Long-term dose response of trabecular bone in mice to proton radiation

Astronauts on exploratory missions will experience a complex environment, including microgravity and radiation. While the deleterious effects of unloading on bone are well established, fewer studies have focused on the effects of radiation. We previously demonstrated that 2 Gy of ionizing radiation has deleterious effects on trabecular bone in mice 4 months after exposure. The present study investigated the skeletal response after total doses of proton radiation that astronauts may be exposed to during a solar particle event. We exposed mice to 0.5, 1 or 2 Gy of whole-body proton radiation and killed them humanely 117 days later. Tibiae and femora were analyzed using microcomputed tomography, mechanical testing, mineral composition and quantitative histomorphometry. Relative to control mice, mice exposed to 2 Gy had significant differences in trabecular bone volume fraction (-20%), trabecular separation (+11%), and trabecular volumetric bone mineral density (-19%). Exposure to 1 Gy radiation induced a nonsignificant trend in trabecular bone volume fraction (-13%), while exposure to 0.5 Gy resulted in no differences. No response was detected in cortical bone. Further analysis of the 1-Gy mice using synchrotron microCT revealed a significantly lower trabecular bone volume fraction (-13%) than in control mice. Trabecular bone loss 4 months after exposure to 1 Gy highlights the importance of further examination of how space radiation affects bone.