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-t erminal extension peptide of procollagen (PICP), total and skeletal al kaline phosphatase (ALP), and osteocalcin. Moreover, the osteoblast-st imulating growth factor, insulin-like growth factor I (IGF-I), was mea sured 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 y r in both sexes), osteocalcin, and total and skeletal ALP (peak values earlier in girls than in boys) and a small increase in PICP were obse rved. All osteoblast markers and IGF-I were markedly lower in normal a dults (n = 229; age, 21-69 yr) than in children. All osteoblast parame ters showed a high degree of correlation (P < 0.001) with each other. In adolescents (n = 104) treated for insulin-dependent diabetes mellit us (IDDM), serum IGF-I (-19%), osteocalcin (-28%), and skeletal ALP (- 28%) were markedly decreased, whereas total ALP was significantly incr eased (29%), and serum PICP remained normal. In adult IDDM (n = 125), both serum IGF-I (-41%) and osteocalcin (-24%) were decreased, but ske letal 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 s ignificantly correlated (r greater than or equal to 0.9) with total AL P in both normal and diabetic subjects, but the slope of the regressio n was significantly different, indicating the presence of other, proba bly intestinal, ALP in all types of diabetes. In conclusion, the osteo blast function is significantly decreased in diabetic patients, which can best be characterized as a maturation defect, since the early oste oblast marker, PICP, remained normal in all types of diabetes, whereas a later marker, skeletal ALP, is frankly abnormal only in diabetic ch ildren. The most mature osteoblast marker, osteocalcin, is decreased i n all types of diabetes irrespective of age.