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Low serum iron is associated with high serum intact FGF23 in elderly men : The Swedish MrOS study

Lewerin, Catharina; Ljunggren, Östen; Nilsson-Ehle, Herman; Karlsson, Magnus K. LU ; Herlitz, Hans; Lorentzon, Mattias; Ohlsson, Claes and Mellström, Dan (2017) In Bone 98. p.1-8
Abstract

Background Fibroblast growth factor (FGF23) is a protein that is produced by osteoblasts and osteocytes. Increased serum levels of FGF23 have been associated with increased risks of osteoporotic fractures and cardiovascular disease, particularly in participants with poor renal function. Serum iron (Fe) has been suggested as a regulator of FGF23 homeostasis. Objective To determine whether Fe and iron status are determinants of the levels of intact FGF23 (iFGF23) in elderly men. Methods The MrOS study is a population-based study of elderly men (N = 1010; mean age, 75.3 years; range, 69–81 years). The levels of Fe, transferrin saturation (TS), and ferritin were evaluated in relation to the serum concentrations of iFGF23 before and after... (More)

Background Fibroblast growth factor (FGF23) is a protein that is produced by osteoblasts and osteocytes. Increased serum levels of FGF23 have been associated with increased risks of osteoporotic fractures and cardiovascular disease, particularly in participants with poor renal function. Serum iron (Fe) has been suggested as a regulator of FGF23 homeostasis. Objective To determine whether Fe and iron status are determinants of the levels of intact FGF23 (iFGF23) in elderly men. Methods The MrOS study is a population-based study of elderly men (N = 1010; mean age, 75.3 years; range, 69–81 years). The levels of Fe, transferrin saturation (TS), and ferritin were evaluated in relation to the serum concentrations of iFGF23 before and after adjustments for confounders. Results TS < 15% was found in 3.5% (34/977) of the participants, who had a higher median level iFGF23 compared with the remaining subjects (47.4 μmol/L vs. 41.9 μmol/L, p = 0.008). The levels of iFGF23 correlated negatively (un-adjusted) with the levels of Fe (r = − 0.17, p < 0.001), TS (r = − 0.16, p < 0.001) and serum ferritin (r = − 0.07, p = 0.022). In addition, in participants with estimated glomerular filtration rate eGFRCystatin C > 60 mL/min, the levels of iFGF23 correlated (age-adjusted) negatively with the levels of Fe (r = − 0.15, p < 0.001) and TS (r = − 0.17, p < 0.001). The level of iFGF23 correlated positively (un-adjusted) with lumbar spine bone mineral density (BMD) (r = 0.14, p < 0.001), total body BMD (r = 0.11, p = 0.001), and total hip BMD (r = 0.09, p = 0.004). The corresponding correlations, when adjusted for age, weight, and height were: r = 0.08, p = 0.018; r = 0.05, p = 0.120; and r = 0.02, p = 0.624, respectively. No associations were found between BMD and the levels of Fe or TS. Multiple step-wise linear regression analyses [adjusting for age, body mass index (BMI), comorbidity index, cystatin C, C-reactive protein (hs-CRP), serum vitamin D 25-OH (25OHD), phosphate, calcium, parathyroid hormone (PTH), erythropoietin, hemoglobin, lumbar spine BMD, apolipoprotein B/A1 ratio] were performed in three separate models with Fe, TS or ferritin as potential explanatory variables. Fe and TS, but not ferritin, were independent predictors of iFGF23 level (standardized β-values: − 0.10, p < 0.001; − 0.10, p < 0.001; and − 0.05, p = 0.062, respectively). Conclusion Low levels of Fe in elderly men are associated with high levels of iFGF23, independently of markers of inflammation and renal function, suggesting an iron-related pathway for FGF23 regulation.

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Contribution to journal
publication status
published
subject
keywords
Bone mineral density, Elderly, Fibroblast growth factor 23, Intact FGF23, Iron, Men
in
Bone
volume
98
pages
8 pages
publisher
Elsevier
external identifiers
  • scopus:85013902911
  • wos:000400227800001
ISSN
8756-3282
DOI
10.1016/j.bone.2017.02.005
language
English
LU publication?
yes
id
9e3ab3c8-62f4-4027-9a0e-84b67627ea73
date added to LUP
2017-03-13 07:37:12
date last changed
2018-01-07 11:54:54
@article{9e3ab3c8-62f4-4027-9a0e-84b67627ea73,
  abstract     = {<p>Background Fibroblast growth factor (FGF23) is a protein that is produced by osteoblasts and osteocytes. Increased serum levels of FGF23 have been associated with increased risks of osteoporotic fractures and cardiovascular disease, particularly in participants with poor renal function. Serum iron (Fe) has been suggested as a regulator of FGF23 homeostasis. Objective To determine whether Fe and iron status are determinants of the levels of intact FGF23 (iFGF23) in elderly men. Methods The MrOS study is a population-based study of elderly men (N = 1010; mean age, 75.3 years; range, 69–81 years). The levels of Fe, transferrin saturation (TS), and ferritin were evaluated in relation to the serum concentrations of iFGF23 before and after adjustments for confounders. Results TS &lt; 15% was found in 3.5% (34/977) of the participants, who had a higher median level iFGF23 compared with the remaining subjects (47.4 μmol/L vs. 41.9 μmol/L, p = 0.008). The levels of iFGF23 correlated negatively (un-adjusted) with the levels of Fe (r = − 0.17, p &lt; 0.001), TS (r = − 0.16, p &lt; 0.001) and serum ferritin (r = − 0.07, p = 0.022). In addition, in participants with estimated glomerular filtration rate eGFRCystatin C &gt; 60 mL/min, the levels of iFGF23 correlated (age-adjusted) negatively with the levels of Fe (r = − 0.15, p &lt; 0.001) and TS (r = − 0.17, p &lt; 0.001). The level of iFGF23 correlated positively (un-adjusted) with lumbar spine bone mineral density (BMD) (r = 0.14, p &lt; 0.001), total body BMD (r = 0.11, p = 0.001), and total hip BMD (r = 0.09, p = 0.004). The corresponding correlations, when adjusted for age, weight, and height were: r = 0.08, p = 0.018; r = 0.05, p = 0.120; and r = 0.02, p = 0.624, respectively. No associations were found between BMD and the levels of Fe or TS. Multiple step-wise linear regression analyses [adjusting for age, body mass index (BMI), comorbidity index, cystatin C, C-reactive protein (hs-CRP), serum vitamin D 25-OH (25OHD), phosphate, calcium, parathyroid hormone (PTH), erythropoietin, hemoglobin, lumbar spine BMD, apolipoprotein B/A1 ratio] were performed in three separate models with Fe, TS or ferritin as potential explanatory variables. Fe and TS, but not ferritin, were independent predictors of iFGF23 level (standardized β-values: − 0.10, p &lt; 0.001; − 0.10, p &lt; 0.001; and − 0.05, p = 0.062, respectively). Conclusion Low levels of Fe in elderly men are associated with high levels of iFGF23, independently of markers of inflammation and renal function, suggesting an iron-related pathway for FGF23 regulation.</p>},
  author       = {Lewerin, Catharina and Ljunggren, Östen and Nilsson-Ehle, Herman and Karlsson, Magnus K. and Herlitz, Hans and Lorentzon, Mattias and Ohlsson, Claes and Mellström, Dan},
  issn         = {8756-3282},
  keyword      = {Bone mineral density,Elderly,Fibroblast growth factor 23,Intact FGF23,Iron,Men},
  language     = {eng},
  month        = {05},
  pages        = {1--8},
  publisher    = {Elsevier},
  series       = {Bone},
  title        = {Low serum iron is associated with high serum intact FGF23 in elderly men : The Swedish MrOS study},
  url          = {http://dx.doi.org/10.1016/j.bone.2017.02.005},
  volume       = {98},
  year         = {2017},
}