Iron, inflammation, and fibroblast growth factor 23: Integrating molecular crosstalk, cardiovascular biology, and therapeutic perspectives

Table 3 Clinical contexts linking iron status and fibroblast growth factor 23 biology

Clinical setting	Typical FGF23 pattern	Potential relevance
Iron-deficiency anemia	High cFGF23 with relatively preserved iFGF23	Efficient cleavage may protect phosphate homeostasis despite increased production. Human observational and interventional evidence[9,42]
ADHR with iron deficiency	Increased iFGF23 because the mutant hormone resists cleavage	Hypophosphatemia and osteomalacia; oral iron may correct the biochemical phenotype. Small open-label human trial[48]
X-linked hypophosphatemia	Iron is associated mainly with variation in cFGF23	Iron-sensitive regulation persists in a primary FGF23-excess disorder. Human observational evidence[43]
Chronic inflammatory disorders	Variable FGF23 pattern influenced by cytokines, hepcidin and iron restriction	Clinical evidence remains limited and disease-specific. Small human studies; uncertain generalizability[77,78]
Heart failure	Iron deficiency and elevated FGF23 frequently coexist	Associations with congestion, remodeling, hospitalization and mortality; causality remains uncertain. Human observational evidence; causality unproven[21,79]
Chronic kidney disease	Elevated intact and C-terminal measurements; production, processing, clearance, and mineral metabolism contribute	Cardiovascular, heart-failure and mortality associations. Human observational evidence with experimental support; causal contribution uncertain[10,22]
General population	Higher FGF23 associated with incident heart failure and coronary events	May integrate iron status, erythropoietic drive, kidney function and inflammation. Human observational evidence; no established testing indication[15,20,80]

ADHR: Autosomal dominant hypophosphatemic rickets; cFGF23: C-terminal fibroblast growth factor 23 assay result; FGF23: Fibroblast growth factor 23; iFGF23: Intact FGF23.