Oral Iron Replacement Normalizes Fibroblast Growth Factor 23 in Iron-Deficient Patients With Autosomal Dominant Hypophosphatemic Rickets.
Study Goal
The researchers aimed to determine if oral iron replacement could normalize FGF23 concentrations in patients with autosomal dominant hypophosphatemic rickets (ADHR) and iron deficiency.
Results Summary
Oral iron supplementation significantly reduced intact FGF23 levels, normalized serum phosphorus in symptomatic patients, and allowed discontinuation of calcitriol and phosphate. The primary outcome (≥20% decrease in FGF23) was achieved by 80% of subjects by month 4, and all subjects had normal FGF23 levels by month 12.
Population
Adults (n=6, three male, three female) with ADHR due to the FGF23-R176Q mutation and iron deficiency.
Effective Dosage
Started at 65 mg daily, titrated based on fasting serum iron concentration.
Duration
12 months
Interactions
None mentioned
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
oral iron replacement | decrease | FGF23 concentrations | ADHR patients | - | normalize | #1 |
oral iron supplementation | decrease | fasting intact FGF23 | ADHR patients | ≥20% from baseline | decrease | #2 |
oral iron supplementation | decrease | intact FGF23 concentration | ADHR patients | from 172 (20, 192) pg/mL at baseline to 47 (17, 78) pg/mL at month 4 | decreased | #3 |
oral iron supplementation | decrease | intact FGF23 concentration | ADHR patients | from 172 (20, 192) pg/mL at baseline to 42 (19, 63) pg/mL at month 12 | decreased | #4 |
oral iron supplementation | increase | ferritin | ADHR patients | from 18.6 (7.7, 82.5) ng/mL at baseline to 78.0 (49.6, 261.0) ng/mL at month 12 | increased | #5 |
iron treatment | increase | serum phosphorus | subjects with baseline hypophosphatemia | - | normalized | #6 |
iron treatment | increase | symptoms | subjects with baseline hypophosphatemia | - | markedly improved | #7 |
oral iron repletion | decrease | FGF23 | symptomatic, iron-deficient ADHR subjects | - | normalized | #8 |
oral iron repletion | increase | phosphorus | symptomatic, iron-deficient ADHR subjects | - | normalized | #9 |
Autosomal dominant hypophosphatemic rickets (ADHR) is caused by mutations impairing cleavage of fibroblast growth factor 23 (FGF23). FGF23 gene expression increases during iron deficiency. In humans and mice with the ADHR mutation, iron deficiency results in increased intact FGF23 concentrations and hypophosphatemia. We conducted a prospective open label pilot clinical trial of oral iron replacement over 12 months in ADHR patients to test the hypothesis that oral iron administration would normalize FGF23 concentrations. Eligibility criteria included: FGF23 mutation; and either serum iron <50 μg/dL; or serum iron 50 to 100 μg/dL combined with hypophosphatemia and intact FGF23 >30 pg/mL at screening. Key exclusion criteria were kidney disease and pregnancy. Oral iron supplementation started at 65 mg daily and was titrated based on fasting serum iron concentration. The primary outcome was decrease in fasting intact FGF23 by ≥20% from baseline. Six adults (three male, three female) having the FGF23-R176Q mutation were enrolled; five completed the 12-month protocol. At baseline three of five subjects had severely symptomatic hypophosphatemia (phosphorus <2.5 mg/dL) and received calcitriol with or without phosphate concurrent with oral iron during the trial. The primary outcome was met by 4 of 5 (80%) subjects all by month 4, and 5 of 5 had normal intact FGF23 at month 12. Median (minimum, maximum) intact FGF23 concentration decreased from 172 (20, 192) pg/mL at baseline to 47 (17, 78) pg/mL at month 4 and 42 (19, 63) pg/mL at month 12. Median ferritin increased from 18.6 (7.7, 82.5) ng/mL at baseline to 78.0 (49.6, 261.0) ng/mL at month 12. During iron treatment, all three subjects with baseline hypophosphatemia normalized serum phosphorus, had markedly improved symptoms, and were able to discontinue calcitriol and phosphate. Oral iron repletion normalized FGF23 and phosphorus in symptomatic, iron-deficient ADHR subjects. Thus, the standard approach to ADHR should include recognition, treatment, and prevention of iron deficiency. © 2019 American Society for Bone and Mineral Research.