37-Day Microgravity Exposure in 16-Week Female C57BL/6J Mice is Associated with Weight Bearing Site-Specific Bone Loss

Exposure to space environment factors, including microgravity unloading and space radiation, is well-known to be associated with rapid bone loss in mammals, but significant questions remain about mechanistic aspects of this process. Specifically, bone loss may vary depending on many interacting factors including age and skeletal maturity, physical activity, social versus individual housing, and habitat configuration. Likewise cellular tissue loss mechanisms in space may include changes to mineral homeostasis by activation of bone degradation by osteoclasts, or inhibition of bone formation by osteoblasts, and be caused by microgravity mechanical unloading or increased space radiation. In this study we used microcomputed tomography to quantify bone loss in multiple skeletal sites of group housed mice either exposed to 37 days in space on ISS during the Rodent Research 1, (RR1), experiments using the NASA Rodent Habitat, (RH), versus ground controls in the same habitats or standard vivarium cages. Our results in space versus matched RH ground controls show significant cancellous and cortical bone loss in the femur and tibia, but not in vertebrae, indicating that only weight-bearing bones experience significant bone loss during spaceflight. This finding suggests that space radiation at the low levels found in low Earth Orbit may not be a significant contributing factor to bone loss in space. Interestingly while mice maintained in the RH maintained or gained bone relative to Basal controls, mice kept in standard vivarium cages for 37 days showed significant loss in weight bearing bones, not as acute, but comparable in magnitude to spaceflight effects. These results suggest the RH configuration versus vivarium cages, may allow for greater mechanical loading of weight bearing bones as mice climb internal habitat surfaces, promoting maintenance of bone regenerative health.