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ABSTRACT
Original Research
Received December 15, 2015
Revision May 20, 2016
Accepted July 8, 2016
Corresponding author: Sung-Ho Kim
College of Veterinary Medicine, Chonnam
National University, 77, Yongbong-ro,
Buk-gu, Gwangju 61186, Korea
Tel: +82-62-530-2837
Fax: +82-62-530-2841
E-mail: shokim@jnu.ac.kr
This is an Open-Access article distributed under the
terms of the Creative Commons Attribution Non-
Commercial License (http://creativecommons.org/
licenses/by-nc/4.0) which permits unrestricted non-
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cited.
Copyright © 2016 The Korean Association for
Radiation Protection
Evaluation of the Efcacy of Zoledronic Acid and
Amifostine on Radiation-induced Bone Loss in Mice
Jinwook Kim
1
, Sueun Lee
1
, Sohi Kang
1
, Changjong Moon
1
, Jong-Choon Kim
1
, Uhee Jung
2
, Sung-Kee Jo
2
,
Jong-Sik Jang
3
, Sung-Ho Kim
1,
*
1
College of Veterinary Medicine, Chonnam National University, Gwangju;
2
Advanced Radiation Technology Institute, Jeungeup;
3
College of Ecology and
Environmental Science, Kyungpook National University, Sangju, Korea
Background: Tis study investigated the efects 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). Te irradiated mice were treated for 12 weeks with vehicle, amifos-
tine (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 μg · kg
-1
· week
-1
) signifcantly preserved trabec-
ular bone volume, trabecular thickness, trabecular number, trabecular separation, bone min-
eral density of proximal tibia metaphysic, and cortical bone volume, but did not alter the uterus
weight of the mice. Te administration of ZA for 12 weeks lowered serum ALP and TRAP lev-
els in irradiated mice, suggesting that ZA can reduce the bone turnover rate in mice. No difer-
ences were apparent between the amifostine-treated group and the irradiation control group.
Conclusion: Te results indicate that ZA can prevent radiation-induced bone loss in mice.
Keywords: Bone loss, Micro-computed tomography, Radiation, Zoledronic acid
pISSN 2508-1888 | eISSN 2466-2461
Introduction
Developments in cancer therapies and diagnostic techniques have improved the
long-term survival of cancer patients [1]. There has been a corresponding increase in
the prevalence of specific and chronic side effects of cancer treatment among survi-
vors. Certain cancer treatments, such as radiotherapy, often harm normal tissue as well
as the specifically targeted cancer cells [2]. The underlying mechanism of these adverse
effects and the prognoses associated with them deserve greater research attention.
High doses of radiation induce bone loss. Irradiation of bone principally causes atro-
phy accompanied by compromised function and structure of the bone tissue, but does
not result in alterations of the bone size. Changes in vasculature, composition of bone
matrix, and cellular components are putative etiologies of irradiation-induced damage
in bone [3]. Irradiation of bone has also been associated with fractures [4]. Osteoporo-
sis is a public health concern with a heavy financial burden on both society and pa-
tients [5]. Drugs for osteoporosis aim to augment the bone regeneration process as op-
posed to the bone resorption process. Inhibitors of bone resorption include estrogen,
calcitonin, bisphosphonates, calcium, vitamin D, and raloxifene. Accelerators of bone
Journal of
Radiation Protection and Research 2016;41(3):253-259
https://doi.org/10.14407/jrpr.2016.41.3.253
JRP R