Ionizing Radiation Exacerbates the Bone Loss Induced by Iron Overload in Mice

  • Jian ZhangEmail author
  • Penghai Qiao
  • Gang Yao
  • Hai Zhao
  • Yanjun Wu
  • Shuguang Wu


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.


Iron overload Ionizing radiation Bone loss Osteoblast Osteoclast 



Alkaline phosphatase


bone mineral density


Bone marrow macrophages


Bone sialoprotein


Bone volume fraction


Collagen 1


Cathepsin K


Dentin matrix acidic phosphoprotein 1


Ferric ammonium citrate


Glyceraldehyde-3-phosphate dehydrogenase


Hepcidin antimicrobial peptide


Ionizing radiation


Mineral apposition rate


Macrophage colony stimulating factor


Matrix metallopeptidase 9




Receptor activator for nuclear factor-κB ligand


Runt-related transcription factor 2


Trabecular thickness


Trabecular separation


Trabecular number


Total body irradiation


Tartrate-resistant acid phosphatase


Vacuolar-type H (+)-ATPase


Funding Information

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 ([2019]44).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical approval

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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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Institute of Laboratory Animal ScienceGuizhou University of Traditional Chinese MedicineGuiyangChina

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