Effects of ferric carboxymaltose in a murine model of iron deficiency

Circulating FGF23 levels are regulated by a balance between Fgf23 transcription and FGF23 cleavage within osteocytes. In health, correcting iron deficiency rapidly decreases concentrations of C-terminal FGF23 fragments without changing intact hormone levels consistent with parallel reductions in transcription and cleavage. Mutations at the FGF23 cleavage site stabilize FGF23 and cause autosomal dominant hypophosphatemic rickets (ADHR). In ADHR, iron deficiency results in excess FGF23 that is protected from cleavage, and the high levels of intact FGF23 cause hypophosphatemia. Therefore decreased FGF23 cleavage may account for elevated iFGF23 levels. Despite clinical evidence that restoring iron stores and treating iron deficiency anemia, decreases FGF23 production, reduced serum phosphate has been shown to occur following intravenous administration of several iron preparations, associated with an increase in iFGF23. Ferric carboxymaltose is a parenteral form of iron that can be used to treat iron deficiency when oral iron is either ineffective or contraindicated. Several reports have shown that patients receiving ferric carboxymaltose developed transient and asymptomatic reductions in serum phosphate levels, due to increase in intact FGF23, despite reductions of total FGF23 production. The purpose of this proposal is to study the impact of ferric carboxymaltose on FGF23 production in a well-characterized mouse model of iron deficiency anemia with high relevance to human disease.