Follow-up study of Gambian children with rickets-like bone deformities and elevated plasma FGF23: Possible aetiological factors

摘要

We have previously reported on a case-series of children (n = 46) with suspected calcium-deficiency rickets who presented in The Gambia with rickets-like bone deformities. Biochemical analyses discounted vitamin D-deficiency as an aetiological factor but indicated a perturbation of Ca-P metabolism involving low plasma phosphate and high circulating fibroblast growth factor-23 (FGF23) concentrations.A follow-up study was conducted 5. years after presentation to investigate possible associated factors and characterise recovery. 35 children were investigated at follow-up (RFU). Clinical assessment of bone deformities, overnight fasted 2. h urine and blood samples, 2-day weighed dietary records and 24. h urine collections were obtained. Age- and season-matched data from children from the local community (LC) were used to calculate standard deviation scores (SDS) for RFU children.None of the RFU children had radiological signs of active rickets. However, over half had residual leg deformities consistent with rickets. Dietary Ca intake (SDS-Ca=-0.52 (0.98) p=0.04), dietary Ca/P ratio (SDS-Ca/P=-0.80 (0.82) p=0.0008) and TmP:GFR (SDS-TmP:GFR=-0.48 (0.81) p=0.04) were significantly lower in RFU children compared with LC children and circulating FGF23 concentration was elevated in 19% of RFU children. Furthermore an inverse relationship was seen between haemoglobin and FGF23 (R 2=25.8, p=0.004).This study has shown differences in biochemical and dietary profiles between Gambian children with a history of rickets-like bone deformities and children from the local community. This study provided evidence in support of the calcium deficiency hypothesis leading to urinary phosphate wasting and rickets and identified glomerular filtration rate and iron status as possible modulators of FGF23 metabolic pathways.