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 language||English (US)|
|Number of pages||10|
|Journal||Calcified Tissue International|
|State||Published - Jan 2012|
Bibliographical noteFunding Information:
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.
- Animal model
- Bone turnover
- Bone turnover marker
- Clinical radiation