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1.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 55(7): 509-514, 2020 Jul 09.
Artigo em Chinês | MEDLINE | ID: mdl-32634892

RESUMO

Medication-related osteonecrosis of the jaw (MRONJ) is a severe complication of anti-resorption drugs and anti-angiogenesis drugs. Its mechanism is still unclear, which may be related to bone remodeling inhibition, angiogenesis inhibition, inflammation, etc. The main clinical symptoms are continuous infection, recurrent swelling and pain and impacting the patients' quality of life. Because of its serious symptoms and unclear treatment, MRONJ has attracted wide attention. Now there are many researches on the treatment and prevention of MRONJ. The treatment includes conservative treatment and surgical treatment. There is no clear evidence of the effectiveness of existing methods of prevention and treatment of MRONJ, and lacking the unified and accepted standard methods of prevention and treatment. In this article, current researches of the prevention and treatment of MRONJ are reviewed, including the mechanism of the methods.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/terapia , Conservadores da Densidade Óssea , Osteonecrose , Remodelação Óssea , Difosfonatos , Humanos , Qualidade de Vida
2.
J Bone Miner Metab ; 38(6): 819-825, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32507944

RESUMO

INTRODUCTION: Our aim is to track the development of the epidemiological characteristics in patient populations diagnosed with MRONJ at the Sheba Medical Center. MATERIALS AND METHODS: The files of patients diagnosed with MRONJ from 2003 until December 2017 were retrieved. Data on demographics, medical background, type and duration of drug use and triggering events at presentation was collected. RESULTS: The study included 448 patients, 336 females and 112 males. A decrease in the proportion of multiple myeloma patients (p < 0.05) and an increase in the proportion of patients with bone metastases of solid tumors has been observed recently. An increase in the proportion of cases in osteoporosis patients compared with oncology patients is evident (p < 0.01). Overtime a higher proportion of patients presented at an earlier stage of MRONJ (p < 0.01). CONCLUSIONS: As a result of changes in treatment protocols and increased awareness of oncology caregivers, including referral and consultation with Oral Medicine specialists, there has been a change in the demographics and presentation of the disease.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/diagnóstico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/terapia , Conservadores da Densidade Óssea/uso terapêutico , Comorbidade , Difosfonatos/uso terapêutico , Prescrições de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/tratamento farmacológico , Fatores de Risco
3.
Support Care Cancer ; 28(9): 4019-4029, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32307659

RESUMO

BACKGROUND: Medication-related osteonecrosis of the jaw (MRONJ) is an infrequent, but potentially serious, adverse event that can occur after exposure to bone-modifying agents (BMAs; e.g., bisphosphonates, denosumab, and antiangiogenic therapies). BMAs are typically used at higher doses to prevent skeletal-related events in cancer patients and at lower doses for osteoporosis/bone loss. MRONJ can cause significant pain, reduce quality of life, and can be difficult to treat, requiring a multiprofessional approach to care. METHODS: We reviewed the literature and guidelines to summarize a practical guide on MRONJ for nurses and other allied healthcare professionals. RESULTS: While there is a risk of MRONJ with BMAs, this should be considered in relation to the benefits of treatment. Nurses and other allied healthcare professionals can play a key role alongside physicians and dentists in assessing MRONJ risk, identifying MRONJ, counseling the patient on the benefit-risk of BMA treatment, preventing MRONJ, and managing the care pathway of these patients. Assessing patients for MRONJ risk factors before starting BMA treatment can guide preventative measures to reduce the risk of MRONJ. Nurses can play a pivotal role in facilitating multiprofessional management of MRONJ by communicating with patients to ensure compliance with preventative measures, and with patients' physicians and dentists to ensure early detection and referral for prompt treatment of MRONJ. CONCLUSIONS: This review summarizes current evidence on MRONJ and provides practical guidance for nurses, from before BMA treatment is started through to approaches that can be taken to prevent and manage MRONJ in patients receiving BMAs.


Assuntos
Pessoal Técnico de Saúde/normas , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/prevenção & controle , Enfermeiras e Enfermeiros/normas , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/diagnóstico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de Risco
4.
Support Care Cancer ; 28(11): 5397-5404, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32144584

RESUMO

PURPOSE: To assess the current knowledge regarding medication-related osteonecrosis of the jaw (MRONJ); the adverse effects of anti-resorptive (AR) and anti-angiogenic (AA) drugs; strategies for MRONJ prevention and treatment; and perception of the dentist's role in assisting patients who use these drugs among physicians, dentists, and nurses. METHODS: Using questionnaires, the current knowledge of MRONJ was assessed among dentists, physicians, and nurses, who were divided into group I, which included specialties that directly assist cancer patients, and group II, which included other specialties. The questionnaires assessed the characteristics of the health professionals, training time, and specialties; their knowledge of AR and AA drugs; and their knowledge of MRONJ. RESULTS: A total of 1370 health professionals participated in the study, including 1032 dentists, 239 physicians, and 99 nurses. Among dentists and physicians, the training time (p = 0.036 and p < 0.001, respectively) and specialization in group I domains (p < 0.001 and p < 0.001, respectively) had a significant impact on MRONJ knowledge, while nurses showed no significant impact regardless of the training time and specialty. Less than 10% of the physicians and dentists could correlate the signs and symptoms of all stages of MRONJ. CONCLUSION: The findings indicated a notable lack of knowledge regarding MRONJ among dental surgeons and physicians, and especially among nurses. More experienced professionals and specialists in the areas that assist cancer patients usually have a greater understanding of the dentist's role in MRONJ prevention, diagnosis, treatment, and patient care and will introduce or are already using AR and AA drugs.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/diagnóstico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/terapia , Pessoal de Saúde/psicologia , Pessoal de Saúde/estatística & dados numéricos , Conhecimento , Adulto , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/prevenção & controle , Conservadores da Densidade Óssea/uso terapêutico , Brasil/epidemiologia , Estudos Transversais , Odontólogos/psicologia , Odontólogos/estatística & dados numéricos , Diagnóstico Diferencial , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Enfermeiras e Enfermeiros/estatística & dados numéricos , Médicos/psicologia , Médicos/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Inquéritos e Questionários
5.
Orv Hetil ; 161(8): 283-289, 2020 Feb.
Artigo em Húngaro | MEDLINE | ID: mdl-32073291

RESUMO

Introduction: The potential risk factors of the medication-related osteonecrosis of the jaw remain the subject of research because of the different results of the studies. Aim: In our study, we examined the potential prognostic factors of the medication-related osteonecrosis of the jaw. Method: Patients with medication-related osteonecrosis of the jaw presenting between June 2006 and November 2013 were included in this study. Prognosis was examined, based on stage improvement, healing and the rate of relapse. The minimum follow-up time was 5 years. Statistical analysis: The results were evaluated by Fisher's exact test, Mann-Whitney test, Kruskal-Wallis probe and chi-square test. The outcomes were accepted as significant when the p value was <0.05. Results: The stage stated at the first check-up indicated poor prognosis (p = 0.009). The relapse rate of patients with non-insulin-dependent diabetes mellitus was significantly higher than the relapse rate of those without diabetes mellitus (p = 0.050). Regarding the relapse rate, the relationship between patients receiving anti-estrogen therapy and those without hormonal therapy was significant (p = 0.036). The prognosis of mandibular necrosis was significantly worse (p = 0.003) than the prognosis of maxillary necrosis. We did not find significant connection between prognosis and gender, age, administration route of bisphosphonate, invasive procedures preceding the necrosis, chemotherapeutic and steroid treatment. Conclusion: Of the factors studied here, the stage stated at the first check-up, the localization of the necrotic bone parts, diabetes mellitus and anti-estrogen therapy used simultaneously with the antiresorptive therapy affected the prognosis of the medication-related osteonecrosis of the jaw. Orv Hetil. 2020; 161(8): 283-289.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/terapia , Humanos , Prognóstico
6.
J Bone Miner Metab ; 38(4): 581-588, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32076874

RESUMO

INTRODUCTION: Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) is a rare but serious complication in patients receiving antiresorprtive agents (AR). However, the incidence of ARONJ after tooth extraction in patients with autoimmune disease (AID) remains unclear. The present study aimed to clarify the high-risk population of ARONJ in patients with AID. MATERIALS AND METHODS: The study population comprised 232 patients treated with AR, AID or non-AID, who had undergone dental extraction from January 2011 to September 2017. The incidence and risk factors of ARONJ were analysed retrospectively. Additionally, the relationship between ARONJ and osteoporotic fracture (OF) and AR discontinuation during dental procedures was investigated. RESULTS: Of 232 patients, 10 developed ARONJ within 1 year of dental extraction. The incidence of ARONJ in patients with AID was higher than that in non-AID patients (2.0/100 person-year vs 0.5/100 person-year; p = 0.03). Among the AID patients, RA patients had strikingly high incidence of ARONJ (3.6/100 person-year). The incidence of neither ARONJ nor OF significantly differed between patients who continued and discontinued AR in the perioperative period. CONCLUSION: Patients with AID who undergo dental extraction are at high risk of ARONJ. Discontinuation of AR would not significantly contribute to reduce the incidence of ARONJ in those patients.


Assuntos
Doenças Autoimunes/complicações , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/epidemiologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Extração Dentária/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/terapia , Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/efeitos adversos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fraturas por Osteoporose/complicações , Estudos Retrospectivos , Fatores de Risco , Suspensão de Tratamento , Adulto Jovem
7.
BMJ Case Rep ; 13(1)2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31907213

RESUMO

In 2003, Marx reported the first case of osteonecrosis of the jaw in 36 cases related to zoledronic acid or pamidronate. Painful bone exposure in the mandible or maxilla unresponsive to medical or surgical management was observed. In 2014, the American Association of Oral and Maxillofacial Surgeons proposed the term 'medication-related osteonecrosis of the jaw' (MRONJ). However, a non-exposed variant may also occur. MRONJ can lead to debilitating clinical sequelae with limited treatment options. We present the case of a 73-year-old woman with metastatic breast cancer and MRONJ of her mandible and maxilla following treatment with intravenous zoledronic acid and denosumab. Six months following dental extractions, she was referred to the Department of Oral and Maxillofacial Surgery for assessment of extensive necrosis of her maxilla and mandible. Extraoral draining sinuses were observed. A CT mandible showed cortical destruction with an ill-defined mixed sclerotic-lucent pattern in keeping with osteonecrosis. Due to her metastatic breast cancer, the extent of her necrosis and poor performance status, free flap reconstruction of her mandible was ruled out. She was treated conservatively.


Assuntos
Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/terapia , Conservadores da Densidade Óssea/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Denosumab/efeitos adversos , Idoso , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/diagnóstico por imagem , Diagnóstico Diferencial , Evolução Fatal , Feminino , Humanos , Mandíbula , Maxila , Tomografia Computadorizada por Raios X , Extração Dentária
8.
Br J Oral Maxillofac Surg ; 58(3): 256-267, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31926767

RESUMO

The feasibility of laser-assisted treatments of medication-related osteonecrosis of the jaw (MRONJ) remains poorly understood, so we have therefore systematically evaluated their effectiveness. We made a comprehensive search of MEDLINE, Pubmed, and Embase to find randomised controlled trials, case-control studies, and prospective cohort studies that assessed them. We assessed the eligible studies in duplicate, and if possible conducted a meta-analysis. Ten studies with a low to high risk of bias met the inclusion criteria. We found that a comparison of pain scores before and after using visible and infrared GaAs laser in the low-level laser treatment based on the Numerical Pain Rating Scale (mean difference 4.28; 95% CI 3.62 to 4.93; p<0.00001), showed that there were significant differences in the amount of pain. The effectiveness of other laser-assisted treatments on the reduction of pain - for example, Er:YAG laser surgical treatment, and laser-assisted treatment plus platelet-rich plasma, and the effect of other techniques on wound healing of laser-assisted treatments, are uncertain. We found that the results of the studies that were deemed to be high-to-low quality and to have high-to-low statistical power suggested that there may be considerable clinical improvement in MRONJ by using laser-assisted treatment; we cautiously consider that low-level laser treatment may manage pain and symptoms in these patients. More randomised studies of good quality and with a low risk of bias are needed to test whether laser-assisted treatment should be a routine part of management of patients with MRONJ.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Terapia a Laser , Lasers de Estado Sólido , Plasma Rico em Plaquetas , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/terapia , Estudos de Casos e Controles , Humanos , Estudos Prospectivos
9.
J Biol Regul Homeost Agents ; 34(6 Suppl. 2): 37-48, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33541063

RESUMO

Medication-related osteonecrosis of the jaw (MRONJ) is a major disease under study for over the last twenty years. Different classifications have been proposed and many therapies for the different stages have been applied. The evolution of treatments lead to an increasingly conservative approach. Numerous adjuvant treatments have been proposed in the last decade. All these complementary treatments have been proposed mainly to resolve or reduce the painful stress, predominantly caused by bacterial infection, simplifying the wound healing process and improving patients' compliance. Nowadays "secondary" treatments, such as autologous platelet concentrates (APCs, more specifically PRP, PRGF or PRF), hyperbaric oxygen (HBO), Auto/tetracycline fluorescence-guided bone surgery (AF-GBS/TF-GBS), medical drugs like teriparatide or the combination between pentoxifylline and tocopherol, fluorodeoxyglucose positron emission tomography (FDG-PET), laser and/or low-laser therapy and ozone therapy are more or less well documented and known considering their clinical effectiveness. The aim of the present review is the evaluation of the quantity and quality of scientific studies concerning this specific topic.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/diagnóstico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/terapia , Antibacterianos/uso terapêutico , Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/efeitos adversos , Humanos , Terapia a Laser , Tocoferóis/uso terapêutico , Resultado do Tratamento
10.
Braz. dent. sci ; 23(1): 1-6, 2020. tab, ilus
Artigo em Inglês | LILACS, BBO - Odontologia | ID: biblio-1049815

RESUMO

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)


Assuntos
Animais , Masculino , Ratos , Relaxina/uso terapêutico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/terapia , Distribuição Aleatória , Ratos Sprague-Dawley , Modelos Animais , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/prevenção & controle , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/tratamento farmacológico , Arcada Osseodentária/patologia
11.
Sci Rep ; 9(1): 18896, 2019 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-31827217

RESUMO

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse effect of antiresorptive and antiangiogenic therapies. MRONJ is identified by chronic wounds in the oral mucosa associated with exposed necrotic bone. We hypothesized that zoledronic acid (ZOL) impairs keratinocyte and fibroblast function and reduces soft tissue vascularization; therefore, treating MRONJ with proangiogenic cells may benefit MRONJ patients. The effect of ZOL and dexamethasone (DEX) on gingival fibroblasts and keratinocytes was investigated. In-vitro, ZOL inhibited fibroblast and keratinocyte proliferation, delaying scratch healing. In-vivo, exposed bone was detected at tooth extraction sites, mainly in ZOL(+)/DEX(+) rats; and was associated with significantly decreased soft tissue vascularization, serum-VEGF, and tissue-VEGF. Local injection of early and late endothelial progenitor cells (EPCs) healed 13 of 14 MRONJ lesions compared with 2/7 lesions in the mesenchymal stem cells, and 2/6, in culture-medium group. The EPCs reduced necrotic bone area, increased serum and tissue VEGF levels. EPCs engraftment was minimal, suggesting their paracrine role in MRONJ healing. The EPC-conditioned medium improved scratch healing of keratinocytes and fibroblasts via VEGF pathway and elevated mRNA of VEGFA and collagen1A1. In conclusion, a novel MRONJ treatment with EPCs, increased vascularization and improved epithelial and fibroblast functions as well as cured the lesion.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/terapia , Proliferação de Células/efeitos dos fármacos , Transplante de Células , Dexametasona/farmacologia , Células Progenitoras Endoteliais/transplante , Ácido Zoledrônico/farmacologia , Animais , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/patologia , Conservadores da Densidade Óssea/farmacologia , Difosfonatos/farmacologia , Modelos Animais de Doenças , Fibroblastos/efeitos dos fármacos , Humanos , Queratinócitos/efeitos dos fármacos , Ratos , Cicatrização/efeitos dos fármacos
12.
Cient. dent. (Ed. impr.) ; 16(3): 181-190, sept.-dic. 2019. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-185992

RESUMO

Introducción: La osteonecrosis de los maxilares inducida por medicamentos (MRONJ) es una reacción adversa severa causada por determinados fármacos empleados para el tratamiento del cáncer y la osteoporosis que cursa con una destrucción progresiva del hueso de los maxilares. Actualmente, no se ha establecido un protocolo de tratamiento ideal para el manejo de la enfermedad. En los últimos años, el desarrollo de los concentrados plaquetarios autólogos (CPA) y su empleo en la mejora de la cicatrización ósea en el área oral ha ido en aumento. El objetivo de este trabajo es determinar la efectividad de la aplicación de CPA en el lecho quirúrgico en pacientes con riesgo de desarrollar MRONJ o con MRONJ ya establecida. Material y métodos: Se realizó una búsqueda bibliográfica en las plataformas MEDLINE/PubMed, Science Direct y Cochrane Central Registred of Controlled Trials (CENTRAL) desde el año 2003 al 2018.Resultados: Fueron incluidos 28 artículos originales en los cuáles se trataron 299 casos con MRONJ con CPA logrando la curación en 274 (92%). Y se emplearon los CPA en la prevención de la enferme-dad en 1.970 situaciones quirúrgicas en pacientes con riesgo de MRONJ sometidos a cirugías orales y no se desarrolló la enfermedad en ninguno de los casos. Conclusiones: Debido al bajo nivel de evidencia de los estudios revisados, a la heterogeneidad entre los mismos y al tamaño muestral reducido, los resultados obtenidos no aportan evidencia científica suficiente que demuestre una ventaja objetiva en el empleo de CPA en el tratamiento y prevención de la MRONJ


Purpose: Medication related osteonecrosis of the jaws (MRONJ) is an adverse drug reaction consisting on progressive bone destruction in the maxilofacial region of patients with cancer or osteoporosis under treatment with certain drugs. The management of patients with MRONJ remains controversial as an ideal treatment protocol has not been yet established. Autologous platelet concentrates (APC) have demonstrated to improve bone healing. The aim of the present systematic review is to evaluate the effectiveness of APC’s application for treatment and prevention of MRONJ. Methods: a bibliographic research was performed on the following databases: MEDLINE/PubMed, ScienceDirect and Cochrane Central Registred of Controlled Trials (CENTRAL). Results: 28 studies were included, reporting on 299 patients affected by MRONJ were treated in combination with APC, satisfactory healing was observed in 92%. Additionaly, APC for MRONJ prevention were used in 1.970 risky patients undergoing oral surgery procedures, and none of them developed osteonecrosis.Conclusion: Although the results obtained using APC for MRONJ prevention are satisfactory, due to the low level of evidence, the heterogenety and small simple size of the studies, cannot be demonstrated that the use of APC is beneficial for the treatment and prevention of MRONJ


Assuntos
Humanos , Osteonecrose/induzido quimicamente , Osteonecrose/prevenção & controle , Fibrina Rica em Plaquetas , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/epidemiologia , Osteonecrose/terapia , Mandíbula/efeitos dos fármacos , Mandíbula/fisiopatologia , Plaquetas/metabolismo , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/diagnóstico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/terapia
13.
Head Neck ; 41(12): 4209-4228, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31502752

RESUMO

BACKGROUND: We investigated the efficacy of hyperbaric oxygen (HBO), low-intensity laser (LIL), and platelet-rich plasma (PRP) in the management of medication-related osteonecrosis of the jaws (MRONJ). METHODS: A literature search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Two examiners independently assessed eligibility and risk of bias and extracted data. RESULTS: There was improvement in 75.6% of the 41 patients submitted to HBO, with positive effects on pain relief and decreased size and number of lesions at a faster rate, with better effects when the drug was discontinued. For LIL, 158 (64.2%) of the 246 patients/sites improved the symptoms and 98 (39.8%) healed completely. Fourteen (17.3%) of the 81 patients treated with PRP significantly improved the symptoms and 65 (80.2%) completely healed. CONCLUSIONS: These therapies served as safe and effective adjuvant modalities for MRONJ treatment. The lack of randomized clinical trials evidences the need for more high-quality investigations on the subject.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/terapia , Oxigenação Hiperbárica/métodos , Terapia a Laser/métodos , Plasma Rico em Plaquetas , Idoso , Idoso de 80 Anos ou mais , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/patologia , Conservadores da Densidade Óssea/efeitos adversos , Terapia Combinada , Denosumab/efeitos adversos , Difosfonatos/efeitos adversos , Feminino , Humanos , Doenças Maxilomandibulares/induzido quimicamente , Doenças Maxilomandibulares/terapia , Masculino , Pessoa de Meia-Idade , Osteonecrose/induzido quimicamente , Osteonecrose/terapia , Manejo da Dor , Pamidronato/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
J Clin Oncol ; 37(25): 2270-2290, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31329513

RESUMO

PURPOSE: To provide guidance regarding best practices in the prevention and management of medication-related osteonecrosis of the jaw (MRONJ) in patients with cancer. METHODS: Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) and ASCO convened a multidisciplinary Expert Panel to evaluate the evidence and formulate recommendations. Guideline development involved a systematic review of the literature and a formal consensus process. PubMed and EMBASE were searched for studies of the prevention and management of MRONJ related to bone-modifying agents (BMAs) for oncologic indications published between January 2009 and December 2017. Results from an earlier systematic review (2003 to 2008) were also included. RESULTS: The systematic review identified 132 publications, only 10 of which were randomized controlled trials. Recommendations underwent two rounds of consensus voting. RECOMMENDATIONS: Currently, MRONJ is defined by (1) current or previous treatment with a BMA or angiogenic inhibitor, (2) exposed bone or bone that can be probed through an intraoral or extraoral fistula in the maxillofacial region and that has persisted for longer than 8 weeks, and (3) no history of radiation therapy to the jaws or metastatic disease to the jaws. In patients who initiate a BMA, preventive care includes comprehensive dental assessments, discussion of modifiable risk factors, and avoidance of elective dentoalveolar surgery (ie, surgery that involves the teeth or contiguous alveolar bone) during BMA treatment. It remains uncertain whether BMAs should be discontinued before dentoalveolar surgery. Staging of MRONJ should be performed by a clinician with experience in the management of MRONJ. Conservative measures comprise the initial approach to MRONJ treatment. Ongoing collaboration among the dentist, dental specialist, and oncologist is essential to optimal patient care.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/terapia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/diagnóstico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/prevenção & controle , Consenso , Humanos , Guias de Prática Clínica como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
Braz Oral Res ; 33: e050, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31269114

RESUMO

The present study aimed to investigate the use of platelet-rich plasma (PRP) on tooth extraction sites in rats treated with bisphosphonates. Thirty Albinus Wistar male rats were administered 0.035 mg/kg zoledronic acid intravenously for 8 weeks, divided into four administrations with a 2-week interval between each application, after which their upper right central incisors were extracted to induce the development of bisphosphonate-related osteonecrosis of the jaw (BRONJ). The samples were divided into the following two groups: Group 1 (G1) underwent marginal resection of BRONJ followed by the use of PRP, while Group 2 (G2) underwent resection of BRONJ but without the use of PRP. The treatment groups were evaluated after 14, 28, and 42 days. Clinical, microtomographic, microscopic, and immunohistochemical (IHC) evaluations were performed. Microtomography results revealed no significant difference between the groups (p <0.05) in any time period. Histomorphometric analysis showed increased bone formation over time for both groups (p < 0.001). G1 demonstrated a greater amount of new bone formation than G2 at 28 and 42 days (p < 0.001), with G1 presenting greater vascularization and a slightly higher VEGF expression. For both groups, RANKL/OPG expression levels were sufficient as a parameter for indicating the rate of bone remodeling in a previously treated area of osteonecrosis groups. Taken together, our findings indicated that the use of PRP improves the resolution process of BRONJ.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/terapia , Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Plasma Rico em Plaquetas , Animais , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/patologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/fisiopatologia , Modelos Animais de Doenças , Masculino , Osteoclastos/efeitos dos fármacos , Ratos , Ratos Wistar , Extração Dentária/efeitos adversos , Cicatrização
17.
Stem Cell Res Ther ; 10(1): 209, 2019 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-31311585

RESUMO

BACKGROUND: Definitive treatment strategies for bisphosphonate-related osteonecrosis of the jaw (BRONJ) have not been developed. Cell-based therapy is an attractive treatment method for intractable diseases in the medical and dental fields; however, approval has been challenging in dentistry. Recently, we developed quality- and quantity (QQ)-controlled peripheral blood mononuclear cells (PBMNCs) that have anti-inflammatory and pro-angiogenesis effects. The aim of this study was to investigate the effects of QQ-controlled PBMNC transplantation on BRONJ-like lesions in mice. METHODS: To create high-prevalence BRONJ-like lesions, cyclophosphamide (CY) and zoledronate (ZA) were used with tooth extraction. Drug treatment was performed for 5 weeks. QQ-controlled PBMNC transplantation was performed immediately following tooth extraction of both maxillary first molars at 3 weeks after drug administration. Mice were euthanized at 2 weeks post-extraction. Histomorphometric and immunohistochemical analyses, microcomputed tomography assessment, and quantitative polymerase chain reaction evaluation were conducted using maxillae and long bones. RESULTS: ZA effects on long bones were noted, regardless of CY. Severely inhibited osseous and soft tissue wound healing of tooth extraction sockets was induced by CY/ZA combination therapy, which was diagnosed as BRONJ-like lesions. QQ-controlled PBMNC transplantation reduced BRONJ-like lesions by improving soft tissue healing with increased M1 and M2 macrophages and enhanced neovascularization in the connective tissue of tooth extraction sockets. QQ-controlled PBMNC transplantation also reduced inflammation by decreasing polymorphonuclear cells and TNF-α expression in the tooth extraction sockets. Additionally, QQ-controlled PBMNC transplantation partially improved osseous healing of tooth extraction sockets. Interestingly, only 20,000 QQ-controlled PBMNCs per mouse induced these transplantation effects. QQ-controlled PBMNC transplantation did not affect the systemic microenvironment. CONCLUSIONS: Our findings suggest that transplantation of a small amount of QQ-controlled PBMNCs may become novel therapeutic or prevention strategies for BRONJ without any adverse side effects.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/terapia , Macrófagos/transplante , Transplante de Células-Tronco de Sangue Periférico , Cicatrização , Animais , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/diagnóstico por imagem , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/fisiopatologia , Ciclofosfamida/toxicidade , Modelos Animais de Doenças , Humanos , Leucócitos Mononucleares/transplante , Camundongos , Dente Molar/diagnóstico por imagem , Dente Molar/efeitos dos fármacos , Dente Molar/crescimento & desenvolvimento , Extração Dentária , Microtomografia por Raio-X , Ácido Zoledrônico/toxicidade
18.
Stem Cell Res Ther ; 10(1): 169, 2019 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-31196208

RESUMO

BACKGROUND: Due to its complex pathogenesis and low clinical cure rate, bisphosphonate-related osteonecrosis of the jaw (BRONJ) poses a substantial challenge for oral and maxillofacial surgeons. Therefore, the treatment of BRONJ should focus on prevention. In clinical studies, primary wound closure can significantly reduce the incidence of BRONJ. Whether local stem cell transplantation can promote primary gingival healing in patients with a medication history and prevent BRONJ has not been reported. METHODS: In this study, animals were divided into a healthy group (non-drug treatment), a BP group, a hydroxyapatite (HA) group, and an adipose-derived stem cell (ADSC) group. All groups except the healthy group were treated with BPs and immunosuppressive drugs once per week for 8 weeks, simulating clinical use for the treatment of cancer patients with bone metastasis, to induce BRONJ-like animals. After the sixth drug treatment, the bilateral premolars were extracted in all groups. In contrast to the healthy and BP groups, the extraction sockets in the HA and ADSC groups were filled with HA or HA + ADSCs simultaneously post extraction to observe the preventive effect of ADSCs on the occurrence of BRONJ. At 2 and 8 weeks post extraction, animals from all groups were sacrificed. RESULTS: At 8 weeks post transplantation, ADSCs prevented the occurrence of BRONJ, mainly through accelerating healing of the gingival epithelium at 2 weeks post extraction. We also found that ADSCs could upregulate the expression of transforming growth factor ß1 (TGF-ß1) and fibronectin in tissue from animals with a medication history by accelerating gingival healing of the extraction socket. A rescue assay further demonstrated that TGF-ß1 and fibronectin expression decreased in TGF-ß1-deficient ADSC-treated animals, which partially abolished the preventive effect of ADSCs on the onset of BRONJ. CONCLUSION: ADSCs prevent the onset of BRONJ, mainly by upregulating the expression of TGF-ß1 and fibronectin to promote primary gingival healing, ultimately leading to bone regeneration in the tooth extraction socket. Our new findings provide a novel stem cell treatment for the prevention of BRONJ.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/terapia , Fibronectinas/genética , Transplante de Células-Tronco Mesenquimais , Fator de Crescimento Transformador beta1/genética , Animais , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/genética , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/patologia , Modelos Animais de Doenças , Regulação da Expressão Gênica no Desenvolvimento , Gengiva/lesões , Gengiva/patologia , Gengiva/transplante , Humanos , Células-Tronco Mesenquimais/citologia , Coelhos , Cicatrização/genética , Ácido Zoledrônico/farmacologia
19.
Photodiagnosis Photodyn Ther ; 27: 117-123, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31152878

RESUMO

BACKGROUND: Medication-related osteonecrosis of the jaw (MRONJ) is a debilitating complication strongly associated to antiresorptive agents. The present study aimed to describe the use of antimicrobial photodynamic therapy (aPDT) in the prevention of MRONJ. METHODS: The sample consisted of 11 non-oncologic osteoporotic subjects in therapy with non-intravenous antiresorptive agents, requiring tooth extractions and/or implant removal. After minimally invasive surgical extractions, each alveolar socket was debrided and bony edges were smoothened. At this point, aPDT was performed using methylene blue-based phenothiazine chloride dye irradiated with a hand-held 100 mW diode laser with a wavelength of 660 ±â€¯10 nm. Flaps were sutured to achieve first intention closure. Soft tissue healing was promoted with weekly applications of low-level laser therapy for 6 weeks. Recall visits were scheduled weekly for the first two months and monthly thereafter up to 6 months. At the 6-month appointment, healing was assessed clinically and radiographically. RESULTS: A total of 62 surgical extractions were performed in both jaws, including 51 natural elements and 11 dental implants. No intraoperative complications were observed. Immediate post-operative period was generally uneventful except for mild pain and ecchymosis that occurred rarely and resolved spontaneously. Healing proceeded uneventfully, with no clinical or radiological prodromal manifestations of MRONJ up to the latest follow-up visit. CONCLUSIONS: aPDT might constitute a promising preventive treatment to reduce the risk of MRONJ in non-oncologic osteoporotic patients treated with non-intravenous antiresorptive agents that underwent dentoalveolar surgery.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/tratamento farmacológico , Azul de Metileno/uso terapêutico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Cicatrização/efeitos dos fármacos , Idoso , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/terapia , Desbridamento , Feminino , Humanos , Lasers Semicondutores , Masculino , Extração Dentária/métodos
20.
J Oral Implantol ; 45(4): 289-296, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31207196

RESUMO

Oral bisphosphonates are commonly used to improve bone density in patients who suffer from a variety of pathologies. However, they have also been known to cause bisphosphonate-related osteonecrosis of the jaws (BRONJ). The aim of this clinical case presentation is to (1) determine whether the currently recommended length of time that oral bisphosphonates should be discontinued, before performing dental implant surgery, is sufficient to prevent BRONJ and (2) to describe an alternative treatment for BRONJ. A 65-year-old female patient developed BRONJ after receiving mandibular dental implants 5 months after discontinuing alendronic acid (Fosamax). The BRONJ was treated by surgical osteotomy and plasma rich in growth factors (PRGF), and the patient was followed up with biweekly examinations, which included 0.2% chlorhexidine mouthwashes and removal of any remaining necrotic bone. The dental implants were loaded 41 weeks after surgery and followed up with periapical radiographs and implant stability quotient measurements at 3, 6, 12, and 24 months postloading. Although the Association of Oral and Maxillofacial Surgeons protocols for suspension of presurgical oral bisphosphonates were followed, this patient still developed BRONJ after implant surgery. While a multitude of treatments have been described in the literature, there is not enough scientific evidence to support any one treatment. Based on this clinical case, it can be concluded that the potential adverse effects of oral bisphosphonates on the jaws could be greater than expected and that treatment with PRGF produces promising results, although more long-term studies are necessary to confirm these findings.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Conservadores da Densidade Óssea , Implantes Dentários , Osteonecrose , Plasma Rico em Plaquetas , Idoso , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/terapia , Implantes Dentários/efeitos adversos , Difosfonatos , Feminino , Humanos , Arcada Osseodentária
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