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

Abstract

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.

Correlation between vitamin D serum levels and severity of diabetic retinopathy in patients with type 2 diabetes mellitus

“…Vitamin D decreases the production of several proinflammatory cytokines (IL-2, IL-6, IL-8, IL-12 and TNF-α). 6,33 Vitamin D also exerts an anti-inflammatory effect by decreasing the proliferation of helper T-cells, cytotoxic T-cells and natural killer cells. 32 Vitamin D deficiency has been found to be associated with vascular endothelial dysfunction in middle-aged and elderly adults.…”

Salvianolate Ameliorates Osteopenia and Improves Bone Quality in Prednisone-Treated Rheumatoid Arthritis Rats by Regulating RANKL/RANK/OPG Signaling

“…The abbreviations of the bone histomorphometric parameters used were recommended by the American Society for Bone and Mineral Research Histomorphometric Nomenclature Committee ( Dempster et al, 2013 ). All histomorphometric parameters and procedures were in accordance with a previously published study ( Liang et al, 2019 ).…”

Thioredoxin-interacting protein: A new therapeutic target in bone metabolism disorders?

“…vitamin D3 significantly reduces T2DM-induced bone loss, improves bone microstructure and biomechanical properties, and reduces serum glucose and glycosylated serum protein levels. Meanwhile, TXNIP expression in the bone decreases, whereas bone formation biomarkers increase significantly (16).…”

“…Simultaneously, in this model, bone formation-related parameters, such as OCN expression, are significantly reduced, whereas the levels of bone resorption markers, such as tartrate-resistant acid phosphatase (TRAP), are significantly increased. Moreover, calcitriol treatment reduces MDA and TXNIP expression in GK rats, suggesting that TXNIP-mediated oxidative stress reduces bone quality in these rats ( 16 ). In rats, oral administration of aluminum for 12 weeks significantly upregulated the expression of TXNIP protein in the femur, activated the NLRP3 inflammasome pathway, and increased the serum levels of IL-1β and IL-18, resulting in bone loss ( 20 ).…”

“…Treatment with 1,25-dihydroxy vitamin D3 significantly reduces T2DM-induced bone loss, improves bone microstructure and biomechanical properties, and reduces serum glucose and glycosylated serum protein levels. Meanwhile, TXNIP expression in the bone decreases, whereas bone formation biomarkers increase significantly ( 16 ). A previous study showed that tanshinol improved microcirculation disorder and damaged bone formation in rats by inhibiting the activation of the TXNIP signaling pathway in glucocorticoid-induced OP rats and human OB-like cells (MG63), reversing the downregulation of the Wnt and vascular endothelial growth factor pathways ( 17 ).…”