Circulating insulin-like growth factor binding protein-4 (IGFBP-4) is not regulated by parathyroid hormone and vitamin D in vivo: Evidence from children with rickets

Objective: insulin-like growth factor binding protein-4 (igfbp-4),inhibits igf actions under a variety of experimental conditions. parathyroid hormone (pth),1.25-hydroxy(oh)vitamin d,igf-i,igf-ii and transforming growth factor (tgf)-β are the major regulators of igfbp-4 production in vitro. however,little is known about the in vivo regulation of circulating igfbp-4 in humans. methods: we measured serum concentrations of calcium (ca),phosphorus (p),alkaline phosphatase (alp),pth,vitamin d,igf-i,igfbp-3,and igfbp-4 in infants (n=22) with nutritional rickets before and after treatment of rickets with vitamin d (300 000 u single dose po). results: the mean±sd age of the patients was 1.3±1.6 years (range 0.2-3). serum ca and p increased,whereas alp and pth decreased after treatment (ca from 6.6±1.4 to 9.5±1.6 mg/dl,p from 3.9±1.4 to 5.4±0.8 mg/dl,alp from 2590±2630 to 1072±776 iu/ml and pth from 407±248 to 27.4±20.8 ng/dl,respectively). vitamin d levels were low (7.8±2.5 ng/ml) and increased after treatment (18.1±4.0 ng/ml,p<0.001). serum igf-i and igfbp-3 levels both increased after treatment (igf-i: 13.5±12.2 vs. 23.7±14.2 ng/ml,p<0.001 and igfbp-3: 1108±544 vs. 1652±424 ng/ml,p<0.001). however,serum igfbp-4 levels did not change significantly after treatment (18.8±8.0 vs. 21.5±4.8 ng/ml). no correlation between pth and igf-i,igfbp-3 or igfbp-4 was detected. significant correlations were observed between pth and alp (r=0.53,p<0.05),and between igf-i and igfbp-3 (r=0.46,p<0.05). conclusion: the results demonstrate that contrary to in vivo studies,circulating igfbp-4 levels are not influenced by secondary hyperparathyroidism in vitamin d deficiency rickets since igfbp-4 levels did not change after normalization of pth with vitamin d treatment. © journal of clinical research in pediatric endocrinology,published by galenos publishing.