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.