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Exposure to Ionizing Radiation and Development of Bone Sarcoma: New Insights Based on Atomic-Bomb Survivors of Hiroshima and Nagasaki

Samartzis, Dino DSc; Nishi, Nobuo MD, PhD; Hayashi, Mikiko BA; Cologne, John PhD; Cullings, Harry M. PhD; Kodama, Kazunori MD, PhD; Miles, Edward F. MD; Funamoto, Sachiyo BS; Suyama, Akihiko MD, PhD; Soda, Midori MD; Kasagi, Fumiyoshi PhD

Journal of Bone & Joint Surgery - American Volume: 1 June 2011 - Volume 93 - Issue 11 - p 1008–1015
doi: 10.2106/JBJS.J.00256
Scientific Articles

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.

1Department 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:;

2Departments 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

3Department of Radiation Oncology, Box 3085, Duke University Medical Center, Durham, NC 27710

4Department of Epidemiology, Radiation Effects Research Foundation, 8-6 Nakagawa 1-chone, Nagasaki City, Japan

Copyright 2011 by The Journal of Bone and Joint Surgery, Incorporated
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