title: 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.
abstract: 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)-b 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Marmara University Medical Faculty, Department of Pediatric Endocrinology, İstanbul, Turkey. abereket@e-kolay.net
authors.forename: Abdullah
authors.initials: A
authors.lastname: Bereket
authors.forename: Yaşar
authors.initials: Y
authors.lastname: Cesur
authors.forename: Behzat
authors.initials: B
authors.lastname: Özkan
authors.forename: Erdal
authors.initials: E
authors.lastname: Adal
authors.forename: Serap
authors.initials: S
authors.lastname: Turan
authors.forename: Sertaç Hanedan
authors.initials: SH
authors.lastname: Onan
authors.forename: Hakan
authors.initials: H
authors.lastname: Döneray
authors.forename: Teoman
authors.initials: T
authors.lastname: Akçay
authors.forename: Goncagül
authors.initials: G
authors.lastname: Haklar
mesh_terms: D002675:Child, Preschool; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000209:etiology; D007223:Infant; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000378:metabolism; D010281:Parathyroid Hormone / Q000097:blood*; D012279:Rickets / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D014807:Vitamin D / Q000097:blood* / Q000627:therapeutic use
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D018974:Insulin-Like Growth Factor Binding Protein 4; D010281:Parathyroid Hormone; D014807:Vitamin D; D007334:Insulin-Like Growth Factor I