Abstract
Recent studies showed that in patients with type 2 diabetes mellitus (T2DM), Sodium-dependent glucose transporters 2 inhibitor (SGLT2I) may cause potential adverse effects on skeleton such as increasing the risk of fracture. This risk is possibly mediated by effects induced by all SGLT2I class drugs but whether Dapagliflozin aggravates osteoporosis in patients with T2DM remains controversial. Therefore, we designed this study to explore how Dapagliflozin affects the metabolism and the quality of bone in. T2DM animal models The effect of Dapagliflozin on skeleton was evaluated on male ZDF (Zucker Diabetic Fatty) rats—a rat model of diet induced spontaneous T2DM. Dapagliflozin was administrated via gavage at the dosage of 1.0 mg/kg/day. Bone tissue mineral density and the microarchitecture of tibiae were measured with micro-CT and biomechanics characteristic of the femora were tested using a three-point bending test. Serum bone biomarkers and other metabolic parameters were also tested via ELISA or other assays. Our results found that diabetic rats demonstrated symptoms of osteoporosis and Dapagliflozin could help to alleviate these defections caused by diabetes. Compared to the negative controls, the serum CT (calcitonin) level in ZDF rats as well as the uric calcium and phosphate levels were elevated, and these symptoms were alleviated by Dapagliflozin. Tibiae of Dapagliflozin treated rats demonstrated decreased cortical tissue mineral density while trabecular tissue mineral density and mean bone mineral density received a rise when compared to the matched controls. ZDF rats also showed defections in femora stiffness which could be relieved by Dapagliflozin administration. The mechanism of Dapagliflozin affecting bone quality is possibly connected to the suppression of serum calcitonin and excretion of calcium via urine rose by hyperglycemia. In conclusion, Dapagliflozin can prevent osteoporosis in ZDF rats by alleviating hypercalciuria.
Highlights
Diabetes mellitus describes a group of metabolic disorders characterized by increased blood glucose concentration
We choose ZDF rats over STZ add on high fat diets induced diabetic models, to study the effect of diabetes and Sodiumdependent glucose transporters 2 inhibitor (SGLT2I) on bone metabolism, because the pathologic characteristics of ZDF rats are more similar to type 2 diabetes mellitus (T2DM) [9]
The beta cells in T2DM individuals tend to secrete more insulin in order to fight against hyperglycemia, this increased insulin secretion may cause intensive calcium uptake in beta cells lowering the level of serum calcium [16]
Summary
Diabetes mellitus describes a group of metabolic disorders characterized by increased blood glucose concentration. The global prevalence of diabetes in adults has increased dramatically over recent decades. Long-term hyperglycemia and inadequate glycemic control both contribute to the development of diabetic complications, including diabetic related osteoporosis, characterized by a number of detrimental effects on bone metabolism, which has significant consequences for patients with diabetes in terms of decreased bone mineral density and increased risk of fractures [2]. Diabetes related osteoporosis can increase the risk of fractures, which can impact the life quality and life span of diabetes patients adversely. The main treatment means of diabetes related osteoporosis are restricted to relieving hyperglycemia and providing enough calcium via food or drugs. Exploring new methods of treating diabetes related osteoporosis is crucial in the near future
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