Lab Anim Res.  2013 Mar;29(1):55-62. 10.5625/lar.2013.29.1.55.

Establishment of a murine model for radiation-induced bone loss using micro-computed tomography in adult C3H/HeN mice

Affiliations
  • 1General Toxicity Team, Korea Testing & Research Institute, Seoul, Korea.
  • 2Radiological Effect Research Department, Korea Institute of Radiological & Medical Science, Seoul, Korea.
  • 3College of Veterinary Medicine, Chonnam National University, Gwangju, Korea. shokim@chonnam.ac.kr
  • 4Division of Radiation Biotechnology, Advanced Radiation Technology Institute, Jeongeup, Korea.
  • 5Faculty of Animal Science & Biotechnology, Kyungpook National University, Sangju, Korea.

Abstract

Bone changes are common sequela of radiation therapy for cancer. The purpose of this study was to establish an experimental model of radiation-induced bone loss in adult mice using micro-computed tomography (microCT). The extent of changes following 2 Gy gamma irradiation (2 Gy/min) was studied at 4, 8, 12 or 16 weeks after exposure. Adult mice that received 1, 2, 4 or 6 Gy of gamma-rays were examined 12 weeks after irradiation. Tibiae were analyzed using microCT. Serum markers and biomechanical properties were measured and the osteoclast surface was examined. A significant loss of trabecular bone in tibiae was evident 12 weeks after exposure. Measurements performed after irradiation showed a dose-related decrease in trabecular bone volume fraction (BV/TV) and bone mineral density (BMD), respectively. The best-fitting dose-response curves were linear-quadratic. Taking the controls into accounts, the lines of best fit were as follows: BV/TV (%)= -0.071D2-1.799D+18.835 (r2=0.968, D=dose in Gy) and BMD (mg/cm3) = -3.547D2-14.8D+359.07 (r2=0.986, D=dose in Gy). Grip strength and body weight did not differ among the groups. No dose-dependent differences were apparent among the groups with regard to mechanical and anatomical properties of tibia, serum biochemical markers and osteoclast activity. The findings provide the basis required for better understanding of the results that will be obtained in any further studies of radiation-induced bone responses.

Keyword

Radiation; bone loss; murine model; microcomputed tomography

MeSH Terms

Adult
Animals
Biomarkers
Body Weight
Bone Density
Hand Strength
Humans
Mice
Models, Theoretical
Osteoclasts
Tibia
X-Ray Microtomography

Figure

  • Figure 1 Micro-CT images of the tibia for control (A, B, C) and irradiated (D, E, F) C3H/HeN mice. Cross sectional view (A, D), vertical view (B, E) and reconstructed three-dimensional image (C, F).

  • Figure 2 Hematoxylin & eosin (A) and tartrate-resistant acid phosphatase (TRAP) staining (B) of trabecular bone in tibia (× 40).


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