title: The association between insulin-like growth factor I and bone turnover markers in the general adult population.
abstract: OBJECTIVE
  Growth hormone (GH) and its main mediator, insulin-like growth factor I (IGF-I), play a fundamental role in human metabolism. Previous epidemiological studies investigating the association of IGF-I and bone turnover markers (BTMs) yielded conflicting results and were limited by study design or sample size. Therefore, we aimed to investigate the associations between serum levels of IGF-I or the IGF-I/IGF binging protein 3 (IGFBP-3) ratio and levels of BTMs including procollagen type 1 N-terminal propeptide (PINP), C-terminal telopeptides of type 1 collagen (CTX), and bone-specific alkaline phosphatase (BAP).
  
  
  METHODS
  Data from 1463 men and 1481 women who participated in the first follow-up of the Study of Health in Pomerania were used. IGF-I and IGFBP-3 levels were measured using chemiluminescent immunometric assays on an Immulite 2500 analyzer. BTM levels were measured on the IDS-iSYS Multi-Discipline Automated Analyser. Analyses of variance (ANOVA) and quantile regression models were calculated.
  
  
  RESULTS
  In men <55 years and premenopausal women ANOVA and quantile regression analyses revealed positive associations between IGF-I or even stronger the IGF-I/IGFBP-3 ratio and PINP [per unit increase in IGF-I/IGFBP-3 ratio in men: beta (95%-CI) 2.33 ng/ml (0.91; 3.75), p < 0.01; women: 3.63 ng/ml (2.31; 4.95), p < 0.01] or CTX [men: 20.8 ng/l (3.5; 38.0), p = 0.02; women: 12.0 ng/l (-1.2; 25.2), p = 0.07]. Furthermore in postmenopausal women, IGF-I and the IGF-I/IGFBP-3 ratio were inversely related with CTX levels, whereas an inverse U-shaped relation between IGF-I/IGFBP-3 ratio and PINP was found. Regarding BAP, we observed borderline significant associations with IGF-I or the IGF-I/IGFBP-3 ratio in older subjects only.
  
  
  CONCLUSIONS
  IGF-I levels and particularly free IGF-I, estimated by the IGF-I/IGFBP-3 ratio, are positively related with PINP as a bone formation marker and CTX as a bone resorption marker in healthy adult men younger than 55 years and premenopausal women. In older subjects the found positive as well as negative relations with BTMs have to be further investigated.
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Germany.
authors.forename: Inga
authors.initials: I
authors.lastname: Niemann
authors.forename: Anke
authors.initials: A
authors.lastname: Hannemann
authors.forename: Matthias
authors.initials: M
authors.lastname: Nauck
authors.forename: Christin
authors.initials: C
authors.lastname: Spielhagen
authors.forename: Henry
authors.initials: H
authors.lastname: Völzke
authors.forename: Henri
authors.initials: H
authors.lastname: Wallaschofski
authors.forename: Nele
authors.initials: N
authors.lastname: Friedrich
mesh_terms: D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D016723:Bone Remodeling; D024042:Collagen Type I / Q000097:blood; D005260:Female; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D011347:Procollagen / Q000097:blood; D055815:Young Adult
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D018972:Insulin-Like Growth Factor Binding Protein 3; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D007334:Insulin-Like Growth Factor I; D000469:Alkaline Phosphatase
keywords: BAP; Bone turnover markers; CTX; Insulin-like growth factor I; PINP; Study of Health in Pomerania