Effects of antidepressant escitalopram oxalate on fracture healing: a study with growing rats, healthy adults and adults with osteoporosis

• Grant number: 18/17396-8
• Support Opportunities: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): January 01, 2019
• Effective date (End): May 31, 2022
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: José Batista Volpon
• Grantee: Roberta Carminati Shimano
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Current scientific evidences highlight to the negative effects of antidepressants on bone tissue, causing a significant decrease in bone mass. However, the effects of the use of this medication on the fracture healing require further investigations, especially at different ages. Therefore, the aim of this study will be to analyze bone and fracture callus quality in rats submitted to the use of escitalopram oxalate under the following conditions: growing rats, healthy adults and adults with osteoporosis. Materials and methods: A total of 126 Hannover rats at the age of 4 or 8 weeks according to the experimental group (n = 21 / group) will be used: 1- PC (growing placebo): growing animals with 4 weeks age submitted to placebo treatment; 2- PA (placebo adult with 8 weeks age); 3-PO (placebo osteoporosis with 8 weeks age); 4- EC (growing escitalopram): growing animals with 4 weeks age undergoing escitalopram oxalate treatment; 5- EA (escitalopram adult with weeks age) and; 6- EO (escitalopram osteoporosis). Daily administration of escitalopram oxalate (or saline solution) at the dose of 2.0 mg/kg will be given during 35 days, whence a bone fracture will be performed on the 21st experimental day. In the ovariectomized animals, the drug treatment (or placebo) will began 90 days after bilateral ovarian removal, when osteoporosis will be installed. Bone quality analysis will be performed on both non-fractured femur and callus, by using bone mineral density analysis (DXA), computed micro-tomography (qualitative and quantitative microstructure analysis), bone strength (mechanical test), histomorphometric (quantification of bone trabeculation and collagen), immunohistochemistry (bone formation and resorption evaluation, by means of dosage of OPG, RANK and RANKL) and gene expression (RUNX- 2, RANKL, OPG and TGF²-1). Furthermore, by ELISA method serum bone markers will be assessed (OPG, RANK, RANKL, PINP, CTX-I, IGF-1). Results will assess the effects of escitalopram oxalate on intact bone and fracture healing in growing animals, healthy adults and adults with osteoporosis.