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.

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)

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)

Surgery Combined with LPRF in Denosumab Osteonecrosis of the Jaw: Case Report

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.

Surgical Treatment of Bisphosphonate-Related Osteonecrosis of the Jaws with the Use of Buccal Fat Pad: Case Report

Bisphosphonate-related osteonecrosis of the jaws (BROJ) has been described since 2003 as an adverse effect of bisphosphonate medications. These drugs act on the vasculature and bone remodeling, mainly on osteoclastic activity and can cause areas of necrotic bone exposure. Treatment for the BROJ is not yet defined, but surgical treatment is one of the forms proposed, which may cause oral deformities like sinus communication in some cases. In situations like this the buccal fat pad is an important alternative for coating nasal-oral communications, due its large blood supply, elasticity, absence of restriction by age and safety. This paper presents the case of a 58-year-old woman with BROJ in the left maxilla caused by the use of zoledronic acid for metastatic breast cancer. The extensive necrotic bone area was surgically removed resulting in oral sinus communication. A buccal fat pad was used to cover the defect. More studies should be performed regarding the treatment of BROJ but, if necessary, a buccal fat pad flap could be an alternative to solve nasal-oral communications related to BROJ.

Osteonecrose dos maxilares por bifosfonatos (OMB) tem sido descrita desde 2003 como um efeito adverso dos medicamentos bifosfonatos. Essas drogas atuam sobre a vascularização e remodelação óssea, principalmente na atividade osteoclástica, podendo gerar áreas de exposição óssea necrótica. O tratamento para a doença ainda não é definido, mas o tratamento cirúrgico é uma das formas preconizadas que, em algumas situações podem ocasionar deformações orais como as comunicações buco-sinusais. Em situações como esta o tecido adiposo bucal é uma alternativa importante para o recobrimento da comunicação oro-nasal, devido ao seu grande suprimento sanguíneo, elasticidade, ausência de restrição pela idade e segurança. Este trabalho apresenta um caso clínico de paciente de 58 anos do sexo feminino, portadora de OMB em maxila esquerda pelo uso de ácido zoledrônico para câncer metastático. A extensa remoção da porção óssea necrótica resultou em fístula buco-sinusal. O retalho do tecido adiposo bucal foi utilizado para cobrir o defeito. Mais estudos devem ser realizados com relação ao tratamento de OMB, no entanto, se necessário, o retalho de tecido adiposo bucal poderia ser uma alternativa para resolver a comunicação oro-nasal relacionada à OMB.

A systematic review of microsurgical reconstruction of the jaws using vascularized fibula flap technique in patients with bisphosphonate-related osteonecrosis

OBJECTIVE: The aim of this systematic review was to assess the role of microsurgical reconstruction of the jaws in patients with bisphosphonate-related osteonecrosis, and biological complications after an observation period of at least 12 months. Material and methods: An electronic MEDLINE search supplemented by manual searching was conducted to identify studies reporting data of at least 12 months observation on the microsurgical reconstruction of the jaws in patients with bisphosphonate-related osteonecrosis. RESULTS: Four studies resulted eligible for the analysis yielded. Three out of five studies were free of complications, with a success rate of 100 percent as no recurrence of osteonecrosis was registered. CONCLUSIONS: Microsurgical reconstruction of the jaws represents a valid treatment modality in patients with bisphosphonate-related osteonecrosis at 3rd stage of the disease.