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 56Fe 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 56Fe 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 56Fe 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 56Fe-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.
Highlights
Bone is sensitive to altered mechanical loading; spaceflight induces significant losses in mass and structural integrity
This study aims to investigate the bone response to, and ability to recover from, low-dose, high-linear energy transfer (LET) radiation exposure combined with partial weightbearing simulating the 1/6 g of the Lunar environment
The primary findings of these experiments are (1) radiation, contrary to our initial hypothesis, resulted in improved cancellous bone microarchitecture in both WB and G/6 mice and improved energy absorption characteristics in the femur of WB mice; (2) there were site-specific responses to radiation in the distal femur and lumbar vertebra, with a greater impact of radiation on the cancellous bone of the distal femur than that of L4; and (3) after recovery (~45 days after irradiation), the positive impact of radiation on cancellous microarchitecture of the distal femur was maintained, but this did not hold true for mid-shaft femur energy absorption
Summary
Bone is sensitive to altered mechanical loading; spaceflight induces significant losses in mass and structural integrity. Lowbone quality in astronauts upon returning to Earth or landing on Mars is an area of high priority to solve prior to exploration class missions due to an increased risk of fracture, which could be detrimental to a long-duration mission outside of low earth orbit.[1] Due to the minimal medical capabilities of future extra-planetary missions it is possible that a broken bone could become a serious health risk.[2] In-flight studies and those using ground-based analogs in humans and rodents have shown bone loss to be an important risk faced by astronauts if effective countermeasures are not employed.[1,3,4,5,6] Whether exercise equipment enabling high intensity resistance training will be available on exploration class missions is yet to be determined. Important to understand how partial mechanical loading, such as Mars’ one-third and the Lunar one-sixth gravity environments, may affect bone mass and mechanical integrity
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