1,25-Dihydroxy vitamin D3 treatment attenuates osteopenia, and improves bone muscle quality in Goto-Kakizaki type 2 diabetes model rats

PURPOSE: Osteopenia and skeletal fragility are considered to be the complications associated with type 2 diabetes mellitus (T2DM). The relationship between glucose metabolism, skeletal quality, and vitamin D have not been completely understood. We aimed to demonstrate a comprehensive bone quality profile in a T2DM model subject and to investigate whether 1, 25-dihydroxy vitamin D3 could prevent osteopenia and skeletal fragility in the diabetes model rats. METHODS: Daily calcitriol (a 1, 25-dihydroxy vitamin D3 formulation, 0.045 μg/kg/day) treatment was administered to 21-week-old male Goto-Kakizaki (GK) rats (a genetic non-obese and non-insulin-dependent spontaneous diabetes rat model) for 20 weeks and the results were compared with those in untreated GK rats, and wild-type animals. RESULTS: Micro-computed tomography, histomorphometry, and bone mineral density analysis demonstrated that T2DM induced significant osteopenia, and impairment of bone microarchitecture and biomechanical properties in GK rats. T2DM also significantly decreased bone formation and increased bone resorption parameters in three regions of the skeleton (proximal tibia, mid-shaft of the tibia, and lumbar vertebrae), and increased carboxy-terminal type I collagen crosslinks, tartrate-resistant acid phosphatase, muscle ubiquitin C, and bone thioredoxin interacting protein (TXNIP) expression. Calcitriol treatment significantly alleviated bone loss, and improved bone microarchitecture and biomechanical properties and also decreased serum glucose and glycated serum protein levels. Biomarkers of bone formation were significantly increased, while muscle ubiquitin C and bone TXNIP expression were significantly decreased following calcitriol treatment. CONCLUSIONS: These results suggest that 1,25-dihydroxy vitamin D3 treatment effectively attenuates osteopenia, and improves bone and muscle quality in GK type 2 diabetes model rats.