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      Prevalencia de osteonecrosis de los maxilares asociada a medicamentos en pacientes tratados con bifosfonatos intravenosos: análisis epidemiológico en Centro del Cáncer - Red de Salud UC-CHRISTUS Translated title: Prevalence of medication-related osteonecrosis of the jaws in patients treated with intravenous bisphosphonates: an epidemiologic analysis at Centro del Cáncer - Red de Salud UC-CHRISTUS

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          Abstract

          Resumen Introducción: La osteonecrosis de los maxilares asociada a medicamentos (OMAM) es una patología que involucra la exposición necrótica de hueso maxilar o mandibular, relacionada al uso de fármacos antirresortivos y antiangiogénicos, con una prevalencia de 0,94%-13% en pacientes oncológicos y con osteoporosis que hacen uso de ellos. Objetivo: Determinar la prevalencia de osteonecrosis de los maxilares en pacientes en tratamiento con bifosfonatos intravenosos (BFIV) en el Centro del Cáncer de la Red de Salud UC-Christus, Santiago de Chile. Material y Método: Se analizaron los datos de pacientes que recibieron tratamiento de bifosfonatos intravenoso entre marzo y septiembre de 2016, con seguimiento por los equipos tratantes. Se consideró para la extracción de datos el género, edad, diagnóstico primario, bifosfonato intravenoso utilizado, tiempo de seguimiento, presencia de metástasis óseas y diagnóstico de OMAM. Resultados: Se obtuvo una muestra de 143 pacientes, con una relación hombre:mujer de 1:2; promedio de edad de 63,2 años; 78% de ellos fueron tratados con ácido zoledrónico y un 22% con pamidronato. Del total de pacientes un 1,4% (n = 2) desarrolló OMAM. Ambos casos con diagnóstico de cáncer de mama en tratamiento con ácido zoledrónico, lo que corresponde al 1,8% de los pacientes en tratamiento con este fármaco. Conclusión: Si bien la OMAM es una patología infrecuente, esta se presenta con alta morbilidad y es de manejo complejo. La prevención y tratamiento de focos infecciosos odontogénicos de pacientes antes, durante o después del tratamiento con BFIV es fundamental para prevenir su desarrollo.

          Translated abstract

          Abstract Introduction: Medication-related osteonecrosis of the jaw (MRONJ) is a disease involving exposition of necrotic maxillary and mandibular bone and it's related to antiresorptive and antiangiogenic drugs, with a prevalence that variates from 0,94%-13% in oncologic and osteoporosis patients treated with them. Aim: To determine the prevalence of MRONJ in patients that underwent treatment with intravenous bisphosphonates (IVBP) at Centro del Cancer de la Red de Salud UC-CHRISTUS of Santiago, Chile. Material and Method: Data from patients who received intravenous bisphosphonate treatment between March and September 2016 were analyzed, with follow-ups by their treating teams. Data extraction considered gender, age, primary diagnosis, intravenous bisphosphonate used, follow up time, bone metastases and diagnosis of MRONJ. Results: A sample of 143 patients was obtained with a men:women ratio of 1:2; an average age of 63,2 years, 78% of the patients were treated with zoledronic acid and 22% of the patients with pamidronate. From the total number of patients,1.4% (n = 2) developed MRONJ, both cases had breast cancer as primary diagnosis and in treatment with zoledronic acid, which corresponds to 1.8% of patients being treated with this drug. Conclusion: Although MRONJ is an infrequent disease, it presents high morbidity and complex management. Prevention and treatment of odontogenic infectious foci in patients before, during and after treatment with IVBP drugs is fundamental to prevent this pathology.

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          Most cited references26

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          Incidence, risk factors, and outcomes of osteonecrosis of the jaw: integrated analysis from three blinded active-controlled phase III trials in cancer patients with bone metastases.

          Osteonecrosis of the jaw (ONJ) has been reported in patients receiving bisphosphonates for metastatic bone disease. ONJ incidence, risk factors, and outcomes were evaluated in a combined analysis of three phase III trials in patients with metastatic bone disease receiving antiresorptive therapies. Patients with bone metastases secondary to solid tumors or myeloma were randomly assigned to receive either s.c. denosumab (120 mg) or i.v. zoledronic acid (4 mg) every 4 weeks. On-study oral examinations were conducted by investigators at baseline and every 6 months. Oral adverse events were adjudicated by an independent blinded committee of dental experts. Of 5723 patients enrolled, 89 (1.6%) patients were determined to have ONJ: 37 (1.3%) received zoledronic acid and 52 (1.8%) received denosumab (P = 0.13). Tooth extraction was reported for 61.8% of patients with ONJ. ONJ treatment was conservative in >95% of patients. As of October 2010, ONJ resolved in 36.0% of patients (29.7% for zoledronic acid and 40.4% for denosumab). In this combined analysis of three prospective trials, ONJ was infrequent, management was mostly conservative, and healing occurred in over one-third of the patients. Educating physicians about oral health before and during bone-targeted therapy may help reduce ONJ incidence and improve outcomes.
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            Frequency and risk factors associated with osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates.

            Osteonecrosis of the jaw (ONJ) has been reported in patients treated with bisphosphonates. The incidence and risk factors associated with this disorder have not been clearly defined. We conducted a retrospective analysis of 4019 patients treated with intravenous bisphosphonates between 1996 and 2004. Our goals were to estimate the frequency, understand the clinical presentation, and identify risk factors associated with ONJ development. Sixteen of 1338 patients with breast cancer (1.2%) and 13 of 548 patients with multiple myeloma (2.4%) developed ONJ. The median dose and duration of treatment with pamidronate or zoledronic acid were significantly higher in patients with ONJ (p < 0.0001). Multivariate Cox proportional hazards regression analysis identified treatment with zoledronic acid (hazards ratio [HR], 15.01; 95% CI: 2.41-93.48; p = 0.0037), treatment with pamidronate followed by zoledronic acid (HR, 4.00; 95% CI: 0.86-18.70; p = 0.078), and dental extractions (HR, 53.19; 95% CI: 18.20-155.46; p < 0.0001) as significant risks for ONJ in breast cancer. In multiple myeloma, dental extractions (HR, 9.78; 95% CI: 3.07-31.14; p = 0.0001) and osteoporosis (HR, 6.11; 95% CI: 1.56-23.98; p = 0.0095) were significant risk factors while controlling for bisphosphonate therapy. Thirteen of 29 patients were followed for a median of 17.1 mo (range, 7-67 mo); lesions healed in 3 patients during this period. ONJ is an uncommon but long-lasting disorder that occurs mainly in breast cancer and multiple myeloma patients treated with intravenous bisphosphonates. High cumulative doses of bisphosphonates, poor oral health, and dental extractions may be significant risk factors for ONJ development. ONJ resolved in 23% of patients with conservative therapy.
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              Bisphosphonates: mode of action and pharmacology.

              R. Russell (2007)
              The profound effects of the bisphosphonates on calcium metabolism were discovered over 30 years ago, and they are now well established as the major drugs used for the treatment of bone diseases associated with excessive resorption. Their principal uses are for Paget disease of bone, myeloma, bone metastases, and osteoporosis in adults, but there has been increasing and successful application in pediatric bone diseases, notably osteogenesis imperfecta. Bisphosphonates are structural analogues of inorganic pyrophosphate but are resistant to enzymatic and chemical breakdown. Bisphosphonates inhibit bone resorption by selective adsorption to mineral surfaces and subsequent internalization by bone-resorbing osteoclasts where they interfere with various biochemical processes. The simpler, non-nitrogen-containing bisphosphonates (eg, clodronate and etidronate) can be metabolically incorporated into nonhydrolysable analogues of adenosine triphosphate (ATP) that may inhibit ATP-dependent intracellular enzymes. In contrast, the more potent, nitrogen-containing bisphosphonates (eg, pamidronate, alendronate, risedronate, ibandronate, and zoledronate) inhibit a key enzyme, farnesyl pyrophosphate synthase, in the mevalonate pathway, thereby preventing the biosynthesis of isoprenoid compounds that are essential for the posttranslational modification of small guanosine triphosphate (GTP)-binding proteins (which are also GTPases) such as Rab, Rho, and Rac. The inhibition of protein prenylation and the disruption of the function of these key regulatory proteins explains the loss of osteoclast activity. The recently elucidated crystal structure of farnesyl diphosphate reveals how bisphosphonates bind to and inhibit at the active site via their critical nitrogen atoms. Although bisphosphonates are now established as an important class of drugs for the treatment of many bone diseases, there is new knowledge about how they work and the subtle but potentially important differences that exist between individual bisphosphonates. Understanding these may help to explain differences in potency, onset and duration of action, and clinical effectiveness.
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                Author and article information

                Journal
                orl
                Revista de otorrinolaringología y cirugía de cabeza y cuello
                Rev. Otorrinolaringol. Cir. Cabeza Cuello
                Sociedad Chilena de Otorrinolaringología, Medicina y Cirugía de Cabeza y Cuello (Santiago, , Chile )
                0718-4816
                December 2020
                : 80
                : 4
                : 469-476
                Affiliations
                [1] Santiago Santiago de Chile orgnamePontificia Universidad Católica de Chile orgdiv1Facultad de Medicina orgdiv2Departamento de Cirugía Oncológica y Maxilofacial Chile
                Article
                S0718-48162020000400469 S0718-4816(20)08000400469
                f0bd727b-c308-425f-bfe8-257133973ec4

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 06 May 2020
                : 29 June 2020
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 26, Pages: 8
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                SciELO Chile

                Categories
                ARTÍCULOS DE INVESTIGACIÓN

                ácido zoledrónico,pamidronato,bisphosphonates,osteonecrosis de los maxilares,zoledronic acid,pamidronate,osteonecrosis of the jaw,bifosfonatos

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