Patients with radiotherapy are at significant risks of bone loss and fracture. On the other hand, osteoporosis often occurs in disorders characterized by iron overload. Either ionizing radiation (IR) or iron overload alone has detrimental effects on bone metabolism, but their combined effects are not well defined. In this study, we evaluated the effects of IR on bone loss in an iron-overload mouse model induced by intraperitoneal injection of ferric ammonium citrate (FAC). In the present study, we found that IR additively aggravated iron overload induced by FAC injections. Iron overload stimulated hepcidin synthesis, while IR had an inhibitory effect and even inhibited the stimulatory effects of iron overload. Micro-CT analysis demonstrated that the loss of bone mineral density and bone volume, and the deterioration of bone microarchitecture were greatest in combined treatment group. Iron altered the responses of bone cells to IR. Iron enhanced the responses of osteoclasts to IR with elevated osteoclast differentiation, but did not affect osteoblast differentiation. Our study indicates that IR and iron in combination lead to a more severe impact on the bone homeostasis when compared with their respective effects. IR aggravated iron overload induced bone loss by heightened bone resorption relative to formation. The addictive effects may be associated with the exacerbated iron accumulation and osteoclast differentiation.
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bone mineral density
Bone marrow macrophages
Bone volume fraction
Dentin matrix acidic phosphoprotein 1
Ferric ammonium citrate
Hepcidin antimicrobial peptide
Mineral apposition rate
Macrophage colony stimulating factor
Matrix metallopeptidase 9
- Opn :
Receptor activator for nuclear factor-κB ligand
Runt-related transcription factor 2
Total body irradiation
Tartrate-resistant acid phosphatase
Vacuolar-type H (+)-ATPase
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This study was funded by the National Natural Science Foundation of China (31600674), the Science and Technology Fund of Guizhou Health Commission (gzwjkj2019-1-226), and doctoral funds of Guizhou University of Traditional Chinese Medicine (44).
Conflict of Interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving animals were in accordance with the ethical standards of Guizhou University of Traditional Chinese Medicine at which the studies were conducted (Animal Ethics and Welfare Committee at Guizhou University of Traditional Chinese Medicine; Permit No. GZY20190005).
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Zhang, J., Qiao, P., Yao, G. et al. Ionizing Radiation Exacerbates the Bone Loss Induced by Iron Overload in Mice. Biol Trace Elem Res 196, 502–511 (2020). https://doi.org/10.1007/s12011-019-01929-7
- Iron overload
- Ionizing radiation
- Bone loss