Growth hormone (GH) treatment of GH-deficient children increases serum levels of insulin-like growth factors (IGFs), IGF-binding protein-3 and -5, and bone alkaline phosphatase isoenzyme.

To investigate the contribution of the insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) to the regulation of bone growth in 10 GH-deficient Japanese children receiving recombinant GH therapy, we determined the percent increase from pretreatment levels of serum IGF-I, IGF-II, IGFBP-3, IGFBP-5, and bone-specific alkaline phosphatase isoenzyme (B-ALP). For 10 children between 6-13 yr of age, serum IGF-I and IGF-II were increased after 1 month of treatment by 53% and 7%, respectively; after 12 months of therapy, IGF levels remained elevated at 51% and 17%, respectively. Serum IGFBP-3 and IGFBP-5 were also increased after 1 month of GH therapy by 17% and 13% respectively; after 12 months of therapy, they remained elevated at 22% and 15%, respectively. After 12 months of treatment, the bone formation marker B-ALP was also elevated to 23% greater than pretreatment levels. The elevation of IGF-I induced by GH was significantly correlated with the increases in IGFBP-3 (r = 0.735; P < 0.0001) and IGFBP-5 (r = 0.795; P < 0.0001), and the elevation of B-ALP was also significantly positively correlated with the increases in IGF-I, IGF-II, IGFBP-3, and IGFBP-5 (r = 0.544, P < 0.0001; r = 0.268, P = 0.0399; r = 0.414, P = 0.0010; and r = 0.500, P < 0.0001, respectively). Our data are consistent with the anabolic effect on bone growth of GH treatment being mediated by IGF-II, IGFBP-3, and IGFBP-5 as well as by IGF-I. This is the first evidence that GH treatment increases IGF-II in GH-deficient children. This finding was probably the result of application of a valid assay that measures IGF-II without interference of IGFBPs.