Sinergic action of systemic risedronate and local rutherpy in perimplantar repair of ovariectomized rats with metabolic syndrome: biomechanical and molecular analysis

Abstract

Hormonal changes in the post-menopausal period lead to the onset of diseases such as osteoporosis and metabolic syndrome, both negatively affecting bone turnover. The first suggested treatment option corresponds to the use of bisphosphonates, which, despite having an undeniable anti-resorptive action, may impair peri-implant bone repair. The functionalization of the implant surface with TERPY (nitric oxide donor) seeks improvements in peri-implant bone repair, due to the angiogenic and vasodilator properties of nitric oxide to benefit this tissue. The objective of this work is to characterize, by using biomechanical and real-time PCR analysis, the osteointegration and peri-implant repair provided by the incorporation of TERPY on the implant surface in female normal rats and female rats under conditions that mimic osteoporosis and metabolic syndrome.For this study, 72 young adult and female Wistar rats will be divided into 3 groups: Sham (animals submitted to fictitious bilateral ovariectomy surgery), OVX+SM (bilateral ovariectomy) and OVX+SM+RIS (bilateral ovariectomy + risedronate treatment). The OVX+SM and OVX+SM+RIS groups will receive a high-calorie diet and will be kept in sedentary conditions, in order to simulate the condition of metabolic syndrome, while the Sham group will receive a balanced diet and water ad libitum. The treatment of the OVX+SM+RIS group with sodium risedronate (0.35mg / kg), once a week, will begin 30 days after bilateral ovariectomy surgery. 60 days after the administration of risedronate or vehicle, the animals will undergo surgery to install conventional implants or implants functionalized with TERPY in different concentrations (10mM and 100 mM) in the tibial metaphysis. Euthanasia will occur 28 days after the implant installation and the tibia will undergo biomechanical analysis of counter torque on the implants and real-time PCR (expression of the OPG, RANKL, OPN, ALP, OCN, VEGF, Wnt3a genes). Quantitative data will be subjected to the normality test and this will indicate the most appropriate statistical test. A significance level of 5% will be adopted for all tests.