Improved fatigue properties, bone microstructure and blood glucose in type 2 diabetic rats with verapamil treatment

Background: Type 2 diabetes mellitus is a global epidemic disease, which leads to a severe complication named increased bone fracture risk. This study aimed to explore if verapamil treatment could improve bone quality of type 2 diabetes mellitus. Methods: Rat models of control, diabetes and verapamil treatment with 4/12/24/48 mg/kg/d were established, respectively. Blood glucose was monitored during 12-week treatment, and bilateral tibiae were collected. Microstructural images of bilateral metaphyseal cancellous bone and high-resolution images of cortical bone of left tibial shafts were obtained by micro-computed tomography. Fatigue properties of bone were evaluated via cyclic compressive tests of right tibial shafts. Findings: Verapamil treatment had no significant effect on blood glucose, but blood glucose tended to decline with the increase of verapamil-treated time and dose. Compared with controls, osteocyte lacunar and canal porosities in diabetes and verapamil-treated groups were significantly decreased (P < 0.05), trabecular separation and degree of anisotropy were significantly increased (P < 0.05), while trabecular tissue mineral density, trabecular bone volume fraction and trabecular number in verapamil-treated (48 mg/kg/d) group were significantly higher than those in diabetes (P < 0.05). Compared with diabetes, initial compressive elastic moduli in verapamil-treated (12/24/48 mg/kg/d) groups were significantly increased (P < 0.05), while secant modulus degradations in verapamil-treated (24/48 mg/kg/d) groups were significantly decreased (P < 0.05). Interpretation: Verapamil could improve bone microstructure and fatigue properties in type 2 diabetic rats; and high-dose verapamil presented a significant effect on improving bone quality. These findings provided a new possibility for preventing the high bone fracture risk of type 2 diabetes mellitus in clinics.