Shaping the bone through iron and iron-related proteins

Well-controlled iron levels are indispensable for health. Iron deficiency is the most common cause of anemia, whereas iron overload, either hereditary or secondary due to disorders of ineffective erythropoiesis, causes widespread organ failure. Bone is particularly sensitive to fluctuations in systemic iron levels as both iron deficiency and overload are associated with low bone mineral density and fragility. Recent studies have shown that not only iron itself, but also iron-regulatory proteins that are mutated in hereditary hemochromatosis can control bone mass. This review will summarize the current knowledge on the effects of iron on bone homeostasis and bone cell activities, and on the role of proteins that regulate iron homeostasis, i.e. hemochromatosis proteins and proteins of the bone morphogenetic protein pathway, on bone remodeling. As disorders of iron homeostasis are closely linked to bone fragility, deeper insights into common regulatory mechanisms may provide new opportunities to concurrently treat disorders affecting iron homeostasis and bone.