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1.
Braz. dent. sci ; 23(1): 1-6, 2020. tab, ilus
Article in English | LILACS, BBO | ID: biblio-1049815

ABSTRACT

Objective: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a challenging complication of chronic bisphosphonate (BP) use. The hormone relaxin is able to induce the multistep differentiation process of human osteoclastogenesis, exhibits antifibrotic and anti-inflammatory actions, and promotes vasodilatation, wound healing, and angiogenesis. The present study aimed to evaluate the effects of relaxin in the prevention and management of BRONJ. Material and Methods: Thirty-six male Sprague Dawley rats were randomly divided into four groups. Rats in group 1 (n = 10) received relaxin and BP simultaneously for 12 weeks. Rats in group 2 (n = 10) received injections of BP for 12 weeks, followed by relaxin for another 12 weeks. Rats in group 3 (n = 10) received only BP injections, and those in group 4 (control, n = 6) received only saline. Necrosis and inflammation in the rats' mandibles were evaluated as indicators of BRONJ. Results: Necrosis and inflammation were not detected in group 1 (BP + relaxin). In group 3 (BP only), incidence rates of necrosis and inflammation were 90% and 60%, respectively. Conclusions: Our findings suggest that relaxin may be potently effective in preventing BRONJ and have some benefit in the treatment of existing BRONJ (AU)


Objetivo: A osteonecrose da mandíbula relacionada ao bisfosfonato (BRONJ) é uma desafiadora complicação do uso crônico de bisfosfonato (BP). O hormônio relaxina é capaz de induzir o processo múltiplo de diferenciação da osteoclastogênese humana, exibe ações anti-fibróticas e anti-inflamatórias e promove vasodilatação, cicatrização de feridas e angiogênese. O presente estudo teve como objetivo avaliar os efeitos da relaxina na prevenção e tratamento do BRONJ. Material e Métodos: Trinta e seis ratos Sprague Dawley machos foram divididos aleatoriamente em quatro grupos. Os ratos do grupo 1 (n = 10) receberam relaxina e BP simultaneamente por 12 semanas. Os ratos do grupo 2 (n = 10) receberam injeções de BP por 12 semanas, seguidos de relaxina por mais 12 semanas. Os ratos do grupo 3 (n = 10) receberam apenas injeções de BP e os do grupo 4 (controle, n = 6) receberam apenas solução salina. Necrose e inflamação nas mandíbulas dos ratos foram avaliadas como indicadores de BRONJ. Resultados: Necrose e inflamação não foram detectadas no grupo 1 (BP + relaxina). No grupo 3 (somente BP), as taxas de incidência de necrose e inflamação foram de 90% e 60%, respectivamente. Conclusões: Nossos resultados sugerem que a relaxina pode ser potentemente eficaz na prevenção do BRONJ e ter algum benefício no tratamento do BRONJ existente.(AU)


Subject(s)
Animals , Male , Rats , Relaxin/therapeutic use , Bisphosphonate-Associated Osteonecrosis of the Jaw/therapy , Random Allocation , Rats, Sprague-Dawley , Models, Animal , Bisphosphonate-Associated Osteonecrosis of the Jaw/prevention & control , Bisphosphonate-Associated Osteonecrosis of the Jaw/drug therapy , Jaw/pathology
2.
Rev. Asoc. Odontol. Argent ; 107(2): 72-78, abr.-jun. 2019. tab
Article in Spanish | LILACS | ID: biblio-1016110

ABSTRACT

El objetivo de este trabajo es revisar los conocimientos actuales sobre el manejo clínico-odontológico de pacientes que consumen medicamentos antirresortivos y medicamentos antiangiogénicos o quimioterapéuticos, en relación con la prevención y/o el tratamiento de la osteonecrosis de los maxilares asociada a medicamentos. Se evaluaron similitudes y diferencias entre los bifosfonatos, denosumab y medicamentos antiangiogénicos, así como el manejo clínico de pacientes, vacaciones de medicamentos y el manejo de osteonecrosis de los maxilares ya instalada. Se encontraron similitudes en la presentación clínica, la prevención, el uso de antibioticoterapia antes de procedimientos invasivos y el tratamiento de la osteonecrosis ya instalada. Entre las diferencias, podemos mencionar que el tratamiento quirúrgico respondería mejor en pacientes medicados con denosumab o antiangiogénicos, y su suspensión sería más efectiva si se iniciara un proceso de osteonecrosis, al igual que su tasa de resolución. En cuanto a las vacaciones de medicamentos, no hay datos concluyentes para guiar esta decisión, al igual que no existe un protocolo clínico de atención en pacientes que consumen denosumab o antiangiogénicos (AU)


The aim of this study is to review the currents knowledge about the clinical and dental management of patients who consume antiresorptive and antiangiogenic agents or chemotherapeutic drugs, in relation to the prevention and/or treatment of osteonecrosis of the jaws related to medication. Similarities and differences between bisphosphonates, denosumab and antiangiogenic medications were evaluatted, as well as the clinical management of patients, drugs holidays and management of osteonecrosis of the jaws already setted. Similarities were found in the clinical presentation, prevention, use of antibiotic therapy before invasive procedures and the treatment of osteonecrosis already installed. Regarding the differences, we can mention that the surgical treatment would be better in patients medicated with denosumab or antiangiogenics and its suspension would be more effective if an osteonecrosis process is initiated, as well as its resolution rate. There are no conclusive data about drug holidays to guide this decision, and no clinical protocol of care in patients who consume denosumab or antiangiogenic agents (AU)


Subject(s)
Humans , Angiogenesis Inhibitors , Diphosphonates/adverse effects , Bisphosphonate-Associated Osteonecrosis of the Jaw/complications , Denosumab/adverse effects , Risk Factors , Bisphosphonate-Associated Osteonecrosis of the Jaw/prevention & control , Bisphosphonate-Associated Osteonecrosis of the Jaw/drug therapy
3.
Braz. oral res. (Online) ; 33: e086, 2019. tab, graf
Article in English | LILACS | ID: biblio-1019605

ABSTRACT

Abstract Treatment of patients with bisphosphonate usage is a significant concern for oral surgeons because it interferes with jaw bone turnover and regeneration. In case of adverse effects manifesting related to bisphosphonate use, oral surgeons are usually treating and keep the patient's symptoms under control. In this study, we aimed to investigate a new treatment protocol for medication-related osteonecrosis of the jaw (MRONJ). This treatment protocol consisted of administering human parathyroid hormone (hPTH) loaded chitosan microspheres which were prepared by ionotropic gelation method or/and the prepared microspheres were suspended in a poloxamer gel. After in-vitro optimization studies, the efficacy of the chosen formulations was evaluated in-vivo studies. Zoledronic acid was administered daily to forty-eight adult female Sprague-Dawley rats, divided into four experimental groups, at a daily concentration of 0.11 mg/kg over three weeks to induce the MRONJ model. At the end of this period, maxillary left molar teeth were extracted. In the first group, the subjects received no treatment. In the negative control group, poloxamer hydrogel containing empty microspheres were immediately applied to the soft tissues surrounding the extraction socket. The treatment group-1 was treated with local injections of poloxamer hydrogel containing hPTH. The treatment group-2 was treated with a single local injection of poloxamer hydrogel containing hPTH-loaded chitosan microspheres. Both treatment groups received a total of 7 µg of hPTH at the end of the treatment protocol. Our study demonstrates successful attenuation of MRONJ through a local drug delivery system combined with hPTH, as opposed to previously attempted treatment strategies.


Subject(s)
Humans , Animals , Female , Parathyroid Hormone/pharmacology , Chitosan/pharmacology , Bone Density Conservation Agents/pharmacology , Maxilla/drug effects , Parathyroid Hormone/therapeutic use , Rats, Sprague-Dawley , Poloxamer/administration & dosage , Poloxamer/chemistry , Models, Animal , Delayed-Action Preparations , Chitosan/therapeutic use , Bone Density Conservation Agents/adverse effects , Bone Density Conservation Agents/therapeutic use , Bisphosphonate-Associated Osteonecrosis of the Jaw , Bisphosphonate-Associated Osteonecrosis of the Jaw/drug therapy , Zoledronic Acid/adverse effects , Maxilla/pathology , Microspheres
4.
Bauru; s.n; 2017. 89 p. ilus, tab, graf.
Thesis in Portuguese | LILACS, BBO | ID: biblio-883240

ABSTRACT

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)


Subject(s)
Animals , Rats , Bisphosphonate-Associated Osteonecrosis of the Jaw/drug therapy , Bone Density Conservation Agents/administration & dosage , Cancellous Bone/drug effects , Diphosphonates/administration & dosage , Femur/drug effects , Imidazoles/administration & dosage , Mandibular Diseases/drug therapy , Bisphosphonate-Associated Osteonecrosis of the Jaw/physiopathology , Bone Density , Random Allocation , Rats, Wistar , Reproducibility of Results , Time Factors , Treatment Outcome , X-Ray Microtomography
5.
Braz. dent. j ; 27(3): 353-358, May-June 2016. graf
Article in English | LILACS | ID: lil-782833

ABSTRACT

Abstract This paper describes two cases in which the use of leucocyte-rich and platelet-rich fibrin (LPRF) combined with bone resection did not result in complete tissue response in the treatment of medication-related osteonecrosis of the jaw (MRONJ). It has been recently described in patients receiving subcutaneous administration of RANK-inhibitors, such as Denosumab, and anti-angiogenic drugs, such as Bevacizumab, as observed in our cases. Due to promising results in recent studies, more patients will receive these medications in order to avoid skeletal complications due to metastatic bone disease and, therefore, this scenario has a potential to become a comparable challenge to the bisphosphonate- induced jaw necrosis in the area of Oral and Maxillofacial Surgery. No convincing surgical technique has been described to overcome the non-healing mucosal lesions with exposed bone due to RANK-inhibitor therapy. Based on the findings in the literature and in both cases described herein can be concluded that the use of LPRF should be considered in the treatment of patients with DRONJ.


Resumo Este artigo descreve dois casos onde a ressecção óssea associada à fibrina rica em plaquetas e leucócitos (LPRF) não resultou em resposta completa no tratamento da osteonecrose dos maxilares relacionados à medicações (MRONJ). Como observado nos casos aqui relatados, MRONJ foi recentemente descrito na literatura em pacientes que recebem a administração subcutânea de inibidores-RANK, como Denosumab ou drogas anti-angiogenicas, como Bevacizumab. Estudos recentes com resultados promissores indicam que mais pacientes serão tratados com estas terapias para evitar complicações esqueléticas devido às metástases ósseas. Portanto, este cenário pode tornar-se um desafio clínico comparável às osteonecroses dos maxilares relacionados aos bisfosfonatos na área de Cirurgia Bucomaxilofacial. Até o momento, nenhuma técnica cirúrgica foi descrita com eficiência para superar as lesões da mucosa com exposição óssea e que não cicatrizam devido a terapia com inibidores de RANK. Com base na literatura e nos achados dos casos reportados, podemos concluir que o uso do LPRF pode ser considerado no tratamento de pacientes com osteonecrose dos maxilares relacionados ao Denosumab.


Subject(s)
Humans , Male , Female , Adult , Aged , Bisphosphonate-Associated Osteonecrosis of the Jaw/drug therapy , Bisphosphonate-Associated Osteonecrosis of the Jaw/surgery , Bone Density Conservation Agents/adverse effects , Denosumab/adverse effects , Combined Modality Therapy
6.
Rev. cuba. estomatol ; 51(1): 107-112, ene.-mar. 2014.
Article in English | LILACS, CUMED | ID: lil-721275

ABSTRACT

Bisphosphonate-related osteonecrosis of the jaws is characterized by alveolar bone exposure, especially after mucosal trauma or after surgical procedures, in patients who have previously received or who are currently receiving bisphosphonates without a history of radiation therapy in the maxillofacial region. The condition is refractory to treatment, and attempts at debridement are not completely effective in eradicating the necrotic bone. We report here a case of a severe osteonecrosis of the jaws in a 77-year-old male patient, who had been subjected to chemotherapy and treatment with zoledronic acid and corticosteroid. The patient also had comorbidities such as diabetes and periodontal disease, which might have contributed to the lesion development. Bisphosphonate-related osteonecrosis of the jaws has become a reality in dental clinical practice. Although palliative treatment aiming at controlling pain, infection and injury progression is indicated, the therapeutic strategy is still challenging. So far, the best approach available is prevention, based on oral care before, during, and after bisphosphonate therapy(AU)


La osteonecrosis de los maxilares asociada al uso de bifosfonatos se traduce en la aparición de hueso alveolar expuesto y necrótico, especialmente después de un trauma de la mucosa o después de procedimientos quirúrgicos, en pacientes que han recibido previamente o que están recibiendo bifosfonatos pero sin historia de radioterapia a región máxilofacial. La afección es refractaria al tratamiento, y los intentos de desbridamiento no son totalmente eficaces en la erradicación del hueso necrótico. Se presenta aquí un caso de una grave osteonecrosis de los maxilares en un paciente masculino de 77 años de edad, que había sido sometido a quimioterapia y tratamiento con ácido zoledrónico y corticosteroides. El paciente también tenía comorbilidades como diabetes y enfermedad periodontal, que pueden haber contribuido al desarrollo de la lesión. El creciente número de casos de esta enfermedad en la literatura ha llamado la atención. Dado que el enfoque terapéutico sigue siendo difícil, la prevención es la mejor estrategia disponible(AU)


Subject(s)
Humans , Male , Aged , Review Literature as Topic , Maxillary Diseases/prevention & control , Bisphosphonate-Associated Osteonecrosis of the Jaw/drug therapy
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