5 doses. And 2 control groups CO and CO-Cirúrgico (CO-C) with administration of sodium chloride at 0.9% in the same volume and frequency of zoledronic acid. All solutions were administered intraperitoneally. The group AZ-C and CO-C underwent to extraction of the first, second and third molars 45 days after the first application of the solutions. All animals were sacrificed after 150 days from the beginning of the experiment (105 days after extractions). The maxilla of the animals were assessed macroscopically for the presence of spontaneous lesions, and with a clinical probe number five the regions of the molar extractions were evaluated for the presence or absence of loss of continuity of the oral epithelium. After macroscopic evaluation, the upper left molar and contralateral side of the extraction regions of each animal were submitted to qualitative and quantitative analyzes for the presence of bone sequestrum, root fragments, osteonecrosis area, trabecular space area, area of periosteal reaction, through optical microscopic studies by hematoxylin and eosin staining. And quantitative analysis of mRNA expression of proteins involved in bone repair (RANK, RANKL, OPG and VEGF), by the method of RealTimePCR were carried out. Macroscopic evaluation showed that 91.66% of the AZ -C group and 41.66% of the CO-C group presented a loss of continuity of the epithelium...

Clinical and image findings in bisphosphonate-related osteonecrosis of the jaws.

Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is characterized as exposed bone in the jaws for more than 8 weeks in patients with current or previous history of therapy with bisphosphonates (BPs) and no history of radiotherapy in the head and neck. We report a case series of 7 patients with BRONJ and analyze the variations of clinical and imaging signs, correlating them with the presence or absence of bone exposure. Among the patients, 6 were women and 1 was a man, aged 42-79 years. Five of the patients were using zoledronic acid and the other 2 alendronate. The use of BPs varied from 3 to 13 years. In 5 patients, tooth extraction was the triggering event of injuries. Panoramic radiographs and computed tomography (CT) were evaluated by a radiologist blinded to the cases. There were persistent unremodeled extraction socket even several months after tooth extraction in 3 of the cases that were consistent wit CT findings that also showed areas of osteosclerosis and osteolysis. Patients were treated according to the recommendations of the AAOMS, with surgical debridement and antibiotic coverage with amoxicillin in the symptomatic patients. The follow-up of these patients ranged from 8 to 34 months, with a good response to treatment. The image findings in this case series were not specific and showed no difference between each stages of BRONJ (AAOMS, 2009). The image features were similar in presence or absence of exposed bone.

Reconstrução de rebordo alveolar com osso homógeno em bloco: uma revisão sistemática / Alveolar ridge augmentation with homogenous bone block: a systematic review

A utilização de próteses implantossuportadas é, nos dias de hoje, uma alternativa segura e viável para reabilitação de áreas edêntulas. Porém, muitas vezes a instalação de implantes osseointegrados pode ser comprometida ou impossibilitada devido a reabsorções extensas dos rebordos alveolares. O objetivo deste trabalho foi revisar sistematicamente a literatura relacionada à reconstrução de rebordo alveolar com osso homógeno em bloco para subsequente instalação de implantes. O levantamento bibliográfico sistemático foi realizado na base de dados Pubmed e na Bibliografia Brasileira de Odontologia (BBO) entre os anos de 1966 e outubro de 2009. Além disso, foi realizada uma busca manual nas referências dos artigos incluídos na revisão. O resultado dessa revisão de literatura identificou apenas 7 estudos relacionados a essa técnica que preenchiam os critérios de inclusão. A espessura do rebordo aumentou significativamente com uso do enxerto homógeno, apresentando padrões de reabsorção dentro de limites aceitáveis. Os enxertos homógenos e os implantes instalados nas áreas enxertadas apresentaram altos índices de sucesso nos artigos incluídos. Esses demonstraram a previsibilidade da utilização dos enxertos homógenos e posterior instalação de implantes por um período de até 3 anos. No entanto, não há na literatura dados histológicos que confirmem existir uma osseointegração satisfatória com o uso desse material. São, portanto, necessários mais estudos controlados com avaliações histológicas para confirmar a eficiência e a segurança da utilização dos enxertos homógenos.

The use of implant-supported prosthesis is nowadays a safe alternative for rehabilitation of edentulous areas. But most of the time the implant placement can be compromised because of extensive alveolar resorption. The purpose of this study was to systematic review the literature related to the reconstruction of alveolar ridge with homogenous bone block for implant placement. The systematic review was performed on Pubmed and Brazilian Bibliography of Odontology (BBO) from 1966 to October 2009. Therefore, a hand-search in dental journals was done on the references of the selected articles. The results of this literature review identified only 7 studies related to this technique that filled the criteria of inclusion. The alveolar ridge width increased significantly with the use of block allograft, showing acceptable resorption standards. Allografts and implants inserted on grafted areas presented high success rates on the included articles. These ones showed the predictability of using allograft and implants placed after 3 years. However, there is no histological data on the literature that assures a satisfactory osseointegration using this kind of material. Controlled trials with histological evaluation are necessary to confirm the efficacy and security of allografts.

Ultrastructural and immunohistochemical study of the influence of fluoride excess on the development of rat incisor tooth buds

Little information is available on the pathogenesis of fluorosis during the fetal and initial postnatal period. In the present study, female rats received 0 (control), 7 or 100 ppm of sodium fluoride in drinking water, one week before breeding and throughout gestation and nursing periods. The hemimandibles of the offspring were collected at 0, 7 and 14 days of postnatal life (n = 5) and processed for morphological analyses by light and electron microscopy, immunohistochemical analysis for amelogenin and morphometric study of enamel matrix and ameloblasts of incisors. The results showed a decrease in matrix production at the secretory phase at all study periods for the 100 ppm group. In this same group, the secretory ameloblasts showed reduction of enamel matrix secretion, disorganization of mitochondrial crests, large vacuoles at the apical portion of the cytoplasm, retention of intracisternal material and dilatation of some cisterns in the rough endoplasmic reticulum. In the groups of animals aged 7 and 14 days, analysis of variance showed significant reduction (p<0.05) in cytoplasmic volume of 23.80 percent and 24.75 percent, respectively, in relation to the control group. The smooth-ended maturation ameloblasts exhibited a large number of vacuoles with electron-dense endocytic matrix, suggesting a delay in the resorption process. Immunohistochemical analysis showed no difference in the intensity and labeling pattern of the enamel matrix in any study group. Interestingly, in offspring at the age of 14 days for the 7 ppm group, there was an increase in the matrix length at the secretory phase. Therefore, part of the excessive dose of sodium fluoride given to the mother in drinking water can reach the offspring through the placenta and mother's milk, causing morphological changes in ameloblasts and suggesting a reduction in secretion and a delay in matrix resorption.

Ultrastructural and immunohistochemical study of the influence of fluoride excess on the development of rat incisor tooth buds.

Little information is available on the pathogenesis of fluorosis during the fetal and initial postnatal period. In the present study, female rats received 0 (control), 7 or 100 ppm of sodium fluoride in drinking water, one week before breeding and throughout gestation and nursing periods. The hemimandibles of the offspring were collected at 0, 7 and 14 days of postnatal life (n = 5) and processed for morphological analyses by light and electron microscopy, immunohistochemical analysis for amelogenin and morphometric study of enamel matrix and ameloblasts of incisors. The results showed a decrease in matrix production at the secretory phase at all study periods for the 100 ppm group. In this same group, the secretory ameloblasts showed reduction of enamel matrix secretion, disorganization of mitochondrial crests, large vacuoles at the apical portion of the cytoplasm, retention of intracisternal material and dilatation of some cisterns in the rough endoplasmic reticulum. In the groups of animals aged 7 and 14 days, analysis of variance showed significant reduction (p<0.05) in cytoplasmic volume of 23.80% and 24.75%, respectively, in relation to the control group. The smooth-ended maturation ameloblasts exhibited a large number of vacuoles with electron-dense endocytic matrix, suggesting a delay in the resorption process. Immunohistochemical analysis showed no difference in the intensity and labeling pattern of the enamel matrix in any study group. Interestingly, in offspring at the age of 14 days for the 7 ppm group, there was an increase in the matrix length at the secretory phase. Therefore, part of the excessive dose of sodium fluoride given to the mother in drinking water can reach the offspring through the placenta and mother's milk, causing morphological changes in ameloblasts and suggesting a reduction in secretion and a delay in matrix resorption.