Knowledge of Brazilian dentists about bisphosphonate-associated osteonecrosis of the jaw / Conhecimento de dentistas brasileiros sobre a osteonecrose dos maxilares associada ao uso de bisfosfonatos

Osteonecrosis of the jaw associated with bisphosphonate use is a matter of utmost importance in clinical practice for the safe treatment of patients using this medication. Objective: The aim of this study was to evaluate the level of knowledge of dentists who carry out clinical practice about bisphosphonate-associated jaw osteonecrosis. Material and Methods: The methodology used in the present research consisted of a non-probability sampling approach for the selection of participants. To conduct the study, a questionnaire created on the Google Forms platform was sent via Direct on Instagram to the professionals who agreed to participate. The data were sent for analysis, using the frequency for each response, and the professionals were divided into subcategories according to their time of professional practice. Results: Participants were familiar with the purpose of the medication (65%) or had heard of it (34%); regarding the professionals' opinion on their knowledge and practice about bisphosphonate-related osteonecrosis a significant percentage (93.24%) responded positively regarding the existence of side effects resulting from the therapeutic use of bisphosphonates and 48.65% self-evaluated their level of knowledge on the subject as insufficient. Conclusion: The study reveals that almost all participating dentists have good knowledge about the effects caused by bisphosphonates, but some of them still do not feel specifically confident about the management and knowledge of jaw osteonecrosis (AU)

A osteonecrose dos maxilares associada ao uso de bisfosfonatos é um assunto de suma importância na prática clínica para o atendimento seguro dos pacientes que fazem uso terapêutico do medicamento. Objetivo: O objetivo deste trabalho foi avaliar o nível de conhecimento de cirurgiões dentistas que realizam atendimento clínico acerca da osteonecrose dos maxilares associada ao uso dos bisfosfonatos. Material e Métodos: A metodologia utilizada na presente pesquisa consistiu em uma abordagem de amostragem não probabilística para a seleção dos participantes. Para conduzir o estudo, enviamos um questionário criado na plataforma Google Forms via Direct no Instagram para os profissionais que concordaram em participar. Os dados foram enviados para análise, usando a frequência para cada resposta, sendo que os profissionais foram divididos em subcategorias por tempo de formação. Resultados: Os participantes estavam familiarizados com a finalidade do medicamento (65%) ou já haviam ouvido falar deles (34%); em relação à opinião dos profissionais sobre seu conhecimento e prática acerca da osteonecrose relacionada aos bisfosfonatos, observou-se que 48,65% autoavaliaram seu nível de conhecimento sobre o assunto como insuficiente e uma parcela expressiva (93,24%) respondeu positivamente em relação à existência de efeitos colaterais decorrentes ao uso terapêutico dos bisfosfonatos. Conclusão: O estudo revela que quase todos os dentistas participantes possuem um bom conhecimento acerca dos efeitos causados pelos bisfosfonatos, mas que parte deles ainda não se sentem seguros especificamente em relação ao manejo e conhecimento da osteonecrose dos maxilares (AU)

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)

Descriptive assessment of 54 cases with complex regional pain syndrome in lower limbs / Evaluación descriptiva de 54 casos con síndrome dolo roso regional complejo en miembros inferiores

Abstract Introduction: Complex regional pain syndrome (CRPS), also known as Sudeck syndrome, is a chronic painful condition usually affecting the limbs after trauma or surgery. Its presentation is heterogeneous and its physio pathology, diagnosis and treatment remain controversial. The objective of this study was to analyze a group of patients with this rare syndrome, describing in detail the results of the dual energy X-ray absorptiometry (DXA) and the response to bisphosphonate treatment. Method: We retrospectively analyzed 54 patients with CRPS, taking into account their demographic features, inciting events and diagnostic tests. As regards treat ment, we analyzed the results and adverse events of the use of bisphosphonates Results: We found a female predominance (74%), with 55 ± 13 years. The most common inciting event was trauma (59%), followed by surgery. The difference in bone mineral density between the affected limb and the healthy one was 12 to 15%. Forty-four patients were treated with bisphosphonates (pamidronate, iban dronate, zoledronic acid) and showed a clinical im provement, mainly in terms of pain intensity. Only six patients presented with adverse events, like pseudoflu syndrome and acute phase symptoms. Conclusion: In our cohort, lower limbs CRPS pre dominantly affects middle aged women. DXA scans are tests used to quantify bone loss and the response to treatment. The use of bisphosphonates is an interest ing therapeutic option to improve clinical symptoms in most patients. Future prospective randomized studies will be needed to confirm our results.

Resumen Introducción: El síndrome doloroso regional complejo (SDRC), también conocido como síndrome de Sudeck, es una enfermedad dolorosa crónica que generalmente afecta a las extremidades luego de un trauma o cirugía. Su presentación es heterogénea y existen controversias sobre su fisiopatología, adecuado diagnóstico y trata miento. El objetivo de este trabajo es describir un grupo de pacientes con SDRC en miembros inferiores, describi endo los resultados de la densitometría mineral ósea (DMO) y la respuesta al tratamiento con bifosfonatos. Método: Analizamos retrospectivamente 54 pacientes con SDRC, teniendo en cuenta características demográ ficas, factores desencadenantes y estudios diagnósticos. En relación al tratamiento, analizamos los resultados y efectos adversos del uso de bifosfonatos. Resultados: Encontramos un predominio femenino (74%), con una edad de 55 ± 13 años. Los factores des encadenantes más comunes fueron los traumatismos (59%) y la cirugía. La diferencia de densidad mineral ósea entre el miembro comprometido y el sano fue 12 a 15%. En los 44 pacientes fueron tratados con bifosfona tos (pamidronato, ibandronato y ácido zoledrónico), su uso se asoció a mejoría clínica, especialmente del dolor. Seis pacientes tuvieron efectos adversos como sindrome pseudogripal y síntomas de fase aguda. Conclusión: En nuestra población, el SDRC de miem bros inferiores predomina en mujeres de edad media. La DMO es un método que permite cuantificar la pérdida ósea y la respuesta al tratamiento. Los bifosfonatos son una buena opción terapéutica para el control de síntomas. Son necesarios futuros estudios de naturaleza prospectiva y aleatorizada para confirmar nuestros resultados.

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.

Persistent bilateral atypical femoral fractures in an antiresorptive-naïve Singaporean Chinese patient with Graves’ Disease / Journal of the ASEAN Federation of Endocrine Societies

@#Atypical femoral fractures (AFFs) are rare adverse effects of bisphosphonate therapy. We report an unusual case of bilateral diaphyseal AFFs in an antiresorptive-naïve Singaporean Chinese female with Graves’ disease. She presented with complete right AFF requiring surgical fixation, and persistent left incomplete AFF for over four years. Femoral bowing, varus femoral geometry, and ethnic influence likely contributed to the AFFs’ formation. This case may provide insights into the pathogenesis of AFFs in high-risk Asian populations.

Efficacy and safety of denosumab versus bisphosphonates in the treatment of osteoporosis：a meta-analysis / 中国药房

OBJECTIVE To systematically evaluate the efficacy and safety of denosumab versus bisphosphonates in the treatment of osteoporosis， and to provide evidence-based reference for clinical treatment. METHODS Randomized controlled trials （RCTs） about denosumab （trial group） versus bisphosphonates （control group） in the treatment of osteoporosis were retrieved from PubMed， Embase， Medline， the Cochrane Library， Chinese Journal Fulltext Database， Chinese Science and Technology Journal Database， Wanfang database from January 2012 to December 2022. After the data extraction of included clinical studies， the quality of included studies was evaluated with Cochrane Handbook for Systematic Review 5.1.0， and meta-analysis was performed by using RevMan 5.3 software. RESULTS A total of 6 RCTs were included， involving 3 145 patients. Meta-analysis showed that the improvement rate of lumbar bone mineral density （BMD） [MD＝1.78， 95%CI（1.13， 2.43）， P＜0.000 01]， femoral neck BMD [MD＝1.26， 95%CI （1.08， 1.45）， P＜0.000 01] and total hip BMD [MD＝1.16，95%CI（0.93，1.39），P＜0.000 01] in trial group were significantly better than control group. C-terminal telopeptide of type Ⅰ collagen after 6 months [MD＝－0.09， 95%CI （－0.16， －0.02）， P＝0.01] and N-terminal propeptide of type Ⅰ collagen after 12 months [MD＝－9.07， 95%CI （－11.22， －6.92）， P＜ 0.001] in trial group were significantly higher than control group. There was no statistical difference in the fracture incidence rate after 12 months [OR＝1.02， 95%CI （0.67，1.54）， P＝0.92] and the incidence of adverse reaction [OR＝0.99， 95%CI （0.67，1.46）， P＝0.97] between 2 groups. CONCLUSIONS Denosumab has more advantages in improving BMD and bone metabolism， compared with bisphosphonates.

Osteonecrosis of the jaw induced by arsenic trioxide therapy in acute promyelocytic leukemia patient: a case report and literature review / 口腔疾病防治

Objective @#To investigate the etiology, clinical manifestations, treatment and prevention of jaw necrosis caused by arsenic trioxide to provide a reference for clinical diagnosis and treatment. @*Methods@#To analyze the clinical data and related literature of patients with jaw necrosis caused by acute promyelocytic leukemia treated with arsenic trioxide@*Results@#We report a case of jaw necrosis caused by the use of arsenic trioxide (10 mg once a day for one month) during the treatment of acute promyelocytic leukemia. About 20 days after treatment, the patient developed right maxillary pain accompanied by gingival redness and swelling and mucosal ulcer, 14-17 teeth had buccal and palatal alveolar bone exposed, gingival mucosa was missing, gingival tissue was damaged to the bottom of vestibular groove, and palatal soft tissue was damaged to 5-8 mm of palatal suture. Due to the unstable condition of acute promyelocytic leukemia, the patient was given conservative treatment such as oral vitamin and Kangfuxin liquid gargle to keep his mouth clean. Drug induced jaw necrosis reported in the literature can be caused by bisphosphonates. Arsenic trioxide can also cause local jaw necrosis. Clinically, it is often manifested as long-term wound nonunion, pus, alveolar bone or jaw bone exposure, dead bone formation, accompanied by pain, loose teeth, facial swelling and other symptoms. Anti inflammation, debridement and surgical removal of dead bone are commonly used treatment methods.@*Conclusion @# In clinical practice, we should be alert to drug-induced jaw necrosis and strengthen prevention.

Evaluation of trabecular bone changes according to the type of prosthesis in patients using bisphosphonates: a retrospective study

Abstract The objective of the study was to retrospectively compare the fractal size values calculated in the trabecular bone according to the type of complete removable denture, removable partial denture, and partial fixed prosthesis between patients using bisphosphonates and healthy patients, retrospectively. Panoramic radiographs of a total of 200 patients, (100 using bisphosphonates,100 control group), were taken from the right and left molar regions before and after treatment with 72 × 72 pixels. The fractal dimension (FD) was computed by using ImageJ Software using the box-counting method on the images obtained. There was an interaction effect between the trabecular bone change-patient group-the type of prosthesis used and the parameters of the area (p < 0.05). In patients using complete removable dentures and removable partial dentures in the maxilla and mandibula in the molar region, a greater decrease in FD values was observed in the control group than in the patient group using bisphosphonates. An increase in FD values over time was observed in the patient group using bisphosphonates with partial fixed maxillary and mandibular prostheses compared to the control group. Partial fixed prostheses should be preferred primarily instead of complete removable or removable partial dentures in patients using bisphosphonates to prevent osteonecrosis due to dental trauma.

Risk factors for medication-related osteonecrosis of the jaw and salivary IL-6 IN cancer patients / Fatores de risco para osteonecrose dos maxilares relacionada à medicação e níveis salivares de IL-6 em pacientes com câncer

Abstract Introduction Medication-related osteonecrosis of the jaws is a severe complication of the use of antiresorptive and antiangiogenic therapy, with limited treatment options and great impact on patient's quality pf life. Objective The aim of this study was to assess the risk factors associated with medication-related osteonecrosis of the jaws in oncologic patients undergoing bisphosphonate treatment. In addition, salivary levels of interleukin-6, IL-6, were measured to investigate their association with severity and risk of medication-related osteonecrosis of the jaws. Methods Case-control study with 74 patients with bone metastases from solid tumors and multiple myeloma was included. Patients were divided into three groups: 1) those undergoing bisphosphonate treatment with medication-related osteonecrosis of the jaws; 2) those undergoing bisphosphonate without medication-related osteonecrosis of the jaws; and 3) those with bisphosphonate pretreatment. The demographic and medical data of the patients were collected to assess risk. The clinical evaluation was performed to diagnose medication-related osteonecrosis of the jaws and unstimulated saliva was collected for quantification of IL-6. Results As result, it was observed that patients diagnosed with medication-related osteonecrosis of the jaws were submitted to higher number of bisphosphonate doses (p= 0.001) and monthly infusion protocol (p= 0.044; OR = 7.75). Patients who did not have routine followup with specialized dentists during therapy with bisphosphonate and smoking were associated with medication-related osteonecrosis of the jaws (p= 0.019; OR = 8.25 and p= 0.031; OR = 9.37 respectively). Group 1 had a higher frequency of treatment with chemotherapy and corticosteroids concomitant with bisphosphonate, and surgical dental procedures (p= 0.129). Salivary IL-6 levels showed no statistically significant difference between the groups (p= 0.571) or association with medication-related osteonecrosis of the jaws severity (p= 0.923). Conclusion A higher number of bisphosphonate cycles, monthly infusion protocol, no dental follow-up for oral health maintenance and smoking were associated with medication-related osteonecrosis of the jaws. Specialized dental follow up during bisphosphonate treatment has been shown to be an important factor in preventing this complication.

Resumo Introdução A osteonecrose dos maxilares relacionada à medicação é uma complicação grave da terapia antirreabsortiva e antiangiogênica, com opção de tratamento limitada e grande impacto na qualidade de vida do paciente. Objetivo Avaliar os fatores de risco associados à osteonecrose dos maxilares relacionada à medicação em pacientes oncológicos em tratamento com bifosfonato Além disso, os níveis salivares de interleucina-6 (IL-6) foram medidos para investigar sua associação com a gravidade e o risco de osteonecrose dos maxilares relacionada à medicação. Método Estudo caso-controle com 74 pacientes com metástases ósseas de tumores sólidos e mieloma múltiplo. Os pacientes foram divididos em três grupos: 1) em tratamento por bifosfonato com osteonecrose dos maxilares relacionada à medicação; 2) submetidos ao bifosfonato sem osteonecrose dos maxilares relacionada à medicação; e 3) pré-tratamento de bifosfonato. Os dados demográficos e médicos dos pacientes foram coletados para avaliar o risco. A avaliação clínica foi feita para diagnosticar osteonecrose dos maxilares relacionada à medicação e a saliva não estimulada foi coletada para quantificação da IL-6. Resultados Observou-se que os pacientes diagnosticados com osteonecrose dos maxilares relacionada à medicação foram submetidos a maior número de doses de bifosfonato (p = 0,001) e protocolo de infusão mensal (p = 0,044; OR = 7,75). Pacientes que não tiveram acompanhamento de rotina com dentistas especializados durante a terapia com bifosfonato e tabagismo foram associados ao osteonecrose dos maxilares relacionada à medicação (p = 0,019; OR = 8,25 e p = 0,031; OR = 9,37, respectivamente). O grupo 1 apresentou maior frequência de tratamento com quimioterapia e corticosteroides concomitantes ao bifosfonato e procedimentos odontológicos cirúrgicos (p = 0,129). Os níveis salivares de IL-6 não apresentaram diferença estatisticamente significante entre os grupos (p = 0,571) ou associação com a gravidade do osteonecrose dos maxilares relacionada à medicação (p = 0,923). Conclusão Maior número de ciclos de bifosfonato, protocolo de infusão mensal, ausência de acompanhamento odontológico para manutenção da saúde bucal e tabagismo foram associados ao osteonecrose dos maxilares relacionada à medicação. O acompanhamento odontológico especializado durante o tratamento demonstrou ser importante na prevenção dessa complicação.

Clinical features, diagnostic evaluation and responses to treatment in Paget's disease of bone in a center specialized in bone metabolism / Características clínicas, evaluación diagnóstica y respuestas al tratamiento de la enfermedad de Paget ósea en un centro especializado en metabolismo óseo

Abstract The epidemiology of Paget's disease of bone (PDB) has changed in the last years but there is no update data on its clinical presentation, diagnosis and management in Latin America. Our aim was to describe its clinical features, diagnostic evaluation and responses to treatment in a group of PDB patients treated between June 2012 and December 2019 in an institution specialized in bone diseases, in Buenos Aires, Argentina. The frequency of PDB (180/10 714) was 1.68%. Median age was 67 (range 39-97) years and 59.5% were women. Most patients were asymptomatic (58.6%) and had monostotic disease (54.3%). Favorable responses were obtained in all patients who were treated with zoledronate (n = 36), in 10 out of 14 treated with pamidronate, in 9 out of 10 who received intravenous ibandronate and in 12 out of 13 who received oral bisphosphonates. The response rates were not significantly different when we compared monostotic vs. polyostotic disease. Among the biochemical parameters, mean values of bone specific and total alkaline phosphatase, and C-terminal cross-linked telopeptide of type I collagen decreased significantly after treatment with bisphosphonates. It seems that our results reflect the change in PDB epidemiology towards a more indolent disease. In the future, this would probably allow physicians to use lower doses of bisphosphonates than the ones historically recommended for these patients.

Resumen La epidemiología de la en fermedad de Paget ósea (EPO) ha cambiado en los últimos años. Son necesarios datos actualizados sobre su forma de presentación clínica, diagnóstico y tratamiento en nuestra región. Nuestro objetivo fue describir las características clínicas, evaluación diagnóstica y respuestas al tratamiento de un grupo de pacientes con EPO en un centro especializado en salud ósea de Buenos Aires, Argentina. Se evaluaron todos los pacientes que fueron atendidos en nuestra institución por enfermedades óseas entre junio de 2012 y diciembre de 2019. La frecuencia de EPO (180/10 714) fue de 1.68%. La mediana de edad fue de 67 (rango 39-97) años. El 59.5% eran mujeres. La mayoría se encontraba asintomático (58.6%) y tenían enfermedad monostótica (54.3%). Se objetivaron respuestas favorables en todos los que recibieron zoledronato (n = 36), en 10 de 14 pacientes que recibieron pamidronato, en 9 de 10 que utilizaron ibandronato endovenoso y en 12 de 13 con bifosfonatos orales. Los porcentajes de respuesta no variaron significativamente entre pacientes con formas monostóticas y poliostóticas. Entre los parámetros bioquímicos, los valores de fosfatasa alcalina total y ósea y de β cross-laps disminuyeron significativamente luego del tratamiento con bifosfonatos. Nuestros resultados reflejarían un cambio en la epidemiología de la EPO hacia una forma de presentación más indolente. Esto permitiría probablemente el uso de dosis más bajas de bifosfonatos que las históricamente recomendadas para estos pacientes.

Osteonecrosis mandibular: hallazgos clínicos e imagenológicos en un paciente tratado con denosumab / Mandibular osteonecrosis: clinical and imaging findings in a patient treated with denosumab

Introducción: La administración de bifosfonatos y medicamentos antiangiogénicos en pacientes con cáncer es un esquema terapéutico usual en oncología. Existen reportes de osteonecrosis de los maxilares en pacientes sometidos a este esquema de tratamiento, luego de realizar un procedimiento dental invasivo. Objetivo: A partir de las características clínicas e imagenológicas de la patología, ilustrar al odontólogo sobre los medicamentos para el tratamiento del cáncer, susceptibles de generar osteonecrosis de los maxilares. Presentación de caso: Paciente masculino de 89 años, con cáncer de próstata tratado con denosumab, que desarrolló osteonecrosis del maxilar inferior posterior a una extracción dental. Es de vital importancia que el odontólogo identifique los medicamentos, factores de riesgo y las medidas para minimizar el riesgo de osteonecrosis de los maxilares en pacientes susceptibles(AU)

Introduction: The administration of bisphosphonates and antiangiogenic drugs in cancer patients is a usual therapeutic scheme in oncology. There are reports of osteonecrosis of the jaws in patients undergoing this treatment scheme, after performing an invasive dental procedure. Objective: Show the dentist from the clinical and imaging characteristics of the pathology on the drugs for the treatment of cancer sensitivity to generate osteonecrosis of the jaws. Case presentation: An 89-year-old male patient with prostate cancer treated with denosumab developed osteonecrosis of the lower jaw after tooth extraction. It is vitally important that the dentist identifies medications, risk factors and measures to minimize the risk of osteonecrosis of the jaws in sensitivy patients(AU)

Osteonecrosis de los Maxilares, Puesta al Día

RESUMEN: La osteonecrosis también conocida como una necrosis avascular del hueso, es una condición degenerativa producida por la pérdida en la irrigación sanguínea, debido a la toxicidad directa en los tejidos óseos provocadas por quimioterapia, radioterapia, daño térmico, fumar y en la última década con la aparición de medicamentos como los bifosfonatos (BF), denosumab y medicamentos antigiogénicos, con los cuales hemos ido conociendo más sobre esta patología. La principal hipótesis de la fisiopatología de esta enfermedad es la inhibición de la angiogénesis, pero también se considera como hipótesis la toxicidad de los tejidos blandos o la disfunción adquirida de la inmunidad. En el año 2003 fue relatada por primera vez la relación entre BF y osteonecrosis maxilar (ONM). Ese mismo año fue descrito que pacientes con mieloma múltiple que recibían pamidronato podrían desarrollar necrosis avascular de los maxilares. Otras publicaciones informaban sobre pacientes que requerían tratamiento para necrosis ósea intra-oral de ocurrencia espontánea después de extracciones dentales o trauma oral. La primera denominación a esta patología fue (BRONJ) por sus siglas en inglés, se refería a ONM relacionada a BF. En 2014 la Asociación Americana de Cirujanos Orales y Maxilofaciales (AAOMS) publicó una nueva definición (position paper) renombrándolo como MRONJ (osteonecrosis de los maxilares relacionada a medicamentos) ONMRM. El rol en la identificación de pacientes con riesgo de ONMRM es fundamental. Los estudios han demostrado que el riesgo de desarrollar la afección se puede reducir sustancialmente si los pacientes son evaluados por un profesional dental y se toman medidas preventivas. La presente revisión narrativa realiza un recorrido desde la historia, los medicamentos involucrados, y diferentes estrategias de tratamientos propuestos, haciendo hincapié en la conducta que debemos seguir los cirujanos dentistas para enfrentar estos casos de forma temprana y prevenir su evolución.

ABSTRACT: Osteonecrosis is also known as avascular necrosis of the bone, it is a degenerative condition produced by the loss of blood flow, due to direct toxicity in the bone tissues caused by chemotherapy, radiotherapy, thermal damage, smoking and in the last decade with the arrival of drugs such as bisphosphonates (BP), denosumab and antigiogenic drugs we have been learning more about this pathology. The main hypothesis of the pathophysiology of this disease is the inhibition of angiogenesis, but soft tissue toxicity or acquired immunity dysfunction are also considered as hypotheses. In 2003, the relationship between BP and osteonecrosis of the jaws (ONJ) was reported for the first time. In the same year it was described that multiple myeloma patients receiving pamidronate could develop avascular necrosis of the jaws. Other publications reported about patients requiring treatment for spontaneously intra-oral bone necrosis after dental extractions or oral trauma. The first name for this pathology was (BRONJ) for its English acronym, it referred to ONJ related to BF. In 2014 the American Association of Oral and Maxillofacial Surgeons (AAOMS) published a new definition (position paper) renaming it MRONJ (drug-related osteonecrosis of the jaws) ONMRM. The role of identifying patients at risk of ONMRM is fundamental. Studies have shown that the risk of developing the condition can be substantially reduced if patients are evaluated by a dental professional and preventive measures are taken Exposure of bone or fistula that can be probed down to the bone in the maxillofacial region that persists for more than 8 weeks, with these conditions it is considered that there is a diagnosis of ONMRM This narrative review takes a journey from history, the drugs involved, and different proposed treatment strategies, emphasizing the behavior that dental surgeons must follow to face these cases early and prevent their evolution.

Atypical femoral fractures due to the use of bisphosphonates: epidemiologic study in a tertiary hospital / Fraturas atípicas de fêmur por uso de bifosfonatos: estudo epidemiológico em um hospital terciário

ABSTRACT Objective: Show the relationship between atypical femoral fractures and prolonged use of bisphosphonates and analyze the limit of its beneficial use. Methods: Retrospective cohort study (level of evidence 2B). From Atypical fracture cases, patients who used bisphosphonates were selected and the time period of their use was analyzed. Additionally, the variables sex, age, and the side most affected were studied. Results: Nine atypical femur fractures were found, all associated with the use of bisphosphonates. The average period of use of this medication was nine years (minimum of three years; maximum of 14 years). The patients' mean age was of 78 years (69-88 years) and all were women, with the right member being the most affected. Conclusion: The use of bisphosphonates to prevent osteoporotic fractures has been increasingly frequent and, when used for a prolonged period, it has been related to atypical fractures. Further scientific studies on doses, maximum periods of treatment, and risk-benefit in the indication of these medications are needed to assist in therapeutic management for each case. Level of Evidence II, Retrospective Study.

RESUMO Objetivo: Demonstrar relação entre as fraturas atípicas de fêmur e o uso prolongado de bifosfonatos, descrever sua incidência e analisar até qual momento o seu uso é benéfico. Métodos: Estudo de coorte retrospectivo (nível de evidência 2B). Análise de 151 prontuários de pacientes com diagnóstico de fratura de fêmur em um hospital terciário, no período de janeiro de 2013 a dezembro de 2018. Foram selecionados os casos de fraturas atípicas e, dentre esses, os que faziam uso de bifosfonatos e o tempo de utilização. Ademais, foram estudadas as variáveis sexo, idade e lado mais acometido. Resultados: Constatadas 9 fraturas atípicas de fêmur, todas associadas ao uso de bifosfonatos. O período médio de uso dessa medicação foi de 9 anos (mínimo - 3 anos; máximo - 14 anos). A idade média dos pacientes foi de 78 anos (69-88 anos) e ocorrência unicamente em mulheres, tendo como membro mais acometido o direito. Conclusão: O uso dos bifosfonatos na prevenção de fraturas osteoporóticas tem sido cada vez mais frequente e relacionado às fraturas atípicas, quando empregado por tempo prolongado. A coleta de mais informações científicas que estudem doses, períodos máximos de tratamento e risco-benefício na indicação dessas medicações é essencial para auxiliar no manejo terapêutico apropriado para cada caso. Nível de Evidência II, Estudo Retrospectivo .

Knowledge of dentistry students on bisphosphonate-related osteonecrosis of the jaw / Conhecimento de alunos do curso de Odontologia sobre osteonecrose dos maxilares relacionada ao uso de bisfosfonatos

Objective: Bisphosphonates are anti-resorptive drugs used in the control and treatment of calcium and bone metabolism disorders. Despite their high clinical efficacy, these drugs have been associated with bisphosphonate-related osteonecrosis of the jaw. The goal of this study is to evaluate the knowledge of final year undergraduate dentistry students on bisphosphonate-related osteonecrosis of the jaw. Material and Methods: A sample of 100 students from private institutions in the state of São Paulo was invited to complete a questionnaire relating to bisphosphonates and the risk factors associated with the development of osteonecrosis of the jaws. Results: 66% of the students did not recognize any bisphosphonate (p=0.0019) and 79% did not recognize their trademark names (p<0.0001). 60% of the students recognized osteonecrosis of the jaws as a side effect of bisphosphonates (p<0.0001) and 56% identified at least one risk factor associated with the drug that may contribute to the side effect (p<0.0001). 66% of the students stated that their course did not provide any lectures on the topic (p<0.0001). Conclusion: The knowledge of dentistry students about bisphosphonates and bisphosphonate-related osteonecrosis of the jaw is variable. This may be related to an inadequate discussion of this topic during their undergraduate studies(AU)

Objetivo: Os bisfosfonatos são medicamentos antirreabsortivos utilizados no controle e tratamento de desordens do cálcio e do metabolismo ósseo. Apesar da elevada eficácia clínica, a terapia com estes medicamentos tem sido associada a uma importante complicação denominada de osteonecrose dos maxilares relacionada ao uso de bisfosfonatos. O objetivo deste estudo é avaliar conhecimento sobre a osteonecrose dos maxilares relacionada ao uso de bisfosfonatos entre os alunos do último ano do curso de graduação de Odontologia. Material e Métodos: Uma amostra de 100 alunos de instituições privadas do estado de São Paulo foi convidada a responder um questionário sobre as principais informações dos bisfosfonatos e fatores de risco associados com o desenvolvimento da osteonecrose dos maxilares. Resultados: Os 100 questionários foram respondidos: 66% dos estudantes não reconheceram algum bisfosfonato (p=0,0019), 79% não reconheceram seus nomes de marcas comerciais (p<0,0001); 60% dos alunos reconheceram a osteonecrose dos maxilares como um efeito colateral dos bisfosfonatos (p<0,0001) e 56% apontaram pelo menos um fator de risco associado com o medicamento que pode causar o desenvolvimento do efeito colateral (p<0,0001); 66% dos estudantes afirmaram que o curso não forneceu alguma aula abordando esta temática (p<0.0001). Conclusão: O grau de conhecimento dos alunos de Odontologia sobre bisfosfonatos e osteonecrose dos maxilares relacionada ao uso de bisfosfonatos é variável e está relacionado com a pouca discussão deste tema durante a graduação(AU)

Tratamiento de la osteonecrosis de los maxilares asociada a medicamentos: Enfoque médico-quirúrgico de estadios II y III

Resumen Introducción: La osteonecrosis de los maxilares asociada a medicamentos (OMAM) se define como la presencia de hueso necrótico expuesto de los maxilares en pacientes con historia de tratamiento farmacológico antirresortivo o antiangiogénico. Se describen diferentes estadios se severidad, con tratamiento conservador para estadios 0 y I, y tratamiento médico-quirúrgico para II-III. Objetivo: Describir los factores desencadenantes, opciones de tratamiento médico-quirúrgico y resultados en pacientes con OMAM estadios II-III. Material y Método: Estudio retrospectivo, descriptivo, de pacientes diagnosticados con OMAM estadios II y III que requirieron manejo médico-quirúrgico en la Red de Salud UC-Christus entre los años 2007 y 2018. Resultados: Todos los pacientes presentaron historia de tratamiento con bifosfonatos intravenosos. La mayoría de los registros de seguimiento de pacientes estuvo disponible para su análisis. El tratamiento consistió en aseo quirúrgico, decorticación y secuestrectomía. Se reportó disminución de la sintomatología con resolución parcial en la mitad de los casos y cierre completo de la exposición ósea en los restantes. Conclusión: Sugerimos que el tratamiento médico-quirúrgico en pacientes con OMAM en etapas II y III es efectivo en términos de disminución de sintomatología y control de infección. Sin embargo, es necesario realizar nuevos estudios prospectivos, con mayor cantidad de pacientes y tiempo de seguimiento.

Abstract Introduction: Medication-associated osteonecrosis of the jaws (MRONJ) is defined as the presence of exposed necrotic bone of the jaws in patients with a history of antiresorptive or antiangiogenic drug treatment. Different stages of severity are described, with conservative treatment for stages 0 and I, and medical-surgical treatment for II-III. Aim: To describe the triggers, medical-surgical treatment options and outcomes in patients with stage II-III MRONJ. Material and Method: Retrospective, descriptive study of patients diagnosed with MRONJ stages II and III that required medical-surgical management in the UC-Christus Health Network between 2007 and 2018. Results: All patients had a history of treatment with intravenous bisphosphonates. Most of the patient follow-up records were available for analysis. Treatment consisted of surgical grooming, decortication, and sequestrectomy. A decrease in symptoms was reported with partial resolution in half of the cases, and complete closure of bone exposure in the remainder. Conclusion: We suggest that medical-surgical treatment in patients with MRONJ in stages II and III is effective in terms of reducing symptoms and controlling infection. However, it is necessary to carry out new prospective studies, with a greater number of patients and follow-up time.

Fracturas atípicas de fémur, un evento adverso infrecuente de los bisfosfonatos en oncología. Reporte de caso / Atypical femur fractures, a rare adverse event of bisphosphonates in oncology: Case report

Resumen Los bisfosfonatos constituyen uno de los pilares fundamentales en el manejo de la morbilidad ósea de los pacientes con varios tipos de tumores sólidos (1, 3). Sin embargo, a pesar de la experiencia que tenemos por su uso desde hace décadas, existen eventos adversos como las fracturas atípicas (FA) que por su baja frecuencia pueden pasar desapercibidas y no recibir un manejo adecuado. Existen pocos reportes en la literatura de FA en el manejo de pacientes con cáncer. Se presenta un caso en el cual una paciente con un tumor metacrónico de mama con metástasis ósea al debut, actualmente en remisión, presenta una FA de fémur tras recibir bisfosfonatos durante 8 años.

Abstract Bisphosphonates are one of the fundamental pillars in the treatment of bone morbidities in patients with different types of solid tumors.1-3 However, despite the experience that we have accumulated during decades, there are adverse events such as atypical fractures (AF) that due to their low frequency can go unnoticed and might not receive adequate management. There are few reports in the literature about AF in cancer treatments. We present a case of a patient with metachronous breast cancer and bone metastases at initial diagnosis, currently in remission, who presents AF of the femur after receiving bisphosphonates for 8 years.

Hipercalcemia en paciente pediátrica con disgerminoma ovárico: a propósito de un caso / Hypercalcemia in a pediatric patient with ovarian dysgerminoma: A case report

La hipercalcemia asociada a tumores malignos es una entidad poco frecuente en pediatría (0,5-1,3 % de los cánceres pediátricos). Es causada por diferentes mecanismos fisiopatológicos y los síntomas de presentación suelen ser inespecíficos, pero potencialmente graves. Presentamos un caso clínico de una paciente de 12 años con diagnóstico de disgerminoma ovárico bilateral. La enfermedad se presentó con hipercalcemia grave, tratada con hiperhidratación asociada a diuréticos de asa, bifosfonatos y, por último, la resección quirúrgica del tumor, que permitió la resolución definitiva del cuadro. A pesar de tratarse de un trastorno hidroeléctrico poco habitual en pediatría, dada la potencial gravedad de la hipercalcemia, es importante la detección y el tratamiento tempranos, con el fin de evitar complicaciones en el corto y el largo plazo

Hypercalcemia associated with malignant tumors is a rare entity in pediatrics (0.5-1.3 % of pediatric cancers). It responds to different pathophysiological mechanisms and the typical symptoms shown are usually nonspecific, but potentially serious. We present a clinical case of a 12-year-old patient with a bilateral ovarian dysgerminoma who was diagnosed with severe hypercalcemia at the onset, which required hyperhydration associated with loop diuretics, bisphosphonates and, eventually, the tumor resection surgery that allowed the final resolution of the clinical picture.Despite being a rare hydroelectric disorder in pediatrics, given the potential severity of hypercalcemia, early detection and treatment are important in order to avoid potential short- and long-term complications.

Efecto sinérgico de un bifosfonato con vitamina D / Synergic effect of a biphosphonate with vitamin D

Introducción: Los bifosfonatos son considerados como un grupo de fármacos de gran utilidad en el tratamiento de enfermedades del tejido óseo ya que promueven su resorción. Han sido la primera línea para el tratamiento de la osteoporosis, enfermedad de Paget, mieloma múltiple e hipercalcemia maligna. Por su parte, la vitamina D es un nutriente esencial cuya función principal es la homeostasis de calcio (Ca+2) y fosfato (P4 3-). Objetivo: Describir los aspectos moleculares y farmacológicos de la acción de un bifosfonato (alendronato sódico) y la vitamina D, por los cuales potencian mutuamente sus efectos en enfermedades óseas. Métodos: Fueron seleccionadas las referencias más actualizadas que abordaran aspectos relevantes acerca del alendronato y la vitamina D. Se consultaron las bases de datos de PubMed, Uniprot y Protein Databank. Conclusiones: El sinergismo entre alendronarto y vitamina D generan efectos benéficos en el tejido óseo. Sin embargo, existen efectos colaterales que pueden afectar a otros tejidos, por lo que su uso debe ser controlado(AU)

Introduction: Biphosphonates are considered to be a group of very useful drugs used to treat osseous tissue conditions, since they foster resorption. They are first line in the treatment of osteoporosis, Paget's disease, multiple myeloma and malignant hypercalcemia. Vitamin D, on the other hand, is an essential nutrient whose main function is calcium (Ca+2) and phosphate (P4 3-) homeostasis. Objective: Describe the molecular and pharmacological aspects of the action of a biphosphonate (alendronate sodium) and vitamin D on osseous diseases. Methods: A selection was made of the most updated references about relevant aspects of alendronate and vitamin D. The databases consulted were Pubmed, Uniprot and Protein Databank. Conclusions: The synergy between alendronate and vitamin D generates beneficial effects on osseous tissue. However, their use should be controlled, since side-effects may affect other tissues(AU)

Caracterización clínico-terapéutica de pacientes diagnosticados con Osteonecrosis en los maxilares relacionada con medicación / Clinical and therapeutic characterization of patients diagnosed with medication-related osteonecrosis of the jaws

Introducción: La osteonecrosis en los maxilares por medicación es una afección asociada al tratamiento con bifosfonatos, antireabsortivos y antiangiogénicos. Objetivo: Caracterizar clínica y terapéuticamente los pacientes diagnosticados de Osteonecrosis en los Maxilares relacionada con medicación. Material y Método: Se realizó una serie de casos de 19 pacientes, la totalidad de los diagnosticados con la entidad en el Servicio de Cirugía Maxilofacial. Facultad de Estomatología Raúl González Sánchez, enero 2018-enero 2019. Se identificó severidad, factores de riesgo y se estandarizó tratamiento que incluyó la curación con aceite ozonizado y la aplicación de láser infrarrojo. Se evaluó el tratamiento a los 90 días. Se operacionalizaron las variables: sexo, tipo de medicación, vía y tiempo de administración, localización y evaluación al tratamiento. Resultados: La edad promedio de los pacientes fue 69±8,5 años, un 52,63 por ciento fueron masculinos, el zolendronato fue el agente mas asociado en el 78,95 por ciento de los casos, la enfermedad periodontal fue el factor local preponderante (57,89 por ciento), la localización mandibular postero lateral y el estadio evolutivo 2 predominaron en el 63,16 por ciento y 52,63 por ciento de las lesiones. El 78,94 por ciento de los casos presentó evolución satisfactoria a los 90 días. Conclusiones: La medicación con bifosfosfonatos parenterales predominantemente con el zolendronato, fue la causa principal de las osteonecrosis, las cuales prevalecieron en el sector postero lateral de mandíbula y con el estadio 2. La variante de tratamiento de curación con aceite ozonizado e irradiación con láser fue la más implementada. Los valores de lesiones resueltas y mejoradas a los 90 días fueron satisfactorios(AU)

Introduction: Medication-related osteonecrosis of the jaws is an affection associated with the treatment with bisphosphonates, antiresorptive agents or antiangiogenic medications. Objective: To perform a clinical and therapeutic characterization of patients with the diagnosis of medication-related osteonecrosis of the jaws. Material and Method: A case series of a total of 19 patients with the diagnosis of medication-related osteonecrosis of the jaws was carried out in the Department of Dental and Maxillofacial Surgery of ¨Raúl González Sánchez¨ Dental School of Havana from January 2018 to January 2019. The severity and risk factors were identified and the treatment including the healing with ozone oil and the application of infrared laser was standardized. The patients were evaluated in the 90 days after treatment. The operationalization of variables included: sex, type of medications, ways and time of administration, localization, and evaluation of treatment. Results: The average age of patients was 69±8,5 years and 52,63 percent of them were male. Zolendronate was the most associated agent in 78,95 percent of cases. Periodontal disease was the most identified local factor (57, 89 percent). The posterolateral area of the mandible and stage 2 disease evolution predominated in 63,16 percent and 52, 63 percent of lesions, respectively. Also 78, 94 percent of cases had a satisfactory evolution in the 90 days after treatment. Conclusions: The administration of intravenous bisphosphonates, particularly Zolendronate, was the main cause of osteonecrosis. These lesions were mainly located in the posterior lateral area of the mandible and presented stage 2 disease evolution. Healing with ozone oil and application of infrared laser was the most implemented alternative treatment. The values of resolved and improved lesions were satisfactory in the 90 days after treatment(AU)

VIH y salud ósea / HIV and bone health

Con el advenimiento de la terapia antirretroviral, el pronóstico y la sobrevida de los pacientes infectados con el virus de la inmunodeficiencia humana (VIH) han cambiado de manera radical, por lo cual en la actualidad se evidencia un aumento en el riesgo de padecer enfermedades no relacionadas con el VIH como, por ejemplo, la osteoporosis. La disminución de la densidad mineral ósea (DMO) se observa en el 40-90% de las personas infectadas por el VIH, con una prevalencia de osteopenia y osteoporosis del 52 y 15%, respectivamente. Esta población de pacientes tiene un mayor riesgo de fracturas (60%) en comparación con personas no infectadas y un riesgo de fracturas vertebrales 2,3 veces mayor que en la población general. El tenofovir fumarato se asoció con un aumento de pérdida renal de fósforo e hiperparatiroidismo secundario. El efavirenz y los inhibidores de proteasas (IP) afectan el metabolismo de la vitamina D; actúan a nivel enzimático aumentando la expresión de la enzima CYP24 que lleva a producción de vitamina D inactiva. El FRAX es una herramienta sencilla y accesible, por lo que su uso está recomendado en pacientes con VIH. Además de las medidas higiénico-dietéticas, actividad física, calcio y vitamina D, el uso de bifosfonatos está indicado en el tratamiento de la osteoporosis en estos pacientes. (AU)

With the advent of antiretroviral therapy, the prognosis and survival of patients infected with the human immunodeficiency virus (HIV) have radically changed, which is why there is now evidence of an increased risk of suffering from diseases not related to HIV such as osteoporosis. The decrease in bone mineral density (BMD) is observed in 40-90% of people infected with HIV, with a prevalence of osteopenia and osteoporosis of 52 and 15%, respectively. This patient population has a 60% higher risk of fractures compared to uninfected people and a risk of vertebral fractures 2.3 times higher than in the general population. Tenofovir fumarate administration is associated with increased renal phosphorus loss and secondary hyperparathyroidism. Efavirenz and protease inhibitors (IP) affect the metabolism of vitamin D, they act at the enzymatic level by increasing the expression of the CYP24 enzyme that leads to the production of inactive vitamin D. The FRAX is a simple and accessible tool, so its use is recommended in patients with HIV and in addition to dietary hygiene measures, physical activity, calcium, and vitamin D, the use of bisphosphonates is indicated in the treatment of osteoporosis in these patients. (AU)