title: The influence of therapeutic radiation on the patterns of bone remodeling in ovary-intact and ovariectomized mice.
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 (45)Ca. Thirty days post-(45)Ca administration, the hind limbs of 17 mice were exposed to a single dose of 16 Gy radiation (R). The time course of (45)Ca 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 (45)Ca 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 (45)Ca excretion) and local effects (via bone microarchitecture and surface activity) of clinically relevant, therapeutic radiation exposure. The I and OVX murine models have similar (45)Ca excretion but different bone microarchitectural responses. The (45)Ca 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.
authors: Department of Therapeutic Radiology, University of Minnesota, 420 Delaware Street SE, Mayo Mail Code 494, Minneapolis, MN 55455, USA. huixx019@umn.edu
authors: Susanta K
authors: SK
authors: Hui
authors: Gregory R
authors: GR
authors: Fairchild
authors: Louis S
authors: LS
authors: Kidder
authors: Manju
authors: M
authors: Sharma
authors: Maryka
authors: M
authors: Bhattacharya
authors: Scott
authors: S
authors: Jackson
authors: Chap
authors: C
authors: Le
authors: Anna
authors: A
authors: Petryk
authors: Mohammad Saiful
authors: MS
authors: Islam
authors: Douglas
authors: D
authors: Yee
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016723:Bone Remodeling / Q000502:physiology / Q000528:radiation effects*; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000528:radiation effects*; D002132:Calcium Radioisotopes / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D015675:Osteocalcin / Q000378:metabolism; D010052:Ovariectomy; D010053:Ovary / Q000502:physiology / Q000601:surgery*; D010455:Peptides / Q000378:metabolism; D011878:Radiotherapy; D013997:Time Factors; D055114:X-Ray Microtomography
chemical_list: D015415:Biomarkers; D002132:Calcium Radioisotopes; D024042:Collagen Type I; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin