title: Serum fibroblast growth factor 23, serum iron and bone mineral density in premenopausal women.
abstract: Fibroblast growth factor 23 (FGF23) circulates as active protein and inactive fragments. Low iron status increases FGF23 gene expression, and iron deficiency is common. We hypothesized that in healthy premenopausal women, serum iron influences C-terminal and intact FGF23 concentrations, and that iron and FGF23 associate with bone mineral density (BMD). Serum iron, iron binding capacity, percent iron saturation, phosphorus, and other biochemistries were measured in stored fasting samples from healthy premenopausal white (n=1898) and black women (n=994), age 20-55years. Serum C-terminal and intact FGF23 were measured in a subset (1631 white and 296 black women). BMD was measured at the lumbar spine and femur neck. Serum phosphorus, calcium, alkaline phosphatase and creatinine were lower in white women than black women (p<0.001). Serum iron (p<0.0001) and intact FGF23 (p<0.01) were higher in white women. C-terminal FGF23 did not differ between races. Phosphorus correlated with intact FGF23 (white women, r=0.120, p<0.0001; black women r=0.163, p<0.01). However, phosphorus correlated with C-terminal FGF23 only in black women (r=0.157, p<0.01). Intact FGF23 did not correlate with iron. C-terminal FGF23 correlated inversely with iron (white women r=-0.134, p<0.0001; black women r=-0.188, p<0.01), having a steeper slope at iron <50mcg/dl than ≥50mcg/dl. Longitudinal changes in iron predicted changes in C-terminal FGF23. Spine BMD correlated with iron negatively (r=-0.076, p<0.01) in white women; femur neck BMD correlated with iron negatively (r=-0.119, p<0.0001) in black women. Both relationships were eliminated in weight-adjusted models. BMD did not correlate with FGF23. Serum iron did not relate to intact FGF23, but was inversely related to C-terminal FGF23. Intact FGF23 correlated with serum phosphorus. In weight-adjusted models, BMD was not related to intact FGF23, C-terminal FGF23 or iron. The influence of iron on FGF23 gene expression is not important in determining bone density in healthy premenopausal women.
authors.affiliation: Department of Medicine, Indiana University School of Medicine, USA; Department of Pediatrics, Indiana University School of Medicine, USA. Electronic address: eimel@iu.edu.
authors.forename: Erik A
authors.initials: EA
authors.lastname: Imel
authors.affiliation: Indiana University School of Public Health, Department of Biostatistics, USA.
authors.forename: Ziyue
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Medicine, Indiana University School of Medicine, USA.
authors.forename: Amie K
authors.initials: AK
authors.lastname: McQueen
authors.affiliation: Department of Medicine, Indiana University School of Medicine, USA.
authors.forename: Dena
authors.initials: D
authors.lastname: Acton
authors.affiliation: Department of Medicine, Indiana University School of Medicine, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Acton
authors.affiliation: Department of Pharmacology and Toxicology, Indiana University School of Medicine, USA.
authors.forename: Leah R
authors.initials: LR
authors.lastname: Padgett
authors.affiliation: Department of Medicine, Indiana University School of Medicine, USA.
authors.forename: Munro
authors.initials: M
authors.lastname: Peacock
authors.affiliation: Department of Medicine, Indiana University School of Medicine, USA; Medical and Molecular Genetics, Indiana University School of Medicine, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Econs
mesh_terms: D000328:Adult; D015519:Bone Density; D015331:Cohort Studies; D005260:Female; D005272:Femur Neck / Q000502:physiology; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D007501:Iron / Q000097:blood*; D008137:Longitudinal Studies; D008159:Lumbar Vertebrae / Q000502:physiology; D015999:Multivariate Analysis; D017697:Premenopause / Q000097:blood*; D044465:White People
chemical_list: C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D007501:Iron
keywords: Bone mineral density; DXA; FGF23; Fibroblast growth factor 23; Iron; Premenopausal women