Albertine Donker

Iron Function and Iron Handling from Fetus to Adult 63 2 Iron is critically involved in the production of collegen I, a crucial component of bone, since its synthesis is dependent of hydroxylases requiring iron for their catalytic activity. 62 Iron is also essential for the activation of vitamin D that is indispensable for bone formation, by enzymes of the cytochrome P450 family containing heme. 62 Furthermore, iron influences the differentiation from mesenchymal stem cells to osteoblasts and also the production and activity of osteoclasts 62 ( Table 1 ). Accumulatingclinical evidenceexists that IOconditions as hereditary hemochromatosis and thalassemia syndromes are associated with decreased bone mineral density. 66 In vitro studies indicate that iron excess inhibits osteoblast formation 67 and enhances osteoclast differenation and activity. 68 Inceased bone resorption in IO conditions is thought to be at least partially mediated by oxidative stress inducing inflammatory changes that affect bone composition with altered microarchitecture. 69 Furthermore, hepcidin deficiency relative to ferritin, which is characteristic for most forms of hereditary hemochromatosis and iron loading anemias, is associated with decreased osteoblast activity. 70 Of note, clinical reports indicate that parenteral iron treatment induces renal phosphate wasting, thereby suggesting that iron, and especially iron treatment, may also influence bone health in an indirect manner. 71 Conversely, the effect of ID on bone health is less clear; in vitro data suggest a biphasic effect of low iron with osteoblast acitivy increasing in case of mild ID and decreasing in case of severe ID. 72 Clinical data regarding the possible association between ID and bone mass and bone density are scarce but indicate that low iron status results in increased bone resorption 73 that might be reversed by iron treatment. 74 Data from child studies exploring the effects of ID and iron excess on peak bone mass are lacking. One study on bone disease in children suffering from β-thalassemia major shows osteoporosis of multifactorial origin, whereby iron loading may play a role. 75 Iron and development of the brain Iron is essential for the development of the central nervous system. 76 Iron and iron- containing enzymes are crucial for neuronal and glial energy metabolism, myelin and neurotransmitter synthesis. 1 Iron demands of the growing and developing brain are temporally and spatially sensitive. 12,77 MRI imaging in children suggests that the iron content of the brain increases considerably during childhood and adolescence, although quantities are unknown. 78