Influence of Iron on Bone Homeostasis

Abstract

Bone homeostasis is a complex process, wherein osteoclasts resorb bone and osteoblasts produce new bone tissue. For the maintenance of skeletal integrity, this sequence has to be tightly regulated and orchestrated. Iron overload as well as iron deficiency disrupt the delicate balance between bone destruction and production, via influencing osteoclast and osteoblast differentiation as well as activity. Iron overload as well as iron deficiency are accompanied by weakened bones, suggesting that balanced bone homeostasis requires optimal-not too low, not too high-iron levels. The goal of this review is to summarize our current knowledge about how imbalanced iron influence skeletal health. Better understanding of this complex process may help the development of novel therapeutic approaches to deal with the pathologic effects of altered iron levels on bone.

Keywords: bone homeostasis; iron deficiency; iron overload; osteoblast; osteoclast; osteoporosis.

Figure 1

Associations of iron metabolism and bone homeostasis. (A) Association between iron metabolism and bone homeostasis. (B) The effect of iron overload on differentiation and function of osteoclasts. Osteoclasts derive from myeloid cells of the monocyte/macrophage lineage. Osteoclastogenesis is initiated by macrophage colony-stimulating factor (M-CSF). Bone-resorbing multinuclear osteoclasts are formed from mononuclear osteoclast precursors via fusion. The process is initiated by receptor activator of nuclear factor κB ligand (RANKL). Iron excess triggers osteoclast differentiation and activation and subsequent bone destruction. (C) Osteoblasts differentiate from multipotent mesenchymal stem cells (MSCs). Iron attenuates osteogenic differentiation of MSCs and function of mature osteoblasts. Weak bone phenotype observed in patients with systemic iron overload is a consequence of increased bone resorption by osteoclasts and decreased bone formation by osteoblasts.