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Skeletal Remodeling Following Clinically Relevant Radiation-Induced Bone Damage Treated with Zoledronic Acid

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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.

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Acknowledgement

This study was supported by the National Institutes of Health (grants 1R03AR055333-01A1 and 1K12-HD055887-01), by PHS Cancer Center Support grant P30 CA77398, and by the Joseph E. Wargo Cancer Research Fund from the University of Minnesota. S. K. H. is a scholar of the Building Interdisciplinary Careers in Women’s Health program. The authors thank Dr. Seymour Levitt for fruitful discussion of the manuscript.

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Authors and Affiliations

  1. Department of Therapeutic Radiology, University of Minnesota, 420 Delaware Street SE, Mayo Mail Code 494, Minneapolis, MN, 55455, USA

    Susanta K. Hui, Gregory R. Fairchild, Louis S. Kidder & Manju Sharma

  2. United States Navy, Medical Service Corps, Minneapolis, MN, USA

    Gregory R. Fairchild

  3. Departments of Medicine and Orthopaedic Surgery, Medical College of Georgia, Georgia Health Sciences University, Augusta, GA, USA

    Maryka Bhattacharya

  4. Biostatistics and Bioinformatics shared resource of Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA

    Scott Jackson

  5. Department of Biostatistics, University of Minnesota, Minneapolis, MN, USA

    Chap Le

  6. Department of Medicine, Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA

    Douglas Yee

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  1. Susanta K. Hui
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Correspondence to Susanta K. Hui.

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The authors have stated that they have no conflict of interest.

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Hui, S.K., Fairchild, G.R., Kidder, L.S. et al. Skeletal Remodeling Following Clinically Relevant Radiation-Induced Bone Damage Treated with Zoledronic Acid. Calcif Tissue Int 90, 40–49 (2012). https://doi.org/10.1007/s00223-011-9547-4

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  • DOI: https://doi.org/10.1007/s00223-011-9547-4

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