Avaliação do reparo ósseo após a instalação de implantes funcionalizados com medicação anabólica associada à administração sistêmica de antireabsortivo em ratas com deficiência de estrógeno e síndrome metabólica / Evaluation of bone repair after installation of implants functionalized with anabolic medication associated with systemic administration of antiresorptive in rats with estrogen deficiency and metabolic syndrome

O objetivo do presente estudo foi investigar a ação da associação de medicação sistêmica (bifosfonato oral) e teriparatida como medicação local funcionalizando as superfícies dos implantes. Para a realização deste projeto, o mesmo foi divido em 2 etapas. A primeira etapa consistiu na determinação do melhor protocolo para a funcionalização de implantes com teriparatida, a partir da técnica layer by layer. Ainda nesta etapa, foram realizados testes físicos e in vitro (culturas de células) a fim de avaliar as propriedades da superfície funcionalizada, quanto à melhora nas respostas osteogênicas. A segunda etapa consistiu na realização de experimentos in vivo para avaliar o efeito desta superfície funcionalizada durante o reparo periimplantar. Para isso, 96 ratas Wistar, adultas jovens foram divididas em seis grandes grupos: 1. Grupo SHAM (n=16), no qual os animais foram submetidos à ovariectomia fictícia e dieta balanceada. 2. Grupo SHAM/SM (n=16), no qual os animais receberam dieta de cafeteria. 3. Grupo OVX (n=16), no qual os animais foram submetidos a cirurgia de ovariectomia e não receberam tratamento medicamentoso. 4. Grupo OVX/SM (n=16), no qual os animais foram submetidos à cirurgia ovariectomia e receberam dieta de cafeteria. 5. Grupo OVX/RIS (n=16), no qual os animais foram submetidos à cirurgia de ovariectomia e tratados com risedronato de sódio. 6. Grupo OVX/SM/RIS (n=16), no qual os animais foram submetidos à cirurgia de ovariectomia e à dieta de cafeteria associada ao tratamento medicamentoso com risedronato de sódio. Em cada grande grupo há dois subgrupos: A- implantes convencionais e B- implantes funcionalizados com teriparatida. No dia 0 foi realizada a ovariectomia ou cirurgia fictícia. Passados 30 dias foi iniciado o tratamento medicamentoso com risedronato de sódio. Após 30 dias do início do tratamento medicamentoso, os animais foram submetidos à exodontia do primeiro molar superior direito, em seguida receberam os implantes na região onde foi realizada a exodontia. Aos 28 dias após a instalação dos implantes, os animais foram submetidos à eutanásia para mensuração do torque de remoção. Os dados foram submetidos ao teste de homocedasticidade (Shapiro Wilk). Houve a confirmação de distribuição normal dos dados amostrais e na sequência, foi realizado o teste paramétrico ANOVA One Way, seguido do pós teste de Tukey, com o nível de significância de 5% (p< 0,05). Os implantes funcionalizados apresentaram os maiores valores de torque de remoção em todos os grupos experimentais. A associação sistêmica entre o risedronato de sódio e teriparatida de forma tópica fez com que o grupo OVX/SM/RIS teriparatida obtivesse o maior torque de remoção quando comparado aos demais grupos. Com isso, conclui-se que o desempenho clínico dos implantes funcionalizados com teriparatida foi favorável, no entanto, quando associado à administração sistêmica de risedronato de sódio, os resultados se tornam mais promissores(AU)

The objective of this study was to investigate the action of the association of systemic medication (oral biphosphonate) and teriparatide as local medication functionalized to the surfaces of implants. For the execution of this project, it was divided in 2 stages. The first stage consisted in determining the best protocol for the functionalization of implants with teriparatide, based on the layer by layer technique. Still in this stage, physical and in vitro tests (cell cultures) were performed in order to evaluate the properties of the functionalized surface, regarding the improvement in osteogenic responses. The second stage consisted in conducting in vivo experiments to evaluate the effect of this surface functionalized during the peri-implant repair. For this, 96 Wistar rats, young adults were divided into six large groups: 1. SHAM Group (n=16), where the animals underwent sham surgery and balanced diet. 2. SHAM/SM Group (n=16), in which the animals received a cafeteria diet. 3) Group OVX (n=16), in which the animals underwent ovariectomy without drug treatment. 4. Group OVX/SM (n=16), in which the animals underwent ovariectomy and received a cafeteria diet. 5. Group OVX/SM/RIS (n=16), in which the animals underwent ovariectomy surgery and cafeteria diet associated with drug treatment with sodium risedronate. 6. Group OVX/RIS (n=16), in which the animals underwent ovariectomy and were treated with sodium risedronate. In each large group there are two subgroups: A- conventional implants and B- implants functionalized with teriparatide. After 30 days of beginning the drug treatment, the animals were submitted to bilateral first molar exodontia, then received the implants in the region where the exodontia was performed. At 28 days after installation of the implants, the animals were euthanized to measure the removal torque. The data were submitted to the homoscedasticity test (Shapiro Wilk). There was confirmation of normal distribution of the sample data and in the sequence, the parametric test ANOVA One Way was performed, followed by Tukey's post-test, with the significance level of 5% (p< 0.05). The functionalized implants had the highest removal torque values in all experimental groups. The systemic association between sodium risedronate and teriparatide topically resulted in the OVX/SM/RIS teriparatide group obtaining the highest removal torque when compared to the other groups. Thus, it is concluded that the clinical performance of implants functionalized with teriparatida was favorable, however, when associated with systemic administration of sodium risedronate, the results become more promising(AU)

Losartan improves alveolar bone dynamics in normotensive rats but not in hypertensive rats.

OBJECTIVES: Hypertension is one of the main causes of premature death in the world; also, it is associated with several bone alterations. Preclinical studies have demonstrated delayed alveolar bone healing in hypertensive rats. However, losartan has been favorable for consolidation of bone grafts and reduction in active periodontitis. Therefore, losartan is suggested to be effective in bone formation stages, as well as in the synthesis of matrix proteins and mineralization. To evaluate the alveolar bone dynamics in hypertensive rats treated with losartan by laser confocal microscopy and histological analysis. METHODOLOGY: Thirty-two rats, 16 spontaneously hypertensive rats (SHR) and 16 Wistar albinus rats, treated or not with losartan (30 mg/kg/day) were used. Calcein fluorochrome at 21 days and alizarin red fluorochrome at 49 days were injected in rats (both 20 mg/kg). The animals were submitted to euthanasia 67 days after treatment, and then the right maxilla was removed for laser confocal microscopy analysis and the left maxilla for histological analysis. RESULTS: This study showed a greater calcium marking in normotensive animals treated with losartan in relation to the other groups. Laser confocal microscopy parameters showed higher values of bone volume formed, mineralized surface, active surface of mineralization and bone formation rate in normotensive animals treated with losartan. However, a smaller mineralized surface was observed in all hypertensive animals. CONCLUSION: Losartan can improve bone mineralization parameters under normal physiological conditions, but the same anabolic effect does not occur under hypertension.

Losartan improves alveolar bone dynamics in normotensive rats but not in hypertensive rats

Abstract Hypertension is one of the main causes of premature death in the world; also, it is associated with several bone alterations. Preclinical studies have demonstrated delayed alveolar bone healing in hypertensive rats. However, losartan has been favorable for consolidation of bone grafts and reduction in active periodontitis. Therefore, losartan is suggested to be effective in bone formation stages, as well as in the synthesis of matrix proteins and mineralization. Objectives: To evaluate the alveolar bone dynamics in hypertensive rats treated with losartan by laser confocal microscopy and histological analysis. Methodology: Thirty-two rats, 16 spontaneously hypertensive rats (SHR) and 16 Wistar albinus rats, treated or not with losartan (30 mg/kg/day) were used. Calcein fluorochrome at 21 days and alizarin red fluorochrome at 49 days were injected in rats (both 20 mg/kg). The animals were submitted to euthanasia 67 days after treatment, and then the right maxilla was removed for laser confocal microscopy analysis and the left maxilla for histological analysis. Results: This study showed a greater calcium marking in normotensive animals treated with losartan in relation to the other groups. Laser confocal microscopy parameters showed higher values of bone volume formed, mineralized surface, active surface of mineralization and bone formation rate in normotensive animals treated with losartan. However, a smaller mineralized surface was observed in all hypertensive animals. Conclusion: Losartan can improve bone mineralization parameters under normal physiological conditions, but the same anabolic effect does not occur under hypertension.