Positive impact of low-dose, high-energy radiation on bone in partial- and/or full-weightbearing mice

Abstract

Astronauts traveling beyond low Earth orbit will be exposed to galactic cosmic radiation (GCR); understanding how high energy ionizing radiation modifies the bone response to mechanical unloading is important to assuring crew health. To investigate this, we exposed 4-mo-old female Balb/cBYJ mice to an acute space-relevant dose of 0.5 Gy 56 Fe or sham ( n = ~8/group); 4 days later, half of the mice were also subjected to a ground-based analog for 1/6 g (partial weightbearing) (G/6) for 21 days. Microcomputed tomography (µ-CT) of the distal femur reveals that 56 Fe exposure resulted in 65–78% greater volume and improved microarchitecture of cancellous bone after 21 d compared to sham controls. Radiation also leads to significant increases in three measures of energy absorption at the mid-shaft femur and an increase in stiffness of the L4 vertebra. No significant effects of radiation on bone formation indices are detected; however, G/6 leads to reduced % mineralizing surface on the inner mid-tibial bone surface. In separate groups allowed 21 days of weightbearing recovery from G/6 and/or 56 Fe exposure, radiation-exposed mice still exhibit greater bone mass and improved microarchitecture vs. sham control. However, femoral bone energy absorption values are no longer higher in the 56 Fe-exposed WB mice vs. sham controls. We provide evidence for persistent positive impacts of high-LET radiation exposure preceding a period of full or partial weightbearing on bone mass and microarchitecture in the distal femur and, for full weightbearing mice only and more transiently, cortical bone energy absorption values.

The Protective Role of Neurogenetic Components in Reducing Stress-Related Effects during Spaceflights: Evidence from the Age-Related Positive Memory Approach

“…However, the effect of radiation on bones is still under investigation. In fact, in a study on skeletally mature mice (16 weeks of age) exposed to 0.5 Gy of 56 Fe, some positive effects were documented [ 82 ]. Aside from IR, MG can be harmful to the skeletal system for many reasons (e.g., mechanical loading, altered calcium homeostasis, decreased hematopoiesis, and altered metabolism) [ 83 ].…”

Unloading-Induced Cortical Bone Loss is Exacerbated by Low-Dose Irradiation During a Simulated Deep Space Exploration Mission

“…Previous research already identified synchronous effects of HLU and high doses of radiation, with the majority supporting the hypothesis that high-dose irradiation exacerbates the skeletal consequences of mechanical unloading [19][20][21][22]. For example, cancellous bone losses were driven by similar osteoclastic bone resorption in HLU and gamma irradiation, in 4-month-old C57BL/6 mice, with an additive effect of these two interventions [20].…”

“…Furthermore, proton radiation and high atomic number and energy radiation (HZE) also produced additive bone losses in the C57BL/6 mouse strain [21]. However, one must consider the interesting finding of the protective effects of high-linear energy radiation exposure with 0.5 Gy 56 Fe, prior to mechanical unloading, in the weight-bearing bones of the legs of 4-month-old female Balb/cBYJ mice [22]. Nevertheless, despite the increasing body of research combining HLU with relatively high doses of radiation, combined low-dose radiation and HLU research remain sparse.…”