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.
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 micrograms/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 HbA1C 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 HbA1C levels (p < 0.05). 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 (p < 0.05). Basal BALP tended to be negatively correlated with HbA1C, 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.
Inaba
M
M
Second Department of Internal Medicine, Osaka City University Medical School, Japan.
Nishizawa
Y
Y
Mita
K
K
Kumeda
Y
Y
Emoto
M
M
Kawagishi
T
T
Ishimura
E
E
Nakatsuka
K
K
Shioi
A
A
Morii
H
H
D000469:Alkaline Phosphatase / Q000097:blood; D000596:Amino Acids / Q000652:urine; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D001851:Bone Diseases, Metabolic / Q000209:etiology* / Q000378:metabolism; D016723:Bone Remodeling / Q000187:drug effects*; D002117:Calcitriol / Q000008:administration & dosage; D002120:Calcium Channel Agonists / Q000008:administration & dosage; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000378:metabolism*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D013268:Stimulation, Chemical
D000469:Alkaline Phosphatase; D000596:Amino Acids; D015415:Biomarkers; D001786:Blood Glucose; D002117:Calcitriol; D002120:Calcium Channel Agonists; D006442:Glycated Hemoglobin; D015675:Osteocalcin; D010446:Peptide Fragments; D011347:Procollagen; C042813:procollagen type I carboxy terminal peptide; C015484:pyridinoline; C036020:deoxypyridinoline