Evaluation of a collagen matrix in a mandible defect in rats submitted to the use of bisphosphonates

Purpose: To assess the effect of a collagen matrix (Mucograft®) on the inflammatory process in a semi-critical experimental defect model in rats treated with bisphosphonates. Methods: Eighteen Wistar rats were randomly divided into three groups: saline (CG), alendronate (ALD) 5mg/kg (AG) or zoledronic acid (ZA) 0.2mg/kg (ZG). ALD was administered orally for 10 weeks and ZA was administered intravascularly on days 0, 7 and 14 and 49. On day 42, a 2mm defect was created and filled with Mucograft® collagen matrix. The contralateral side was filled with a clot (control side). The animals were euthanized 70 days after the beginning of the experiment and the hemimandibles were radiographically and histologically (counting of empty osteocyte lacunae (%), apoptotic (%) and total osteoclasts, neutrophil and mononuclear inflammatory cells) analyzed. The variables were submitted to ANOVA/Bonferroni and t test (parametric data) (p 0.05, GraphPad Prism 5.0). Results: Significant bone repair occurred in the groups treated with Mucograft®. High number of total inflammatory cells and neutrophils cells were showed in AG (p=0.026 and p=0.035) and AZ groups (p=0.005, p=0.034) on the control sides associated with delayed bone repair and the presence of devitalized bone tissue in AG and ZG on the Mucograft® side. Conclusion: Mucograft® collagen matrix attenuated the inflammatory process in a mandible defect in rats submitted to the use of bisphosphonates (AG and ZG).(AU)

Preparation of Zoledronate liposome and its impact on apoptosis of Kupffer cells in rat liver

Purpose:To establish a method for the preparation of zoledronate liposome and to observe its effect on inducing the apoptosis of rat liver Kupffer cells.Methods:Zoledronate was encapsulated in liposomes, and then the entrapment rate was detected on a spectrophotometer. The prepared Zoledronate liposome (0.01 mg/mL) was injected into the tail vein of SD rats. Three days later, the number of Kupffer cells (CD68 positive) in rat liver tissue was detected by immunohistochemistry. Flow cytometry was used to detect the apoptosis rate of the isolated liver Kupffer cell cultured in vitro.Results:The entrapment rate of Zoledronate was 43.4±7.8%. Immunohistochemistry revealed that the number of Kupffer cells was 19.3±2.1 in PBS group and 5.5±1.7 in Zoledronate liposome group, with a significant difference (P<0.05). The apoptosis rate of Kupffer cells was 4.1±0.8% in PBS group, while it was 9±2.2% and 23.3±5.9% in Zoledronate liposomes groups with different concentrations of Zoledronate liposome (P<0.05).Conclusions:Zoledronate liposomes can effectively induce the apoptosis of Kupffer cells in vivo and in vitro, and the apoptosis rate is related to the concentration of Zoledronate liposome. To establish a rat liver Kupffer cell apoptosis model can provide a new means for further study on Kupffer cell function.(AU)

Effects of local alendronate administration on bone defect healing. Histomorphometric and radiological evaluation in a rabbit model

Purpose: To performed a histomorphometric and radiological study to evaluate the effects of alendronate sodium administered locally in mandibular bone defects created in rabbits. Methods: Two circular defects 5 mm in diameter were created bilaterally in the mandibular corpus of 20 New Zealand rabbits (i.e., four defects per animal). Each defect received one of four treatments: no treatment (EC group), alendronate irrigation (AL group), autogenous bone grafting (AG group), or alendronate irrigation with autogenous bone grafting (AL+AG group). Histomorphometric and radiological assessments were conducted at 4 and 8 weeks after surgery. Results: Between-group comparisons of the new bone area, the value of the AL+AG group was significantly lower thanthe remaining three groups at 4 weeks postoperatively. In all groups, the new bone area was significantly larger at 8 weeks than at 4 weeks. The residual graft area at 4 and 8 weeks was significantly higher in the AL+AG group than in the AG group, although it was significantly smaller at 8 weeks than at 4 weeks in both these groups. Conclusion: The use of alendronate sodium in conjunction with autogenous bone grafting improves the osteoconductive properties of the graft, enhances graft retention in the defect, and improves ossification.(AU)

Bifosfonatos no tratamento da dor oncológica em cães e gatos: revisão de literatura / Biphosphonates in treatment of oncological pain in dogs and cats: a literature review / Bifosfonatos en el tratamiento del dolor oncológica en perros y gatos: revisión de literatura

Atualmente, os Bifosfonatos (BFS) vem ganhando espaço na Medicina Veterinária, tendo seu emprego em várias possibilidades terapêuticas, dentre elas o manejo da dor em pacientes com câncer ósseo. A dor é uma das complicações mais temidas do câncer, e seu manejo tem se tornado umgrande foco de importância clínica ao longo destes anos. A dor do câncer ósseo é relacionada à destruição óssea, ao aumento no número e na atividade de osteoclastos no local da lesão, e fraturas patológicas que acontecem frequentemente em animais acometidos com este tipo de neoplasia.Osteoclastos são células que promovem a reabsorção do tecido ósseo, e com sua atividade aumentada acontece a sensação de dor. O principal mecanismo de ação dos BFS é diminuir a atividade destas células, e por isso se mostra uma boa opção no tratamento da dor dos pacientes com este tipo deneoplasia. O objetivo deste trabalho foi realizar uma revisão de literatura a respeito do uso de BFS no manejo da dor óssea oncológica em cães e gatos. Para tanto, utilizou-se a base de dados Pubmed, Scielo, Vine Dovepress para levantamento de artigos científicos publicados no período de 2002 a 2017,e os termos utilizados para a pesquisa foram: Oncologia Veterinária, câncer ósseo, dor em cães e gatos, Bifosfonatos e oncologia.(AU)

Currently, Biphosphonates (BFS) have been conquering its space in Veterinary Medicine, being employed in many therapeutic possibilities such as pain management in bone cancer patients. Pain is one of the most feared complications in cancer's field, and its treatment has become an issue of major clinical importance over the years. Bone cancer pain is related to bone destruction, increase of the osteoclast numbers on the injury spot and patological fractures that happen frequently in patients affected with this kind of tumor. Osteoclasts are cells that promote bone tissue reabsortion, and with its activity increased, the sensation of pain occurs. The main action mechanism of BFS is reduce the activity of this cells, and thats why the medication have proved being a great option to treat pain in patients in these conditions. The purpose of this project was to realize a literature review about employing BFS on bone cancer pain management in dogs and cats. The search of scientifical articles published among2002 and 2017 was done in Pubmed, Scielo Vin and Dovepress database and the therms used for research were: Veterinary oncology, bone cancer, pain in dogs and cats and oncology.(AU)

Actualmente, los Bifosfonatos (BFS) vienen ganando espacio en Ia Medicina Veterinaria, teniendo su empleo en varias posibilidades terapéuticas, como por ejemplo el manejo del dolor em pacientes con cáncer óseo. El dolor es una de Ias complicaciones más temidas dei cáncer, y su manejo se ha convertido en un gran foco de importancia clínica a 10 largo de estos anos. EI dolor del câncer óseo se relaciona con Ia destrucción ósea, el aumento en el número y Ia actividad de los osteoclastosen el lugar de Ia lesión, y Ias fracturas patológicas que ocurren frecuentemente en animales acometidos con este tipo de neoplasia. Los osteoclastos son células que promueven Ia reabsorción dei tejido óseo, y con su actividad aumentada ocurre Ia sensación de dolor. El principal mecanismo de acción de los BFS es disminuir Ia actividad de estas células, y por eso se muestra una buena opción en el tratamientodel dolor de los pacientes con este tipo de neoplasia. El objetivo de este trabajo fue realizar una revisión de literatura acerca dei uso de BFS en el manejo dei dolor óseo oncológico en perros y gatos. Para ello, se utilizó Ia base de datos Pubmed, Scielo, Vin y Dovepress para ellevantamiento de artículos científicos publicados en el período 2002 a 2017, y los términos utilizados para Ia investigación fueron: Oncología Veterinaria, cáncer óseo, dolor en perros y gatos Bifosfonatos y oncología.(AU)

Bifosfonatos no tratamento da dor oncológica em cães e gatos: revisão de literatura / Biphosphonates in treatment of oncological pain in dogs and cats: a literature review / Bifosfonatos en el tratamiento del dolor oncológica en perros y gatos: revisión de literatura

Atualmente, os Bifosfonatos (BFS) vem ganhando espaço na Medicina Veterinária, tendo seu emprego em várias possibilidades terapêuticas, dentre elas o manejo da dor em pacientes com câncer ósseo. A dor é uma das complicações mais temidas do câncer, e seu manejo tem se tornado umgrande foco de importância clínica ao longo destes anos. A dor do câncer ósseo é relacionada à destruição óssea, ao aumento no número e na atividade de osteoclastos no local da lesão, e fraturas patológicas que acontecem frequentemente em animais acometidos com este tipo de neoplasia.Osteoclastos são células que promovem a reabsorção do tecido ósseo, e com sua atividade aumentada acontece a sensação de dor. O principal mecanismo de ação dos BFS é diminuir a atividade destas células, e por isso se mostra uma boa opção no tratamento da dor dos pacientes com este tipo deneoplasia. O objetivo deste trabalho foi realizar uma revisão de literatura a respeito do uso de BFS no manejo da dor óssea oncológica em cães e gatos. Para tanto, utilizou-se a base de dados Pubmed, Scielo, Vine Dovepress para levantamento de artigos científicos publicados no período de 2002 a 2017,e os termos utilizados para a pesquisa foram: Oncologia Veterinária, câncer ósseo, dor em cães e gatos, Bifosfonatos e oncologia.

Currently, Biphosphonates (BFS) have been conquering its space in Veterinary Medicine, being employed in many therapeutic possibilities such as pain management in bone cancer patients. Pain is one of the most feared complications in cancer's field, and its treatment has become an issue of major clinical importance over the years. Bone cancer pain is related to bone destruction, increase of the osteoclast numbers on the injury spot and patological fractures that happen frequently in patients affected with this kind of tumor. Osteoclasts are cells that promote bone tissue reabsortion, and with its activity increased, the sensation of pain occurs. The main action mechanism of BFS is reduce the activity of this cells, and that’s why the medication have proved being a great option to treat pain in patients in these conditions. The purpose of this project was to realize a literature review about employing BFS on bone cancer pain management in dogs and cats. The search of scientifical articles published among2002 and 2017 was done in Pubmed, Scielo Vin and Dovepress database and the therms used for research were: Veterinary oncology, bone cancer, pain in dogs and cats and oncology.

Actualmente, los Bifosfonatos (BFS) vienen ganando espacio en Ia Medicina Veterinaria, teniendo su empleo en varias posibilidades terapéuticas, como por ejemplo el manejo del dolor em pacientes con cáncer óseo. El dolor es una de Ias complicaciones más temidas dei cáncer, y su manejo se ha convertido en un gran foco de importancia clínica a 10 largo de estos anos. EI dolor del câncer óseo se relaciona con Ia destrucción ósea, el aumento en el número y Ia actividad de los osteoclastosen el lugar de Ia lesión, y Ias fracturas patológicas que ocurren frecuentemente en animales acometidos con este tipo de neoplasia. Los osteoclastos son células que promueven Ia reabsorción dei tejido óseo, y con su actividad aumentada ocurre Ia sensación de dolor. El principal mecanismo de acción de los BFS es disminuir Ia actividad de estas células, y por eso se muestra una buena opción en el tratamientodel dolor de los pacientes con este tipo de neoplasia. El objetivo de este trabajo fue realizar una revisión de literatura acerca dei uso de BFS en el manejo dei dolor óseo oncológico en perros y gatos. Para ello, se utilizó Ia base de datos Pubmed, Scielo, Vin y Dovepress para ellevantamiento de artículos científicos publicados en el período 2002 a 2017, y los términos utilizados para Ia investigación fueron: Oncología Veterinaria, cáncer óseo, dolor en perros y gatos Bifosfonatos y oncología.

Pamidronate and zoledronate effects in the increment of bone mineral density and histomorphometry in rats

PURPOSE: To compare increment of bone mineral density (BMD) with pamidronate, zoledronate and the isolated effect of proteinous diet in undernourished oophorectomized and non-oophorectomized female rats, besides validating BMD's indexes. METHODS: 60 young female Lewis rats were divided into five experimental groups and a control group, oophorectomized and non-oophorectomized. The administration of drugs were submitted to proteinous and aproteinous diets. The variables analyzed were weight, bone densitometry, histomorphometry and biochemical evolution. RESULTS: In weight evaluation, the first interval showed a statistically meaningful increase in oophorectomized sample. In densitometry evaluation, the first interval showed statistically meaningful decrease in four medicated groups and third showed a statistically meaningful increase in 2 non-oophorectomized groups. In laboratory evaluation, there were an increase of total proteins and globulin, decrease of alkaline phosphatase, phosphorus and calcium (except for the oophorectomized) in four medicated groups and increase of phosphorus and calcium in 2 not medicated groups. In histomorphometric evaluation, the oophorectomized groups had smaller increment of BMD. CONCLUSIONS: The pamidronate and zoledronate have shown effectives in the increment of BMD. The proteinous diet itself possesses therapeutic effect in BMD though not significant compared with medicated animals. The results of histomorphometry allow validating BMD's indexes in this experimental model.

OBJETIVO: Comparar o incremento de densidade mineral óssea (DMA) com pamidronato, zoledronato e o efeito isolado de dieta protéica em ratas desnutridas ooforectomizadas e não ooforectomizadas, além de validar índices de DMA. MÉTODOS: 60 ratas jovens Lewis foram divididas em cinco grupos experimentais e um grupo controle, com e sem ooforectomia. A administração das drogas foi submetida às dietas protéica e aprotéica. As variáveis analisadas foram peso, densitometria óssea, histomorfometria e evolução bioquímica. RESULTADOS: Na avaliação ponderal, o primeiro intervalo mostrou aumento estatisticamente significante nos grupos ooforectomizados. Na avaliação densitométrica, o primeiro intervalo mostrou diminuição estatisticamente significante nos quatro grupos medicados e o terceiro mostrou aumento estatisticamente significante nos dois não ooforectomizados. Na avaliação laboratorial, houve aumento de proteínas totais e globulina, diminuição de fosfatase alcalina, fósforo e cálcio (exceto nos ooforectomizados) nos quatro grupos medicados e aumento de fósforo e cálcio nos dois não medicados. Na avaliação histomorfométrica, os grupos ooforectomizados tiveram incremento menor de DMA. CONCLUSÕES: O pamidronato e o zoledronato se mostraram efetivos no incremento de DMA. A dieta protéica em si possui efeito terapêutico na DMA, porém menos significativa, comparada aos animais medicados. Os resultados da histomorfometria permitem validar os índices de DMA neste modelo experimental.

Efeitos do pamidronato e zoledronato no incremento da densitometria óssea e histomorfometria em ratos / Pamidronate and zoledronate effects in the increment of bone mineral density and histomorphometry in rats

PURPOSE: To compare increment of bone mineral density (BMD) with pamidronate, zoledronate and the isolated effect of proteinous diet in undernourished oophorectomized and non-oophorectomized female rats, besides validating BMD's indexes. METHODS: 60 young female Lewis rats were divided into five experimental groups and a control group, oophorectomized and non-oophorectomized. The administration of drugs were submitted to proteinous and aproteinous diets. The variables analyzed were weight, bone densitometry, histomorphometry and biochemical evolution. RESULTS: In weight evaluation, the first interval showed a statistically meaningful increase in oophorectomized sample. In densitometry evaluation, the first interval showed statistically meaningful decrease in four medicated groups and third showed a statistically meaningful increase in 2 non-oophorectomized groups. In laboratory evaluation, there were an increase of total proteins and globulin, decrease of alkaline phosphatase, phosphorus and calcium (except for the oophorectomized) in four medicated groups and increase of phosphorus and calcium in 2 not medicated groups. In histomorphometric evaluation, the oophorectomized groups had smaller increment of BMD. CONCLUSIONS: The pamidronate and zoledronate have shown effectives in the increment of BMD. The proteinous diet itself possesses therapeutic effect in BMD though not significant compared with medicated animals. The results of histomorphometry allow validating BMD's indexes in this experimental model.(AU)

OBJETIVO: Comparar o incremento de densidade mineral óssea (DMA) com pamidronato, zoledronato e o efeito isolado de dieta protéica em ratas desnutridas ooforectomizadas e não ooforectomizadas, além de validar índices de DMA. MÉTODOS: 60 ratas jovens Lewis foram divididas em cinco grupos experimentais e um grupo controle, com e sem ooforectomia. A administração das drogas foi submetida às dietas protéica e aprotéica. As variáveis analisadas foram peso, densitometria óssea, histomorfometria e evolução bioquímica. RESULTADOS: Na avaliação ponderal, o primeiro intervalo mostrou aumento estatisticamente significante nos grupos ooforectomizados. Na avaliação densitométrica, o primeiro intervalo mostrou diminuição estatisticamente significante nos quatro grupos medicados e o terceiro mostrou aumento estatisticamente significante nos dois não ooforectomizados. Na avaliação laboratorial, houve aumento de proteínas totais e globulina, diminuição de fosfatase alcalina, fósforo e cálcio (exceto nos ooforectomizados) nos quatro grupos medicados e aumento de fósforo e cálcio nos dois não medicados. Na avaliação histomorfométrica, os grupos ooforectomizados tiveram incremento menor de DMA. CONCLUSÕES: O pamidronato e o zoledronato se mostraram efetivos no incremento de DMA. A dieta protéica em si possui efeito terapêutico na DMA, porém menos significativa, comparada aos animais medicados. Os resultados da histomorfometria permitem validar os índices de DMA neste modelo experimental.(AU)

The effect of zoledronate on bone remodeling during the healing process / Os efeitos do zoledronato na remodelação óssea durante o processo de reparação

PURPOSE: To check the effect of zoledronate in bone remodeling during bone healing. METHODS: Thirty rabbits were divided into two groups of fifteen animals each (control and experimental group respectively). Shaft osteotomy was performed on the cranial portion of the fibula of each animal. In the experimental group, a single dose of 0.04mg/kg of zoledronate was administered. In the control group, the same volume of bi-distilled water was administered. After one, two and four weeks, animals of both groups were killed and histological sections of the fibular metaphyseal area were examined histomorphometrically. The parameters analyzed were tissue volume (TV), fractional trabecular bone volume (BV/TV) and fractional medullary fibrous volume (FbV/TV). RESULTS: Tissue volume increased in the experimental group (237.2mm².10-2) compared to the control (166.62mm².10-2). Trabecular bone volume was significantly larger in the experimental (60.2 percent) than in the control group (34.8 percent).The amount of fibrosis volume decreased in the experimental group (22 percent) compared to the control (49.4 percent). CONCLUSION: The effect of zoledronate is characterized by accentuated stimulus of bone formation in the metaphyseal area, resulting in a larger amount of trabecular bone volume and little fibrosis volume.(AU)

OBJETIVO: Verificar os efeitos do zoledronato na remodelação óssea durante a reparação óssea. MÉTODOS: Trinta coelhos foram divididos em dois grupos de quinze animais cada (grupos controle e experimento, respectivamente). Realizou-se osteotomia na diáfise proximal da fíbula de cada animal. No grupo experimento, aplicou-se dose única de 0,04mg/Kg de zoledronato. No grupo controle, a mesma quantidade de água bi-destilada foi administrada. Após uma, duas e quatro semanas, os animais de ambos os grupos foram sacrificados e cortes histológicos da metáfise fibular foram examinados histomorfometricamente. Os parâmetros analisados foram volume tecidual (TV), fração do volume ósseo trabecular (BV/TV) e fração do volume fibroso medular (FbV/TV). RESULTADOS: O volume tecidual aumentou no grupo experimento (237.2mm².10-2) em comparação com o controle (166.62mm².10-2). O volume ósseo Trabecular teve aumento significativo no grupo experimento (60.2 por cento) em relação ao grupo controle (34.8 por cento). A quantidade de fibrose medular diminuiu no grupo experimento (22 por cento) em comparação com o controle (49.4 por cento). CONCLUSÃO: O efeito do zoledronato é caracterizado por acentuado estímulo da formação óssea na área metafisária, resultando em grande quantidade de volume ósseo trabecular e pouca fibrose medular.(AU)