Skeletal remodeling following clinically relevant radiation-induced bone damage treated with zoledronic acid

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

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Our aim was to determine if zoledronic acid (ZA) changes 45Ca pharmacokinetics and bone microstructure in irradiated, ovary-intact (I) and irradiated, ovariectomized mice (OVX), two groups with different patterns of skeletal damage. The hind limbs of I and OVX BALB/c mice received a single 16-Gy radiation dose, simulating pre- and postmenopausal female cancer patients undergoing radiation treatment. All I and OVX mice were radiolabeled with 15 μCi 45Ca. Mice were treated with or without a 0.5 mg/kg injection of ZA. The time course of bone mineral remodeling was evaluated using a fecal 45Ca assay, measured by liquid scintillation. A group of nonirradiated, intact mice were used for the longitudinal evaluation of 45Ca biodistribution. Distal femur bone histomorphometric parameters were measured using microCT at 50 days post-ZA intervention. Most 45Ca was incorporated into the skeleton and eliminated from the soft tissues within 3-5 days postirradiation, attaining a steady state of excretion at 25-30 days. ZA intervention in both groups resulted in a rapid decrease in fecal 45Ca excretion. There was a significant difference in 45Ca excretion in the OVX ± ZA (P = 0.005) group but not in the I ± ZA (P = 0.655) group. The rate of excretion of fecal 45Ca was slower in the OVX + ZA compared to the I + ZA group (P = 0.064). 45Ca assay is useful to monitor the time course of bone mineral remodeling after an antiresorptive intervention in irradiated mice, providing a basis to investigate bone effects of cancer therapy protocols. For equivalent doses of ZA, recovery may depend on the nature and degree of skeletal damage.

Original languageEnglish (US)
Pages (from-to)40-49
Number of pages10
JournalCalcified Tissue International
Volume90
Issue number1
DOIs
StatePublished - Jan 2012

Keywords

  • Animal model
  • Bisphosphonate
  • Bone turnover
  • Bone turnover marker
  • Clinical radiation
  • Remodeling

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