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Master's Dissertation
DOI
https://doi.org/10.11606/D.17.2022.tde-03022023-144951
Document
Author
Full name
Victor Augusto Minari
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2022
Supervisor
Committee
Macedo, Leandro Dorigan de (President)
Alves, Fábio de Abreu
Antunes, Héliton Spíndola
Title in Portuguese
Avaliação dos fatores de risco para o desenvolvimento de osteonecrose dos maxilares induzida por bisfosfonatos (ONMB) em pacientes oncológicos usuários de bisfosfonato intravenoso
Keywords in Portuguese
Bisfosfonatos
Câncer
Infecção
Maxilares
Osteonecrose
Abstract in Portuguese
A associação entre o uso dos bisfosfonatos e a osteonecrose dos maxilares tem sido amplamente relatada na literatura. Apesar de os pacientes oncológicos apresentarem a maior frequência de necrose, há poucos estudos na literatura que avaliem os fatores de risco especificamente nesta população. Este foi um estudo retrospectivo e observacional que teve como objetivo avaliar os fatores clínicos de risco para o desenvolvimento de osteonecrose em maxila e mandíbula em uma coorte de pacientes oncológicos usuários de ácido zoledrônico intravenoso. Foram incluídos no estudo pacientes oncológicos, com histórico de uso de ácido intravenoso, entre junho de 2016 e fevereiro de 2019. Os seguintes dados foram coletados: idade, sexo, doença de base, comorbidades, tabagismo, avaliação odontológica antes do início do medicamento, uso crônico de corticoide, uso de imunossupressor, de antigiogênico, de quimioterapico, indicação de uso de bisfofonato, tempo, frequência e número total de doses de ácido zoledrônico, uso prévio de bisfosfonato por via oral e o desenvolvimento de necrose óssea. A análise de risco foi realizada a partir de regressão logística multivariada ajustada pelas variáveis com significância na análise exploratória, o nível de confiança foi de 95% para todas as avaliações. Dos 3.996 prontuários avaliados, foram incluídos 354 pacientes, a mediana de idade foi de 73 anos (23-99), 72% eram do sexo masculino, 31% tabagista, 32% usuários de corticoide, 28% de imunossupressor, 21% de antiagniogênico, 51% fizeram quimioterapia, 67,8% foram submetidos a avaliação e preparo odontológico antes do início do bisfosfonato, 56% eram portadores de câncer de próstata, 16% de mieloma múltiplo, 12% de câncer de mama, as comorbidades mais frequentes foram as cardiovasculares (58%) e nutricionais, metabólicas e endocrinológicas (26%), 43% usavam o medicamento a mais de 2 anos, o número de dose acumulada de bisfosfonato foi de 7 (1-73) e a incidência de necrose de 5%. O uso crônico de corticoide (9,6%x2,9%, p: 0,029), de imunossupressor (10,5%x3,1%, p: 0,033), pacientes que não foram submetidos a avaliação odontológica antes do início do medicamento (14%x0,8%, p: 0,000), que faziam uso mensal do bisfosfonato (14,7%, p: 0,006), com tempo de uso maior que 4 anos (14,9%, p: 0,012) e os portadores de doenças nutricionais, metabólicas e endocrinológcas (11,7%, p:0,05) foram mais frequentes no grupo de osteonecrose na análise exploratória. A regressão logística multivariada identificou como fatores de risco independentes o maior tempo de uso (odds:2,20, IC:1,11-4,59) e a presença de doenças nutricionais, metabólicas e endocrinológicas (odds:5,16, IC:1,28-21,34). Enquanto a menor frequência de uso do medicamento (odds:0,20, IC:0,05-0,71) e a avaliação odontológica previa ao início do uso de ácido zoledrônico (odds:0,05, IC:0,01-0,23) foram fatores protetores para o desenvolvimento da complicação. Podemos concluir que, este primeiro estudo brasileiro com pacientes oncológicos, usuários de bisfosfonatos intravenoso apontou a presença de doenças nutricionais, metabólicas e endocrinológicas, a maior frequência e tempo de uso do medicamento como fatores de risco. Enquanto, a avaliação odontológica antes do início do tratamento medicamentoso foi fator protetor para o desenvolvimento de necrose em maxilares associada ao uso de ácido zoledrônico intravenoso.
Title in English
Evaluation of risk factors for the development of osteonecrosis of the jaws induced by bisphosphonates (BRONJ) in cancer patients using intravenous bisphosphonates
Keywords in English
Bisphosphonates
Cancer
Infection
Jaws
Osteonecrosis
Abstract in English
The association between the use of bisphosphonates and osteonecrosis of the jaws has been widely reported in the literature. Although cancer patients have the highest frequency of necrosis, there are few studies in the literature that assess risk factors specifically in this population. This was a retrospective and observational study that aimed to evaluate the clinical risk factors for the development of osteonecrosis in the maxilla and mandible in a cohort of cancer patients using intravenous zoledronic acid. Cancer patients with a history of intravenous zoledronic acid use between June 2016 and February 2019 were included in the study. The following data were collected: age, sex, underlying disease, comorbidities, smoking, dental evaluation before starting the drug, chronic use of corticosteroids, use of immunosuppressants, antiogiogenic, chemotherapy, indication of bisphosphonate use, time, frequency and total number of doses of zoledronic acid, previous use of oral bisphosphonate and the development of bone necrosis. Risk analysis was performed using multivariate logistic regression adjusted for variables with significance in the exploratory analysis, the confidence level was 95% for all assessments. Of the 3,996 medical records evaluated, 354 patients were included, the median age was 73 years (23-99), 72% were male, 31% were smokers, 32% were steroid users, 28% were immunosuppressed, 21% were antiangiogenic, 51% underwent chemotherapy, 67.8% underwent dental evaluation and preparation before starting the bisphosphonate, 56% had prostate cancer, 16% had multiple myeloma, 12% had breast cancer, the most frequent comorbidities were cardiovascular (58%) and nutritional, metabolic and endocrinological (26%), 43% had used the drug for more than 2 years, the number of accumulated doses of bisphosphonate was 7 (1-73) and the incidence of necrosis was 5 %. Chronic use of corticosteroids (9.6%x2.9%, p:0.029), immunosuppressants (10.5%x3.1%, p:0.033), patients who did not undergo dental evaluation before starting the drug (14%x0.8%, p:0.000), who used bisphosphonates monthly (14.7%, p:0.006), with a time of use greater than 4 years (14.9%, p:0.012) and patients with nutritional, metabolic and endocrinological diseases (11.7%, p:0.05) were more frequent in the osteonecrosis group in the exploratory analysis. Multivariate logistic regression identified longer duration of use (odds:2.20, CI:1.11-4.59) and the presence of nutritional, metabolic and endocrinological diseases (odds:5.16, CI: :1.28-21.34). While the lower frequency of drug use (odds:0.20, CI:0.05-0.71) and the dental evaluation prior to the beginning of the use of zoledronic acid (odds:0.05, CI:0.01- 0.23) were protective factors for the development of the complication. We can conclude that this first Brazilian study with cancer patients, users of intravenous bisphosphonates, pointed to the presence of nutritional, metabolic and endocrinological diseases, the greater frequency and duration of drug use as risk factors. On the other hand, the dental evaluation before the beginning of the drug treatment was a protective factor for the development of necrosis in the jaws associated with the use of intravenous zoledronic acid.
 
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Publishing Date
2023-02-06
 
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