Bone Abstracts

Fibroblast growth factor-23 (FGF23) is a bone derived phosphate-regulating hormone which is elevated in hypophosphataemic rickets. Recent findings demonstrate iron deficiency as a potential mediator of FGF23 expression and murine studies have shown in utero effects of maternal iron deficiency leading to increased FGF23 concentration and disordered bone development (Clinkenbeard. JBMR 2013). Children with rickets in rural Gambia, West Africa, have high prevalences of iron deficiency and elevated FGF23. The aim of this study was to elucidate potential in utero effects of iron status on infant FGF23 and mineral metabolism as potential antecedents of rickets in The Gambia.

Infants born to mothers with normal (NI n=25) and low (LI n=25) iron status during pregnancy, from a Gambian mother-infant trial ISRCTN49285450 had blood and plasma samples analysed at 12, 24, 52, 78 and 104 weeks of life for circulating haemoglobin (Hb), C-terminal (C-FGF23; Immutopics, USA) and intact-FGF23 (I-FGF23; Kainos, Japan), phosphate (Phos), total alkaline phosphatase (TALP) and cystatin C (Cys C) (Kone Analyser 20i, Finland).

Circulating I-FGF23, Phos, TALP and Hb decreased and estimated glomerular filtration rate (eGFR; 74.835/(cys C (mg/l)^1.333) increased over time (mean(S.D.) I-FGF23: 49.1(13.1) to 34.3 (10.9) pg/ml, Phos: 1.86(0.13) to 1.69(0.17) mmol/l, TALP: 406(133) to 318(135) U/l, Hb: 10.7(1.6) to 9.4(1.6) g/dl and eGFR: 59.9(11.2) to 94.5(23.4) ml/min. All P≤0.0001)). C-FGF23 did not change significantly over-time (402(218) to 487(502) RU/ml, P=0.15). C-FGF23 and TALP were significantly higher in LI compared with NI from 52 week and from 24 week for TALP. Adjusted for timepoint Hb was the strongest negative predictor of C-FGF23 concentration (Beta coefficient (SE) −104.1(27.28) RU/ml, P≤0.0002; group difference P=0.03) and Phos the strongest positive predictor of I-FGF23 (31.4(3.9) pg/ml, P≤0.0001, group difference P=0.8) and I-FGF23 did not predict C-FGF23 (−2.68(3.56) RU/ml, P=0.45, group difference P=0.03).

In conclusion, this study suggests that poor maternal iron status is associated with an increased infant C-FGF23 and TALP concentration in humans. Further studies are required to investigate the role of maternal iron status in the regulation of offspring FGF23 and mineral metabolism as antecedents of rickets.

Funded by the UK MRC & DFID. MRC programmes: U105960371, U123261351 & MC-A760-5QX00.

Disclosure: The authors declared no competing interests.