The influence of therapeutic radiation on the patterns of bone remodeling in ovary-intact and ovariectomized mice

Susanta K. Hui, Gregory R. Fairchild, Louis S. Kidder, Manju Sharma, Maryka Bhattacharya, Scott Jackson, Chap Le, Anna Petryk, Mohammad Saiful Islam, Douglas Yee

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Our purpose was to characterize changes in bone remodeling associated with localized radiation that models therapeutic cancer treatment in ovary-intact (I) and ovariectomized (OVX) mice and to evaluate the influence of radiation on the pattern of bone mineral remodeling. Young adult, female BALB/c mice, I and OVX, were used (n = 71). All mice were intravenously injected with 15 μCi 45Ca. Thirty days post-45Ca administration, the hind limbs of 17 mice were exposed to a single dose of 16 Gy radiation (R). The time course of 45Ca excretion, serum CTx and osteocalcin markers, and cancellous bone volume fraction (BV/TV) and cortical thickness (Ct.Th) of the distal femur were assayed. Cellular activity and dynamic histomorphometry were performed. Irradiation resulted in rapid increases in fecal 45Ca excretion compared to control groups, indicating increased bone remodeling. CTx increased rapidly after irradiation, followed by an increase in osteocalcin concentration. BV/TV decreased in the I mice following irradiation. Ct.Th increased in the OVX groups following irradiation. I+R mice exhibited diminished osteoblast surface, osteoclast number, and mineral apposition. Our murine model showed the systemic effects (via 45Ca excretion) and local effects (via bone microarchitecture and surface activity) of clinically relevant, therapeutic radiation exposure. The I and OVX murine models have similar 45Ca excretion but different bone microarchitectural responses. The 45Ca assay effectively indicates the onset and rate of systemic bone mineral remodeling, providing real-time assessment of changes in bone histomorphometric parameters. Monitoring bone health via a bone mineral marker may help to identify the appropriate time for clinical intervention to preserve skeletal integrity.

Original languageEnglish (US)
Pages (from-to)372-384
Number of pages13
JournalCalcified Tissue International
Volume92
Issue number4
DOIs
StatePublished - Apr 2013

Keywords

  • Biodistribution
  • Bone remodeling
  • Ca
  • Ca surrogate
  • Clinically relevant radiation

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