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Braz. j. oral sci ; 21: e226585, jan.-dez. 2022. ilus
Article in English | LILACS, BBO | ID: biblio-1393018


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

Surgery, Oral , Bone Density Conservation Agents , Bisphosphonate-Associated Osteonecrosis of the Jaw/epidemiology , Mandible
Rev. cir. traumatol. buco-maxilo-fac ; 22(3): 14-21, jul.-set. 2022. ilus, tab
Article in Portuguese | LILACS, BBO | ID: biblio-1399579


O objetivo foi avaliar o nível de conhecimento dos discentes do último ano do curso de odontologia da Universidade de Pernambuco, acerca da etiológia e manejo da osteonecrose dos maxilares. Metodologia: Trata-se de um estudo transversal realizado com os alunos do 9° e 10° períodos, onde 45 alunos responderam voluntariamente, após firmarem o aceite do termo de Consentimento Livre e Esclarecido, questionário estruturado mediante informações básicas sobre drogas antirreabsortivas e antiangiogênicas, além do manejo de pacientes com osteonecrose dos maxilares. Resultados: Dos 45 discentes que aceitaram responder o questionário 22 (48,8%) eram do 9° período e 23 (51,11%) do 10° período; 82% relataram que não aprenderam sobre medicamentos antirreabsortivos e antiangiogênicos; 84,4% tiveram informações sobre a osteonecrose durante a formação acadêmica. Em relação à possibilidade terapêutica 43,6% indicaram o tratamento cirúrgico (desbridamento); 20,5% laser de baixa intensidade e antibiótico; 12,8% ressecção cirúrgica; 10,3% laser de baixa intensidade; 7,7% oxigenação hiperbárica; (5,12%) infusão de PRP (plasma rico em plaquetas). Conclusão: O atual padrão de conhecimento passado sobre a etiologia e manejo da osteonecrose dos maxilares, induzida por fármacos, não está dando o suporte necessário para a tomada de decisão ao término do processo formal de ensino e aprendizagem no curso de odontologia... (AU)

The objective was to evaluate the level of knowledge of the final-year dental students of the Universidade de Pernambuco about the etiology and management of osteonecrosis of the jaws. Methodology: This is a cross-sectional study carried out with students from the 9th and 10th periods. Informed Consent, a structured questionnaire with basic information about antiresorptive and antiangiogenic drugs, besides the management of patients with osteonecrosis of the jaws. Results: Of the 45 students who agreed to answer the questionnaire, 22 (48.8%) were from the 9th period and 23 (51.11%) from the 10th period; 82% reported that they did not learn about antiresorptive and antiangiogenic drugs; 84.4% had information about osteonecrosis during their academic training. Regarding the therapeutic possibility 43.6% indicated surgical treatment (debridement); 20.5% low intensity laser and antibiotic; 12.8% surgical resection; 10.3% low intensity laser; 7.7% hyperbaric oxygenation; (5.12%) infusion of PRP (platelet rich plasma). Conclusion: The current pattern of past knowledge on the etiology and management of drug-induced osteonecrosis of the jaws is not providing the necessary support for decision making at the end of the formal teaching and learning process in the dental course... (AU)

El objetivo es evaluar el nivel de conocimiento de los estudiantes del último año del curso de odontología de la Universidad de Pernambuco, sobre la etiología y el manejo de la osteonecrosis de los maxilares. Metodología: Se trata de un estudio transversal realizado con los estudiantes de los periodos 9° y 10°, en el que 45 estudiantes respondieron voluntariamente, tras firmar el término de Consentimiento Livre y Esclarecido, a un cuestionario estructurado mediante información básica sobre drogas antirreabsortivas y antiangiogénicas, además del manejo de pacientes con osteonecrosis de los maxilares. Resultados: De los 45 estudiantes que accedieron a contestar el cuestionario, 22 (48,8%) eran del 9º periodo y 23 (51,11%) del 10º periodo; el 82% informó de que no había aprendido sobre los fármacos antirresortivos y antiangiogénicos; el 84,4% tuvo información sobre la osteonecrosis durante su formación académica. En cuanto a la posibilidad terapéutica, el 43,6% indicó tratamiento quirúrgico (desbridamiento); el 20,5%, láser de baja intensidad y antibiótico; el 12,8%, resección quirúrgica; el 10,3%, láser de baja intensidad; el 7,7%, oxigenación hiperbárica; el 5,12%, infusión de PRP (plasma rico en plaquetas). Conclusión: El modelo actual de conocimientos previos sobre la etiología y el tratamiento de la osteonecrosis de los maxilares inducida por fármacos no está proporcionando el apoyo necesario para la toma de decisiones al final del proceso formal de enseñanza y aprendizaje en el curso de odontologia... (AU)

Humans , Male , Female , Osteonecrosis , Students, Dental , Health Knowledge, Attitudes, Practice , Cross-Sectional Studies , Angiogenesis Inhibitors , Bone Density Conservation Agents , Schools, Dental , Clinical Decision-Making , Jaw
Rev. ADM ; 79(4): 232-238, jul.-ago. 2022. tab
Article in Spanish | LILACS | ID: biblio-1396500


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)

Humans , Male , Female , Angiogenesis Inhibitors/adverse effects , Bone Density Conservation Agents/adverse effects , Bisphosphonate-Associated Osteonecrosis of the Jaw/complications , Patient Care Team , Jaw Diseases/etiology , Clinical Protocols , Dental Care for Chronically Ill/methods , Bisphosphonate-Associated Osteonecrosis of the Jaw/prevention & control
Chinese Journal of Stomatology ; (12): 128-135, 2022.
Article in Chinese | WPRIM | ID: wpr-935838


Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse event related to administration of antiresorptive or antiangiogenic medications. With the increasing usage of bone-modifying agents in cancer therapy, the incidence of MRONJ enhanced gradually, which affects the life quality of patients and interferes with cancer therapy. In 2019, Multinational Association of Supportive Care in Cancer (MASCC), International Society of Oral Oncology (ISOO) and American Society of Clinical Oncology (ASCO) convened a multidisciplinary Expert Panel to evaluate the evidence and formulate recommendations on practices in the prevention and management of MRONJ in patients with cancer. The present article made an interpretation of Medication-Related Osteonecrosis of the Jaw: MASCC/ISOO/ASCO Clinical Practice Guideline so as to provide clinicians with diagnostic and therapeutic approaches for cancer patients with MRONJ.

Bisphosphonate-Associated Osteonecrosis of the Jaw/therapy , Bone Density Conservation Agents/adverse effects , Humans , Jaw , Medical Oncology , Neoplasms/drug therapy , Osteonecrosis/chemically induced , Quality of Life
Article in English | WPRIM | ID: wpr-929144


Bacterial infection is a common finding in patients, who develop medication-related osteonecrosis of the jaw (MRONJ) by the long-term and/or high-dose use of anti-resorptive agents such as bisphosphonate (BPs). However, pathological role of bacteria in MRONJ development at the early stage remains controversial. Here, we demonstrated that commensal microbiota protects against MRONJ development in the pulp-exposed periapical periodontitis mouse model. C57/BL6 female mice were treated with intragastric broad-spectrum antibiotics for 1 week. Zoledronic acid (ZOL) through intravenous injection and antibiotics in drinking water were administered for throughout the experiment. Pulp was exposed on the left maxillary first molar, then the mice were left for 5 weeks after which bilateral maxillary first molar was extracted and mice were left for additional 3 weeks to heal. All mice were harvested, and cecum, maxilla, and femurs were collected. ONJ development was assessed using μCT and histologic analyses. When antibiotic was treated in mice, these mice had no weight changes, but developed significantly enlarged ceca compared to the control group (CTL mice). Periapical bone resorption prior to the tooth extraction was similarly prevented when treated with antibiotics, which was confirmed by decreased osteoclasts and inflammation. ZOL treatment with pulp exposure significantly increased bone necrosis as determined by empty lacunae and necrotic bone amount. Furthermore, antibiotics treatment could further exacerbate bone necrosis, with increased osteoclast number. Our findings suggest that the commensal microbiome may play protective role, rather than pathological role, in the early stages of MRONJ development.

Animals , Bisphosphonate-Associated Osteonecrosis of the Jaw/prevention & control , Bone Density Conservation Agents , Diphosphonates , Female , Humans , Mice , Microbiota , Periapical Diseases , Zoledronic Acid
Article in Chinese | WPRIM | ID: wpr-928342


OBJECTIVE@#To investigate the effect of intra-articular berberine injection on the structural remodeling of subchondral bone plate and osteoprotegerin/receptor activator of nuclear factor kappa-B ligand(OPG/RANKL) system expression in rabbits with osteoarthritis(OA).@*METHODS@#Forty 12-month-old male rabbits with an average of(2.73±0.18) kg of body weight, underwent left anterior cruciate ligament transection(ACLT), and were divided into berberine group and placebo groups after operation, 20 rabbits in each group. The berberine group received intra-articular injection of 100 μmol/L berberine 0.3 ml every week for 6 weeks. In placebo group, the same dose of 0.9% sodium chloride injection was injected into the left knee joint cavity every week for 6 weeks. Another 20 12-month-old male rabbits, weighing (2.68±0.18) kg, underwent sham operation on the left knee joint without intra-articular injection intervention (sham operation group). On the last day of the sixth week after operation, three groups of animals were sacrificed to obtain knee joint specimens. The femoral medial condyle samples were obtained for histological evaluation of cartilage and subchondral bone, Mankin scoring system was used to evaluate articular cartilage structure. Image-Pro Plus(IPP) software was used to evaluate subchondral bone plate bone volume(BV), bone volume/total volume(BV/TV), trabecular circumference(TC), mean trabecular thickness (Tb.Th). Real-time quantitative reverse transcription polymerization Enzyme chain reaction(reverse transcription-polymerase chain reaction, RT-PCR) was used to detect the mRNA expression levels of OPG and RANKL in subchondral bone tissue at 6 weeks after operation.@*RESULTS@#The cartilage structure evaluation showed that the surface of cartilage tissue in the sham operation group was smooth and flat, and the safranin coloration was full in the full thickness of the cartilage;the cartilage tissue in the berberine group showed uneven surface layer, and the staining of safranin O was mildly decreased;the surface layer fibrosis was seen in placebo group, Safranin O faded significantly. The Mankin score in the berberine group was lower than that in placebo group(P<0.01), but higher than that in sham operation group(P<0.01). The structural evaluation of subchondral bone plate showed that the trabecular bone in sham-operated group was densely arranged;after berberine intervention, the trabeculae were closely arranged;the subchondral bone trabeculae in placebo group were relatively sparse, and the distance between trabeculae was wider. Subchondral bone plate IPP software evaluation showed that BV, BV/TV, TC, Tb.Th in berberine group were higher than those in placebo group(P<0.01), BV, BV/TV, TC, Tb.Th in berberine group were higher than those in placebo group(P<0.01), while lower than the sham operation group (P<0.01). PCR test results showed that the expression of OPG mRNA in the berberine group was significantly higher than that in placebo group(P<0.01), and OPG mRNA in the berberine group was lower than that in sham operation group (P<0.01). There was no significant difference in mRNA expression of RANKL among three groups(P>0.05);the ratio of OPG/RANKL in berberine group was higher than that in placebo group(P<0.01), but lower than that in sham operation group(P<0.01).@*CONCLUSION@#Intra-articular injection of berberine can effectively inhibit the resorption of subchondral bone in the early stage of OA and delay the development of the disease. The specific mechanism may be that berberine maintains the balance of OPG/RANKL system by up-regulating the expression of OPG gene in subchondral bone.

Animals , Berberine/therapeutic use , Bone Density Conservation Agents/therapeutic use , Bone Plates , Cartilage, Articular , Humans , Ligands , Male , NF-kappa B/metabolism , Osteoarthritis/metabolism , Osteoprotegerin/metabolism , RNA, Messenger/therapeutic use , Rabbits
Medicina (B.Aires) ; 81(5): 767-773, oct. 2021. graf
Article in Spanish | LILACS | ID: biblio-1351049


Resumen El tumor de células gigantes óseo es una neoplasia de agresividad local intermedia, que raramente metastatiza. En los últimos años el denosumab, anticuerpo monoclonal humano, surgió como una alternativa de tratamiento para esta enfermedad, al bloquear el comportamiento lítico tumoral. El objetivo de este trabajo fue determinar sus indicaciones y efectos adversos, analizando también los resultados oncológicos, y las tasas de recurrencia local en pacientes con diagnóstico de tumor de células gigantes óseo que recibieron denosumab como tratamiento neoadyuvante. Entre 2010 y 2018 se analizaron 80 pacientes con tumor de células gigantes, de los cuales 14 recibieron denosumab como tratamiento neoadyuvante. El seguimiento mínimo fue 12 meses. En 8 pacientes se trató de un tumor primario, mientras que 6 fueron pacientes con recidiva tumoral. En todos los casos se evidenció una mejoría clínica. Trece presentaron cambios radiográficos, y 11 respuesta histológica completa. En 6 de 14 pacientes se evidenció una recurrencia local y en 7 se identificó al menos un efecto adverso relacionado con el denosumab (incluyendo una malignización tumoral). A pesar de ser una herramienta útil para el tratamiento del tumor de células gigantes, el uso de denosumab está asociado a mayor tasa de recurrencias locales y no está exento de efectos adversos.

Abstract Giant cell tumor of bone is an intermediate, locally aggressive and rarely metastasiz ing, primary bone neoplasia. In recent years denosumab emerged as a treatment alternative for this pathology. The objective of this work was to analyze its indications as well as the clinical outcomes, side effects and local recurrence rates in patients diagnosed with giant cell tumor of bone, who received denosumab as neoadjuvant treatment. Between 2010 and 2018, 80 patients with giant cell tumor were analyzed, of whom 14 received deno sumab as a neoadjuvant treatment. The minimum follow-up was 12 months. In 8 patients it was a primary tumor, while 6 showed tumor recurrence. In all cases, clinical improvement was evident. Thirteen patients presented radiographic changes, and 11 showed complete histological response. A local recurrence was evidenced in 6 of 14 patients, and at least one adverse effect related to denosumab (including tumor malignancy) was identified in 7. Despite being a useful tool for treating giant cell tumor, the use of denosumab is associated with a higher rate of local recurrences and is not free of adverse effects.

Humans , Bone Neoplasms/drug therapy , Bone Neoplasms/diagnostic imaging , Giant Cell Tumor of Bone/drug therapy , Giant Cell Tumor of Bone/diagnostic imaging , Bone Density Conservation Agents/adverse effects , Denosumab/adverse effects , Neoplasm Recurrence, Local/drug therapy
Medicina (B.Aires) ; 81(5): 749-753, oct. 2021. graf
Article in English | LILACS | ID: biblio-1351046


Abstract Anabolic drugs are the treatment of choice for osteoporotic patients with very high risk of fractures. Post anabolic treatment with an antiresorptive drug maintains the bone mineral density (BMD) gained. The recommendations regarding the ideal antiresorptive drug are not precise. The aim of this paper is to compare the usefulness of zoledronate and denosumab in a group of 28 women with very high risk of fractures. All of them completed at least one year of treatment with teripatide and latter 14 received zolendronate and 14 denosumab for another year. We retrospectively review their biochemical and densitometric changes. Both treat ment groups experienced a reduction in bone turnover markers of the same magnitude at the end of the second year. In Lumbar Spine BMD increase of 3.96 ± 8.56% Median (Me) 2.54 p = 0.21 in zolendronate group and 3.55 ± 5.36% (Me 5.14) p = 0.07 in denosumab group. Femoral Neck BMD changed -0.09 ± 6.50% (Me 0.29) p = 0.85 in zolendronate group, and - 3.41 ± 5.08% (Me 5.35) p = 0.59 in denosumab group, with no difference between both groups. In Total Hip BMD an increase of 0.55 ± 4.20% (Me 0.43) p = 0.70 in zoledronate group, and 4.53 ± 5.13% (Me 0.64) p = 0.04 with denosumab. We conclude that both antiresortive treatments have a similar effect in biochemical markers after one year of treatment. BMD increase significantly in total hip and changed with a trend toward in lumbar spine with denosumab, but without differences between both groups of treatment.

Resumen Los anabólicos son el tratamiento de elección en la osteoporosis con muy alto riesgo de fracturas. Después del tratamiento anabólico un fármaco antirresortivo mantiene la densidad mineral ósea (DMO) ganada. Las reco mendaciones sobre el fármaco antirresortivo ideal no son precisas. El objetivo de este trabajo es comparar la utilidad de zoledronato y denosumab en un grupo de 28 mujeres con muy alto riesgo de fracturas. Todas ellas completaron al menos un año de tratamiento con teripatide y luego 14 recibieron zolendronato y 14 denosumab durante un año. Revisamos retrospectivamente sus cambios bioquímicos y densitométricos. Ambos grupos de tratamiento experimentaron una reducción de los marcadores de recambio óseo de la misma magnitud al final del segundo año. En columna lumbar la DMO aumentó 3.96 ± 8.56% Mediana (Me) 2.54, p = 0.21 en el grupo zolendronato y 3.55 ± 5.36% (Me 5.14) p = 0.07 en el grupo denosumab. La DMO del cuello femoral cambió -0.09 ± 6.50% (Me 0.29) p = 0.85 en el grupo zolendronato y - 3.41 ± 5.08% (Me 5.35) p = 0.59 en el grupo de denosumab, sin diferencias entre ambos grupos. En la Cadera Total la DMO aumentó 0.55 ± 4.20% (Me 0.43) p = 0.70 con zoledronato y 4.53 ± 5.13% (Me 0.64) p = 0.04 con denosumab. Concluimos que ambos tratamien tos antiresortivos tuvieron un efecto similar en los marcadores bioquímicos después de un año de tratamiento. La DMO aumentó significativamente en la cadera total y mostró una tendencia similar en columna lumbar con denosumab, sin diferencias entre ambos tratamientos.

Humans , Female , Teriparatide/therapeutic use , Bone Density Conservation Agents/therapeutic use , Bone Density , Retrospective Studies , Denosumab/therapeutic use
Rev. habanera cienc. méd ; 20(1): e3212, ene.-feb. 2021. tab
Article in Spanish | LILACS, CUMED | ID: biblio-1156683


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)

Humans , Aged , Osteonecrosis/chemically induced , Surgery, Oral , Oral Medicine , Bone Density Conservation Agents , Selection of the Waste Treatment Site , Aftercare , Bisphosphonate-Associated Osteonecrosis of the Jaw/therapy
Clinics ; 76: e3155, 2021. tab, graf
Article in English | LILACS | ID: biblio-1345811


Vitamin D is a fat-soluble vitamin that plays a role not only in calcium homeostasis, but also in several other functions, including cell growth and immune functions, and is considered a neurosteroid. Vitamin D deficiency is highly prevalent worldwide and has been suggested to be associated with an increased risk of emotional disorders. Therefore, the association between vitamin D levels and psychophysiological disorders, such as depression, anxiety, and mood, has been investigated. To list these variables, a bibliographical literature research was conducted in the MEDLINE/PubMed, Web of Science, Scopus, Science Direct and PsycINFO databases, between November and December 2020, with no year limits of publication. The studies involved humans aged between 18 and 59 years without associated diseases. This review presents evidence of the main variables involved in this association, main tools used to verify these variables, and methods used to verify circulating vitamin D levels in populations. Most studies have indicated that the main psychophysiological variables involved with vitamin D levels are depression and anxiety followed by mood, and an association has been observed between increased serum vitamin D levels and reduction in symptoms of depression, anxiety, and mood, and there is a heterogeneity of methods for assessing vitamin D. More studies are clearly needed to improve our understanding of their role in modulating the psychophysiological aspects of vitamin D levels.

Humans , Adolescent , Adult , Middle Aged , Young Adult , Vitamin D Deficiency/complications , Bone Density Conservation Agents , Anxiety , Anxiety Disorders , Vitamin D
Rev. Ateneo Argent. Odontol ; 64(1): 22-27, 2021. ilus, tab
Article in Spanish | LILACS | ID: biblio-1248381


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

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

Humans , Female , Diphosphonates/adverse effects , Bone Density Conservation Agents/adverse effects , Bisphosphonate-Associated Osteonecrosis of the Jaw , Radiotherapy/adverse effects , Breast Neoplasms/complications , Risk Factors , Diphosphonates/pharmacokinetics , Interprofessional Relations
Rev. Soc. Bras. Clín. Méd ; 19(3): 149-153, set 2021.
Article in English | LILACS | ID: biblio-1391841


Objective: To evaluate the link between calcium supplementa- tion and cardiovascular disease in postmenopausal women (aged 55 years or older). Methods: A standardized questionnaire was employed to collect data about calcium supplements, eart di- sease, and demographic of women attended at Primary Care in the South Region of Brazil. Generalized linear regression models were performed to evaluate the association and adjust for poten- tial confounders. Results: Overall, 1,057 women completed the questionnaire. Information about calcium supplementation was present in 1,035 questionnaires. The mean ± standard deviation of the age of participants was 67.2±7.6 years. The frequency of calcium supplementation was 18.6%. There was no association between heart failure, stroke, and ischemic heart disease and cal- cium supplementation (prevalence ratio; 95% confidence interval of 0.3; -0.9-0.4, -0.2; -0.8-0.4 and -0.5; -1.0-0.02, respectively. Con- clusions: Our study did not find an association of higher risk of cardiovascular disease in women using calcium supplementation at Primary Care in South Brazil.

Objetivo: Avaliar a ligação entre a suplementação de cálcio e doença cardiovascular em mulheres na pós-menopausa (com 55 anos ou mais). Métodos: Um questionário padronizado foi em- pregado para coletar dados sobre suplementos de cálcio, doenças cardíacas e demográficos de mulheres que frequentavam a Aten- ção Primária na Região Sul do Brasil. Modelos de regressão linear generalizada foram realizados para avaliar a associação e ajustar os potenciais fatores de confusão. Resultados: No total, 1.057 mulheres responderam ao questionário. As informações sobre su- plementação de cálcio estavam presentes em 1.035 questionários. A média ± desvio-padrão da idade dos participantes foi de 67,2 ± 7,6 anos. A frequência de suplementação de cálcio foi de 18,6%. Não houve associação entre insuficiência cardíaca, acidente vas- cular cerebral e doença cardíaca isquêmica e suplementação de cálcio (razão de prevalência; intervalo de confiança de 95% de -0,3; -0,9-0,4, -0,2; -0,8-0,4 e -0,5; -1,0-0,02, respectivamente). Con- clusão: Nosso estudo não encontrou associação de maior risco de doença cardiovascular em mulheres em uso de suplementação de cálcio na Atenção Primária no Sul do Brasil.

Humans , Female , Middle Aged , Aged , Primary Health Care , Cardiovascular Diseases/chemically induced , Postmenopause , Calcium Compounds/administration & dosage , Dietary Supplements/adverse effects , Vitamin D/administration & dosage , Brazil , Cross-Sectional Studies , Surveys and Questionnaires , Stroke/chemically induced , Bone Density Conservation Agents/administration & dosage , Heart Disease Risk Factors
Actual. osteol ; 17(3): 95-104, 2021. ilus
Article in Spanish | LILACS, BINACIS, UNISALUD | ID: biblio-1395543


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

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

Humans , Female , Adult , Middle Aged , Diphosphonates/adverse effects , Bone Density Conservation Agents/adverse effects , Bisphosphonate-Associated Osteonecrosis of the Jaw/therapy , Bisphosphonate-Associated Osteonecrosis of the Jaw/diagnostic imaging , Neoplasm Metastasis/diagnostic imaging , Ovarian Neoplasms/complications , Breast Neoplasms/complications , Radiography , Dental Care/methods , Bisphosphonate-Associated Osteonecrosis of the Jaw/physiopathology , Bisphosphonate-Associated Osteonecrosis of the Jaw/prevention & control
Chinese Journal of Oncology ; (12): 622-628, 2021.
Article in Chinese | WPRIM | ID: wpr-887466


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

Bone Density Conservation Agents/adverse effects , Consensus , Diphosphonates/adverse effects , Humans , Osteoporosis/drug therapy , Quality of Life , Safety Management
Article in English | WPRIM | ID: wpr-878439


The morbidity rate of medication-related osteonecrosis of the jaws (MRONJ) increased rapidly in recent years. Thusfar, the mechanism of MRONJ has no consensus. The possible mechanisms may include bone remodeling inhibition theory, angiogenesis inhibition theory, oral microorganism infection theory, immunosuppression theory, cytotoxicity-targeted oral epithelial cells, microcrack formation of maxillary or mandibular bone, and single nucleotide polymorphism. However, the efficacy of prevention and treatment based on a single mechanism is not ideal. Routine oral examination before MRONJ-related drug treatment, treatment of related dental diseases, and regular oral follow-up during drug treatment are of great significance for the prevention of MRONJ. During the treatment of MRONJ, the stage of MRONJ must be determined accurately, treatment must be standardized in accordance with the guidelines, and personalized adjustments must be made considering the specific conditions of patients. This review aimed to combine the latest research and guidelines for MRONJ and the experiences on the treatment of MRONJ in the Maxillofacial Surgery Department of West China Hospital of Stomatology, Sichuan University, and discuss the strategies to improve the clinical process.

Bisphosphonate-Associated Osteonecrosis of the Jaw/prevention & control , Bone Density Conservation Agents , Bone Remodeling , China , Humans , Jaw
Rev. Ateneo Argent. Odontol ; 63(2): 13-17, nov. 2020. ilus
Article in Spanish | LILACS | ID: biblio-1150415


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

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

Humans , Female , Aged , Bone Resorption , Diphosphonates/adverse effects , Bone Density Conservation Agents , Bisphosphonate-Associated Osteonecrosis of the Jaw , Bone Diseases , Dental Care for Chronically Ill , Angiogenesis Inhibitors , Denosumab , Mouthwashes/therapeutic use
Arch. endocrinol. metab. (Online) ; 64(4): 331-336, July-Aug. 2020. graf
Article in English | LILACS | ID: biblio-1131117


ABSTRACT Osteoporosis is a systemic skeletal disease characterized by reduced bone mass and deterioration of bone tissue microarchitecture leading to an increased risk of fractures. Fragility fractures, especially hip fractures, are associated with a significant reduction in the physical function and quality of life of affected patients, as well as increased mortality, leading to a major financial impact on health care. Many drugs have been registered for the treatment of osteoporosis and very recently, a new anabolic agent, romosozumab, has been approved in some countries. Despite the expansion of efficacious antiresorptive and anabolic therapies in recent years, a concomitant increase in concerns have been raised by physicians, patients and the lay press about the potential for adverse events, especially atypical femoral fractures (AFF) following prolonged use of bisphosphonates. Whatever the mechanism(s) may be, direct or indirect, linking prolonged bisphosphonate use to atypical femoral fractures, this adverse event is very rare in comparison to the magnitude of risk reduction of typical osteoporotic fractures. An estimated 162 osteoporosis-related fractures are prevented for each atypical femoral fracture associated with an anti-resorptive medication. Until a risk calculator for predicting risk of atypical fractures, becomes available in clinical practice, and we view this as an unlikely scenario, it is up to the physician to consider continuing or discontinuing bisphosphonate use after the critical 3-5 year period of treatment with zoledronic acid or alendronate, but close monitoring for the residual bone effects overtime should be planned. For other bisphosphonates, in which no residual effects are expected, drug holiday is usually not applied.

Humans , Female , Osteoporosis, Postmenopausal , Diphosphonates/therapeutic use , Quality of Life , Alendronate , Bone Density Conservation Agents/therapeutic use
Säo Paulo med. j ; 138(4): 326-335, July-Aug. 2020. tab, graf
Article in English | LILACS, SES-SP | ID: biblio-1139704


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.

Humans , Female , Middle Aged , Tooth Extraction , Diphosphonates/adverse effects , Bone Density Conservation Agents/adverse effects , Bisphosphonate-Associated Osteonecrosis of the Jaw/surgery , Osteoporosis/drug therapy , Brazil , Breast Neoplasms/drug therapy , Dental Care , Treatment Outcome , Angiogenesis Inhibitors , Diphosphonates/administration & dosage , Bone Density Conservation Agents/administration & dosage , Bisphosphonate-Associated Osteonecrosis of the Jaw/etiology , Bisphosphonate-Associated Osteonecrosis of the Jaw/diagnostic imaging
J. appl. oral sci ; 28: e20200204, 2020. tab, graf
Article in English | LILACS, BBO | ID: biblio-1134802


Abstract Objective This study aims to evaluate bone repair and the development of the medication related osteonecrosis of the jaw (MRONJ) associated with the use of zoledronic acid in Wistar rats. Methodology 48 male Wistar rats were divided into four groups: ZA, treated with intraperitoneal zoledronic acid, 0.6 mg/kg every 28 days, totaling five doses; control (C), treated with 0.9% sodium chloride; ZA-surgical (SZA) and C-surgical (SC), submitted to extraction of the right upper molars 45 days after the first application. Alveolar bone repair was evaluated by macroscopic and histological analysis. Protein expression evaluations were performed by qPCR. Results Macroscopic evaluation showed that 91.66% (11) of the animals in the SZA group and 41.66% (5) from the SC group presented solution of epithelium continuity (P<0.05). All animals in the SZA group and none in the SC group had bone sequestration. The area of osteonecrosis was higher in the SZA group than in the SC group (P<0.05). In molecular evaluation, the SZA group presented changes in the expression of markers for osteoclasts, with increased RANK and RANKL, and a decrease in OPG. Conclusion The results highlighted strong and evident interference of zoledronic acid in bone repair of the socket, causing osteonecrosis and delayed bone remodeling.

Animals , Male , Rats , Bone Density Conservation Agents/adverse effects , Bisphosphonate-Associated Osteonecrosis of the Jaw/physiopathology , Zoledronic Acid/adverse effects , Tooth Extraction/adverse effects , Rats, Wistar
Article in Portuguese | LILACS, ColecionaSUS, CONASS, SES-GO | ID: biblio-1118551


Tecnologia: Denosumabe e bifosfonados. Indicação: tratamento de osteoporose para prevenção de fraturas. Pergunta: O denosumabe é mais eficaz e seguro que os bifosfonados orais para tratamento da osteoporose e prevenção de fraturas secundárias à osteoporose? Métodos: Levantamento bibliográfico realizado na PUBMED seguindo estratégia de busca predefinida. Avaliação da qualidade metodológica das revisões sistemáticas com a ferramenta AMSTAR (Assessing the Methodological Quality of Systematic Reviews). Resultados: Foram selecionadas e incluídas 3 revisões sistemáticas, com pontuação de 9 a 11 no AMSTAR. Conclusão: Denosumabe tem menor risco relativo que alendronato e risedronato de sódio para fraturas vertebrais e maior efeito sobre densidade óssea mineral femoral, com risco similar de outros tipos de fratura e eventos adversos (infecções, transtornos cardiovasculares, óbito por infecção, morte cardiovascular ou por qualquer causa). Denosumabe evita 0,00154 fraturas, previne 0,00025 institucionalizações (ou cuidados permanentes de enfermagem no domicílio) e promove um ganho de 0,0018 anos de vida a mais que o alendronato de sódio por paciente tratado. Denosumabe é um pouco mais eficaz e tão seguro quanto os bifosfonados, mas a diferença de eficácia é mínima

Technology: Denosumab and bisphosphonates. Indication: osteoporosis treatment for fracture prevention. Question: Denosumab is more effective and safer than oral bisphosphonates for treating osteoporosis and preventing fractures related to osteoporosis? Methods: Bibliographic search was performed on PUBMED, following predefined search strategies. Evaluation of the methodological quality of systematic reviews was carried out using the AMSTAR (Assessing the Methodological Quality of Systematic Reviews) tool. Results: We selected and included 3 systematic reviews. Their scores ranged from 9 to 11 on AMSTAR. Conclusion: Denosumab has a lower relative risk than sodium alendronate and risedronate for vertebral fractures and greater effect on femoral mineral bone density, with a similar risk for non-vertebral fractures and adverse events (infections, cardiovascular disorders, death caused by infection, cardiovascular death or any cause mortality). Denosumab avoids 0.00154 fractures, prevents 0.00025 nursing home/ residential care admissions and get 0.0018 years of life gained per treated patient more than sodium alendronate. Denosumab is slightly more effective and as safe as bisphosphonates, but the effectiveness difference is minimal

Humans , Osteoporosis/drug therapy , Alendronate/therapeutic use , Bone Density Conservation Agents/therapeutic use , Osteoporotic Fractures/prevention & control , Risedronic Acid/therapeutic use , Denosumab/therapeutic use , Treatment Outcome , Alendronate/adverse effects , Evidence-Based Medicine , Risedronic Acid/adverse effects , Denosumab/adverse effects