Londzin Piotr, Brudnowska Agata, Kurkowska Katarzyna, Wilk Katarzyna, Olszewska Karolina, Ziembiński Łukasz, Janas Aleksandra, Cegieła Urszula, Folwarczna Joanna
Department of Pharmacology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Katowice, Poland.
Department of Pharmacology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Katowice, Poland.
Biomed Pharmacother. 2022 Nov;155:113679. doi: 10.1016/j.biopha.2022.113679. Epub 2022 Sep 12.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs, acting by inhibiting the reabsorption of glucose in the kidneys. They turned out to improve cardiovascular and renal outcomes not only in patients with type 2 diabetes but also in nondiabetic patients. At present, they are more and more widely used in patients without diabetes. Since there were concerns that SGLT2 inhibitors may increase fracture risk in diabetes, the aim of the study was to examine the effect of dapagliflozin and canagliflozin on the musculoskeletal system of nondiabetic, healthy rats. The experiments were carried out on mature female rats, divided into the control rats and rats treated with dapagliflozin (1.4 mg/kg p.o.) or canagliflozin (4.2 mg/kg p.o.) for 4 weeks. Serum bone turnover markers, skeletal muscle strength and mass, bone mass, density, histomorphometric parameters and mechanical properties were determined. Administration of the drugs did not affect the skeletal muscle mass and strength. There was no effect on serum bone turnover markers, and bone mass and composition. However, administration of both drugs resulted in disorders of cancellous bone microarchitecture and worsening of bone mechanical properties. In conclusion, both SGLT2 inhibitors unfavorably affected the skeletal system of healthy rats.
钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂是一类新型抗糖尿病药物，其作用机制是抑制肾脏对葡萄糖的重吸收。事实证明，它们不仅能改善2型糖尿病患者的心血管和肾脏预后，对非糖尿病患者也有同样效果。目前，它们在非糖尿病患者中的应用越来越广泛。由于有人担心SGLT2抑制剂可能会增加糖尿病患者的骨折风险，本研究旨在探讨达格列净和卡格列净对非糖尿病健康大鼠肌肉骨骼系统的影响。实验选用成年雌性大鼠，分为对照组、接受达格列净（口服1.4毫克/千克）治疗的大鼠组和接受卡格列净（口服4.2毫克/千克）治疗的大鼠组，给药4周。测定血清骨转换标志物、骨骼肌力量和质量、骨量、密度、组织形态计量学参数及力学性能。给药后对骨骼肌质量和力量无影响，对血清骨转换标志物、骨量和组成也无影响。然而，两种药物给药均导致松质骨微结构紊乱和骨力学性能恶化。总之，两种SGLT2抑制剂均对健康大鼠的骨骼系统产生不利影响。
