Impacto do uso sistêmico de estatinas e de bisfosfonatos nos tecidos periodontais: revisão narrativa / Impact of the systemic use of statins and bisphosphonates in the periodontal tissues: narrative review

Introdução: A literatura tem apontado uma possível relação entre diversas condições sistêmicas e as doenças periodontais. Dentro das doenças sistêmicas que podem gerar o uso crônico de medicamentos, com potencial associação com as doenças periodontais, destacam-se a hipercolesterolemia e o uso de estatinas; e as doenças do metabolismo ósseo e o uso de bisfosfonatos. Objetivo: Dessa maneira, o presente estudo objetivou revisar a literatura sobre o efeito das estatinas e dos bisfosfonatos nos parâmetros clínicos e radiográficos periodontais de indivíduos adultos. Resultados: Apenas estudos observacionais em humanos foram incluídos. Um estudo mostrou que, em pacientes que apresentam doença periodontal e usam estatina, houve 37% menos bolsas periodontais (profundidade de sondagem ≥4mm) quando comparadas aos que não utilizam a medicação, além de apresentarem menor índice de carga inflamatória e menor perda de inserção clínica. Em relação aos bisfosfonatos em indivíduos com doenças que envolvem o metabolismo ósseo, sugere-se que a utilização do fármaco tem obtido resultados positivos nos parâmetros periodontais, como menores sinais clínicos de inflamação gengival, menor profundidade de sondagem, menor perda de inserção clínica e maior nível de osso alveolar, quando comparados aos que nunca realizam essa terapia. Conclusão: Dessa forma, as estatinas e os bisfosfonatos apresentam efeitos promissores, em pacientes sob tratamento para suas respectivas condições sistêmicas, na melhoria dos parâmetros periodontais, porém é importante salientar que são necessários mais estudos sobre o assunto para melhor entender os reais efeitos a longo prazo do uso desses fármacos.(AU)

Introduction: The literature showed a possible relationship between several systemic conditions and periodontal diseases. Within the systemic diseases that can generate the chronic use of these drugs, potentially related with periodontal diseases, it may be cited the hypercholesterolemia and the use of statins; and bone metabolism diseases and the use of bisphosphonates. Objective: In this sense, the present study aimed to review the literature about the effect of statins and bisphosphonates in the periodontal parameters of adults individuals. Results: Only observational studies in humans were included. A study showed that, in patients with periodontal disease and users of statins, there 37% fewer periodontal pockets (probing depth ≥4mm) when compared to those who do not use the medication, as well as having a lower rate of inflammatory burden and less loss of clinical insertion. Regarding the bisphosphonates in individuals diagnosed with diseases involving bone metabolism, it was suggested that the use of the drug has obtained positive results in periodontal parameters, such as a greater absence of plaque, less clinical signs of gingival inflammation, less probing depth, lower level of clinical insertion and higher level of alveolar bone when compared to those who never undergo this therapy. Conclusion: Thus, statins and bisphosphonates have promising effects in patients under treatment for their respective systemic condition in improving periodontal parameters, but it is important to emphasize that further studies on the subject are needed to better understand the long-term effects of the use of these drugs.(AU)

Osteonecrosis maxilar inferior asociado a bifosfonatos / Lower jaw osteonecrosis associated with bisphosphonates / Osteonecrose do maxilar inferior associada a bisfosfonatos

Introducción: dada la alta prescripción de bifosfonatos, presentamos sus efectos adversos en la esfera odontológica, siendo una complicación poco frecuente, pero de difícil tratamiento. Sin necesidad de suspender el tratamiento, dado el importante beneficio en cuanto a la prevención de fractura por fragilidad. Estas fracturas causan una alta morbimortalidad en contraposición al bajo riesgo que conlleva la Osteonecrosis mandibular asociada a bifosfonatos. Objetivo: orientar al personal de salud que maneja estos fármacos y quien asiste dichas complicaciones a poseer conocimientos para la prevención de osteonecrosis. Identificar y diferenciar los pacientes con mayor riesgo, de acuerdo con la dosis de bifosfonatos y la frecuencia del tratamiento. Materiales y Método: se realizó una revisión bibliográfica en las siguientes fuentes: Scielo, Google académico, Medline/Pubmed, Biblioteca Virtual en Salud (Brasil), desde el año 2005 a la fecha, idiomas español, portugués e inglés. Los descriptores utilizados son bifosfonatos, mandíbula, maxilar, odontología, osteonecrosis, osteonecrosis de los maxilares asociada a bifosfonatos. Resultados: las últimas pautas de tratamiento fueron modificadas en 2014, por consenso de la Asociación Americana de cirugía Oral y Maxilofacial. La patogénesis de la osteonecrosis maxilar asociada a bifosfonatos no está completamente definida, aunque las publicaciones tratan de explicarla. El riesgo de desarrollarla por terapia oral es menor que por su administración vía intravenosa. Discusión: el médico que prescribe el antirresortivo debe conocer el estado de salud dental de su paciente y, en lo posible, remitirlo a examen con el odontólogo antes de iniciar la terapia con bifosfonatos.

Introduction: Given the high prescription of bisphosphonates, we present their adverse effects in the dental sphere, being an infrequent complication, but difficult to treat. There is no need to suspend treatment, given the important benefit in terms of prevention of fragility fractures. These fractures cause high morbimortality as opposed to the low risk associated with bisphosphonate-associated osteonecrosis of the jaw. Objective: To orient the health personnel who handle these drugs and who assist these complications to have knowledge for the prevention of osteonecrosis. To identify and differentiate patients at higher risk, according to the dose of bisphosphonates and frequency of treatment. Materials and Method: A literature review was performed in the following sources: Scielo, Google academic, Medline/Pubmed, Virtual Health Library (Brazil), from 2005 to date, Spanish, Portuguese and English languages. The descriptors used were bisphosphonates, mandible, maxilla, dentistry, osteonecrosis, osteonecrosis of the jaws associated with bisphosphonates. Results: The latest treatment guidelines were modified in 2014, by consensus of the American Association of Oral and Maxillofacial Surgery. The pathogenesis of bisphosphonate-associated maxillary osteonecrosis is not completely defined, although publications try to explain it. The risk of developing it by oral therapy is lower than by intravenous administration. Discussion: The physician who prescribes the antiresorptive drug should know the dental health status of his patient and, if possible, refer him for examination by a dentist before initiating bisphosphonate therapy.

Introdução: dada a alta prescrição de bisfosfonatos, apresentamos seus efeitos adversos na esfera odontológica, uma complicação rara, mas de difícil tratamento. Sem a necessidade de suspender o tratamento, dado o importante benefício em termos de prevenção de fraturas por fragilidade. Essas fraturas causam alta morbidade e mortalidade, em contraste com o baixo risco associado à osteonecrose da mandíbula associada aos bisfosfonatos. Objetivo: orientar a equipe de saúde que manipula esses medicamentos e que atende a essas complicações para que tenham conhecimento sobre a prevenção da osteonecrose. Identificar e diferenciar os pacientes de maior risco, de acordo com a dose de bisfosfonatos e a frequência do tratamento. Materiais e Método: foi realizada uma revisão da literatura nas seguintes fontes: Scielo, Google acadêmico, Medline/Pubmed, Biblioteca Virtual em Saúde (Brasil), de 2005 até a presente data, idiomas espanhol, português e inglês. Os descritores utilizados foram: bisfosfonatos, mandíbula, maxila, odontologia, osteonecrose, osteonecrose dos maxilares associada a bisfosfonatos. Resultados: as diretrizes de tratamento mais recentes foram modificadas em 2014, por consenso da Associação Americana de Cirurgia Oral e Maxilofacial. A patogênese da osteonecrose da mandíbula associada a bisfosfonatos não está totalmente definida, embora a literatura tente explicá-la. O risco de desenvolvê-la com a terapia oral é menor do que com a administração intravenosa. Discussão: o médico que prescreve o medicamento deve estar ciente do estado de saúde bucal do paciente e, se possível, encaminhar o paciente para ser examinado por um dentista antes de iniciar a terapia com bisfosfonatos.

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)

O uso de bisfosfonatos causa implicações na movimentação dentária ortodôntica? / Does the use of biophosphonates cause implications on the orthodontic tooth movement?

Bisfosfonatos são medicamentos que reduzem a reabsorção óssea, inibindo a atividade enzimática dos osteoclastos. Por essa razão, são amplamente utilizados no tratamento de várias doenças, como a osteoporose. Durante o tratamento ortodôntico, a aplicação de forças compressivas no dente promove a reabsorção e remodelação óssea, permitindo sua movimentação. Vários estudos in vivo observaram a diminuição da movimentação ortodôntica por bisfosfonatos, tornando o tema relevante devido à crescente demanda de tratamento ortodôntico em idosos ­ principais usuários dessa droga. Assim sendo, o objetivo deste trabalho é avaliar evidências do uso de bisfosfonatos no decorrer do tratamento ortodôntico e, mais especificamente, examinar seus efeitos na movimentação ortodôntica através de mensurações clínico-laboratoriais. Para isso, foi realizada uma revisão sistematizada na base de dados Pubmed através dos descritores Ortodontia e Bisfosfonatos. Buscou-se estudos em inglês entre 2015 e 2020. De 39 artigos compatíveis à proposta, 8 artigos passaram pelos critérios de inclusão e exclusão. Desses, a maioria dos autores é categórica em se referir ao uso de bisfosfonatos como um fator relevante para índices inferiores de movimentação. Porém, tais dados devem ser vistos com cautela, pois os métodos utilizados são variados, havendo uma grande heterogeneidade. Ademais, pequenas amostras e tempo curto dos experimentos não permitem uma generalização para pacientes de rotina. Como conclusão temos que a administração de bisfosfonatos associada à movimentação ortodôntica aparenta provocar uma duração prolongada no tratamento devido, fundamentalmente, aos índices inferiores de movimentação dentária planejada. Entretanto, os fatores específicos para tal não estão plenamente explicados.

Bisphosphonates are drugs that provide bone resorption by inhibiting the enzyme activity of osteoclasts. For this reason, they are widely used in the treatment of various diseases, such as osteoporosis. During orthodontic treatment, the application of compressive forces on the tooth promotes bone resorption and remodeling, allowing its movement. Several in vivo studies observed a decrease in orthodontic movement caused by bisphosphonates, making the topic relevant due to the growing demand for orthodontic treatment in the elderly - the main users of this drug. Therefore, the aim of this study is to evaluate evidence of the use of bisphosphonates during orthodontic treatment and, more specifically, to examine their effects on orthodontic movement through clinical and laboratory measurements. For this, a systematized review was performed in the Pubmed database using the descriptors Orthodontics and Bisphosphonates. Studies in English between 2015 and 2020 were sought. Of 39 articles compatible with the proposal, 8 articles passed the inclusion and exclusion criteria. Most authors are categorical in referring to the use of bisphosphonates as a relevant factor for lower movement rates. However, such data must be viewed with caution, as the methods used are sundry, with great heterogeneity. Furthermore, small administrations and short experimental times do not allow generalization to routine patients. In conclusion, the administration of bisphosphonates associated with orthodontic movement seems to cause a prolonged duration of treatment, fundamentally due to the lower rates of planned tooth movement. However, the specific factors for this are not fully explained.

Atypical Tibial Fracture Treated with Osteosynthesis Associated with Total Knee Arthroplasty: Case Report / Fratura atípica de tíbia tratada com osteossíntese associada a artroplastia total do joelho: Relato de caso

Abstract Bisphosphonates are widely used in the treatment of osteoporosis but predispose the patient to the appearance of atypical fractures. The femoral subtrochanteric region is usually affected, but other bones can be as well. Atypical tibia fractures in patients with severe gonarthrosis is a therapeutic challenge. The present work reports the case of an elderly patient with advanced gonarthrosis who presented atypical tibial fracture. The patient made prolonged use of bisphosphonates for osteoporosis, presenting with pain and functional limitation resulting from gonarthrosis, which progressed to sudden pain in the right tibial metaphysis, preventing ambulation. The radiographs showed bilateral severe arthrosis; marked varism; tibial and femoral medial erosion; and fracture in the proximal third of the right tibial diaphysis. The fracture and arthrosis on the right side were treated by osteosynthesis with blocked plaque and total knee arthroplasty with posterior stabilization and fixed base. After physical rehabilitation, significant improvement of pain and function was reported, independent gait was reacquired and a range of motion of 0 to 100º was reached. After one year, the radiographs showed fracture consolidation and satisfactory alignment of the lower limbs' axes. The coexistence of severe arthrosis and atypical fracture made treatment difficult. However, the result was satisfactory and the approach with simultaneous osteosynthesis and arthroplasty proved to be adequate.

Resumo Bifosfonatos são amplamente usados no tratamento da osteoporose; porém, predispõem ao surgimento de fraturas atípicas. A região subtrocantérica femoral é usualmente acometida, mas outros ossos também são afetados. Fraturas atípicas da tíbia em pacientes portadores de gonartrose grave são um desafio terapêutico. O presente trabalho relata o caso de uma paciente idosa com gonartrose avançada que apresentou fratura atípica tibial. A paciente fazia uso prolongado de bifosfonatos para osteoporose, com quadro de dor e limitação funcional decorrentes da gonartrose, que progrediu para dor súbita na metáfise tibial à direita, impedindo a deambulação. Radiografias evidenciaram artrose grave bilateral; varismo acentuado; erosão medial tibial e femoral; e fratura no terço proximal da diáfise tibial direita. Trataram-se a fratura e a artrose à direita por osteossíntese com placa bloqueada e artroplastia total do joelho com estabilização posterior e base fixa. Após reabilitação física, relatou-se melhora significativa da dor e da função, readquiriu-se a marcha independente e alcançou-se arco de movimento de 0 a 100º. Após um ano, as radiografias mostraram consolidação da fratura e alinhamento satisfatório dos eixos dos membros inferiores. A coexistência de artrose grave e fratura atípica dificultou o tratamento. Contudo, o resultado foi satisfatório e a abordagem com osteossíntese e artroplastia simultâneas mostrou-se adequada.

A survey on brazilian dentists' awareness, perception, and knowledge of bisphosphonates

Aim: The purpose of the study was to analyze the knowledge of dentists in Belo Horizonte, Brazil, about bisphosphonates and their clinical implications. Methods: A cross-sectional questionnaire-based study was conducted with a convenience sample of dentists in Belo Horizonte, in a period of 8 weeks. The questionnaire was self-applied and was structured with 10 items about the dentists' demographic characteristics, professional profile, and knowledge about bisphosphonates. Associations in the data were analyzed by with the Fischer's exact test with a significance level of 5%. Results: Of the 214 participating dentists, 163 (76.17%) were women, and 51 (23.83%) were men, with age ranged for 21 to 73 years (mean of 30 years) and mean of 6 years of professional activity. Nearly half (106/49.53%) reported having knowledge about bisphosphonates, and undergraduate courses were the primary source of such information (73/34.11%). Osteoporosis was the most identified indication for use (75/35.04%), although no participants correctly identified all indications. Regarding the drugs' side effects, only three dentists (1.40%) could correctly identify all responses, with bone necrosis being recognized by the majority (88/41.12%). Sodium alendronate (54/25.23%) and sodium ibandronate (15/7.01%) were the most identified examples of bisphosphonates. Last, only nine dentists (4.20%) could identify all examples of the drugs, and their capacity was associated with self-reported knowledge (p<0.05). Conclusions: More information about bisphosphonates should be disseminated in Belo Horizonte, ideally via better approaches in local undergraduate and postgraduate courses. Until then, knowledge of the basic aspects of bisphosphonates will remain limited

Conocimiento y conciencia de los médicos sobre la osteonecrosis relacionada con bifosfonatos / Knowledge and awareness of physicians about bisphosphonate-related osteonecrosis of the jaws

Objetivo: Determinar el conocimiento y la conciencia que tienen los médicos sobre la osteonecrosis relacionada con bifosfonatos. Material y métodos: Se realizó un estudio transversal, en el cual se encuestó a médicos generales y especialistas con la finalidad de identificar el nivel de conocimientos y conciencia que tienen sobre el tema. Resultados: Se entrevistó a un total de 475 médicos generales y especialistas, de los cuales 210 (44.2%) mencionaron prescribir bifosfonatos, de este grupo 58.1% no envía a los pacientes con el odontólogo para eliminar factores de riesgo, a pesar de que 61.8% de los mismos mencionó conocer las reacciones adversas; 36 médicos (17.4%) han visto a algún paciente con osteonecrosis por bifosfonatos. El 37% de los médicos que prescriben medicamentos consideran que no es necesario remitir a los pacientes al odontólogo. Conclusiones: La prescripción de bifosfonatos en la práctica médica va en aumento, los médicos deben tener el conocimiento adecuado sobre las reacciones adversas de estos medicamentos para así poder referir oportunamente al odontólogo, educar al paciente y poder prevenir complicaciones como la osteonecrosis relacionada con bifosfonatos (AU)

Objectives : To evaluate the knowledge and awareness of physicians about bisphosphonate-related osteonecrosis of the jaws. Material and methods: A cross-sectional survey was carried out among general practitioners and specialized physicians to determine their knowledge and awareness of bisphosphonate-related osteonecrosis of the jaws. Results: Of the 475 interviewed general practitioners and specialized physicians, 210 (44.2%) claimed to prescribe bisphosphonates. A total of 58.1% of these physicians did not refer their patients to the dentist for the elimination of risk factors, despite the fact that 61.8% of them reported knowledge of the adverse reactions of these drugs. Thirty-six physicians (17.4%) had seen some patient with bisphosphonate-related osteonecrosis of the jaws. A total of 37% of the physicians that prescribed drugs considered it not necessary to refer patients to the dentist. Conclusions: Bisphosphonate prescription is increasingly common in medical practice, and physicians must have adequate knowledge of the adverse reactions of these drugs in order to ensure opportune patient referral to the dentist, educate their patients, and avoid complications such as bisphosphonate-related osteonecrosis of the jaws (AU)

Osteonecrosis asociada a pacientes con consumo de antirresortivos bajo tratamiento oncológico / Osteonecrosis associated to patients who take anti-resorptive drugs, undergoing oncologic treatment

La Asociación Americana de Cirugía Oral y Maxilofacial (American Association of Oral and Maxillofacial Surgeons [AAOMS]): define el concepto de osteonecrosis maxilar asociada a drogas antirresortivas (MRONJ) como: «área ósea necrótica expuesta al medio bucal con más de ocho semanas de permanencia, en presencia de tratamiento crónico con bifosfonatos en ausencia de radioterapia en cabeza y cuello¼. El objetivo de este artículo es asociar la enfermedad oncológica en relación con las drogas antirresortivas consumidas por pacientes, la prescripción de dichas drogas y el depósito de ellas en el organismo. Al mismo tiempo, la interacción médico-odontológico debe implementarse en favor de la salud de nuestros pacientes (AU)

American Association of Oral and Maxillofacial Surgeons AAOMS defined Medication Related of the Jaw (MRONJ) as «necrotic bone area exposed to the oral environment with more than eight weeks of permanence, in the presence of chronic treatment with BPs, in the absence of radiation therapy to the head and neck¼. The objective of this article is associate oncology antiresorptives treatments prescribed by physicians, their prescription and body accumulation in patients whose are treated with them. Interdisciplinary dental and physician clinical treatments must be implemented in patient favours (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)

Expert consensus on safety management of bone-modifying agents / 中华肿瘤杂志

Bone-modifying agents currently include bisphosphonates and desumumab, which are the main drugs for the treatment of malignant tumor bone metastasis, hypercalcemia and osteoporosis. Due to its wide clinical application, the adverse events of this kind of drugs are gradually increasing and affecting the quality of life of patients. Therefore, it needs to arouse the attention of the majority of medical personnel. Based on the substantial evidence, the expert committee has thoroughly discussed the management of adverse reactions of bone modifying agents and put forward reasonable suggestions, to guide clinicians in the safety management of such drugs.

Fundamentos de elección terapéutica: osteonecrosis maxilar asociada a drogas antirresortivas (MRONJ) / Fundamentals of therapeutic choice: anti-resorptive drug-related maxillary osteonecrosis (MRONJ)

La acción terapéutica favorable que los antirresortivos (bifosfonatos BPs, denosumab DS) y drogas antiangiogénicas ocasionan en el tejido óseo en aquellos pacientes que presentan como causa etiológica cáncer o discrasias óseas incluyen hipercalcemias malignas o ­si requieren el consumo de dicha droga a baja concentración­ como ser: osteoporosis, osteopenia, enfermedad de Paget, displasia fibrosa, Osteogénesis Imperfecta. (1) La presente actualización pretende relacionar el tratamiento odontológico con prescripción crónica y drogas antirresortivas, para lo cual American Association of Oral and Maxillofacial Surgeons AAOMS: define el concepto de Osteonecrosis Maxilar Asociada a drogas Antirresortivas (MRONJ) como: «Área ósea necrótica expuesta al medio bucal con más de ocho semanas de permanencia, en presencia de tratamiento crónico con bifosfonatos en ausencia de radioterapia en cabeza y cuello¼. La AAOMS estableció los siguientes grupos de acuerdo con sus características clínicas en 4 estadios (0, 1 ,2 y 3) de acuerdo con el aspecto clínico y radiológico de la lesión osteonecrótica. Estadío 0: lesión osteonecrótica sin evidencia de hueso necrótico en pacientes bajo consumo de drogas antirresortivas. Estadío 1: lesión osteonecrótica con signos clínicos y ausencia de sintomatología clínica. Estadío 2: lesión osteonecrótica con signo y sintomatología clínica evidente. Estadío 3: lesión osteonecrótica con signo y sintomatología evidente que compromete a estructuras nobles: fracturas patológicas, anestesia del nervio dentario inferior, comunicación buco-nasal, comunicación buco-sinusal, fístulas cutáneas (2) (AU)

It is known the favourable action which antiresorptive (Bisphosphonates BPs, Denosumab: DS) and Antiangiogenic drugs produce in bone tissue. High concentrations are primarily used as an effective treatment in the management of cancer-related disorders, including hypercalcemia of malignant. Besides, low concentrations are used for other metabolic bone diseases including Osteoporosis, Osteopenia, Paget's Disease, Fibrous Dysplasia, Imperfect Osteogenesis. (1) The update relate relationship between dentistry and chronic treatment with antiresorptive drugs. According to the American Association of Oral and Maxillofacial Surgeons (AAOMS), MRONJ is defined as exposed or necrotic bone in the maxillofacial region that has persisted for more than 8 weeks in association with current or previous BPs or DS therapy and with a lack of head and neck radiotherapy. AAOMS divided the MRONJ into 4 stages (0,1, 2 and 3) according to the clinical and radiological aspect of the osteonecrotic lesion: Stage 0: osteonecrotic lesion without sign-pathognomonic evidence of osteonecrosis. Stage 1: osteonecrotic lesion with clinical signs and absence of clinical symptoms. Stage 2: osteonecrotic lesion with sign and evident clinical symptoms. Stage 3: osteonecrotic lesion with signs and evident symptoms that involve noble structures: pathological fractures, anaesthesia of the lower dental nerve, oral-nasal communication, oral-sinus communication, skin fistulas (2) (AU)

Actualización de medicamentos asociados a necrosis avascular de los maxilares: perspectiva y revisión de literatura / Update of medications associated with avascular necrosis of the jaws: a perspective and literature review

La osteonecrosis de los maxilares está definida como la exposición de hueso necrótico en la región maxilofacial al menos por ocho semanas en pacientes que están recibiendo medicamentos antirresortivos para el tratamiento del cáncer primario o metastásico hacia el hueso, osteoporosis o enfermedad de Paget, sin historia previa de radiación. Desde el año 2003, la terminología utilizada estaba en relación con los bifosfonatos, en la actualidad ha sido introducido el término osteonecrosis de los maxilares relacionada por medicamentos (OMAM). La cirugía oral (implantología o cirugía periapical) incrementa el riesgo de OMAM, así como los desbalances concomitantes de la salud oral (inflamación dental y formación de abscesos). Las estrategias conservadoras en el tratamiento varían desde el cuidado local conservador hasta la resección quirúrgica radical del hueso necrótico. En el presente artículo se expone un análisis sistemático retrospectivo de la literatura en páginas como PubMed, ScienceDirect y Springer, Cochrane Library. Con el objetivo de resaltar el aumento de la incidencia de OMAM a nivel mundial con el uso de antirresortivos y otros medicamentos asociados en su patogenia en el Hospital Regional «General Ignacio Zaragoza¼ del ISSSTE, UNAM, en la Ciudad de México (AU)

Osteonecrosis of the jaws is defined as the exposure of necrotic bone in the maxillofacial region for at least 8 weeks in patients receiving antiresorptive medications for the treatment of primary or metastatic cancer towards the bone, osteoporosis, or Paget's disease, without previous history of radiation. Since 2003, the terminology used was related to bisphosphonates, the term medication-related osteonecrosis of the jaws has now been introduced. Oral surgery (implantology or periapical surgery) increases the risk of avascular necrosis, as well as concomitant imbalances in oral health (dental inflammation and abscess formation). Conservative strategies in treatment vary from conservative local care to radical surgical resection of the necrotic bone. In this article, a systematic retrospective analysis of the literature is presented on pages such as PubMed, Science Direct and Springer, Cochrane Library. And in which the objective is to highlight the increase in the incidence of medication related osteonecrosis of the jaws worldwide with the use of antiresorptive, and other associated medications in its pathogenesis at the Hospital Regional «General Ignacio Zaragoza¼ ISSSTE, UNAM in Mexico City (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 de los maxilares asociada a medicamentos: revisión de la literatura y propuesta para la prevención y manejo / Osteonecrosis of the jaws

Medication-related osteonecrosis of the jaw is a disease where there is necrotic bone exposed or that can be explored by means of a fistula in the maxillofacial region. It has been associated with the use Biphosphonates and denosumab for osteoporosis. Although its etiology is unclear, it may be related to a decrease in bone turnover produced by these drugs, rendering the bone more prone to generate cell necrosis during invasive dental procedures, especially in the posterior region of the jaw. There is no consensus about the prevention and treatment of this condition. The aim of this paper is to present a review of the literature with the main characteristics of osteonecrosis of the jaws associated with drugs, together with a proposal for prevention and treatment for these patients.

Osteonecrosis de los maxilares asociada a medicamentos (ONMM): guía redactada por expertos invitados por la Asociación Argentina de Osteología y Metabolismo Mineral y por la Sociedad Argentina de Osteoporosis / Medication-related osteonecrosis of the jaw (MRONJ): guideline prepared by experts invited by the Argentine Association of Osteology and Mineral Metabolism, and the Argentine Society for Osteoporosis

La osteonecrosis maxilar asociada a medicamentos (ONMM=MRONJ como se conoce en la literatura en inglés) se define como un área ósea expuesta al medio bucal con más de ocho semanas de permanencia, en pacientes tratados con antirresortivos y/o antiangiogénicos y sin antecedentes de radioterapia en cabeza y cuello. Las fracturas ocasionan una morbimortalidad significativa y los antirresortivos son drogas eficaces y seguras para prevenirlas. Se utilizan principalmente en osteoporosis, pero también en enfermedades oncológicas como mieloma múltiple o metástasis óseas de tumores sólidos. La posología varía según el contexto clínico, siendo mayor la dosis y frecuencia de administración en oncología. Los antirresortivos actualmente más utilizados son los bifosfonatos (BF) y el denosumab (Dmab). Si bien los BF persisten largo tiempo en el tejido óseo, el Dmab tiene un mecanismo de acción reversible y su suspensión abrupta conlleva importante pérdida de masa ósea y riesgo aumentado de fracturas vertebrales múltiples. Ninguna droga puede ser suspendida ni espaciada sin autorización médica, dado que no es de competencia del odontólogo. El diagnóstico presuntivo de ONMM debe ser confirmado clínicamente por un odontólogo, quien solicitará imágenes radiológicas para establecer el estadio de la lesión. La anamnesis correcta permite establecer un diagnóstico diferencial entre ONMM, osteomielitis y osteorradionecrosis. La presentación clínica es variable y puede mostrar distintos estadios. La mayoría de los casos están precedidos por un procedimiento quirúrgico odontológico. Suele ser asintomática, aunque puede haber dolor si se localiza cerca de una estructura neuronal. La localización es variable: 62,3% se produce en el maxilar inferior. La incidencia de ONMM es baja, en un rango de 0,001 a 0,01% y tiene relación con las dosis y el tiempo de administración. La remoción de caries, la operatoria dental, la endodoncia y la rehabilitación protética fija o removible no se asocian a riesgo de ONMM. Con menos de 3 años de tratamiento antirresortivo se pueden efectuar terapéuticas quirúrgicas como exodoncias, apicectomías, cistectomías, tratamientos periodontales de raspaje y alisado subgingival sin riesgo. Con más de 3 años se aconseja evitar la realización de exodoncias y manipulación de tejido óseo. Ante la necesidad de realizar un procedimiento odontológico, no hay evidencia que avale que la suspensión transitoria del tratamiento antirresortivo pueda reducir el riesgo. Tampoco la medición de marcadores de remodelado óseo aporta datos de utilidad. Existen pocos datos en la literatura sobre la colocación de implantes dentales en pacientes que reciben drogas antirresortivas en dosis bajas; si bien existe ONMM asociada, su incidencia sería baja. Antes de iniciar un tratamiento antirresortivo se recomienda realizar interconsulta con el odontólogo para evaluar potenciales necesidades quirúrgicas. Quienes reciben antirresortivos deben realizar controles orales periódicos (semestrales) y, ante cualquier síntoma compatible con un estadio incipiente de ONMM, deben consultar a su odontólogo. El trabajo conjunto del médico y el odontólogo puede prevenir la aparición de la ONMM, un evento infrecuente, pero que puede generar elevada morbilidad en los pacientes. La comunicación fluida entre profesionales tenderá a evitar no solo la incertidumbre y desconfianza de los pacientes, sino también que se produzcan lesiones con la consecuente necesidad de tratamientos de mayor complejidad. (AU)

Medication-Related Osteonecrosis of the Jaw (MRONJ) is defined as a bone area exposed to the oral environment lasting more than eight weeks, in patients treated with antiresorptive and/or antiangiogenic drugs and without a history radiation therapy to the head and neck. Fractures cause significant morbidity and mortality, and antiresorptives are effective and safe drugs to prevent them. They are used to treat not only osteoporosis but also oncological diseases such as multiple myeloma or bone metastases from solid tumors. The dosage varies according to the clinical context; doses and frequencies of administration are higher in oncology. The most commonly used antiresorptive medications are bisphosphonates (BP) and denosumab (Dmab). Whereas BP persist for a long time in bone tissue, Dmab has a reversible mechanism of action and its discontinuation leads to significant loss of bone mass and an increased risk of multiple vertebral fractures. No drug can be suspended or spaced without medical authorization. Dentists should not take decisions about antiresorptive prescription. The presumptive diagnosis of MRONJ must be clinically confirmed by a dentist, who will order radiological studies to establish the stage of the injury. The correct anamnesis helps differentiate MRONJ from osteomyelitis and osteoradionecrosis. Clinical presentation is variable and can present different stages. Most of the cases are preceded by a dental surgical procedure. Usually MRONJ is asymptomatic although patients may feel pain if it is located near a neuronal structure. The location is variable: 62.3% occurs in the lower jaw. The incidence of MRONJ is low, in the range of 0.001 to 0.01%, and is related to the dose and time of administration. Caries removal, dental surgery, endodontics, fixed or removable prosthetic rehabilitation are not associated with risk of MRONJ. With less than 3 years of antiresorptive treatment, surgical therapies such as extractions, apicectomies, cystectomies, periodontal scaling treatments and subgingival smoothing can be performed without risk. With more than 3 years, it is advisable to avoid performing extractions and manipulating bone tissue. Given the need to perform a dental procedure, there is no evidence to support that the temporary suspension of antiresorptive treatment can reduce the risk. Nor does the measurement of bone turnover markers provide useful information. There are few data in the literature on the placement of dental implants in patients receiving antiresorptive drugs at low doses; although there might be an associated risk of MRONJ, its incidence appears to be low. Before starting antiresorptive treatment, consultation with the dentist is recommended to evaluate potential surgical needs. Patients receiving treatment with antiresorptive agents should undergo periodic oral controls (every six months) and in the event of any symptoms compatible with an early MRONJ stage, they should consult their dentists. The collaboration between physician and dentist can prevent the appearance of MRONJ, that is an infrequent event, but can generate high morbidity in patients. Fluid communication between professionals will tend to avoid, not only the uncertainty and distrust of patients, but also the occurrence of injuries needing complex treatments. (AU)

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)

Osteoactivos en insuficiencia renal crónica avanzada: a propósito de un caso / Osteoactive in advanced chronic renal failure: a case report

El propósito de la terapia en el desorden del metabolismo óseo mineral asociado a la enfermedad renal crónica (IRC) consiste en restaurar el balance mineral, y, en la osteoporosis, mantener o aumentar la masa ósea. Ambas terapias tratan de evitar la fractura ósea. La mayoría de los osteoactivos están contraindicados en la insuficiencia renal crónica avanzada (estadios 4 y 5), y las terapias son empíricas. Algunos autores opinan que sin anomalías bioquímicas del desorden del metabolismo óseo mineral asociado a la enfermedad renal crónica avanzada se podría intentar el tratamiento estándar para la osteoporosis. Antes de intentar la terapia osteoactiva se debe corregir el desorden mineral óseo que pudiera presentarse asociado a la IRC, y en la indicación del tipo de osteoactivo se sugiere seleccionar al paciente según su estado óseo. Se aconseja que la administración de los antirresortivos se realice a dosis menores con respecto a los que tienen mejor función renal junto con aportes adecuados de calcio y vitamina D, antes y durante el tratamiento para prevenir el riesgo de severas hipocalcemias y un efecto óseo excesivo. Se presenta el caso clínico de una mujer de 65 años, con diagnóstico de osteoporosis de etiología multifactorial, fractura de pelvis, múltiples fracturas vertebrales e insuficiencia renal crónica avanzada, entre otras comorbilidades, y probable enfermedad ósea adinámica. Recibió inicialmente terapia con teriparatide y luego con denosumab, complicándose con hipocalcemia asintomática. (AU)

The purpose of therapy for the bone mineral metabolism disorder associated with chronic kidney disease is to restore the mineral balance; and to maintain or increase bone mass in osteoporosis. The goal of both types of therapy is to avoid bone fractures. Most antiosteoporotic drugs are contraindicated in advanced chronic renal failure (CRF) stages 4 and 5, and the therapies are empirical. Some authors believe that without biochemical abnormalities of the mineral bone metabolism disorder associated with advanced chronic kidney disease, standard treatment for osteoporosis could be attempted. Before attempting antiosteoporotic therapy, the bone mineral disorder that may be associated with CRF must be corrected, and in the indication of the type drug it is suggested that the patient be selected according to their bone status. It is advised that the administration of anti-resorptives be performed at lower doses in individuals with poor renal function compared to those with better renal function together with adequate calcium and vitamin D, before and during treatment to prevent the risk of severe hypocalcemia, and an excessive bone effect. We present the clinical case of a 65-year-old woman with a diagnosis of osteoporosis of multifactorial etiology, pelvic fracture, multiple vertebral fractures and advanced chronic renal failure, among other comorbidities and probable adynamic bone disease. The patient received initial therapy with teriparatide and followed by denosumab administration and exhibited asymptomatic hypocalcemia. (AU)

Agentes antirresortivos y antiangiogénicos y su relación con la osteonecrosis de los maxilares asociada a medicamentos / Antiresorptive and antiangiogenic agents and their relationship with osteonecrosis of the jaws related to medication

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)

Terapia láser de baja frecuencia en el manejo del dolor en pacientes con osteonecrosis mandibular / Low level laser therapy in the management of pain in patients with osteonecrosis of the jaw

La terapia láser de baja frecuencia (TLBF) o fotobioestimulación es aquella que cuya luz provoca la regeneración y remodelación ósea, la restauración de la función neural, la disminución del dolor y la modulación del sistema inmune; esta terapia es un coadyuvante junto a la terapia conservadora y/o quirúrgica. Se considera un estándar de oro para el manejo del dolor en la osteonecrosis en aquellos pacientes que consumen o han consumido bifosfonatos como terapia para inhibir la resorción ósea. La Sociedad Americana de Investigación de Hueso y Minerales (SAIHM) definió la osteonecrosis mandibular como «un área de hueso expuesto en la región maxilofacial que no cicatriza dentro de las ocho semanas posteriores a la identificación, en un paciente que está recibiendo o ha estado expuesto a bifosfonatos y que no ha recibido radioterapia en la región craneofacial¼. En este reporte presentamos dos casos de pacientes con osteonecrosis mandibular relacionada a bifosfonatos tratados con TLBF. Se evaluó el dolor antes y después de la terapia con la escala visual análoga (EVA). Ambos casos tuvieron disminución del dolor al 100%. Se presentan los métodos de diagnóstico clínico y radiográfico, el tratamiento elegido y los resultados obtenidos (AU)

Low level laser therapy (LLLT) or photobiostimulation is one whose light causes bone regeneration and remodeling, restoration of neural function, reduction of pain, and modulation of the immune system; this therapy is an adjuvant together with conservative and / or surgical therapy. It is considered a gold standard for pain management in osteonecrosis in those patients who consume or have used bisphosphonates as antiresorptive therapy. The American Society for Bone and Mineral Research (ASBMR) defined osteonecrosis of the jaw as «an area of exposed bone in the maxillofacial region that does not heal within eight weeks after identification by a health care provider, in a patient who was receiving or had been exposed to a BP and who has not received radiation therapy to the craniofacial region¼. In this report we present two cases of patients with mandibular osteonecrosis related to bisphosphonates treated with LLLT. Pain before and after visual analogue scale (VAS) was evaluated. Both cases had pain reduction at 100%. The methods of clinical and radiographic diagnosis, the treatment chosen and the results obtained are presented (AU)