201 RADIATION RESEARCH 170, 201–207 (2008) 0033-7587/ 08 $15.00  2008 by Radiation Research Society. All rights of reproduction in any form reserved. Bone Architectural and Structural Properties after 56 Fe 26+ Radiation-Induced Changes in Body Mass J. S. Willey, a L. G. Grilly, a,b S. H. Howard, a M. J. Pecaut, c A. Obenaus, c D. S. Gridley, c G. A. Nelson c and T. A. Bateman a a Department of Bioengineering, Clemson University, Clemson, South Carolina; b Southern Illinois University School of Medicine, Springfield, Illinois; and c Department of Radiation Medicine, Loma Linda University, Loma Linda, California Willey, J. S., Grilly, L. G., Howard, S. H., Pecaut, M. J., Obenaus, A., Gridley, D. S., Nelson, G. A. and Bateman, T. A. Bone Architectural and Structural Properties after 56 Fe 26 Ra- diation-Induced Changes in Body Mass. Radiat. Res. 170, 201– 207 (2008). High-energy, high-charge (HZE) radiation, including iron ions ( 56 Fe 26 ), is a component of the space environment. We recently observed a profound loss of trabecular bone in mice after whole-body HZE irradiation. The goal of this study was to examine morphology in bones that were excluded from a 56 Fe 26 beam used to irradiate the body. Using 10-week-old male Sprague-Dawley rats and excluding the hind limbs and pelvis, we irradiated animals with 0, 1, 2 and 4 Gy 56 Fe 26 ions and killed them humanely after 9 months. Animals grew throughout the experiment. Trabecular bone volume, connec- tivity and thickness within the proximal tibiae were signifi- cantly lower than control in a dose-dependent manner. Irra- diated animals generally had less body mass than controls, which largely accounted for the variability in bone parame- ters as determined by ANCOVA. Likewise, lower cortical pa- rameters were associated with reduced mass. However, lesser trabecular thickness in the 4-Gy group could not be attributed to body mass alone. Indicators of bone metabolism were gen- erally unchanged, suggesting stabilized turnover. Exposure to 56 Fe 26 ions can alter trabecular microarchitecture in shielded bones. Reduced body mass seems to be correlated with these deficits of trabecular and cortical bone.  2008 by Radiation Research Society INTRODUCTION Understanding the health risks associated with exposure to the space environment has become a priority as plans develop for long-duration, manned exploration of the Moon and Mars. Astronauts face unique environmental conditions in space that have an impact on normal physiological pro- cesses and health. Numerous investigations have provided insight into the body’s response to microgravity and have documented the resultant muscle atrophy, cardiovascular 1 Address for correspondence: 501 Rhodes Research Center, Clemson University, Clemson, SC; e-mail: bateman@clemson.edu. effects and immune system impacts (1–4). Bone loss is ob- served in astronauts exposed to microgravity, particularly within skeletal support elements (i.e., lower extremities, pelvic girdle or lumbar vertebrae) (5, 6). Radiation expo- sure will be another challenge in the space environment during missions outside of low-Earth orbit. During long voyages, astronauts will be continually irradiated by high- energy (E), high-charge (Z) particles (HZE) of galactic cos- mic rays. Intense bursts of protons released from the sun during solar particle events, such as solar flares and coronal mass ejections, will also contribute (7, 8). It is uncertain what role radiation exposure may play in microgravity-in- duced bone loss. During missions outside the magnetosphere, astronauts will be exposed to charged-particle species from all stable elements (hydrogen, helium, carbon, oxygen and iron are considered the most important) (4, 9). Protons make up approximately 87% of the fluence of galactic cosmic radi- ation, which is present at an essentially constant low dose rate approximately 100-fold greater than at the Earth’s sur- face (10). Additionally, unpredictable solar particle events can deliver high doses of proton radiation: as much as 3 Gy over a period of hours to days (11). However, the health risks from heavy-ion radiation may be even greater. High- energy 56 Fe 26+ ions are of particular interest because their dense tracks of ionization result in high relative biological effectiveness (RBE), which is associated with concentrated, poorly repairable damage within organisms. Production of secondary fragments by 56 Fe 26+ ions is also of concern (12). Bone damage occurs after direct exposure to low-linear energy transfer (LET) ionizing radiation ( and X rays) and is thought to be a result of physiological changes that occur to both vasculature and bone cells, primarily bone-forming osteoblasts (13–15). Previous studies suggest that bone-re- sorbing osteoclast numbers tend to decrease after carbon- ion (HZE) irradiation (16). Bone loss at 4 months has been documented in mice whole-body irradiated with low-and high-LET radiation (17 ), and clinical studies have demon- strated an increased risk of fractures after radiotherapy (18, 19). Therefore, deterioration has been observed in directly irradiated bone. The purpose of the present study was to