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1.
Acta cir. bras ; 39: e393724, 2024. graf, ilus
Article in English | LILACS, VETINDEX | ID: biblio-1563646

ABSTRACT

Purpose: To evaluate collagen fibers during the bone repair process in critical defects created in the tibias of rats, treated with zoledronic acid (AZ) associated with low-level laser therapy (LLLT). Methods: Ten rats were distributed according to treatment: group 1) saline solution; group 2) LLLT; group 3) AZ; group 4) AZ and LLLT. AZ was administered at the dose of 0.035 mg/kg at fortnightly intervals over eight weeks. Next, 2-mm bone defects were created in the tibias of all animals. The bone defects in groups 2 and 4 were irradiated LLLT in the immediate postoperative period. After periods 14 and 28 of application, the animals were euthanized, and birefringence analysis was performed. Results: Approximately 90% of the total area was occupied by collagen fibers within the red color spectrum, this area being statistically larger in relation to the area occupied by collagen fibers within the green and yellow spectrum, in the four groups. Over the 14-day period, there was no statistically significant difference between the groups. In the 28-day period, group 2 (14.02 ± 15.9%) was superior in quantifying green birefringent fibers compared to group 1 (3.06 ± 3.24%), with p = 0.009. Conclusions: LLLT associated with ZA is effective in stimulating the neoformation of collagen fibers. The LLLT group without the association with ZA showed a greater amount of immature and less organized matrix over a period of 28 days.


Subject(s)
Animals , Rats , Bone and Bones , Collagen , Low-Level Light Therapy , Zoledronic Acid/therapeutic use
2.
Actual. osteol ; 19(3): 211-220, Sept - Dic 2023. ilus
Article in Spanish | LILACS, UNISALUD, BINACIS | ID: biblio-1555794

ABSTRACT

La enfermedad de Erdheim-Chester (EEC) es una patología poco frecuente, caracterizada por presentar infiltración xantogranulomatosa sistémica, con afección de diversos sistemas incluido el óseo. La EEC se encuentra descripta dentro de las enfermedades osteocon-densantes (EO), las cuales se reconocen por presentar aumento de la masa ósea y compromiso tanto de huesos largos como planos. La presentación clínica de la EEC es variada: puede presentar desde un curso indolente hasta manifestaciones multisistémicas. Las características radiológicas son de gran importancia para establecer su diagnóstico. Presentamos una paciente con EEC, con esclerosis bilateral de huesos largos, que exhibe algunas características diferenciales con relación a otros casos reportados: a) afectación exclusivamente ósea a 10 años de evolución, b) compromiso bilateral y simétrico de distinta magnitud, c) esclerosis cortical endóstica y perióstica, d) signos radiológicos sugestivos de periostitis, d) ausencia de compromiso metafisario, e) ausencia de actividad metabólica de las lesiones en las imágenes de 18F-FDG PET/CT.Conclusión: la presencia de lesiones osteocondensantes bilaterales exclusivamente en huesos largos deben hacer sospechar EEC. La ausencia de compromiso metafisario y de actividad metabólica en 18F-FDG PET/CT ha sido raramente descripta. (AU)


Erdheim - Chester disease (ECD) is a rare disease, characterized by systemic xanthogranulomatous infiltration, with involvement of various organs including bone. ECD is described within the sclerosing bone disorders, which are recognized for presenting increased bone mass and involvement of both long and flat bones. The clinical presentation of ECD is diverse, ranging from an asymptomatic course to multisystemic manifestations. Radiological features are of great importance to establish the diagnosis. We describe here a patient with ECD, with bilateral sclerosis of long bones that presents some differential characteristics in relation to other reported cases: a) exclusively bone involvement at 10 years of evolution, b) bilateral and symmetric involvement of different magnitude, c) endosteal and periosteal cortical sclerosis d) radiological signs suggestive of periostitis, d) absence of metaphyseal involvement, e) absence of metabolic activity of the lesions in 18F-FDG PET/CT.Conclusion: the presence of bilateral osteosclerosis exclusively in long bones should lead to suspect ECD. The absence of metaphyseal involvement and metabolic activity in 18F-FDG PET/CT have been rarely described. (AU)


Subject(s)
Humans , Female , Middle Aged , Sclerosis/etiology , Erdheim-Chester Disease/diagnostic imaging , Femur/pathology , Humerus/pathology , Vinblastine/adverse effects , Biopsy, Needle , Prednisone/therapeutic use , Radiography , Radionuclide Imaging , Interferons/adverse effects , Erdheim-Chester Disease/drug therapy , Positron-Emission Tomography , Pain Management , Zoledronic Acid/administration & dosage
3.
Araçatuba; s.n; 2023. 78 p. ilus, tab, graf.
Thesis in Portuguese | LILACS, BBO | ID: biblio-1512684

ABSTRACT

O ozônio tem sido utilizado no processo de reparo ósseo em condições desfavoráveis, como na osteonecrose dos maxilares induzida por medicamentos (OMIM). O objetivo deste trabalho foi avaliar a aplicação de ozonioterapia como prevenção e/ou o tratamento da OMIM. Cento e vinte ratos wistar foram distribuídos entre os grupos tratamentos: eles foram induzidos com Zoledronato e receberam ozonioterapia antes da exodontia (prevenção ­ GOP), após exodontia (tratamento ­ GOT), em ambos momentos (prevenção e tratamento ­ GOPT), um grupo não recebeu ozônio (ZOL), e outro recebeu soro fisiológico ao invés da indução (SAL). Após 14 e 28 dias pós-operatórios foram eutanasiados e as peças submetidas as análises histológicas com eosina e hematoxilina, imunoistoquímica, microtomográfica computadorizada (microCT), confocal a LASER e histomorfométrica. Em 14 dias observamos o início do reparo em GOT, assim como um epitélio presente em SAL e GOT, o mesmo ocorre em 28 dias, e uma intensa imunomarcação de osteocalcina (OC) em GOPT em 14 dias. A microCT demostrou maiores médias de BV/TV em todos grupos quando comparados a ZOL (p< 0,001), ZOL apresentou maior porosidade (p=0,03) e o espaçamento trabecular foi maior no grupo GOT quando comparado ao GOP (p< 0,05). A taxa de aposição mineral (MAR) dos grupos GOP foram maiores (21,46±14,12), seguida do grupo GOT (19,66± 13,23). GOT apresentou a maior média de %NBA (68,322±25,296), quando comparado ao grupo ZOL (p < 0,05), seguido pelo grupo SAL (66,039±28,379) e ZOL (60,856±28,425). Diante dos resultados pode-se observar que a ozonioterapia pode modular o reparo alveolar em animais induzidos com ácido zoledrônico(AU)


Ozone has been used in the bone repair process under unfavorable conditions, such as in druginduced osteonecrosis of the jaws (OMIM). The objective of this work was to evaluate the application of ozone therapy as prevention and/or treatment of OMIM. One hundred and twenty wistar rats were distributed among treatment groups: they were induced with Zoledronate and received ozone therapy before tooth extraction (prevention - GOP), after tooth extraction (treatment - GOT), at both times (prevention and treatment - GOPT), one group I did not receive ozone (ZOL), and another received saline instead of induction (SAL). After 14 and 28 days postoperatively, they were euthanized and the pieces submitted to histological analysis with eosin and hematoxylin, immunohistochemistry, computed microtomography (microCT), confocal LASER and histomorphometric analysis. In 14 days we observed the beginning of repair in GOT, as well as an epithelium present in SAL and GOT, the same occurs in 28 days, with intense immunostaining of osteocalcin (OC) in GOPT in 14 days. The microCT showed higher BV/TV means in all groups when compared to the ZOL (p< 0.001), ZOL showed greater porosity (p=0.03) and the trabecular spacing was greater in the GOT group when compared to the GOP (p< 0 .05). The mineral apposition rate (MAR) of the GOP groups were higher (21,46±14,12), followed by the GOT group (19,66± 13,23). GOT had the highest average of %NBA (68.322±25.296), when compared to the ZOL group (p < 0.05), followed by the SAL group (66.039±28.379) and ZOL (60.856±28.425). In view of the results, it can be observed that ozone therapy can modulate alveolar repair in animals induced with zoledronic acid(AU)


Subject(s)
Animals , Rats , Osteonecrosis , Bisphosphonate-Associated Osteonecrosis of the Jaw , Ozone Therapy , Bone Regeneration , Tooth Socket , Diphosphonates , Zoledronic Acid
4.
Araçatuba; s.n; 2023. 78 p. ilus, graf.
Thesis in Portuguese | LILACS, BBO | ID: biblio-1553304

ABSTRACT

O ozônio tem sido utilizado no processo de reparo ósseo em condições desfavoráveis, como na osteonecrose dos maxilares induzida por medicamentos (OMIM). O objetivo deste trabalho foi avaliar a aplicação de ozonioterapia como prevenção e/ou o tratamento da OMIM. Cento e vinte ratos wistar foram distribuídos entre os grupos tratamentos: eles foram induzidos com Zoledronato e receberam ozonioterapia antes da exodontia (prevenção ­ GOP), após exodontia (tratamento ­ GOT), em ambos momentos (prevenção e tratamento ­ GOPT), um grupo não recebeu ozônio (ZOL), e outro recebeu soro fisiológico ao invés da indução (SAL). Após 14 e 28 dias pós-operatórios foram eutanasiados e as peças submetidas as análises histológicas com eosina e hematoxilina, imunoistoquímica, microtomográfica computadorizada (microCT), confocal a LASER e histomorfométrica. Em 14 dias observamos o início do reparo em GOT, assim como um epitélio presente em SAL e GOT, o mesmo ocorre em 28 dias, e uma intensa imunomarcação de osteocalcina (OC) em GOPT em 14 dias. A microCT demostrou maiores médias de BV/TV em todos grupos quando comparados a ZOL (p< 0,05), seguido pelo grupo SAL (66,039±28,379) e ZOL (60,856±28,425). Diante dos resultados pode-se observar que a ozonioterapia pode modular o reparo alveolar em animais induzidos com ácido zoledrônico(AU)


Ozone has been used in the bone repair process under unfavorable conditions, such as in druginduced osteonecrosis of the jaws (OMIM). The objective of this work was to evaluate the application of ozone therapy as prevention and/or treatment of OMIM. One hundred and twenty wistar rats were distributed among treatment groups: they were induced with Zoledronate and received ozone therapy before tooth extraction (prevention - GOP), after tooth extraction (treatment - GOT), at both times (prevention and treatment - GOPT), one group I did not receive ozone (ZOL), and another received saline instead of induction (SAL). After 14 and 28 days postoperatively, they were euthanized and the pieces submitted to histological analysis with eosin and hematoxylin, immunohistochemistry, computed microtomography (microCT), confocal LASER and histomorphometric analysis. In 14 days we observed the beginning of repair in GOT, as well as an epithelium present in SAL and GOT, the same occurs in 28 days, with intense immunostaining of osteocalcin (OC) in GOPT in 14 days. The microCT showed higher BV/TV means in all groups when compared to the ZOL (p< 0.05), followed by the SAL group (66.039±28.379) and ZOL (60.856±28.425). In view of the results, it can be observed that ozone therapy can modulate alveolar repair in animals induced with zoledronic acid(AU)


Subject(s)
Animals , Rats , Bisphosphonate-Associated Osteonecrosis of the Jaw , Bisphosphonate-Associated Osteonecrosis of the Jaw/prevention & control , Bisphosphonate-Associated Osteonecrosis of the Jaw/therapy , Tooth Socket , X-Ray Microtomography , Zoledronic Acid
5.
Article in English | WPRIM | ID: wpr-929144

ABSTRACT

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.


Subject(s)
Animals , Female , Humans , Mice , Bisphosphonate-Associated Osteonecrosis of the Jaw/prevention & control , Bone Density Conservation Agents , Diphosphonates , Microbiota , Periapical Diseases , Zoledronic Acid
6.
Araçatuba; s.n; 2022. 66 p. ilus, graf.
Thesis in Portuguese | LILACS, BBO | ID: biblio-1510423

ABSTRACT

Objetivo: O objetivo deste trabalho foi avaliar a resposta dos tecidos periimplantares em condições de normalidade e com peri-implantite induzida por ligadura, em implantes osseointegrados na maxila de ratas senescentes submetidas ao tratamento posterior com dosagem oncológica de zoledronato. Material e métodos: Foram utilizadas 28 ratas Wistar (Rattus novergicus) iniciando o experimento com aproximandamente 14 meses de idade e pesando entre 350 e 450g. Os animais foram submetidos à exodontia do incisivo superior direito e instalação imediata de um implante de titânio com 2,5 mm de diâmetro por 5,7 mm de comprimento, onde após quase 2 meses, foi realizada a cirurgia de reabertura dos implantes e instalação de um cicatrizador. Após uma semana, os animais foram divididos de acordo com os seguintes tratamentos: veículo, administração de solução salina estéril 0,9% intraperitoneal (Grupo VEI); zoledronato, com administração de 100 µg/Kg de zoledronato (Grupo ZOL); veículo com peri-implantite experimental (Grupo VEI-PIE) e; zoledronato com peri-implantite experimental (Grupo ZOL-PIE), com a indução da peri-implantite experimental (PIE) por meio de uma ligadura de algodão 5 semanas após o início do tratamento medicamentoso. A porcentagem de tecido ósseo total (PTO-T) e porcentagem de tecido ósseo não vital (PTO-NV) foram analisadas histometricamente, e foram realizadas imunomarcações para fosfatase ácida resistente ao tartarato (TRAP), fator de necrose tumoral alfa (TNFα), interleucina 1 beta (IL1-ß), fator de crescimento endotelial vascular (VEGF) e osteocalcina (OCN). Os dados foram submetidos à análise estatística. Resultados: O grupo ZOL mostrou persistência de inflamação no tecido conjuntivo peri-implantar e uma quantidade considerável de PTO-NV ao redor do implante quando comparado com VEI. A inflamação peri-implantar foi mais exacerbada em ZOL-PIE, assim como, o comprometimento da vitalidade do tecido ósseo ao redor dos implantes quando comparado com VEI-PIE. Conclusão: Conclui-se que o tratamento com altas doses de zoledronato ocasiona alterações ao nível periimplantar, dentre elas, um aumento da inflamação local, e da PTO-NV ao redor do implante osseointegrado, o que pode representar um possível fator de risco para o surgimento da osteonecrose dos maxilares associada à terapia medicamentosa relacionada ao implante odontológico (ONMM-IO). Na presença da PIE há uma exacerbação da inflamação e um aumento ainda maior da PTO-NV, o que implica em um importante fator de risco agravante para o surgimento da ONMM-IO no modelo experimental estudado(AU)


Aim: The aim of this study was to evaluate the response of peri-implant tissues under normal conditions and with ligature-induced peri-implantitis, in osseointegrated implants in the maxilla of senescent rats submitted to subsequent treatment with oncological dosage of zoledronate. Material and methods: Twenty-eight female Wistar rats (Rattus novergicus) were used, starting the experiment at approximately 14 months of age and weighing between 350 and 450g. The animals underwent extraction of the upper right incisor and immediate installation of a titanium implant 2.5 mm wide by 5.7 mm long, where after almost 2 months, surgery to reopen the implants and installation of a healer was performed. After one week, the animals were divided according to the following treatments: vehicle, administration of 0.9% sterile saline intraperitoneally (VEI Group); zoledronate, with administration of 100 µg/Kg of zoledronate (ZOL Group); vehicle with experimental peri-implantitis (VEIPIE Group) and; zoledronate with experimental peri-implantitis (ZOL-PIE Group), with the induction of experimental peri-implantitis (PIE) by means of a cotton suture 5 weeks after the start of drug treatment. The percentage of total bone tissue (PBT-T) and percentage of non-vital bone tissue (PBT-NV) were analyzed histometrically, and immunostaining for tartrate-resistant acid phosphatase (TRAP), tumor necrosis factor alpha (TNFα), interleukin 1 beta (IL1-ß), vascular endothelial growth factor (VEGF) and osteocalcin (OCN). Data were subjected to statistical analysis. Results: The ZOL group showed persistence of inflammation in the peri-implant connective tissue and a considerable amount of PBT-NV around the implant when compared to VEI. Peri-implant inflammation was more exacerbated in ZOL-PIE, as well as compromised bone tissue vitality around the implants when compared to VEI-PIE. Conclusion: It is concluded that treatment with high doses of zoledronate causes changes at the peri-implant level, among them, an increase in local inflammation, and in PBT-NV around the osseointegrated implant, which may represent a possible risk factor for the emergence of medication-related osteonecrosis of the jaws implant- associated (MRONJ-IA). In the presence of PIE, there is an exacerbation of inflammation and an even greater increase in PBT-NV, which implies an important aggravating risk factor for the emergence of MRONJ-IA in the experimental model studied(AU)


Subject(s)
Animals , Rats , Osteonecrosis , Dental Implantation, Endosseous , Zoledronic Acid , Tumor Necrosis Factor-alpha , Vascular Endothelial Growth Factor A , Maxilla
7.
Rev. cuba. med ; 60(1): e1354, tab, graf
Article in Spanish | LILACS, CUMED | ID: biblio-1156553

ABSTRACT

Introducción: El ácido zoledrónico mejora la calidad de vida en pacientes con metástasis óseas por cáncer prostático. Objetivo: Evaluar la calidad de vida relacionada con la salud con el cuestionario EORTC QLQ-BM22 en pacientes con metástasis óseas por cáncer prostático tratados con ácido zoledrónico. Métodos: Se realizó un estudio prospectivo-descriptivo de 71 pacientes con cáncer prostático metastásico a hueso tratados en el servicio de oncología del Hospital Clínico Quirúrgico "Hermanos Ameijeiras" con: edades 18-80 años, ECOG<3, expectativa de vida >6 meses, y seguimiento de al menos doce meses. Se administró ácido zoledrónico cada 21-28 días. Se aplicó la escala visual análoga y el módulo EORTC QLQ-BM22. Resultados: Los pacientes tenían una mediana de 71 años de edad, Gleason ≥ 8: en 57,7 % de los pacientes, PSA al diagnóstico ≥ 20 ng/mL: 70,4 por ciento, ECOG 1: 67,6 por ciento, y estadio IV como presentación inicial: 50,7 por ciento. Metástasis óseas sin toma visceral: 84,5 por ciento, en vértebras 36,6 por ciento, <3 sitios 66,2 por ciento, y metástasis óseas blásticas 60,6 por ciento. Eventos esqueléticos relacionados previos al ácido zoledrónico 7,9 por ciento (fractura), y posteriores, 5,6 por ciento (radioterapia anti-álgica). A doce meses, acorde a la escala visual análoga, se alcanzó respuesta completa: 71 por ciento, y parcial: 29 por ciento (p<0,05). Luego de la aplicación del módulo EORTC QLQ-BM22, se comprobó disminución significativa tanto en la escala de síntomas como en la funcional, independientemente de otros factores. Conclusiones: Los tratamientos específicos para cáncer prostático combinado a zoledrónico mejoran significativamente el dolor y calidad de vida relacionada con la salud en pacientes con metástasis óseas(AU)


Introduction: Zoledronic Acid improves the quality of life of patients suffering from prostate cancer. Objectives: To assess the health-related quality of life using EORTC QLQ-BM22 questioner in patients suffering from prostate cancer, treated with zoledronic acid. Method: A prospective-descriptive study was carried out in 71 patients suffering from prostate cancer involving bones, with ages ranging between 18 and 80 years, and who were treated in the oncology service at Hermanos Ameijeiras Hospital. The ECOG was less than 3, life expectancy> 6 months, and follow-up of at least twelve months. Zoledronic acid was administered every 21-28 days. The visual analog scale and EORTC QLQ-BM22 module were applied. Results: The patients had median age of 71 years, Gleason ≥ 8: in 57.7% of the patients, PSA at diagnosis ≥ 20 ng / mL: 70.4%, ECOG 1: 67.6 percent, and stage IV as initial presentation: 50.7 percent. Bone metastases without visceral intake: 84.5 percent, in vertebrae 36.6 percent, <3 sites 66.2 percent, and blast bone metastases 60.6 percent. Skeletal events related to zoledronic acid before 7.9 percent (fracture), and after 5.6 percent (anti-allergic radiotherapy). At twelve months, according to the visual analog scale, a complete response was achieved, 71 percent, and a partial response, 29 percent (p <0.05). After the application of EORTC QLQ-BM22 module, a significant decrease was found in both the symptom and functional scales, regardless of other factors. Conclusions: Specific treatments for prostate cancer combined with zoledronic significantly improve pain and health-related quality of life in patients with bone metastases(AU)


Subject(s)
Humans , Male , Prostatic Neoplasms/drug therapy , Quality of Life , Bone Neoplasms , Zoledronic Acid/therapeutic use , Neoplasm Metastasis/diagnosis , Epidemiology, Descriptive , Prospective Studies
8.
Araçatuba; s.n; 2021. 80 p. graf, ilus.
Thesis in Portuguese | LILACS, BBO | ID: biblio-1402373

ABSTRACT

Este trabalho teve como objetivo analisar o potencial da terapia com ozônio na dinâmica do tecido ósseo de ratas ovariectomizadas tratadas com ácido zolendrônico. Para tanto, 110 ratas Wistar, fêmeas, 6 meses de idade foram submetidas à ovariectomia bilateral (Ovx). Após três meses, dez animais foram submetidos à eutanásia para caracterização da arquitetura do tecido ósseo em microtomografia (Micro ct), os animais restantes foram divididos em dois grupos, o grupo ZOL e o grupo SAL e foi iniciado o tratamento nos animais do grupo ZOL com ácido zoledrônico (100 µg/Kg/28 dias) e, no grupo SAL foi administrado 0,45 ml de solução salina usando o mesmo protocolo do ZOL. Após três meses desta terapia, 10 animais de cada grupo foram submetidos à eutanásia para caracterização da arquitetura óssea (Micro-ct) e os animais restantes foram novamente divididos aleatoriamente, em que os animais do grupo ZOL foram subdivididos em ZOL (n=20) e ZOL+OZN (n=20) e, os animais dos grupos SAL foram subdivididos em SAL (n=20) e SAL+OZN (n=20). Após este procedimento foi iniciada a ozonioterapia em concentração de 0,7mg/kg a cada dois dias até o final do experimento. Após 30 e 60 dias do início da terapia com ozônio, seis animais de cada grupo foram submetidos à eutanásia para a análise e caracterização estrutural óssea das regiões de mandíbula, cabeça femoral e coluna vertebral. Uma parte das peças correspondentes ao colo femoral foram destinada a testes biomecânicos. As demais amostras coletadas foram descalcificadas e as lâminas histológicas foram coradas em hematoxilina e eosina para a análise histométrica (área de osso neoformado), contagem de células inflamatórias (linfócitos) e contagem de osteócitos. Os órgãos do metabolismo e absorção como mesentério, fígado, rins, pulmão e cérebro foram removidos para a avaliação do infiltrado inflamatório e ou qualquer proliferação celular desordenada. Para os parâmetros quantitativos de porcentagem de tecido ósseo na região de cabeça femoral e mandíbula, o teste ANOVA-2 fatores (grupos vs períodos de análise) foi aplicado e em seguida o pós-teste Tukey, quando p<0,05. Já este parâmetro na coluna vertebral, o teste ANOVA-1 fator (grupos experimentais, somente no período de 30 dias) foi aplicado e pós-teste de Tukey. Em todos os testes foi considerado p<0,05. O tratamento com ácido zoledrônio e ozônio (ZOL+OZN) apresentou maior porcentagem de volume ósseo, maior número de osteócitos e maior número de células inflamatórias na região de cabeça femoral, mandíbula com resultados estatisticamente significantes (p<0,05). Na análise biomecânica do colo femoral, o módulo de elasticidade foi semelhante para os grupos ZOL e ZOL+OZN (p>0,05), em comparação aos grupos SAL e SAL+OZN (p<0,05). Este estudo in vivo mostrou que existe um efeito sinérgico entre o ozônio e o ácido zoledrônico com manutenção da massa óssea e restauração da vitalidade do tecido ósseo em ratas ovariectomizadas. Além disso, que a terapia com ozônio foi segura no modelo experimental proposto nesta investigação(AU)


This work aimed to analyze the potential of ozone therapy in the bone tissue dynamics of ovariectomized rats treated with zoledronic acid. For this purpose, 110 Wistar rats, schoolchildren, 6 months old, underwent bilateral ovariectomy (Ovx). After three months, ten animals were euthanized to characterize bone tissue architecture in microtomography (Microct). The remaining animals were divided into two groups: the ZOL group, the SAL group, and treatment was started on the animals in the group. ZOL with zoledronic acid (100 µg / Kg / 28 days) and no SAL group was administered 0.45 ml of saline using the same protocol as ZOL. After three months of this therapy, 10 animals from each group were euthanized to characterize the bone architecture (Micro-ct), and the remaining animals were again randomly divided, in which the animals in the ZOL group were subdivided into ZOL (n = 20) and ZOL + OZN (n = 20) and, the animals in the SAL groups were subdivided into SAL (n = 20) and SAL + OZN (n = 20). After this procedure, ozone therapy was obtained at a concentration of 0.7 mg/kg every two days until the end of the experiment. After 30 and 60 days from the beginning of ozone therapy, six animals from each group were found to be euthanized for analysis and structural bone characterization of the mandible, femoral head, and spine regions. A part of the pieces corresponding to the cervix was destined for biomechanical tests. The others collected were decalcified, and histological slides were stained in hematoxylin and eosin for histometric analysis (area of newly formed bone), inflammatory cell count (lymphocytes), and osteocyte count. The metabolism and absorption organs such as mesentery, liver, kidneys, lung, and brain were removed to evaluate inflammatory infiltrate and or any disorderly cell proliferation. For the quantitative parameters of the percentage of bone tissue in the femoral head and mandible region, the ANOVA-2 factor test (groups vs analysis periods) was provided and then the Tukey post-test, when p <0.05. Already this parameter in the spine, the ANOVA-1 factor test (experimental groups, only in the period of 30 days) was applied and Tukey's post-test. In all tests, p <0.05 was considered. Treatment with zoledronic acid and ozone (ZOL + OZN) showed a higher percentage of bone volume, a greater number of osteocytes, and a greater number of inflammatory cells in the femoral head and mandible region with statistically significant results (p <0.05). In the biomechanical analysis of the femoral neck, the modulus of elasticity was similar for the ZOL and ZOL + OZN groups (p>0.05), compared to the SAL and SAL + OZN groups (p <0.05). This in vivo study revealed a synergistic effect between ozone and zoledronic acid with the maintenance of bone mass and restoration of bone tissue vitality in ovariectomized rats. Furthermore, that ozone therapy was safe in the experimental model proposed in this investigation(AU)


Subject(s)
Animals , Rats , Osteoporosis , Spine , Bone and Bones , Bone Regeneration , Femur , Zoledronic Acid , Ozone Therapy , Mandible , Rats, Wistar , Systemic Management , X-Ray Microtomography , Femur Head , Femur Neck
9.
Araçatuba; s.n; 2021. 56 p. tab, ilus, graf.
Thesis in Portuguese | LILACS, BBO | ID: biblio-1435689

ABSTRACT

O presente estudo teve como objetivo avaliar a efetividade e a segurança do emprego de múltiplas sessões de aPDT, utilizando o butil azul de toluidina (BuAT) e a irradiação com laser de baixa potência (LBP), no sítio de extração dental de ratas com os principais fatores de risco para a ocorrência da osteonecrose dos maxilares associada à terapia medicamentosa (ONM-M). Vinte e oito ratas senescentes foram distribuídas em quatro grupos experimentais: VEI, VEI-aPDT, ZOL e ZOL-aPDT. O protocolo de tratamento teve duração de 7 semanas. Um dia antes do início deste protocolo foi instalada uma ligadura de algodão ao redor do primeiro molar inferior esquerdo para indução da periodontite experimental (PE). Nos grupos VEI e VEI-aPDT, as ratas receberam injeções intraperitoneais de 0,45ml de solução de cloreto de sódio 0,9% (veículo) a cada três dias. Nos grupos ZOL e ZOL-aPDT, as ratas receberam 0,45ml do veículo acrescido de 100µg/Kg do zoledronato a cada três dias. Após três semanas do início do protocolo de tratamento a ligadura foi removida e foi realizada a exodontia do primeiro molar inferior esquerdo. Nos grupos VEI e ZOL não foi efetuado nenhum tratamento local no sítio de extração dental. Nos grupos VEI-aPDT e ZOL-aPDT foram realizadas sessões de aPDT aos 0, 2, e 4 dias pós exodontia. Para a aPDT depositouse sobre o sítio de extração dental 300µl de BuAT (concentração: 0,5mg/ml; tempo de pré-irradiação, 60s) em seguida foi realizada a irradiação com laser de baixa potência (laser: InGaAIP; 660nm; 35mW; 74,2J/cm²; 60s) emissor: InGaAlP; comprimento de onda: 660 nm, laser visível - vermelho; potência: 35 mW; densidade energética por ponto: 74,2 J/cm2 ; tempo de aplicação: 60s). Decorridos 28 dias pós-operatórios foi realizada a eutanásia. As hemimandíbulas foram devidamente processadas para assegurar que no sítio de extração dental fossem efetuadas: 1) análise clínica; 2) análise histológica da reparação tecidual; 3) análise histométrica da Porcentagem de Tecido Ósseo Neoformado (PTOnf); 4) análise histométrica da Porcentagem de Tecido Ósseo Não Vital (PTOnv) e; análise imunoistoquímica de células TRAPpositivas. Os dados foram submetidos à análise estatística com nível de significância de 5%. Os grupos ZOL e ZOL-aPDT apresentaram menor quantidade de células TRAP-positivas quando comparados com os grupos VEI e VEI-aPDT. O grupo ZOL apresentou grande comprometimento do processo de reparação tecidual, condizentes com um quadro de ONM-M. Os grupos VEI, VEI-aPDT e ZOL-aPDT apresentaram um processo de reparação tecidual favorável do sítio de extração dental. No grupo ZOL a PTOnf no sítio de extração dental se mostrou menor que nos grupos VEI, VEI-aPDT e ZOL-aPDT. No grupo ZOL a PTOnv se mostrou maior que nos grupos VEI, VEIaPDT e ZOL-aPDT. No grupo ZOL-aPDT a PTOnv se apresentou maior que nos grupos VEI e VEI-aPDT. O emprego de múltiplas sessões de aPDT, utilizando o BuAT e LBP, no sítio de extração dental de ratas senescentes tratadas com alta dose de zoledronato se mostrou uma estratégia terapêutica segurança e efetiva para evitar a ocorrência da ONM-M pós exodontia(AU)


The present study aimed to evaluate the effectiveness and safety of using multiple aPDT sessions, using butyl toluidine blue (BuTB) and low-level laser irradiation (LLL), at the dental extraction site of rats with the main risk factors for the occurrence of medication-related osteonecrosis of the jaws (MRONJ). Twenty-eight senescent rats were distributed in four experimental groups: VEH, VEH-aPDT, ZOL and ZOL-aPDT. The treatment protocol lasted 7 weeks. One day before the beginning of this protocol, a cotton ligature was installed around the mandibular first molar left to induce experimental periodontitis (EP). In the VEH and VEH-aPDT groups, the rats received intraperitoneal injections of 0.45 ml of 0.9% sodium chloride solution (vehicle) every three days. In the ZOL and ZOL-aPDT groups, the rats received 0.45 ml of the vehicle plus 100 µg / Kg of zoledronate every three days. Three weeks after the beginning of the treatment protocol, the ligature was removed and extraction of the mandibular first molar left was performed. In the VEH and ZOL groups, no local treatment was performed at the tooth extraction site. In the VEH-aPDT and ZOL-aPDT groups, aPDT sessions were performed at 0, 2, and 4 days after extraction. For aPDT, 300µl of BuTB was deposited on the dental extraction site (0.5mg / ml; pre-irradiation time, 60s), followed by irradiation with low-level laser (laser: InGaAIP; 660nm; 35mW; 74.2J / cm²; 60s). After 28 postoperative days, euthanasia was performed. The hemimandibles were properly processed to ensure that at the tooth extraction site: 1) clinical analysis; 2) histological analysis of tissue repair; 3) histometric analysis of the Percentage of Neoformed Bone Tissue (PNFBT); 4) histometric analysis of the Percentage of NonVital Bone Tissue (PNVBT) and; immunohistochemical analysis of TRAP-positive cells. The data were submitted to statistical analysis with a 5% significance level. The ZOL and ZOL-aPDT groups showed less TRAP-positive cells when compared with the VEH and VEH-aPDT groups. The ZOL group showed great compromise in the tissue repair process, consistent with MRONJ. The groups VEH, VEH-aPDT and ZOL-aPDT presented a favorable tissue repair process at the dental extraction site. In the ZOL group, the PNFBT at the tooth extraction site was lower than in the VEH, VEH-aPDT and ZOL-aPDT groups. In the ZOL group, PNVBT was higher than in the VEH, VEHaPDT and ZOL-aPDT groups. In the ZOL-aPDT group, PNVBT was higher than in the VEH and VEH-aPDT groups. The use of multiple aPDT sessions, using BuTB and LLL, at the dental extraction site of senescent rats treated with a high dose of zoledronate proved to be a safe and effective therapeutic strategy to prevent the occurrence of MRONJ after tooth extraction(AU)


Subject(s)
Animals , Rats , Osteonecrosis , Low-Level Light Therapy , Bisphosphonate-Associated Osteonecrosis of the Jaw , Jaw , Rats, Wistar , Diphosphonates , Bisphosphonate-Associated Osteonecrosis of the Jaw/prevention & control , Zoledronic Acid , Anti-Infective Agents
10.
Araçatuba; s.n; 2021. 91 p. ilus, graf.
Thesis in Portuguese | LILACS, BBO | ID: biblio-1413767

ABSTRACT

A ozonioterapia vem se demonstrando uma ferramenta promissora na prevenção de infecções e no auxílio da reparação tecidual, conciliando com os desafios no tratamento da osteonecrose dos maxilares induzida por medicamentos (ONM-M), este projeto objetiva analisar os efeitos da ozonioterapia, em 55 ratas senis (18 meses), entre 300-350g, induzidas a osteonecrose via medicamentosa (Zoledronato 100µg/kg), após exodontia do primeiro molar inferior. Os animais foram divididos em 4 grupos equitativos (10 ratas por grupo), o primeiro grupo SAL, recebeu aplicações de soro fisiológico por 7 semanas, grupo SAL + OZ recebeu aplicações de soro fisiológico por 7 semanas e o tratamento com a ozonioterapia (0,7mg/kg) a cada 2 dias por 28 dias, o grupo ZOL recebeu aplicações de zoledronato (100µg/kg) por 7 semanas e por último o grupo ZOL + OZ recebeu também aplicações de zoledronato no mesmo protocolo e foi tratado com a ozonioterapia (0,7mg/kg) a cada 2 dias por 28 dias. Todos as ratas receberam a antibioticoterapia (Cristacilina® 0,1ml/kg por dia) iniciando 3 dias antes do procedimento de extração, se estendendo até 4 dias de pós-operatório, passaram pela extração do molar na terceira semana de experimento e foram submetidas a eutanásia na sétima semana de experimento. Após a eutanásia as mandíbulas foram ressecadas, reduzidas e preparadas para as análises microtomográficas (caracterização óssea do osso senil (MCT0) e após terapia com zoledronato (MCT1ZOL) contra seu par controle (MCT1SAL), parâmetros volumétricos (Bv,Bv.Tv,Tb.Th,Tb.N,Tb.Sp,Po.Tot) dos grupos experimentais), histométricas (porcentagem de osso neoformado e porcentagem de osso não vital) e imunoistoquímicas (expressão de TNFa, IL-1b, VEGF, OCN e TRAP). Os resultados da caracterização óssea não apresentaram diferença quando comparado os grupos experimentais (p> 0,05), possivelmente devido ao pouco tempo decorrido na terapia com zoledronato. Os demais resultados comparando os grupos experimentais mostrou com diferenças estatisticamente significativas (p< 0,05) uma característica de osso vítreo, denso, sem vitalidade, pobre em vascularização, com elevados valores para marcadores de inflamação, traduzindo isso em osteonecrose dos maxilares relacionada com a medicação, destoando principalmente do grupo controle SAL, que apresentou melhora na reparação alveolar e características de osso vital e vascularizado. A ozonioterapia (ZOL+OZ, SAL+OZ) apresentou valores significantes estatisticamente quando comparado ao grupo sem tratamento, traduzindo em melhora na vascularização do tecido ósseo, em melhora reparacional do alvéolo, modulação da inflamação local e o aparecimento/manutenção de células osteoblásticas ativas (p< 0,05). Mostrando-se uma terapia viável no controle/tratamento da osteonecrose dos maxilares relacionado com medicamentos(AU)


Ozone therapy has been shown to be a promising tool in the prevention of infections and in the aid of tissue repair, reconciling with the challenges in the treatment of medication-induced jaw osteonecrosis (ONM-M), this project aims to analyze the effects of ozone therapy in 55 rats senile (18 months), between 300-350g, induced to osteonecrosis via medication (Zoledronate 100µg / kg), after extraction of the lower first molar. The animals were divided into 4 equitable groups (ten rats per group), the first SAL group, received saline applications for 7 weeks, SAL + OZ group received saline applications for 7 weeks and ozone therapy (0, 7mg / kg) every 2 days for 28 days, the ZOL group received applications of zoledronate (100µg / kg) for 7 weeks and lastly the ZOL + OZ group also received applications of zoledronate in the same protocol and was treated with ozone therapy (0.7mg / kg) every 2 days for 28 days. All rats received antibiotic therapy (Cristacilina® 0.1ml / kg per day) starting 3 days before the extraction procedure, extending up to 4 days after the operation, underwent molar extraction in the third week of the experiment and were submitted to euthanasia in the seventh week of experiment. After euthanasia, the mandibles were resected, reduced and prepared for microtomographic analysis (bone characterization of senile bone (MCT0) and after therapy with zoledronate (MCT1ZOL) against its control pair (MCT1SAL), volumetric parameters (Bv, Bv.Tv, Tb .Th, Tb.N, Tb.Sp, Po.Tot) of the experimental groups), histometric (percentage of newly formed bone and percentage of non-vital bone) and immunohistochemistry (expression of TNFa, IL-1b, VEGF, OCN and TRAP) . The results of bone characterization did not show any difference when comparing the experimental groups (P> 0.05), possibly due to the short time elapsed in zoledronate therapy. The other results comparing the experimental groups showed with statistically significant differences (P < 0.05) a characteristic of vitreous bone, dense, without vitality, poor in vascularization, with high values for inflammation markers, translating this into a related jaw osteonecrosis with medication, disagreeing mainly with the SAL control group, which showed improvement in alveolar repair and characteristics of a vital and vascularized bone. Ozone therapy (ZOL + OZ, SAL + OZ) showed statistically significant values when compared to the untreated group, translating into an improvement in bone tissue vascularization, a reparational improvement of the alveolus, modulation of local inflammation and the appearance/maintenance of cells active osteoblasts (P < 0.05). Showing to be a viable therapy in the control/treatment of osteonecrosis of the jaws related to drugs(AU)


Subject(s)
Animals , Rats , Osteonecrosis/chemically induced , Abnormalities, Drug-Induced , Bisphosphonate-Associated Osteonecrosis of the Jaw , Zoledronic Acid/adverse effects , Zoledronic Acid/poisoning , Zoledronic Acid/toxicity , Ozone Therapy , Mandible/abnormalities , Maxilla/abnormalities , Osteoblasts , Bone and Bones , Rats, Wistar , Jaw
11.
Acta cir. bras ; 36(6): e360603, 2021. tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1278113

ABSTRACT

ABSTRACT Purpose To evaluate the influence of bioactive glass and photobiomodulation therapy (PBMT) in calvarial bone repair process in rats submitted to zoledronic acid therapy. Methods Twenty-four rats were selected and treated with the dose of 0.035 mg/kg of zoledronic acid every two weeks, totalizing eight weeks, to induce osteonecrosis. After the drug therapy, surgical procedure was performed to create 5-mm diameter parietal bone defects in the calvarial region. The rats were then randomly assigned to groups according to the following treatments: AZC: control group, treated with blood clot; AZBIO: bone defect filled with bioactive glass; AZL: treated with blood clot and submitted to PBMT; and AZBIOL: treated with bioactive glass S53P4 and submitted to PBMT. Tissue samples were collected and submitted to histomorphometric analysis after 14 and 28 days. Results At 14 days, bone neoformation in the AZBIO (52.15 ± 9.77) and AZBIOL (49.77 ± 13.58) groups presented higher values (p ≤ 0.001) compared to the AZC (23.35 ± 10.15) and AZL groups (23.32 ± 8.75). At 28 days, AZBIO (80.24 ± 5.41)still presented significant higher bone recovery values when compared to AZC (59.59 ± 16.92)and AZL (45.25 ± 5.41) groups (p = 0.048). In the 28-day period, the AZBIOL group didn't show statistically significant difference with the other groups (71.79 ± 29.38). Conclusions The bioactive glass is an effective protocol to stimulate bone neoformation in critical defects surgically created in rats with drug induced osteonecrosis, in the studied periods of 14 and 28 days.


Subject(s)
Animals , Rats , Low-Level Light Therapy , Bone Regeneration , Zoledronic Acid , Glass
12.
Rev. bras. ortop ; 55(5): 543-550, Sept.-Oct. 2020. graf
Article in English | LILACS | ID: biblio-1144202

ABSTRACT

Abstract Objective The aim of the present study was to determine the effect of combined zoledronic acid and alendronate therapy on bone edema and knee pain in cases of spontaneous osteonecrosis of the knee. We report our experience with this treatment. Methods A retrospective case series of 11 patients with spontaneous osteonecrosis of the knee confirmed by magnetic resonance image (MRI). The patients were treated with a single dose of 5 mg of intravenous zoledronic acid combined with 35 mg twice a week of oral alendronate, for 16 weeks. The visual analogue scale scores were noted before the beginning of the therapy, at 8 weeks, and at 16 weeks of follow-up. The size of the bone marrow edema adjacent to the lesion was measured on T2-weighted MRI coronal images at the beginning of the therapy and at 16 weeks. Results The average visual analogue scale score at 0 weeks was of 7.72, and of 0.81 at 16 weeks of therapy; the difference was statistically significant (p= 0.03). The mean bone marrow involvement at 0 weeks was of 80%, which reduced to 11.81% at 16 weeks of therapy. This change was statistically significant (p= 0.03). Conclusion Our data shows that the combination therapy causes early pain relief and reduction of the bone edema, and it is safe, effective and well-tolerated for a painful disease entity like spontaneous osteonecrosis of the knee.


Resumo Objetivo Determinar o efeito do tratamento combinado de ácido zoledrônico e alendronato no edema ósseo e na dor no joelho em casos de osteonecrose espontânea do joelho. A experiência dos autores com este tratamento é relatada. Métodos Série de casos retrospectiva, incluindo 11 pacientes com osteonecrose espontânea do joelho confirmada por ressonância magnética. Os pacientes foram tratados com uma dose intravenosa única de 5 mg de ácido zoledrônico combinada com 35 mg de alendronato oral, 2 vezes por semana, por 16 semanas. Os escores da escala visual analógica foram aferidos antes do começo do tratamento, em 8 semanas e em 16 semanas de acompanhamento. O tamanho do edema da medula óssea adjacente à lesão foi medido em imagens de ressonância magnética coronal ponderadas em T2 no início do tratamento e em 16 semanas. Resultados O escore médio da escala visual analógica em 0 semanas foi de 7,72, contra 0,81 em 16 semanas de tratamento, uma diferença estatisticamente significativa (p= 0,03). O envolvimento médio da medula óssea em 0 semanas foi de 80%, e foi reduzido para 11,81% em 16 semanas de tratamento, uma diferença também estatisticamente significativa (p= 0,03). Conclusão Os dados mostram que a terapia combinada proporciona alívio da dor inicial e redução do edema ósseo, sendo segura, eficaz e bem tolerada em uma enfermidade dolorosa como a osteonecrose espontânea do joelho.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Osteoarthritis , Pain , Bone and Bones , Bone Marrow , Magnetic Resonance Spectroscopy , Combined Modality Therapy , Alendronate , Diphosphonates , Dosage , Visual Analog Scale , Zoledronic Acid , Knee Joint , Necrosis
13.
Braz. dent. j ; 31(3): 304-309, May-June 2020. graf
Article in English | LILACS, BBO | ID: biblio-1132294

ABSTRACT

Abstract Among other factors, types of bisphosphonates and treatment regimens seem to be strongly associated with the success or failure of installation of osseointegrated implants. This study investigated the influence of two bisphosphonates, sodium alendronate (SA) and zoledronic acid (ZA), on the metabolism of osteoblasts. Human osteoblasts (Saos-2) were seeded onto machined or acid-treated titanium discs previously placed on 24-well plates in complete culture medium. After 24 h, cells were exposed to bisphosphonates at 0.5, 1 or 5 µM for 24 h, 48 h or 7 days. The effects of SA and ZA on osteoblasts were assessed based on the adhesion of these cells to the titanium surfaces by direct fluorescence, cell viability, total protein and collagen synthesis. Alkaline phosphatase activity and mineral nodule deposition by these cells were also evaluated. Data were evaluated by ANOVA and Tukey tests (α=0.05). Decreased adhesion of cells to the titanium discs was observed when exposed to both bisphosphonates; however, this lack of cell adhesion was more evident for ZA-treated cells. In addition, the exposure of osteoblasts to ZA decreased the viability, ALP activity and mineral nodule deposition, which may be related to poor osseointegration after implant installation.


Resumo Entre outros fatores, os tipos de bisfosfonatos bem como os regimes de tratamento parecem estar diretamente associados com o sucesso ou falhas na instalação de implantes osseointegrados. Este estudo avaliou a influência de dois bisfosfonatos, o alendronato de sódio (AS) e o ácido zoledrônico (AZ), no metabolismo de osteoblastos. Osteoblastos humanos (Saos-2) foram cultivados sobre discos de titânio polidos ou submetidos a tratamento ácido superficial, previamente alocados em placas de 24 compartimentos, utilizando meio de cultura completo. Após 24 horas, as células foram expostas aos bisfosfonatos, nas concentrações de 0,5, 1 ou 5 µM, por 24 h, 48 h, ou 7 dias. Os efeitos do AZ e AZ sobre os osteoblastos foram determinados considerando a adesão destas células às superfícies de titânio, por meio de fluorescência direta, a viabilidade celular, produção de proteína total e síntese de colágeno. A atividade de fosfatase alcalina e a deposição de nódulos mineralizados também foram avaliadas. Os dados foram analisados por meio do teste ANOVA complementado por Tukey (α = 0.05). Menor adesão dos osteoblastos foi observada quando estas células foram expostas a ambos os bisfosfonatos, porém, esta falha na adesão foi mais evidente para as células tratadas com AZ. Além disso, a exposição dos osteoblastos ao AZ também resultou em diminuição da viabilidade, atividade de ALP e deposição de nódulos mineralizados, o que pode estar relacionado a uma pobre osseointegração após a instalação do implante.


Subject(s)
Humans , Titanium , Diphosphonates , Osteoblasts , Surface Properties , Cell Adhesion , Cell Differentiation , Cells, Cultured , Cell Proliferation , Alkaline Phosphatase , Zoledronic Acid
14.
J. bras. econ. saúde (Impr.) ; 12(1): 16-22, Abril/2020.
Article in Portuguese | LILACS, ECOS | ID: biblio-1096402

ABSTRACT

Objetivo: Estimar o custo por evento relacionado ao esqueleto (ERE) e o impacto econômico anual da adoção de denosumabe em pacientes com metástases ósseas secundárias ao câncer de mama, próstata e outros tumores sólidos ou mieloma múltiplo sob a perspectiva do sistema de saúde privado brasileiro. Métodos: Um modelo econômico foi desenvolvido para comparar os custos relacionados com denosumabe versus ácido zoledrônico na prevenção de EREs. O modelo incluiu os seguintes custos: medicamento, administração, monitoramento e manejo de ERE. O custo anual foi apresentado em reais (BRL) para 100 pacientes. Os custos do manejo de ERE [fratura vertebral (FV), fratura não vertebral (FNV), radiação óssea (RO), cirurgia óssea (CO) e compressão da medula espinhal (CME)] foram estimados a partir dos recursos e procedimentos coletados da revisão de literatura, bases de dados e painel Delphi. Dados coletados dos estudos clínicos randomizados relacionados com cada tipo de tumor na análise e de um estudo prospectivo observacional foram utilizados para estimar a eficácia clínica de denosumabe versus ácido zoledrônico. Resultados: O custo por cada tipo de ERE variou de BRL 27.246 a BRL 28.035 para FV, BRL 18.023 a BRL 18.811 para FNV, BRL 42.750 a BRL 43.538 para RO, BRL 18.023 a BRL 18.811 para CO e BRL 12.472 a BRL 13.260 para CME. A introdução de denosumabe foi estimada em economia anual por 100 pacientes de até BRL 1.072.043,14 para câncer de mama, BRL 1.212.822,79 para outros tumores sólidos, BRL 1.929.660,67 para câncer de próstata e BRL 77.965,07 para mieloma múltiplo. Conclusão: Esta análise sugere que EREs adicionam custos substanciais no manejo de pacientes com metástases ósseas. Dessa forma, o uso de denosumabe pode prevenir e retardar EREs em pacientes com câncer e pode possivelmente levar à redução do impacto econômico associado aos EREs sob a perspectiva dos pagadores de saúde privada brasileira.


Objective: To estimate the cost per SRE and annual economic impact of denosumab adoption in patients with bone metastases (BM) secondary to breast cancer, prostate cancer, other solid tumors or multiple myeloma from the Brazilian private healthcare system's perspective. Methods: An economic model was developed to compare the cost outcomes associated with denosumab instead of zoledronic acid for SRE prevention. The model included the following costs: drug, administration, monitoring and SRE management. Annual costs per 100 patients were reported in 2019 Brazilian currency (BRL). The SRE management costs (vertebral fracture (VF), non-vertebral fracture (NVF), radiation to bone (RB), surgery to bone (SB) and spinal cord compression (SCC)) were estimated from the resources and procedures collected from literature review, official database, and a Delphi panel. Data collected from randomized clinical trials related to each tumor type in the analysis and from a prospective observational study was used to estimate the clinical efficacy of denosumab vs zoledronic acid. Results: The cost per each type of SREs across all tumors ranged BRL 27,246 ­ BRL 28,035 for VF, BRL 18,023 ­ BRL 18,811 for NVF, BRL 42,750 ­ BRL 43,538 for RB, BRL 18,023 ­ BRL 18,811 for SB and BRL 12,472 ­ BRL 13,260 for SCC. The introduction of denosumab was estimated to result in annual savings per 100 patients of up to BRL 1,072,043.14 for breast cancer, BRL 1,212,822.79 for other solid tumors, BRL 1,929,660.67 for prostate cancer and BRL 77,965.07 for multiple myeloma. Conclusion: This analysis suggests that SREs add substantial costs to the management of patients with bone metastases. In this way, the use of denosumab would prevent and delay SREs in cancer patients and might possibly lead to reduce the economic burden associated with SREs, borne by Brazilian private healthcare payers.


Subject(s)
Prostatic Neoplasms , Breast Neoplasms , Denosumab , Zoledronic Acid , Multiple Myeloma , Neoplasm Metastasis
15.
Article in Chinese | WPRIM | ID: wpr-827249

ABSTRACT

OBJECTIVE@#To investigate the clinical efficacy of vertebral body stent (VBS) system and percutanous kyphoplasty (PKP) combined with zoledronic acid for the treatment of severely osteoporotic compression vertebral fractures (OVCFs).@*METHODS@#The clinical data of 48 patients with osteoporotic thoracolumbar fractures treated from December 2017 to December 2018 were retrospectively analyzed, including 13 males and 35 females, aged 55 to 92 years old with an average (71.2±10.5) years. All patients were treated with VBS system PKP surgery, and zoledronic acid injection was used for anti-osteoporosis treatment after operation. The VAS scores ODI, the height of diseasedvertebral lost were compared before operation, 3 d and half a year after operation, and whether there was re-fracture of diseased or adjacent vertevrae after operation was observed.@*RESULTS@#Before operation, 3 d and half a year after operation, VAS scores were 7.60±0.12, 3.00±0.46, 1.20±0.23, ODI were(82.00±0.32)%, (30.00±1.50) %, (18.00±0.16) %, the height of diseased vertebral lost were (12.00±0.43) mm, (3.00± 0.15) mm, (3.60±0.51) mm respectively. Postoperative VAS score, ODI, the height of diseased vertebral lost were obviously improved (0.05). All the 48 patients were followed up with an average time of (6.6±0.5) months. All the incisions healed at grade A after operation, and no re-fracture of diseased vertebrae or adjacent vertebrae was found at the final follow-up.@*CONCLUSION@#VBS system and PKP combined with zoledronic acid in the treatment of OVCFs not only may effectively relieve the pain in the thoracolumbar back, improve the mobility of the thoracolumbar, but also can restore the height of the vertebral body to the maximum extent, and prevent the re-fracture of the affected vertebrae and adjacent vertebrae, which is worthy to spread in clinic.


Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Bone Cements , Fractures, Compression , Kyphoplasty , Osteoporotic Fractures , Retrospective Studies , Spinal Fractures , Stents , Treatment Outcome , Zoledronic Acid
16.
Article in Chinese | WPRIM | ID: wpr-827250

ABSTRACT

OBJECTIVE@#To explore the clinical effect of zoledronic acid combined with vitamin K2 regimen in percutaneous vertebroplasty for multi-segment osteoporotic vertebral compression fractures(OVCFs).@*METHODS@#This study was a retrospective control study. A total of 364 patients with OVCFs who were admitted to our spinal surgery department from January 2014 to January 2017 were selected as the study subjects. According to whether zoledronic acid combined with vitamin K2 was used to treat osteoporosis after surgery, the patients were divided into control group and experimental group. Among them, 257 patients in the control group were treated with calcium carbonate and vitamin D regimen, while 107 patients in the experimental group were treated with zoledronic acid combined with vitamin K2 regimen on the basis of the control group. Visual analogue scale (VAS) score and Oswestry Disability Index (ODI) were used to evaluate the clinical effect. Pre- and post-operative bone mineral density of lumbar spine and proximal femur, vertebral height ratio of responsible vertebral body and Cobb angle of vertebral body were observed by image data. Serological indicators related to bone metabolism were detected by laboratory. The complications such as fever, dizziness, osteoarthritis, muscular and soft tissue pain and adjacent vertebral re-fracture were compared between two groups.@*RESULTS@#There was no significant difference in general data between the two groups (0.05);VAS score in the experimental group was significantly lower than that in the control group 1 month, 3 months and 1 year after operation(0.05), and at the 24 hours, 3 months, 1 year after operation, the experimental group was significantly lower than the control group (0.05). The vertebral height ratio of the responsible vertebral body in experimental group was significantly higher than that in control group and Cobb angle in experimental group was significantly lower than that in control group at 3 months and 1 year after operation (0.05), but at 3 months and 1 year after operation, the bone mineral density of lumbar spine and proximal femur in experimental group was significantly lower than that in control group (0.05). At 1 year after operation the total type I collagen amino-terminal elongation peptide and β-collagen degradation products in experimental group was significantly lower than that in the control group (<0.05), but the 25-hydroxyvitamin D operation in experimental group was significantly higher than that in control group(<0.05). The incidence of postoperative complications such as fever, dizziness, osteoarthritis, muscle and soft tissue pain and adjacent vertebral re-fracture in experimental group was significantly lower than that in control group (<0.05).@*CONCLUSION@#Zoledronic acid injection combined with vitamin K2 regimen can be used for anti-osteoporosis treatment of OVCFs vertebroplasty. It has a definite curative effect and a high safety factor. It is worth popularizing.


Subject(s)
Humans , Bone Cements , Fractures, Compression , Kyphoplasty , Osteoporotic Fractures , Retrospective Studies , Spinal Fractures , Treatment Outcome , Vertebroplasty , Vitamin K 2 , Zoledronic Acid
17.
Article in Chinese | WPRIM | ID: wpr-880772

ABSTRACT

OBJECTIVE@#To investigate the effect of zoledronate (ZOL) on osteoclast differentiation and bone resorption under high glucose, and the regulation mechanism of p38 mitogen activated kinase (p38 MAPK) signaling pathway in this process.@*METHODS@#RAW264.7 cells were divided into four groups: low group, high group, low+ZOL group and high+ZOL group after induced into osteoclasts. Cell proliferation activity was determined by MTT assay. The migration of RAW264.7 cells were examined Optical microscopy. Immunofluorescence microscopy was used to observe the cytoskeleton and sealing zones of osteoclasts. After adding group 5: high + ZOL + SB203580 group, trap staining was used to identify the number of positive osteoclasts in each group. The number and area of resorption lacunae were observed by SEM. The mRNA and protein expression of osteoclast related factors were detected by real-time PCR and Western blotting.@*RESULTS@#The cells in the 5 groups showed similar proliferative activity. High glucose promoted the migration of RAW264.7 cells (@*CONCLUSIONS@#High glucose inhibits osteoclast differentiation and bone resorption. ZOL inhibits osteoclast differentiation and bone resorption in high-glucose conditions by regulating p38 MAPK pathway, which can be a new pathway for ZOL to regulate diabetic osteoporosis.


Subject(s)
Animals , Mice , Bone Resorption , Cell Differentiation , Glucose , MAP Kinase Signaling System , NFATC Transcription Factors , Osteoclasts , RANK Ligand , Zoledronic Acid/pharmacology , p38 Mitogen-Activated Protein Kinases
18.
Araçatuba; s.n; 2020. 62 p. ilus, graf, tab.
Thesis in Portuguese | LILACS, BBO | ID: biblio-1434529

ABSTRACT

O processo de senescência acarreta uma série de modificações fisiológicas com declínio das funções das atividades celulares e sistêmicas que se manifestam de maneira mais importante na população feminina pelo evento da menopausa, como a osteoporose. A fim de se minimizar tais efeitos, há a possibilidade de se utilizar medicamentos que diminuem o processo de remodelação óssea como os bifosfonatos nitrogenados (BF). Entretanto, o uso dessas drogas está intimamente relacionado ao desenvolvimento de osteonecrose dos maxilares (OM), principalmente quando associado a outros fatores de risco como as cirurgias bucais. Sabe-se que fisiologicamente a dinâmica do tecido ósseo depende também de eicosanóides derivados do metabolismo do ácido araquidônico (AA), como as enzimas cicloxigenase (COX) e 5 lipoxigenase (5LO). Deste modo, o objetivo do presente trabalho foi analisar o efeito BF ácido zoledrônico (ZL) e sua relação com o desenvolvimento da OM em camundongos fêmeas senescentes 129/Sv com e sem modificação genética para a enzima 5LO. Para tanto, foram utilizados 40 camundongos fêmeas senescentes 129/Sv, sendo 20 WT e 20 com alteração no gene 5LO (129 Alox5tm1Fun/J) (5LOKO), divididas em grupos: WT, tratadas com 0,01 ml de solução salina 0,9% estéril (SS) via intraperitoneal (IP) e ZL, tratadas com 250µg/Kg de ácido zoledrônico (ZL) IP diluído em solução salina estéril, ambas administradas 1 vez/semana por 7 semanas. Os grupos foram compostos por 5 animais cada (WT Controle ­ 7 e 21dias, WT ZL ­ 7 e 21 dias, 5LOKO Controle ­ 7 e 21 dias, 5LOKO ZL ­ 7 e 21dias), sendo as maxilas coletadas para análises em microCT, histopatológica, birrefringência, técnica imunohistoquímica e histomorfométricas. De modo geral, a microCT revelou deficiência significativa na microarquitetura óssea nos animais WT ZL em comparação com os demais. Do mesmo modo, a partir da análise histopatológica e de birrefringência da matriz colagenosa, observou-se padrão compatível com o desenvolvimento de OM no grupo WT ZL, com presença de infiltrado inflamatório intenso, atraso na neoformação óssea, presença de fraturas patológicas, e deficiência da matriz colagenosa e de células Runx-2+, TRAP+ e F4/80+. Os animais 5LOKO ZL apresentaram alterações compatíveis com atraso no processo de reparo especialmente no período de 7 dias, com menor quantidade de células Runx-2+ em comparação com o grupo 5LOKO Controle e pela qualidade da matriz óssea colagenosa com menor quantidade de fibras do espectro vermelho neste período, se igualando, porém, aos 21 dias. Deste modo, concluiu-se que o processo de reparo em camundongos fêmeas senescentes da linhagem 129/Sv WT e 5LOKO associados ao uso do BF ZL ocorreu de modo distinto, levando a quadro de OM nos animais WT e atraso nos animais 5LOKO, sem sinais histopatológicos que caracterizassem a doença. Deste modo, a inibição da enzima 5LO parece influenciar de maneira positiva o processo de reparo ósseo intramembranoso alveolar, mesmo na presença de fenótipo esqueletal osteopetrótico, sugerindo outros fatores relacionados à droga que favoreçam o desenvolvimento da OM no presente modelo animal(AU)


Senescence brings a number of physiological modifications with the decrease of cell and systemic activities and function that manifest in an important way in female population due to the event of menopause, as osteoporosis. In order to diminish these effects, there is the possibility of taking medication that decrease bone remodeling process, as the bisphosphonates containing nitrogen (BF). However, the use of these drugs is intimate related with the development of the osteonecrosis of the jaws (ON), especially when associated to other risk factors as oral surgery. It is known that physiologically, the dynamics of bone tissue also depends on the eicosanoids derivate from the arachidonic acid metabolism (AA), such as cyclooxygenase (COX) and 5 lipoxygenase (5LO) enzymes. In this way, the aim of the present study was to analyze the effects of the BF zoledrônico acid (ZL) and its relation with de development of ON in 129/SV old female mice with or without genetic modification for 5LO. Forty animals, 20 WT and 20 with 5LO gene alteration (129 Alox5tm1Fun/J) (5LOKO) were divided in groups: WT, treated with 0.01 ml of sterile 0.9% saline solution (SS) intraperitoneal (IP), and ZL, treated with 250µg/Kg of ZL IP diluted in SS, both administered once a week for 7 weeks. Groups contained 5 animals each (WT Control ­ 7 and 21 days, WT ZL ,7 and 21 days, 5LOKO Control, 7 and 21 days, and 5LOKO ZL, 7 and 21 days), and the maxillae removed for microCT, histopathology, birefringence, immunohistochemistry, and histomorphometric analysis. In general, microCT revealed significant deficiency in bone microarchitecture in WT ZL group in comparison to the other groups. In the same way, histopathological and birefringence analysis revealed histological pattern compatible with ON development in WT ZL group, presenting intense inflammatory infiltrate, late new bone formation, presence of pathological fractures, and deficiency in collagenous matrix, and also in Runx-2+, TRAP+, and F4/80. 5LOKO ZL animals presented alterations compatible with a late bone repair, especially at day 7, with decreased number of Runx-2+ cells in comparison to 5LOKO Control, and by the quality of collagenous bone matrix with decreased number of red spectra fibers in this period, however, being similar at day 21. From this, it could be concluded that alveolar bone repair of 129/SV WT and 5LOKO old female mice associated with the administration of ZL occurred in different ways, leading to a picture of ON in the WT animals, and late bone repair in the 5LOKO animals, without histopathological signs that could characterize the disease. In this way, inhibition of 5LO seems to influence intramembranous alveolar bone repair in a positive way, even in the presence of osteopetrotic skeletal phenotype, suggesting other factors related to the drug that favors the development of the ON in the present animal model(AU)


Subject(s)
Animals , Mice , Osteoporosis , Arachidonate 5-Lipoxygenase , Aging , Bisphosphonate-Associated Osteonecrosis of the Jaw , Zoledronic Acid , Osteonecrosis , Surgery, Oral , Birefringence , Menopause , Bone Remodeling , Diphosphonates , X-Ray Microtomography
19.
Article in Portuguese | CONASS, SES-GO, ColecionaSUS, LILACS | ID: biblio-1117753

ABSTRACT

Tecnologia: Ácido zoledrônico e bifosfonados orais (alendronato e risedronato de sódio). Indicação: Prevenção de fraturas em pessoas com osteoporose. Pergunta: Em pessoas com osteoporose, o ácido zoledrônico é mais eficaz e seguro que os bifosfonados orais para prevenção de fraturas e outros desfechos de interesse? Métodos: Levantamento bibliográfico foi realizado nas bases eletrônicas Pubmed e BVS usando estratégias de buscas predefinidas. Foi feita avaliação da qualidade metodológica das revisões sistemáticas com a ferramenta Assessing the Methodological Quality of Systematic Reviews (AMSTAR). Resultados: Foram selecionadas e incluídas 5 revisões sistemáticas. Conclusão: O ácido zoledrônico é similar aos bifosfonados orais para prevenir fraturas em mulheres com osteoporose. Seu efeito sobre a densidade mineral óssea femoral é similar ao do alendronato e superior ao do risedronato. Um tratamento por 3 anos com ácido zoledrônico ou por 5 anos com alendronato de sódio é suficiente para prevenir fraturas vertebrais e não vertebrais. Bifosfonados têm similar risco de eventos adversos que o placebo, incluindo transtornos cardiovasculares e taxa de abandono do tratamento devido a distúrbios gastrointestinais. O ácido zoledrônico tem maior incidência de sintomas influenza-like que o placebo. O ácido zoledrônico não provoca eventos adversos do tipo esofágicos, gastrointestinais sérios ou do trato gastrointestinal superior, mas tem maior risco de náuseas, que pode estar relacionada à infusão intravenosa de grandes doses


Technology: Zoledronic acid and oral bisphosphonates. Indication: Prevention of osteoporotic fractures. Question: In people with osteoporosis, is zoledronic acid more effective and safer than oral bisphosphonates for preventing fractures and other outcomes? Methods: Bibliographic search was performed on PUBMED and BVS, using predefined search strategies. Evaluation of the methodological quality of systematic reviews was done by the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) tool. Results: 5 systematic reviews were selected and included. Conclusion: Zoledronic acid is similar to bisphosphonates for preventing fractures in women with osteoporosis and his effect on femoral bone mineral density is similar to that of alendronate and superior to risedronate. A 3 years treatment with zoledronic acid or for 5 years with sodium alendronate is sufficient to prevent vertebral and non-vertebral fractures. Bisphosphonates have a similar risk of adverse events than placebo, including cardiovascular disorders and risk of attrition due to gastrointestinal events. Zoledronic acid has a higher incidence of influenza-like symptoms (myalgia and arthralgia) than placebo, limited to the first dose and lasting a few days. Zoledronic acid does not cause esophageal, serious gastrointestinal or upper gastrointestinal tract adverse events, but has a higher risk of nausea, which can be caused by large doses of intravenous infusion


Subject(s)
Humans , Female , Osteoporosis/drug therapy , Alendronate/therapeutic use , Osteoporotic Fractures/prevention & control , Risedronic Acid/therapeutic use , Zoledronic Acid/therapeutic use , Bone Density/drug effects , Treatment Outcome , Alendronate/adverse effects
20.
J. appl. oral sci ; 28: e20200204, 2020. tab, graf
Article in English | LILACS, BBO | ID: biblio-1134802

ABSTRACT

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.


Subject(s)
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
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