Colocación de implantes en paciente con antecedentes de toma de bifosfonatos / Placement of implants in a patient with a history of bisphosphonates taken

El uso de bifosfonatos es un excelente tratamiento para pacientes con artritis reumatoide y enfermedades óseas, por ejemplo, osteoporosis. Se realiza un reporte de caso de paciente femenino, quien estuvo bajo consumo de este fármaco por prescripción de su médico para la prevención de artritis reumatoide postmenopausia. La paciente acude a consulta para la colocación de implantes en zona desdentada y comenta haber terminado el tratamiento de bifosfonatos hace un año. Se tomaron pruebas de diagnóstico y se realizó la colocación de implantes sin ninguna complicación. Sus citas de control fueron más frecuentes en cuatro meses, sobre todo por el detalle de consumo de bifosfonatos, pero en ninguna cita hubo algún detalle alarmante, la cicatrización iba en forma. Se dio de alta a la paciente después de sus citas periódicas y de asegurar su buena cicatrización a un implante bien situado (AU))

The use of bisphosphonates is an excellent treatment for patients with rheumatoid arthritis and bone diseases such as osteoporosis. Here is a case report of a female patient, who was under consumption of this drug by prescription of her doctor for the prevention of post-menopausal rheumatoid arthritis. The patient went to the consultation for the placement of implants in the edentulous area and comments having finished the bisphosphonate treatment one year ago. The diagnostic tests were taken, and the implant placement was performed well without any complications. The control appointments were more frequent in four months, especially due to the detail of bisphosphonate consumption, but in no appointment, there were any alarming details, the healing was in good shape. The patient discharged after her regular appointments and to ensure that she was healing well and that implant was well placed (AU)

Osteonecrosis maxilar relacionada con medicamentos en pacientes oncológicos con metástasis óseas: resolución de dos casos / Medication-related osteonecrosis of the jaw in oncological patients with bone metastases: resolution of two cases

La osteonecrosis maxilar relacionada con medicamentos (ONMM) es una patología de características clínicas objetivas con signo-sintomatología patognomónica. El criterio clínico aceptado es la presencia de hueso necrótico expuesto y visible sobre el reborde óseo maxilar que no ha cicatrizado luego de 8 semanas, en pacientes con antecedentes de tratamiento antirresortivo. La denominación "relacionada con medicamentos" se utiliza por el creciente número de casos asociados con otros fármacos antirresortivos como denosumab y con terapias antiangiogénicas, más allá de la conocida relación con bifosfonatos.Si bien la incidencia de ONMM en pacientes tratados por osteopatías metabólicas es muy baja, la situación se torna más compleja en pacientes oncológicos con altas dosis de antirresortivos para tratamiento de metástasis ósea. Varios in-formes de casos describen cuadros de ONMM en pacientes con cáncer que reciben terapias dirigidas, específicamente TKI (inhibidores de tirosina quinasa) y anticuerpos monoclonales-VEGF (anticuerpos dirigidos al factor de crecimiento del endotelio vascular). La ONMM afecta negativamente la calidad de vida del paciente oncológico y produce comorbilidad significativa. Resulta imperioso identificar a los pacientes en riesgo y diseñar un protocolo de atención odontológica específico para estos casos. En este artículo se presentan dos casos de ONMM asociado con altas dosis de denosumab y administración simultánea de anticuerpos monoclonales específicos para el tratamiento del cáncer. Ambos casos sorprenden por la prematura instalación de la necrosis y su cuadro insidio-so. El protocolo de tratamiento descripto permitió controlar el cuadro inicial, limitar el avance de la lesión, asegurar el control del dolor y la infección, y finalmente, la curación total de la lesión. (AU)

Medication-related osteonecrosis of the jaws (MRONJ) is a pathology with objective clinical characteristics, with pathognomonic signs and symptoms. The accepted clinical criterion is the presence of exposed and visible necrotic bone on the maxillofacial region that has not healed after 8 weeks, in patients with history of antiresorptive treatment.The name "medication-related" is justified by the growing number of cases associated with other antiresorptive drugs such as denosumab and antiangiogenic therapies, beyond the known relationship with bisphosphonates. Although the incidence of MRONJ in patients treated for metabolic osteopathies is very low, the situation becomes more complex in cancer patients who receive high doses of antiresorptives for the treatment of skeletal metastases. Several case reports describe the presence of MRONJ in cancer patients receiving targeted therapies, specifically TKI (tyrosine kinase inhibitors) and monoclonal antibodies-targeting VEGF (vascular endothelial growth factor). MRONJ negatively affects the quality of life in cancer patients and produces significant comorbidity. It is imperative to identify patients at risk and design a specific dental care strategy for these cases.In this article, we present two cases of MRONJ associated with high doses of Denosumab and simultaneous administration of specific monoclonal antibodies. Both cases are surprising due to premature onset of necrosis. The described treatment strategies made it possible to control the initial symptoms, limit the lesion progression, ensure pain and infection control, and finally, the total healing of the lesion. (AU)

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 por bifosfonatos: presentación de un caso clínico / Osteonecrosis of the jaws: report of a clinical case

La osteonecrosis de los maxilares asociada a bifosfonatosfuedefinida como «Área de hueso expuesto en la región máxilo facial que permanece expuesta al menos por 8 semanas, siempre que los pacientes hayan sido prescriptos con bifosfonatos, y en ausencia de terapia radiante¼. (1) En la actualidad se agregó "hueso expuesto o hueso que se puede sondear a través de una fistula intra o extra oral" (2). Presentamos un caso clínico de una paciente femenina de 70 años de edad, diagnosticada con cáncer de hueso (osteosarcoma) con foco en la pelvis, historia de consumo de bifosfonatosvía endovenosa durante tres años, zolendronato 70mg, semanalmente. Al momento de la consulta, se encontraba en periodo de remisión de la enfermedad de base y sin consumo de medicación antiresortiva desde hace un año (AU)

Osteonecrosis of the jaws associated with bisphosphonates was defined as «Area of exposed bone in the maxillofacial region that remains exposed for at least 8 weeks, provided that patients have been prescribed with bisphosphonates, and in the absence of radiant therapy¼. (1) At present, "exposed bone or bone that can be probed through an intra or extra oral fistula" was added (2). We present a clinical case of a 70-year-old female patient, diagnosed with bone cancer (osteosarcoma) with a focus on the pelvis, history of consumption of bisphosphonates intravenously for three years, zolendronate 70 mg, weekly. At the time of the consultation, he was in the period of remission of the underlying disease and without consumption of antiresortive medication for a year (AU)

Tratamento cirúrgico para osteonecrose dos maxilares induzida por bisfosfonatos: relatos de casos / Surgical treatment for bisphosphonate-induced maxillary osteonecrosis: case reports

Introdução: os bisfosfonatos são um grupo de medicamentos utilizados no tratamento de doenças osteolíticas, tais como mieloma múltiplo, osteoporose e doença de Paget. Uma complicação tardia dessa medicação é a osteonecrose em ossos maxilares. Esta é definida como desenvolvimento de osso necrótico na cavidade bucal de paciente em tratamento atual ou prévio com bisfosfonato, após sofrer algum procedimento cirúrgico bucal invasivo, sem ter realizado radioterapia. Objetivo: descrever, por meio de relatos de casos, a opção de técnica cirúrgica para tratamento da osteonecrose por bisfosfonatos. Materiais e método: em todos os casos relatados, a terapêutica cirúrgica contou com osteotomia e remoção cirúrgica do sequestro ósseo, debridamento, irrigação com soro fisiológico e sutura contínua simples. Resultados: o controle clínico pós-operatório evidenciou boa cicatrização, melhora considerável da lesão e reepitelização significativa, em curto e longo período. Conclusão: os pacientes devem passar por um criterioso exame odontológico, antes do uso desses medicamentos. Nenhum tratamento cirúrgico invasivo deve ser realizado durante a terapia com esses fármacos. (AU)

Introduction: Bisphosphonates are a group of medications used to treat osteolytic diseases such as multiple myeloma, osteoporosis, and Paget's disease. A late complication of this medication is osteonecrosis in the maxillary bones. It is defined as the development of necrotic bone in the oral cavity of a patient under current or with previous treatment with bisphosphonate and subjected to some invasive oral surgical procedure without radiotherapy. Objective: This study aimed to describe, through case reports, the option of a surgical technique for the treatment of osteonecrosis with bisphosphonates. Materials and Method: In all cases reported, surgical therapy included osteotomy and surgical removal of bone sequestration, debridement, irrigation with saline solution, and simple continuous suture. Results: The postoperative clinical control revealed satisfactory healing, considerable lesion improvement, and significant short- and long-term re-epithelialization. Conclusion: Patients should be subjected to a careful dental examination before using these medications. No invasive surgical treatment should be performed during therapy with these drugs. (AU)

Effects of Zoledronic Acid in Experimental Periapical Lesions in Rats: An Imaging and Histological Analysis

Abstract The aim of this study was to assess the imaging and histological features of experimental periapical lesions, including the adjacent alveolar bone, in rats under zoledronic acid treatment. The study used 40 male Wistar rats distributed into 8 groups of 5 animals each: G1: induction of periapical lesion (PL) and weekly intraperitoneal administration (WIPA) of saline solution (0.9% NaCl) for 4 weeks; G2: PL induction and WIPA of zoledronic acid (0.15 mg/kg/week) for 4 weeks; G3: PL induction and WIPA of saline solution for 8 weeks; G4: PL induction and WIPA of zoledronic acid for 8 weeks; G5:WIPA of saline solution for 4 weeks and subsequent PL induction; G6: WIPA of zoledronic acid for 4 weeks and subsequent PL induction; G7: WIPA of saline solution for 8 weeks and subsequent PL induction; G8: WIPA of zoledronic acid for 8 weeks and subsequent PL induction. The administration of zoledronic acid or saline solution continued after PL induction until the euthanasia. Thus, cone beam computed tomography and histological analysis were performed. Statistical analyzes were performed by ANOVA and Kruskal-Wallis test. Groups treated with zoledronic acid showed significantly smaller size of PL than the groups treated with 0.9% NaCl (p<0.05). PLs were formed by chronic inflammation ranging from mild to moderate, with no difference between groups. In all specimens, no mandibular necrosis was observed. In conclusion, the presence of PLs apparently does not represent an important risk factor for the development of bisphosphonate-related osteonecrosis of the jaws.

Resumo O objetivo deste estudo foi avaliar as características histológicas e de imagem de lesões periapicais experimentais, incluindo o osso alveolar adjacente, em ratos sob tratamento com ácido zoledrônico. O estudo utilizou 40 ratos Wistar, machos, distribuídos em 8 grupos de animais cada: G1: indução de lesão periapical (LP) e administração intraperitoneal semanal (AIS) de solução salina (NaCl 0.9%) por 4 semanas; G2: indução de LP e AIS de ácido zoledrônico (0,15 mg/kg/week) por 4 semanas; G3: indução de LP e AIS de solução salina por 8 semanas; G4: indução de LP e AIS de ácido zoledrônico por 8 semanas; G5- AIS de solução salina por 4 semanas e subsequente indução de LP; G6- AIS de ácido zoledrônico por 4 semanas e subsequente indução de LP; G7: AIS de solução salina por 8 semanas e subsequente indução de LP; G8: AIS de ácido zoledrônico por 8 semanas e subsequente indução de LP. A administração de ácido zoledrônico ou solução salina continuou após indução de LP até a eutanásia. Após isso, tomografia computadorizada de feixe cônico e análise histológica foram realizadas. Análises estatísticas foram realizadas por ANOVA e teste de Kruskal-Wallis. Os grupos tratados com ácido zoledrônico mostraram LPs significativamente menores que os grupos tratados com NaCl 0.9% (p <0.05). LPs eram formadas por inflamação crônica variando de leve a moderada, sem diferença entre os grupos. Em todos os espécimes, necrose mandibular não foi observada. Em conclusão, a presença de LPs aparentemente não representa um fator de risco importante para o desenvolvimento de osteonecrose relacionada ao uso de bisfosfonatos.

Osteonecrose dos Maxilares Associada ao uso de Bisfosfonatos / Osteonecrosis of the Jaws Associated with the use of Bisphosphonates

Os bifosfonatos são uma classe de medicamentos, que têm por função a inibição da atividade dos osteoclastos, interferindo na remodelação e no turnover ósseo. São indicados para retardar a metástase óssea em algumas condições malignas, como em mielomas múltiplos, câncer de mama e próstata, e outras condições benignas, como no tratamento da doença de Paget e da osteoporose. Desde 2003, estudos têm associado a osteonecrose avascular dos ossos maxilares ao uso dos bifosfonatos. Dentre os mecanismos de ação dos bifosfonatos, podemos citar a sua atividade antiosteoclástica e antiangiogênica, que altera o metabolismo ósseo, inibindo a reabsorção óssea e diminuindo o turnover ósseo. As exposições ósseas maxilo-mandibulares ocorrem após procedimentos cirúrgicos odontológicos ou, menos comumente, após o uso de próteses apoiadas na fina mucosa de revestimento ósseo da cavidade bucal. O tratamento da osteonecrose associada aos bifosfonatos (OAB) é bastante variado, controverso e desafiador, visto que nenhum tratamento efetivo tem sido proposto até o momento. O objetivo desse relato de caso é descrever a ocorrência de áreas de exposição óssea mandibular em um paciente que fez uso do ácido zolendrônico (Zometa®) bem como apresentar a abordagem terapêutica realizada que resultou em completo recobrimento mucoso das áreas ósseas expostas... (AU)

Biphosphonates are a class of drugs whose function is the inhibition of osteoclast activity, interfering in remodeling and bone turnover. They are indicated to delay bone metastases in some malignancies such as multiple myeloma, prostate cancer and other benign conditions such as in the treatment of Paget's disease and osteoporosis. Since 2003, studies associate avascular osteonecrosis of the jaws to the use of bisphosphonates, especially intra venous. Among the mechanisms of action of bisphosphonates are their osteoclastic and antiangionenic activity which alters bone metabolism, inhibiting bone resorption and reducing bone turnover. Maxillo-mandibular bone exposures occur after surgical dental procedures or less commonly after the use of prostheses supported on thin bone lining mucosa of the buccal cavity. The treatment of osteonecrosis associated with biphosphonates (OAB) is quite varied, controversial and challenging, since no effective treatment has been proposed until this moment. The purpose of this case report is to describe the occurrence of areas of mandibular bone exposure in a patient with history of use of Zolendronic Acid (Zometa) and present the therapeutic approach undertaken which resulted in full mucous covering of the exposed bony áreas... (AU)

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.

Experimental osteonecrosis: development of a model in rodents administered alendronate

Abstract The main objective of this study was to cause bisphosphonate-related osteonecrosis of the jaws to develop in a rodent model. Adult male Holtzman rats were assigned to one of two experimental groups to receive alendronate (AL; 1 mg/kg/week; n = 6) or saline solution (CTL; n = 6). After 60 days of drug therapy, all animals were subjected to first lower molar extraction, and 28 days later, animals were euthanized. All rats treated with alendronate developed osteonecrosis, presenting as ulcers and necrotic bone, associated with a significant infection process, especially at the inter-alveolar septum area and crestal regions. The degree of vascularization, the levels of C-telopeptide cross-linked collagen type I and bone-specific alkaline phosphatase, as well as the bone volume were significantly reduced in these animals. Furthermore, on radiographic analysis, animals treated with alendronate presented evident sclerosis of the lamina dura of the lower first molar alveolar socket associated with decreased radiographic density in this area. These findings indicate that the protocol developed in the present study opens new perspectives and could be a good starting model for future property design.

Sinusitis maxilar por osteonecrosis asociada a bisfosfonatos en pacientes con cáncer de mama: serie de casos / Maxillary sinusitis associated to bisphosphonate-related osteonecrosis in patients with breast cancer: case series

Los bisfosfonatos (BF) son fármacos ampliamente utilizados como estabilizadores óseos en el tratamiento de metástasis óseas, osteoporosis, enfermedad de Paget, entre otras patologías, debido a sus efectos anti-tumorales y a la característica de inhibir la actividad osteoclástica. La osteonecrosis maxilar asociada a BF, hoy en día osteonecrosis maxilar asociada a fármacos (ONMF) es definida como la presencia de hueso expuesto, no-vascularizado y necrótico en la cavidad oral por un periodo mayor a ocho semanas, con una historia positiva de tratamiento con fármacos anti-reabsorción ósea (BP, inhibidores del ligando RANKL) y/o anti-angiogénicos y sin antecedentes de tratamiento con radiación o metástasis obvia en los maxilares. La frecuencia de ONMF es incierta. La mandíbula es más frecuentemente afectada por ONMF que el maxilar. Pocos casos de ONMF en el maxilar han sido descritos con un diagnostico de sinusitis maxilar simultáneo. Tres casos con sinusitis maxilar asociada a ONMF son presentados en este trabajo. Todos los pacientes fueron mujeres con una historia positiva de cáncer de mama y tratamiento con bisfosfonatos. Los primeros dos casos, desarrollaron ONMF después de una extracción del tercer molar maxilar. El tercer caso con ONMF en el maxilar, sólo tenía antecedentes de curetaje periodontal. Una tomografía computada fue realizada y mostró compromiso del seno maxilar en todos los pacientes. Modalidades diagnósticas para evaluar la extensión de la necrosis y el compromiso del seno, como también alternativas de tratamiento son descritas en este estudio. Finalmente, una revisión actualizada de la literatura es presentada.

Bisphosphonates are widely used as bone-stabilizers in the treatment of osseous metastases, osteoporosis, Paget's disease and others,due to their ability to inhibit osteoclast activity and anti-tumor effects. Bisphosphonate-related osteonecrosis of the jaw, nowadays medication-related osteonecrosis of the jaw (MRONJ), is defined as the presence of exposed, non-vascularized and necrotic bone tissue in the oral cavity over a period of 8 weeks with a current or previous history of treatment with antiresorptive (bisphosphonates, RANKL ligand inhibitor) and/or antiangiogenic agents, and no history of radiation therapy to the jaws or obvious metastatic disease to the jaws. The frequency of MRONJ is unclear. The mandible appears to be more frequently affected by MRONJ than the maxilla. Isolated cases of maxillary MRONJ have been described in wich a simultaneous sinusitis maxillaris was diagnosed. Three cases of MRONJ associated with maxillaris sinusitis are presented. All cases were females with a positive history of breast cancer and bisphosphonate therapy. The first two, developed MRONJ after a third molar upper extraction. The third case with MRONJ, had a history of periodontal curettage. A computed tomography was performed and showed a maxillary sinus compromise in all patients. Imaging modalities to evaluate the extent of the necrosis and the sinus compromise, as also treatment options were described in this study. Finally, an updated literature review is presented.