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Scientific Articles   |    
Exposure to Ionizing Radiation and Development of Bone Sarcoma: New Insights Based on Atomic-Bomb Survivors of Hiroshima and Nagasaki
Dino Samartzis, DSc1; Nobuo Nishi, MD, PhD2; Mikiko Hayashi, BA2; John Cologne, PhD2; Harry M. Cullings, PhD2; Kazunori Kodama, MD, PhD2; Edward F. Miles, MD3; Sachiyo Funamoto, BS2; Akihiko Suyama, MD, PhD4; Midori Soda, MD4; Fumiyoshi Kasagi, PhD2
1 Department of Orthopaedics & Traumatology, University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Professorial Block, Room 515, Pokfulam, Hong Kong, SAR, China. E-mail address: dspine@hku.hk; dsamartzis@msn.com
2 Departments of Epidemiology (N.N., M.H., and F.K.), Statistics (J.C., H.M.C., and S.F.), and Chief Scientist (K.K.), Radiation Effects Research Foundation, 5-2 Hijiyama Park, Minami-Ku, Hiroshima City, Japan
3 Department of Radiation Oncology, Box 3085, Duke University Medical Center, Durham, NC 27710
4 Department of Epidemiology, Radiation Effects Research Foundation, 8-6 Nakagawa 1-chone, Nagasaki City, Japan
View Disclosures and Other Information
Disclosure: In support of their research for or preparation of this work, one or more of the authors received outside funding or grants in excess of $10,000 from the U.S. Department of Energy. Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity.

Investigation performed at the Radiation Effects Research Foundation, Hiroshima and Nagasaki, Japan
A commentary by Charles M. Turkelson, PhD, is linked to the online version of this article at jbjs.org.

Copyright © 2011 by The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2011 Jun 01;93(11):1008-1015. doi: 10.2106/JBJS.J.00256
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Abstract

Background: 

Radiation-induced bone sarcoma has been associated with high doses of ionizing radiation from therapeutic or occupation-related exposures. However, the development of bone sarcoma following exposure to lower doses of ionizing radiation remains speculative.

Methods: 

A cohort analysis based on the Life Span Study (n = 120,321) was performed to assess the development of bone sarcoma in atomic-bomb survivors of Hiroshima and Nagasaki followed from 1958 to 2001. The excess relative risk per gray of ionizing radiation absorbed by the bone marrow was estimated. Additional subject demographic, survival, and clinical factors were evaluated.

Results: 

Nineteen cases of bone sarcoma (in eleven males and eight females) were identified among the 80,181 subjects who met the inclusion criteria, corresponding to an incidence of 0.9 per 100,000 person-years. The mean ages at the time of the bombing and at diagnosis were 32.4 and 61.6 years, respectively. The mean bone marrow dose was 0.43 Gy. Osteosarcoma was the most commonly identified bone sarcoma. The most common bone sarcoma site was the pelvis. The overall unadjusted five-year survival rate was 25%. A dose threshold was found at 0.85 Gy (95% confidence interval, 0.12 to 1.85 Gy), with a linear dose-response association above this threshold. The linear slope equaled an excess relative risk of 7.5 per Gy (95% confidence interval, 1.34 to 23.14 per Gy) in excess of 0.85 Gy.

Conclusions: 

On the basis of what we believe is one of the longest and largest prospective studies assessing the development of bone sarcoma in individuals exposed to ionizing radiation, it appears that the development of radiation-induced bone sarcoma may be associated with exposure to much lower doses of ionizing radiation than have previously been reported. Such new insights may potentially improve bone sarcoma prevention measures and broaden our understanding of the role of ionizing radiation from various sources on the development of malignant tumors. This study stresses the need to become increasingly aware of the various health risks that may be attributable to even low levels of ionizing radiation exposure.

Level of Evidence: 

Prognostic Level I. See Instructions to Authors for a complete description of levels of evidence.

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    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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