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Resumen: Introducción: los bifosfonatos se usan para el manejo de osteoporosis postmenopáusica con riesgo elevado de fractura, osteoporosis inducida por glucocorticoides, enfermedad de Paget e hipercalcemia; así como coadyuvante para manejo del hiperparatiroidismo. Los bifosfonatos se han asociado a efectos adversos previamente desconocidos dentro de los que se encuentran fracturas de fémur de trazo atípico. Objetivo: analizar la relación del antecedente de uso de bifosfonatos (BF) como factor de riesgo para presentar fracturas atípicas de fémur (FAF). Material y métodos: se incluyeron pacientes de 40 años o más de dos centros hospitalarios atendidos desde 2009 a 2018 por fractura de fémur. Se revisaron los estudios radiográficos de 441 registros, de los cuales se definió el sitio de fractura. Se analizaron las fracturas de fémur subtrocantéricas (FS) y diafisarias (FD) aplicando los criterios del segundo reporte de la American Society for Bone and Mineral Research para la definición de caso de FAF. Finalmente, se indagó el consumo de bifosfonatos en estos grupos para para estimar una medida de asociación. Resultados: de los 441 registros clínicos, 98 (22.2%) fueron del sexo masculino y 343 (77.7%) del femenino, con edad promedio de 77.8 (40-103) años. Se identificaron 59 FS/FD, de las cuales 53% (31 registros) fueron catalogadas FAF. El consumo de BF se determinó en 80.6% de pacientes con FAF y en 3.57% con FS/FD. El uso de BF se asoció significativamente con la presencia de FAF (OR: 112, p ≤ 0.000, IC 95%: 12.6-1001). Conclusiones: el uso de BF aumenta significativamente el riesgo de presentar FAF. Las FAF en pacientes que usaron BF se presentó tras un consumo mínimo de 24 meses.

Abstract: Introduction: bisphosphonates are used for the management of postmenopausal osteoporosis with high risk of fracture, glucocorticoid-induced osteoporosis, Paget's disease and hypercalcemia; as well as an adjuvant for the management of hyperparathyroidism. Bisphosphonates have been associated with previously unknown adverse effects, including atypical femur fractures. Objective: to analyze the relationship of the history of bisphosphonate (BF) use as a risk factor for presenting atypical femur fractures (AFF). Material and methods: patients aged 40 years or older from two hospital centers seen from 2009 to 2018 for femur fracture were included. The radiographic studies of 441 records were reviewed, from which the fracture site was defined. Subtrochanteric (SF) and diaphyseal (DF) femur fractures were analyzed applying the criteria of the second report of the American Society for Bone and Mineral Research for case definition of AFF. Finally, the consumption of bisphosphonates in these groups was investigated to estimate a measure of association. Results: of the 441 clinical records, 98 (22.2%) were male and 343 (77.7%) were female with a mean age of 77.8 (40-103) years. Fifty-nine FS/FD were identified, of which 53% (31 records) were categorized as AFF. BF use was determined in 80.6% of patients with AFF and 3.57% in FS/FD. BF use was significantly associated with the presence of AFF (OR: 112, p ≤ 0.000, CI 95%: 12.6-1001). Conclusions: BF use significantly increases the risk of presenting AFF. AFF in patients who used BF occurred after a minimum consumption of 24 months.

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INTRODUCTION: Bisphosphonate (BF) therapy is strongly related to the occurrence of medication-related osteonecrosis of the jaw (ONJ). However, no previous study has evaluated if there are sex-related differences on the ONJ establishment together with bone biomechanical alterations, and if they could have a synergy with the ZA treatment. MATERIALS AND METHODS: This study aimed to analyze the physicochemical properties of mineralized tissues in a zoledronate (ZA)-related osteonecrosis mouse model, by a 2 × 2-factorial design, considering sex (female/male) and treatment (ZA/Saline) factors (n = 8/group). After three ZA (1.0 mg/kg) or saline administrations (days 0, 7, 14), the lower left second molar was extracted (day 42). Further ZA administration (day 49) and euthanasia (day 70) were conducted. After confirmation of ZA-induced jaw necrosis (histologic and microtomographic analysis), spectroscopic and mechanical parameters were assessed. RESULTS: ZA-treated groups presented lower bone density due to impaired healing of tooth extraction socket. Sex-related alterations were also observed, with lower bone density in females. Regarding biomechanical parameters, sex and treatment exerted independent influences. ZA, although decreasing flexural modulus and yield stress, increases stiffness mainly due to a higher bone volume. Females show less resistance to higher loads compared to males (considering dimension-independent parameters). Additionally, ZA increases crystallinity in bone and dental structure (p < 0.05). In summary, although strongly related to osteonecrosis occurrence, ZA modifies bone and dental mineral matrix, improving bone mechanical properties. CONCLUSION: Despite sex-dependent differences in bone biomechanics and density, osteonecrosis was established with no sex influence. No synergistic association between sex and treatment factors was observed in this study.

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Objetivo: Este trabalho tem como propósito fornecer uma análise abrangente das características clínicas, etiológicas, radiográficas e histopatológicas da osteonecrose dos maxilares relacionada ao uso de medicamentos, além de abordar os métodos de diagnóstico, prevenção e estratégias terapêuticas. Materiais e métodos: foi realizada uma busca por artigos científicos publicados no período de 2015 a 2023, utilizando as bases de dados Scientific Electronic Library Online (SciELO), US National Library of Medicine (PubMed) e ScienceDirect. Conclusão: Embora infrequente, há um considerável potencial de ocorrência de osteonecrose dos maxilares em pacientes submetidos a terapia prolongada com medicamentos antirreabsortivos e antiangiogênicos, especialmente quando não são adotadas medidas preventivas adequadas. A implementação de práticas preventivas, a vigilância das condições bucais e a colaboração de uma equipe multidisciplinar são fundamentais para reduzir os riscos associados a essa condição patológica.(AU)

Objective: This work aims to provide a comprehensive analysis of the clinical, etiological, radiographic and histopathological characteristics of Medication-Related Jaw Osteonecrosis, in addition to addressing diagnostic methods, prevention and therapeutic strategies. Materials and methods: A search was carried out for scientific articles published between 2015 and 2023, using the Scientific Electronic Library Online (SciELO), US National Library of Medicine (PubMed) and ScienceDirect databases. Conclusion: Although infrequent, there is a considerable potential for osteonecrosis of the jaw to occur in patients undergoing prolonged therapy with antiresorptive and antiangiogenic medications, especially when adequate preventive measures are not adopted. The implementation of preventive practices, surveillance of oral conditions and the collaboration of a multidisciplinary team are essential to reduce the risks associated with this pathological condition.(AU)

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The increase in life expectancy of the world population has led to a concomitant increase in the prevalence of multiple myeloma (MM), a disease that usually affects the elderly population. Bone lesions are frequent in patients with this condition, demanding an early approach, from drug treatment, through radiotherapy to orthopedic surgery (prophylactic or therapeutic) with the objective of preventing or delaying the occurrence of fracture, or, when this event has already occurred, treat it through stabilization or replacement (lesions located in the appendicular skeleton) and/or promote stabilization and spinal cord decompression (lesions located in the axial skeleton), providing rapid pain relief, return to ambulation and resocialization, returning quality of life to patients. The aim of this review is to update the reader on the findings of pathophysiology, clinical, laboratory and imaging, differential diagnosis and therapeutic approach of multiple myeloma bone disease (MMBD).

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Abstract The increase in life expectancy of the world population has led to a concomitant increase in the prevalence of multiple myeloma (MM), a disease that usually affects the elderly population. Bone lesions are frequent in patients with this condition, demanding an early approach, from drug treatment, through radiotherapy to orthopedic surgery (prophylactic or therapeutic) with the objective of preventing or delaying the occurrence of fracture, or, when this event has already occurred, treat it through stabilization or replacement (lesions located in the appendicular skeleton) and/or promote stabilization and spinal cord decompression (lesions located in the axial skeleton), providing rapid pain relief, return to ambulation and resocialization, returning quality of life to patients. The aim of this review isto update the reader on the findings of pathophysiology, clinical, laboratory and imaging, differential diagnosis and therapeutic approach of multiple myeloma multiple myeloma bone disease (MMBD).

Resumo O aumento da expectativa devida da população mundial levou a incremento concomitante na prevalência de mieloma múltiplo (MM), patologia que geralmente afeta a população idosa. Lesões ósseas são frequentes nos portadores desta condição, demandando abordagem precoce, desde o tratamento medicamentoso, passando pela radioterapia até a cirurgia ortopédica (profilática ou terapêutica) com os objetivos de prevenir ou retardar a ocorrência de fratura, ou, quando este evento já ocorreu, tratá-la mediante estabilização ou substituição (lesões situadas no esqueleto apendicular) e/ou promover estabilização e descompressão medular (lesões situadas no esqueleto axial), proporcionando rápido alívio da dor, retorno à deambulação e ressocialização, devolvendo a qualidade de vida aos pacientes. O objetivo desta revisão é atualizar o leitor sobre a fisiopatologia, a clínica, exames laboratoriais e de imagem, diagnóstico diferencial e abordagem terapêutica da doença óssea no mieloma múltiplo (DOMM).

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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.

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Abstract This study evaluated the effect of photobiomodulation therapy (PBMT) with a red or infrared laser on the repair of post extraction sockets in rats administered alendronate (ALN). Forty male rats were randomly allocated into four groups: Control Group (CTR): subcutaneous administration of saline solution throughout the experimental period; Alendronate Group (ALN): subcutaneous administration of alendronate during the entire experimental period; Alendronate/Red Laser Group (ALN/RL): administration of ALN and irradiation with a GaAlAs laser (λ 660 nm); and Alendronate/Infrared Laser Group (ALN/IRL): administration of ALN and irradiation with a GaAlAs laser (λ 830 nm). The first lower molars were extracted 60 days after the beginning of the administration of the drugs. The PBMT was applied after tooth extraction (7 sessions with intervals of 48 hours between sessions). Thirty days after tooth extraction, the animals were euthanized. Micro-CT and histometric analysis were performed to assess the bone healing and soft tissue repair of the tooth socket. The ALN group presented with more bone than the CTR; however, most of this bone was necrotic. ALN does not affect the bone microarchitecture. On the other hand, PBMT with IRL enhances the bone density due to the increase in the number and reduction in the spacing of the trabeculae. The amount of vital bone and connective tissue matrix was higher in the ALN/RL and ALN/IRL groups than in the ALN and CTR groups. PBMT enhanced the healing of the post extraction sockets in rats subjected to ALN administration. Furthermore, IRL improved the new bone microarchitecture.

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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

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ABSTRACT Objective: To determine the level of scientific information of dental surgeons who carry out their professional activities in Brazil about antiresorptive drugs and indicated pharmacological procedures aiming at the prevention of osteonecrosis of the jaws and the therapy of drug sequelae that may occur, considering the time since graduation in Dentistry. Material and Methods: This is a quantitative cross-sectional study in which 339 dentists were consulted using the virtual questionnaire containing topics of personal nature, elements contained in the anamnesis carried out and knowledge about antiresorptive drugs, including indications, adverse effects and treatments applied. Chi-square and Fisher's exact tests were performed to analyze associations of data described by absolute and relative frequencies with professionals' time since graduation. All analyses were performed using the R software, with a 5% significance level. Results: Those who revealed to have graduated for more than five years with the highest academic degree were those who demonstrated maximum knowledge of antiresorptive drugs or revealed that, somehow, they had information about them (p<0.05). Conclusion: Dental surgeons in Brazil who have more than five years since graduation have more scientific information about antiresorptive drugs and pharmacological procedures, which can positively contribute to the prevention of osteonecrosis of the jaws and treatment of drug sequelae that may occur.

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INTRODUCTION: bisphosphonates are used for the management of postmenopausal osteoporosis with high risk of fracture, glucocorticoid-induced osteoporosis, Paget's disease and hypercalcemia; as well as an adjuvant for the management of hyperparathyroidism. Bisphosphonates have been associated with previously unknown adverse effects, including atypical femur fractures. OBJECTIVE: to analyze the relationship of the history of bisphosphonate (BF) use as a risk factor for presenting atypical femur fractures (AFF). MATERIAL AND METHODS: patients aged 40 years or older from two hospital centers seen from 2009 to 2018 for femur fracture were included. The radiographic studies of 441 records were reviewed, from which the fracture site was defined. Subtrochanteric (SF) and diaphyseal (DF) femur fractures were analyzed applying the criteria of the second report of the American Society for Bone and Mineral Research for case definition of AFF. Finally, the consumption of bisphosphonates in these groups was investigated to estimate a measure of association. RESULTS: of the 441 clinical records, 98 (22.2%) were male and 343 (77.7%) were female with a mean age of 77.8 (40-103) years. Fifty-nine FS/FD were identified, of which 53% (31 records) were categorized as AFF. BF use was determined in 80.6% of patients with AFF and 3.57% in FS/FD. BF use was significantly associated with the presence of AFF (OR: 112, p 0.000, CI 95%: 12.6-1001). CONCLUSIONS: BF use significantly increases the risk of presenting AFF. AFF in patients who used BF occurred after a minimum consumption of 24 months.

INTRODUCCIÓN: los bifosfonatos se usan para el manejo de osteoporosis postmenopáusica con riesgo elevado de fractura, osteoporosis inducida por glucocorticoides, enfermedad de Paget e hipercalcemia; así como coadyuvante para manejo del hiperparatiroidismo. Los bifosfonatos se han asociado a efectos adversos previamente desconocidos dentro de los que se encuentran fracturas de fémur de trazo atípico. OBJETIVO: analizar la relación del antecedente de uso de bifosfonatos (BF) como factor de riesgo para presentar fracturas atípicas de fémur (FAF). MATERIAL Y MÉTODOS: se incluyeron pacientes de 40 años o más de dos centros hospitalarios atendidos desde 2009 a 2018 por fractura de fémur. Se revisaron los estudios radiográficos de 441 registros, de los cuales se definió el sitio de fractura. Se analizaron las fracturas de fémur subtrocantéricas (FS) y diafisarias (FD) aplicando los criterios del segundo reporte de la American Society for Bone and Mineral Research para la definición de caso de FAF. Finalmente, se indagó el consumo de bifosfonatos en estos grupos para para estimar una medida de asociación. RESULTADOS: de los 441 registros clínicos, 98 (22.2%) fueron del sexo masculino y 343 (77.7%) del femenino, con edad promedio de 77.8 (40-103) años. Se identificaron 59 FS/FD, de las cuales 53% (31 registros) fueron catalogadas FAF. El consumo de BF se determinó en 80.6% de pacientes con FAF y en 3.57% con FS/FD. El uso de BF se asoció significativamente con la presencia de FAF (OR: 112, p 0.000, IC 95%: 12.6-1001). CONCLUSIONES: el uso de BF aumenta significativamente el riesgo de presentar FAF. Las FAF en pacientes que usaron BF se presentó tras un consumo mínimo de 24 meses.

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Abstract Medication-related osteonecrosis of the jaw (MRONJ) is characterized by bone exposure for more than eight weeks in patients who have used or been treated with antiresorptive or antiangiogenic drugs, without a history of radiation therapy or metastatic diseases in the jaws. Obesity is associated with changes in periodontal tissues and oral microbiota that are linked to bone alterations. This study aimed to analyze the influence of obesity on the development of bisphosphonate-induced osteonecrosis. The experiment randomly and simply divided 24 male Wistar rats (Rattus norvegicus) into four groups: healthy, with osteonecrosis, obese, and obese with osteonecrosis (n=6 per group). Osteonecrosis was induced through weekly intraperitoneal injection for eight weeks at a dose of 250 µg/kg of zoledronic acid in a 4 mg/5 mL solution, combined with trauma (exodontia). Obesity was induced through a high glycaemic index diet. Each group was qualitatively and quantitatively evaluated regarding the development of models and pathological anatomy of the lesions. The results were expressed in mean percentage and standard deviation and statistically analyzed using one-way analysis of variance (ANOVA) followed by Tukey's post-hoc test, with a significance level of 5% (p<0.05) to establish differences found between the groups. Animals in the osteonecrosis group and the obese with osteonecrosis group presented larger necrosis areas (averages: 172.83±18,19 µm2 and 290.33±15,77 µm2, respectively) (p<0,0001). Bone sequestration, hepatic steatosis, and increased adipocyte size were observed in the obese group (average: 97.75±1.91 µm2) and in the obese with osteonecrosis group (average: 98.41±1.56 µm2), indicating greater tissue damage in these groups (p<0,0001). All parameters analyzed (through histological, morphometric, and murinometric analyses) increased for the obese and obese with osteonecrosis groups, suggesting a possible influence of obesity on the results. However, further studies are needed to confirm the role of obesity in the possible exacerbation of osteonecrosis and understand the underlying mechanisms.

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Aim: This study aimed to systematically review existing literature regarding the association between dental procedures­such as tooth extractions and periodontal therapy­and occurrence of medication-related osteonecrosis of the jaw (MRONJ) in individuals using bone-modifying drugs. Methods: Search strategies were performed in PubMed, Scopus, Web of Science and Cochrane Library for a timeframe ending in December 2021. Study selection, data extraction and risk of bias were analyzed independently by two researchers. Three meta-analyses were performed, estimating the crude risk ratio (RR), the adjusted odds ratio (OR) and the adjusted hazard ratio (HR) for the association between tooth extraction and MRONJ. Results: Of the 1,654 studies initially retrieved, 17 were ultimately included. The majority of patients with MRONJ in these studies were female, with a mean age of 64 years. Zoledronic acid was the most commonly used drug among patients with MRONJ, and cancer was the most frequent underlying health condition. Regarding the performed meta-analyses, crude and adjusted analyses demonstrated that tooth extraction increased the risk for MRONJ by 4.28 (95% confidence interval [95%CI]: 1.73­10.58), the OR for MRONJ by 26.94 (95%CI: 4.17­174.17), and the HR for MRONJ by 9.96 (95%CI: 4.04­24.55). Conclusion: It was concluded that performing dental procedures, especially tooth extraction, in patients using bone-modifying drugs increased the risk of MRONJ occurrence and, therefore, should be avoided. Further studies, using adjusted data, are warranted

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BACKGROUND: The treatment of osteoporosis involves medications that reduce the risk of fractures, but some medications can decrease bone density. The aim was to identify the treatments, comorbidities, and prescriptions related to reducing bone mineral density in patients with osteoporosis. RESEARCH DESIGN AND METHODS: A cross-sectional study that identified patterns of anti-osteoporotic drug prescriptions for outpatient use and potentially inappropriate prescriptions for patients with osteoporosis based on the drug-dispensing database of 8.5 million people in Colombia. All patients ≥65 years with a diagnosis of osteoporosis were included. RESULTS: A total of 16,362 patients with osteoporosis were identified. They had a median age of 74.4 years, and 47.9% received anti-osteoporotic therapy, especially bisphosphonates (41.6%), and 86.5% received calcium and/or vitamin D supplement. 41.6% of those who had a history of bone fractures were prescribed anti-osteoporotic drugs. Potentially inappropriate prescriptions, especially corticosteroids at doses greater than 5mg prednisolone equivalent (4.4%), were found in 41.4% of cases and were more common in older patients and those with a history of fractures or with cardiovascular, digestive, neurological, psychiatric or neoplastic comorbidities. CONCLUSIONS: A significant proportion of patients had potentially inappropriate prescriptions, especially older patients, those with certain comorbidities, and those receiving comedication with antirheumatic drugs.

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La osteonecrosis de los maxilares (ONM) secundaria al consumo de medicamentos antirresortivos y antiangiogénicos es una patología oral que afecta el funcionamiento del organismo de los seres humanos no sólo a nivel bucal, sino que disminuye su calidad de vida y aumenta su morbilidad. La ONM se define como la presencia de hueso necrótico expuesto que puede ser explorado mediante una fístula en el territorio maxilofacial, que se mantiene durante un periodo mínimo de ocho se- manas. Los fármacos antirresortivos y antiangiogénicos son indicados a pacientes que presentan patologías osteometabólicas, cáncer, entre otras, de ahí la importancia de mantener una estrecha relación entre médico tratante-odontólogo-paciente. El propósito de este artículo es establecer un protocolo de cuidado oral básico y definir las funciones del médico tratante, cirujano dentista y cirujano maxilofacial mediante una revisión bibliográfica con el fin de crear una propuesta preventiva para el tratamiento de estos pacientes (AU)

Medication-related osteonecrosis of the jaw (MRONJ), secondary to the consumption of antiresorptive and antiangiogenic drugs is an oral pathology that affects the functioning of the human body, not only at the oral level, but also decreasing their quality of life and increasing their morbidity. MRONJ is defined as the presence of exposed necrotic bone that can be explored through a fistula in the maxillofacial territory, which is maintained for a minimum period of eight weeks. Antiresorptive and antiangiogenic drugs are indicated for patients with osteometabolic pathologies, cancer, among others. For the same reasons, the importance of maintaining a close relationship between the treating physician, dentist and patient. The purpose of this article is to establish a clinical guide for basic oral care and define the functions of the treating physician, dental surgeon and maxillofacial surgeon through a bibliographic review; in order to create a preventive proposal for the treatment of these patients (AU)

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Abstract The aim of this study was to evaluate the awareness of patients using bisphosphonates (BP) regarding their risks and benefits. Sixty-five patients using BP were included. Each participant completed a self-administered questionnaire consisting of 13 questions, including sociodemographic and general information on BP. Data were analyzed using descriptive statistics, and a binomial test was used to assess patient knowledge about BP, considering a 5% significance level. Fifty-nine (90.2%) patients were unaware or had never heard of BP drugs and only 3 (4.6%) knew their indications. Only 6 patients (9.2%) said they knew about the oral complications caused by BP. Sixty-three patients (96.9%) said they were not referred to the dentist before starting BP treatment. Patients using BP do not have satisfactory knowledge regarding the risks and benefits of BP. Physicians and dentists must be prepared to inform and counsel BP users about their adverse effects and possible risk factors. Our results emphasize the importance of public policies, whether individual or collective, to be taken to increase knowledge about BP to avoid medication-related osteonecrosis of the jaw.

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Introdução: O osso bovino inorgânico é o enxerto mais utilizado na Odontologia, tendo como desvantagem longo tempo de integração ao leito receptor. Os bifosfonatos têm sido utilizados para modular a quantidade e a qualidade do osso regenerado e diminuir o tempo de integração do enxerto. Objetivo: Avaliar o efeito do bifosfonato alendronato de sódio (ALN) 0,5%, associado ou não ao osso bovino inorgânico, na reparação de defeitos ósseos. Material e método: Dois defeitos ósseos foram confeccionados na calvária de 12 coelhos, sendo a cavidade esquerda/experimental preenchida com: GI = osso bovino inorgânico (Bio-Oss®); GII = Bio-Oss® + ALN 0,5%; GIII = ALN 0,5%; e a cavidade direita por coágulo sanguíneo (controle). Os animais foram mortos aos 60 dias pós-operatórios. Por meio de análise histomorfométrica calculou-se o percentual de osso neoformado e remanescente do biomaterial em relação à área total do defeito. Resultado: Osso neoformado: GI = 38,16 ± 15,44%; GII = 55,77 ± 16,75%; GII I = 60,28 ± 11,45%. Controle = 45,11 ± 11,09%. Remanescente do enxerto: GI = 7,02 ± 5,36% e GII = 16,59 ± 9,56%. Não houve diferença quanto ao percentual de osso neoformado entre os grupos (ANOVA p = 0,15512; teste de Tukey F = 2,089). O percentual de remanescente do enxerto também foi estatisticamente semelhante entre os grupos GI e GII (teste de Tukey F = 5,019). Conclusão: O uso tópico da solução de ALN 0,5% isoladamente ou associado ao osso bovino liofilizado não alterou o percentual de neoformação óssea nem a degradação dos grânulos do enxerto.

Introduction: Inorganic bovine bone is the most used graft in dentistry, with the disadvantage of long integration time into the receptor bed. Bisphosphonates have been used to modulate the quantity and quality of regenerated bone and decrease graft integration time. Objective: To evaluate the effect of alendronate sodium bisphosphonate (ALN) 0.5%, associated or not with Inorganic bovine bone, in the repair of bone defects. Material and method Two bone defects were made in the calvaria of 12 rabbits, and the left/experimental cavity was filled with: GI = Inorganic bovine bone (Bio-Oss®); GII = Bio-Oss® + 0.5% ALN; GIII = 0.5% ALN; and the right cavity/blood clot control. The animals were killed at 60 days after surgery. Through histomorphometric analysis, the percentage of newly formed bone and remnant biomaterial relative to the total area of the defect was calculated. Result: Neoformed bone: GI = 38.16 ± 15.44%, GII = 55.77 ± 16.75%; GIII= 60.28 ± 11.45%; Control=45,11 ± 11,09%. Graft remnant: GI = 7.02 ± 5.36% and GII = 16.59 ± 9.56%. There was no difference in the percentage of newly formed bone between the groups (ANOVA p = 0.15512; Tukey's test F = 2.089). The percentage of graft remnant was also statistically similar between groups GI and GII (Tukey's test F = 5019). Conclusion: Topical use of 0.5% ALN solution alone or associated with lyophilized bovine bone did not change the percentage of bone neoformation, nor the degradation of graft granules.

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Abstract Antiresorptive drugs operate in the bone metabolism modulation and are widely used in the treatment of bone metastases and bone losses related to hormonal deficiency. Although this therapy shows satisfactory results, there are adverse effects associated with its use, such as osteonecrosis of the jaws. Medication-related osteonecrosis of the jaws (MRONJ) is, therefore, a serious and challenging condition with important implications in dentistry. The aim was to conduct a narrative literature review on anti-resorptive drugs and their latest repercussions on the maxillary bones. The review was carried out through a bibliographic search using Decs/Mesh descriptors of interest, in Portuguese and English, in the PubMed, Virtual Health Library (VHL) and Scielo databases. After applying the inclusion and exclusion criteria, a total of 33 studies were selected for analysis. It can be noticed that therapy with anti-resorptive agents is complex, especially in dental practice, since MRONJ is a complication that is difficult to manage. Regarding the therapeutic options, these are divided into conservative, surgical or adjuvant therapy, however, there are no protocols in the literature, and there is no consistency regarding the indication of the suspension of the drug administration - "Drug Holiday". Thus, it is important that the multidisciplinary team seeks strategies that minimize complications and promote control over the use of these drugs. In addition, there is a need for investigations that contribute with guidelines for the management and control of adverse effects resulting from therapy with antiresorptive drugs. (AU)

Resumo As drogas antirreabsortivas atuam na modulação do metabolismo ósseo e são indicadas para o tratamento de metástases ósseas e perdas ósseas relacionadas à deficiência hormonal. Ainda que esta terapia apresente resultados satisfatórios, observam-se efeitos adversos associados ao seu uso, como a osteonecrose dos maxilares. A osteonecrose dos maxilares associada ao uso de medicamentos (OMAM) é, portanto, uma condição séria e desafiadora com implicações importantes na Odontologia. O objetivo foi realizar uma revisão narrativa de literatura sobre as drogas antirreabsortivas e suas respectivas repercussões nos ossos maxilares. A revisão foi realizada através de busca bibliográfica utilizando descritores Decs/Mesh de interesse, em português e inglês, nas bases de dados PubMed, Biblioteca Virtual de Saúde (BVS) e Scielo. Após aplicação dos critérios de inclusão e exclusão, um total de 33 trabalhos foram selecionados para análise. Pode-se constatar que a terapia com agentes antirreabsortivos é complexa, sobretudo na prática odontológica, visto que a OMAM é uma complicação de difícil manejo. Em relação às condutas terapêuticas para esta condição, divide-se em terapia conservadora, cirúrgica ou adjuvante, todavia, não existem protocolos validados na literatura, bem como não há consistência quanto à indicação do intervalo de suspensão da administração da droga - "Drug Holiday". Desse modo, é importante que a equipe multidisciplinar busque estratégias que minimizem as complicações e promovam o controle no uso dessas drogas. Além disso, nota-se a necessidade de realizar investigações que contribuam com diretrizes para o manejo e controle dos efeitos adversos decorrentes da terapia com medicamentos antirreabsortivos. (AU)

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BACKGROUND: Previous systematic reviews showed additional benefit of adjuvant bisphosphonates (BP) in the treatment of periodontitis. In contrast, it is unclear the effect of BP in patients with diabetes and smokers, its pooled effect when administered locally or systemically is also unknown. OBJECTIVES: This study aimed to systematically review the literature about the use of BP as adjuvant to nonsurgical scaling and root planning (SRP). METHODOLOGY: This study followed the PRISMA guideline. This study included randomized clinical trials that administered locally or systemically BPs as adjuvant for periodontal treatment. Five databases were used. Meta-analyses were performed, using the pooled mean differences (MD) for clinical attachment level (CAL) and probing pocket depth (PPD). Standard mean difference (SMD) was used for radiographic assessment (RADIO). Subgroup analyses were performed for locally delivered meta-analyses, considering diabetes and smoking exposure. RESULTS: Thirteen studies were included. It was showed MD of 1.52 â€‹mm (95%CI: 0.97-2.07) and 1.44 â€‹mm (95%CI: 1.08-1.79) for PPD reduction and CAL gain, respectively, for locally delivered BP. BP was not able to provide significant improvements in smokers (subgroup analysis) when considering CAL (MD: 1.37; 95%CI: -0.17-2.91) and PPD (MD: 1.35; 95%CI: -0.13-2.83). Locally delivered BP also improved significantly the RADIO assessments (SMD: 4.34; 95%CI: 2.94-5.74). MD for systemically administered BP was 0.40 â€‹mm (95%CI: 0.21-0.60), 0.51 â€‹mm (95%CI: 0.19-0.83) and 1.05 (95%CI: 0.80-1.31) for PPD, CAL and RADIO, respectively. CONCLUSION: The administration of BP in adjunct to SRP may result in additional clinical effects.

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BACKGROUND: The present study performed a systematic review and meta-analysis of clinical trials using bisphosphonates for bone demineralization in human immunodeficiency virus (HIV) patients. METHODS: A comprehensive literature search was performed from January 2004 to January 2020 considering the bone mineral density (BMD) of the lumbar spine (LS) as the main outcome. Out of 214 titles that met criteria, 9 studies fulfilled the selection criteria. RESULTS: A total of 394 patients were identified, and they were allocated into 2 groups: the intervention group (200 patients), to whom a combination of alendronate or zoledronate with calcium and vitamin D was administered; and control group (194 patients), to whom only calcium and vitamin D was administered. Clinical profile and indicators of bone metabolism of the participants were evaluated regarding effect size, homogeneity, and consistency. No substantial heterogeneity between the groups was found for the baseline variables, and there was high consistency to the main outcome. The meta-analysis shows a significant difference in post-treatment BMD, favoring the intervention over the control treatment. The intervention improved LS density up to 0.227 g/cm², raising the average to the levels of general population. Adverse effects related to intervention were fever immediately after zoledronate administration and gastrointestinal complaints during alendronate usage. Other adverse effects were barely reported and poorly connected to intervention by studies' authors, despite all of them have been successfully resolved. CONCLUSIONS: This study provides evidence that BMD post-treatment is better in HIV patients who used bisphosphonates combined with calcium and vitamin D.

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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.

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