DOI QR코드

DOI QR Code

Evaluation of the Efficacy of Zoledronic Acid and Amifostine on Radiation-induced Bone Loss in Mice

  • Kim, Jinwook (College of Veterinary Medicine, Chonnam National University) ;
  • Lee, Sueun (College of Veterinary Medicine, Chonnam National University) ;
  • Kang, Sohi (College of Veterinary Medicine, Chonnam National University) ;
  • Moon, Changjong (College of Veterinary Medicine, Chonnam National University) ;
  • Kim, Jong-Choon (College of Veterinary Medicine, Chonnam National University) ;
  • Jung, Uhee (Advanced Radiation Technology Institute) ;
  • Jo, Sung-Kee (Advanced Radiation Technology Institute) ;
  • Jang, Jong-Sik (College of Ecology and Environmental Science, Kyungpook National University) ;
  • Kim, Sung-Ho (College of Veterinary Medicine, Chonnam National University)
  • Received : 2015.12.15
  • Accepted : 2016.07.08
  • Published : 2016.09.30

Abstract

Background: This study investigated the effects of zoledronic acid (ZA) on radiation-induced bone loss in C3H/HeN mice. Materials and Methods: C3H/HeN mice were divided into sham control and three irradiated groups (3 Gy, gamma ray). The irradiated mice were treated for 12 weeks with vehicle, amifostine (intraperitoneal injection), or ZA (subcutaneous injection). Grip strength, uterus weight, and serum alkaline phosphatase (ALP), and tartrate-resistant acid phosphatase (TRAP) levels were measured. Tibiae were analyzed using micro-computed tomography. Results and Discussion: Treatment of ZA ($100{\mu}g{\cdot}kg^{-1}{\cdot}week^{-1}$) significantly preserved trabecular bone volume, trabecular thickness, trabecular number, trabecular separation, bone mineral density of proximal tibia metaphysic, and cortical bone volume, but did not alter the uterus weight of the mice. The administration of ZA for 12 weeks lowered serum ALP and TRAP levels in irradiated mice, suggesting that ZA can reduce the bone turnover rate in mice. No differences were apparent between the amifostine-treated group and the irradiation control group. Conclusion: The results indicate that ZA can prevent radiation-induced bone loss in mice.

Acknowledgement

Grant : BK21플러스

Supported by : 전남대학교

References

  1. Oeffinger KC, et al. Chronic health conditions in adult survivors of childhood cancer. N. Engl. J. Med. 2006;355:1572-1582. https://doi.org/10.1056/NEJMsa060185
  2. Zhao W, Robbins ME. Inflammation and chronic oxidative stress in radiation-induced late normal tissue injury: therapeutic implications. Curr. Med. Chem. 2009;16:130-143. https://doi.org/10.2174/092986709787002790
  3. Ergun H, Howland WJ. Postradiation atrophy of mature bone. CRC Crit. Rev. Diagn. Imaging 1980;12:225-243.
  4. Chen HH, Lee BF, Guo HR, Su WR, Chiu NT. Changes in bone mineral density of lumbar spine after pelvic radiotherapy. Radiother. Oncol. 2002;62:239-242. https://doi.org/10.1016/S0167-8140(02)00002-6
  5. Liu Z, et al. The diagnostic criteria for primary osteoporosis and the incidence of osteoporosis in China. J. Bone Miner. Metab. 2002;20:181-189. https://doi.org/10.1007/s007740200026
  6. Harada SI, Rodan GA. Control of osteoblast function and regulation of bone mass. Nature. 2003;423:349-355. https://doi.org/10.1038/nature01660
  7. Hung TT, Chan J, Russell PJ, Power CA. Zoledronic acid preserves bone structure and increases survival but does not limit tumour incidence in a prostate cancer bone metastasis model. PLoS One. 2011;6:e19389. https://doi.org/10.1371/journal.pone.0019389
  8. McClung M, Recker R, Miller P, Fiske D, Minkoff J, Kriegman A, Zhou W, Adera M, Davis J. Intravenous zoledronic acid 5 mg in the treatment of postmenopausal women with low bone density previously treated with alendronate. Bone. 2007;41:122-128. https://doi.org/10.1016/j.bone.2007.03.011
  9. Maricic M. The role of zoledronic acid in the management of osteoporosis. Clin. Rheumatol. 2010;29:1079-1084. https://doi.org/10.1007/s10067-010-1486-3
  10. Johnke RM, Sattler JA, Allison RR. Radioprotective agents for radiation therapy: future trends. Future Oncol. 2014;10:2345-2357. https://doi.org/10.2217/fon.14.175
  11. Lee JH, Lee HJ, Yang M, Moon C, Kim JC, Jo SK, Jang JS, Kim SH. Establishment of a murine model for radiation-induced bone loss using micro-computed tomography in adult C3H/HeN mice. Lab. Anim. Res. 2013;29:55-62. https://doi.org/10.5625/lar.2013.29.1.55
  12. Lee HJ, et al. Amifostine ameliorates recognition memory defect in acute radiation syndrome caused by relatively low-dose of gamma radiation. J. Vet. Sci. 2010;11:81-83. https://doi.org/10.4142/jvs.2010.11.1.81
  13. Arrington SA, Damron TA, Mann KA, Allen MJ. Concurrent administration of zoledronic acid and irradiation leads to improved bone density, biomechanical strength, and microarchitecture in a mouse model of tumor-induced osteolysis. J. Surg. Oncol. 2008;97:284-290. https://doi.org/10.1002/jso.20949
  14. Baxter NN, Habermann EB, Tepper JE, Durham SB, Virnig BA. Risk of pelvic fractures in older women following pelvic irradiation. J. Am. Med. Assoc. 2005;294:2587-2593. https://doi.org/10.1001/jama.294.20.2587
  15. Williams HJ, Davies AM. The effect of x-rays on bone: a pictorial review. Eur. Radiol. 2006;16:619-633. https://doi.org/10.1007/s00330-005-0010-7
  16. Sakurai T, Sawada Y, Yoshimoto M, Kawai M, Miyakoshi J. Radiation-induced reduction of osteoblast differentiation in C2C12 cells. J. Radiat. Res. 2007;48:515-521. https://doi.org/10.1269/jrr.07012
  17. Szymczyk KH, Shapiro IM, Adams CS. Ionizing radiation sensitizes bone cells to apoptosis. Bone. 2004;34:148-156. https://doi.org/10.1016/j.bone.2003.09.003
  18. Bandstra ER, et al. Long-term dose response of trabecular bone in mice to proton radiation. Radiat. Res. 2008;169:607-614. https://doi.org/10.1667/RR1310.1
  19. Hamilton SA, Pecaut MJ, Gridley DS, Travis ND, Bandstra ER, Willey JS, Nelson GA, Bateman TA. A murine model for bone loss from therapeutic and space-relevant sources of radiation. J. Appl. Physiol. 2006;101:789-793. https://doi.org/10.1152/japplphysiol.01078.2005
  20. Sawajiri M, Mizoe J, Tanimoto K. Changes in osteoclasts after irradiation with carbon ion particles. Radiat. Environ. Biophys. 2003;42:219-223. https://doi.org/10.1007/s00411-003-0204-9
  21. Vit JP, Ohara PT, Tien DA, Fike JR, Eikmeier L, Beitz A, Wilcox GL, Jasmin L. The analgesic effect of low dose focal irradiation in a mouse model of bone cancer is associated with spinal changes in neuro-mediators of nociception. Pain. 2006;120:188-201. https://doi.org/10.1016/j.pain.2005.10.033
  22. Furstman LL. Effect of radiation on bone. J. Dent. Res. 1972;51:596-604. https://doi.org/10.1177/00220345720510025901
  23. Hannon RA. and Eastell, R. Biochemical markers of bone turnover and fracture prediction. J. Br. Menopause Soc. 2003;9:10-15.
  24. Garnero P, et al. Markers of bone resorption predict hip fracture in elderly women: the EPIDOS Prospective Study. J. Bone Miner. Res. 1996;11:1531-1538.
  25. Bhattacharya A, Watts NB, Davis K, Kotowski S, Shukla R, Dwivedi AK, Coleman R. Dynamic bone quality: a noninvasive measure of bone's biomechanical property in osteoporosis. J. Clin. Densitom. 2010;13:228-236. https://doi.org/10.1016/j.jocd.2010.01.001