Influence of age, sex, and insulin on osteoblast function: osteoblast dysfunction in diabetes mellitus

The osteoblast function was evaluated in normal and diabetic children and adults by measurements of the serum concentration of the carboxy-terminal extension peptide of procollagen (PICP), total and skeletal alkaline phosphatase (ALP), and osteocalcin. Moreover, the osteoblast-stimulating growth factor, insulin-like growth factor I (IGF-I), was measured in the same samples. In normal children (n = 420; age, 5-20 yr), a marked pubertal increase of serum IGF-I (peak values at age 14-16 yr in both sexes), osteocalcin, and total and skeletal ALP (peak values earlier in girls than in boys) and a small increase in PICP were observed. All osteoblast markers and IGF-I were markedly lower in normal adults (n = 229; age, 21-69 yr) than in children. All osteoblast parameters showed a high degree of correlation (P < 0.001) with each other. In adolescents (n = 104) treated for insulin-dependent diabetes mellitus (IDDM), serum IGF-I (-19%), osteocalcin (-28%), and skeletal ALP (-28%) were markedly decreased, whereas total ALP was significantly increased (29%), and serum PICP remained normal. In adult IDDM (n = 125), both serum IGF-I (-41%) and osteocalcin (-24%) were decreased, but skeletal ALP and PICP remained normal. A similar abnormality in serum IGF-I and osteocalcin was observed in white (n = 61) and Pima Indian (n = 16) non-IDDM patients. The concentration of skeletal ALP was highly significantly correlated (r > or = 0.9) with total ALP in both normal and diabetic subjects, but the slope of the regression was significantly different, indicating the presence of other, probably intestinal, ALP in all types of diabetes. In conclusion, the osteoblast function is significantly decreased in diabetic patients, which can best be characterized as a maturation defect, since the early osteoblast marker, PICP, remained normal in all types of diabetes, whereas a later marker, skeletal ALP, is frankly abnormal only in diabetic children. The most mature osteoblast marker, osteocalcin, is decreased in all types of diabetes irrespective of age.