Histomorphometric analysis of rats femurs submitted to the use of sodium-glucose cotransporter-2 inhibitors

• Grant number: 22/11737-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2022
• End date: November 30, 2023
• Field of knowledge: Biological Sciences - Morphology - Anatomy
• Principal Investigator: Wilson Romero Nakagaki
• Grantee: Janaina Machado da Silva
• Host Institution: Pró-Reitoria de Pesquisa e Pós-Graduação. Universidade do Oeste Paulista (UNOESTE). Presidente Prudente , SP, Brazil

Abstract

Bone tissue is composed of cells as osteoclasts, osteoblasts and osteocytes, which play an important role in the mechanisms of resorption and formation of bone matrix and tissue nutrition. A dysfunction in the activity of these cells can interfere with bone mineral density and consequently bone quality, increasing the risk of fractures. Diabetes Mellitus is a chronic disease that increases fracture risk by itself, and some antidiabetic drugs from the sodium-glucose cotransporter 2 (SGLT2) inhibitor class such as canagliflozin, dapagliflozin and empagliflozin are being associated with a marked increase in the incidence of fractures in diabetics. So, it is necessary to analyze the drugs in isolation, without diabetes. The objective will be to analyze whether the use of SGLT2 inhibitors can increase bone mass loss in femurs of healthy rats. Femurs will be used (biological material stored from another study) of 40 male rats that were randomly divided into control group, Empa group, Dapa group and Cana group, which received by means of gavage: saline solution, empagliflozin, dapagliflozin and canagliflozin respectively. After 8 weeks of treatment the animals were euthanized. In the present project, the morphometric measurements of the bones will be evaluated, both in terms of their anatomical measurements (length, width of the diaphysis, width of the proximal femur and width of the distal femur) and in their tissue architecture, in addition to cell count (osteoblasts and osteoclasts). For this, histological techniques will be performed and trabecular bone histomorphometry of the proximal epiphysis (head and neck) and distal epiphysis (condyles) of the femur will be performed. The statistical analysis will be according to the evaluation of the sample distribution. If normal, parametric tests will be used (One Way ANOVA with Tukey's a posteriori test); if abnormal, a Kruskal-Wallis test will be performed.