Iron Metabolism and Bone Health Dynamics

Iron is indispensable for skeletal integrity, acting as a cofactor in collagen synthesis, vitamin D activation and mitochondrial respiration. Systemic iron homeostasis is regulated by the hepatic peptide hepcidin, which induces internalisation of the iron exporter ferroportin, thereby controlling absorption and cellular release. Within bone, a delicate balance between osteoblast-mediated formation and osteoclast-driven resorption underpins continuous remodelling. Iron deficiency compromises osteoblast function and matrix mineralisation, whereas iron excess generates reactive oxygen species that trigger osteoblast apoptosis and stimulate osteoclastogenesis. Bone marrow mesenchymal stem cells, precursors of osteoblasts, exhibit sensitivity to labile iron pools; oxidative damage and ferroptotic pathways contribute to impaired differentiation. Conversely, macrophage-lineage osteoclast precursors respond to elevated intracellular iron by upregulating mitochondrial metabolism and key transcription factors, accelerating bone resorption. Clinical syndromes such as hereditary haemochromatosis, thalassaemia and postmenopausal iron accumulation illustrate the dual burden of iron overload and bone fragility. Understanding these dynamics has global significance: from addressing nutrient deficiencies in developing regions to refining chelation therapies and iron-modulating agents in ageing populations. Emerging interventions aim to restore redox equilibrium, target the hepcidin–ferroportin axis and harness antioxidant pathways to preserve bone mass and prevent fractures.

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Iron Metabolism and Bone Health Dynamics publication trend

The graph below shows the total number of articles in iron metabolism and bone health dynamics across all publications each year (not limited to Nature Index journals).

Technical terms

Hepcidin: A liver-derived peptide hormone that regulates systemic iron levels by inducing degradation of ferroportin.

Ferroportin: The sole cellular iron exporter, whose activity controls iron absorption and release from storage sites.

Osteoblast: A bone-forming cell responsible for collagen deposition and mineralisation of the bone matrix.

Osteoclast: A multinucleated cell that resorbs mineralised bone, balancing formation and degradation.

Ferroptosis: A regulated form of cell death driven by iron-dependent lipid peroxidation and oxidative stress.

Heme oxygenase-1 (HO-1): An enzyme that degrades heme into iron, biliverdin and carbon monoxide, modulating oxidative stress.

REPIN1: A replication initiator protein that influences iron metabolism and cell survival in osteoblasts under iron-overload conditions.

References

1. REPIN1 regulates iron metabolism and osteoblast apoptosis in osteoporosis. Cell Death & Disease (2023).
2. A Mechanistic Study of the Osteogenic Effect of Arecoline in an Osteoporosis Model: Inhibition of Iron Overload-Induced Osteogenesis by Promoting Heme Oxygenase-1 Expression. Antioxidants (2024).
3. Iron Deficiency and Iron Deficiency Anemia: Potential Risk Factors in Bone Loss. International Journal of Molecular Sciences (2023).