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Impact of hyponatremia on bone tissue

Grant number: 18/17845-7
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): March 01, 2019
Effective date (End): June 30, 2021
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Francisco José Albuquerque de Paula
Grantee:Luciana Tabajara Parreiras e Silva
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Hyponatremia is defined when the serum sodium concentration [Na+] is less than 135 mmol/L and it is the most common electrolyte disturbance found in clinical practice. Hyponatremia affects especially elderly individuals and approximately 50% of chronic hyponatremia are caused by inappropriate syndrome of antidiuretic hormone (AVP) secretion (SIADH). In recent years, several studies have associated the hyponatremic state as a risk factor for the development of osteoporosis and fractures independently of AVP levels, indicating that lower serum sodium can deeply change the activity of bone remodeling. However, the molecular and cellular mechanisms responsible for these alterations are still to be understood. Therefore, the objective of this work is to evaluate the impact of hyponatremia on bone remodeling, bone Marrow Adipose Tissue (MAT), bone microarchitecture and differentiation of bone marrow stromal and hematopoietic stem cells in rats. The study will comprise thirty male Wistar rats, two months old, weighing approximately 200 to 250 g. They will be allocated into three groups with 10 animals, receiving water and food ad libitum. For the Control Group (CG) (n=10) a standard diet without sodium restriction (AIN-93M) will be offered. The other 2 groups will receive a low sodium content diet. In addition to the hyponatremic diet (0.06% Na) one group will receive furosemide (HFG) (n=10) and the other will be treated with hydrochlorothiazide (HHG) (n=10). The experiment will last 12 weeks. It will be evaluated the impact of hyponatremia on body composition, bone remodeling and mineralization activity, microstructure and resistance of bone tissue, and differentiation of mesenchymal stromal and hematopoietic cells, respectively, into osteoblasts and osteoclasts. The present study intends to contribute with new considerations regarding the influence of hyponatremia on the bone structure and its interaction with energy metabolism. (AU)