Poor Glycemic Control Impairs the Response of Biochemical Parameters of Bone Formation and Resorption to Exogenous 1,25-Dihydroxyvitamin D3 in Patients with Type 2 Diabetes

Abstract:

Osteoblast deficit plays a principal role in the development of diabetic osteopenia. We have previously reported that high glucose conditions impair the function of osteoblast-like MG-63 cells. This study was performed to assess the sensitivity of osteoblasts to 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) in patients with type 2 diabetes without insulin deficiency or overt diabetic complications. During stimulation with 1,25(OH)₂D₃ at 2.0 mg/day for 6 consecutive days in 9 type 2 diabetic patients, serum levels of bone alkaline phosphatase (BALP), osteocalcin (OC) and the carboxyterminal propeptide of type 1 procollagen, and the urinary excretion of pyridinoline and deoxypyridinoline (DPYR), were monitored. As parameters of glycemic control, the mean level of fasting plasma glucose (mFPG) throughout the 1,25(OH)₂D₃ stimulation test and the level of HbA_1C were used. 1,25(OH)₂D₃ increased serum 1,25(OH)₂D significantly by day 2, which was followed by a significant reduction in the serum level of intact parathyroid hormone. The maximal increment of serum OC adjusted for that of 1,25(OH)₂D was negatively correlated with both mFPG and HbA_1C levels (p50.05). Furthermore, the magnitude of 1,25(OH)₂D₃-induced bone resorption, as reflected by the maximal increase in urinary DPYR excretion, was negatively correlated with the mFPG level (p50.05). Basal BALP tended to be negatively correlated with HbA_1C, although not to a significant extent. In conclusion, our findings would indicate that poor glycemic control impairs the responses of osteoblasts and osteoclasts to 1,25(OH)₂D₃ in normo-insulinemic type 2 diabetic patients.