title: Skeletal remodeling following clinically relevant radiation-induced bone damage treated with zoledronic acid.
abstract: Our aim was to determine if zoledronic acid (ZA) changes (45)Ca 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 (45)Ca. 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 (45)Ca assay, measured by liquid scintillation. A group of nonirradiated, intact mice were used for the longitudinal evaluation of (45)Ca biodistribution. Distal femur bone histomorphometric parameters were measured using microCT at 50 days post-ZA intervention. Most (45)Ca 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 (45)Ca excretion. There was a significant difference in (45)Ca 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 (45)Ca was slower in the OVX + ZA compared to the I + ZA group (P = 0.064). (45)Ca 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.
authors.affiliation: Department of Therapeutic Radiology, University of Minnesota, 420 Delaware Street SE, Mayo Mail Code 494, Minneapolis, MN 55455, USA. huixx019@umn.edu
authors.forename: Susanta K
authors.initials: SK
authors.lastname: Hui
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Fairchild
authors.forename: Louis S
authors.initials: LS
authors.lastname: Kidder
authors.forename: Manju
authors.initials: M
authors.lastname: Sharma
authors.forename: Maryka
authors.initials: M
authors.lastname: Bhattacharya
authors.forename: Scott
authors.initials: S
authors.lastname: Jackson
authors.forename: Chap
authors.initials: C
authors.lastname: Le
authors.forename: Douglas
authors.initials: D
authors.lastname: Yee
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D016723:Bone Remodeling; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D002127:Calcium Isotopes; D004164:Diphosphonates / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D005269:Femur / Q000187:drug effects / Q000528:radiation effects; D007093:Imidazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D015675:Osteocalcin / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000378:metabolism*; D014018:Tissue Distribution; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D002127:Calcium Isotopes; D004164:Diphosphonates; D007093:Imidazoles; D015675:Osteocalcin; D000077211:Zoledronic Acid