Simulated microgravity accurately models long-duration spaceflight effects on bone and skeletal muscle in skeletally immature mice

Spaceflight (SF) and disuse result in decreases in bone and skeletal muscle volume that increase fracture risk. Hindlimb unloading (HLU) has been widely used to model the effects of microgravity. However, the effects of SF and HLU on bone and skeletal muscle have not been directly compared during long-duration SF. We examined the effects of five weeks of SF and HLU in the femurs of female Balb/c mice. For the first time, SF and HLU were directly compared using mice of the same age, strain, sex, and duration as a mission to the ISS. We hypothesized that HLU would accurately model SF, resulting in similar bone and skeletal muscle loss. Ten-week old female Balb/c mice were assigned to baseline, vivarium control, habitat control, and SF groups (n = 10/group). A separate cohort of 10-week female Balb/c mice were placed in HLU or control (n = 10/group). Femoral cortical area increased from baseline in all groups except HLU. The magnitudes of increases were lower in the SF and HLU groups. Similar effects were seen in trabecular bone. Femoral ultimate force decreased in SF and HLU groups, compared to control groups. Gastrocnemius and quadriceps mass was lower in SF and HLU mice than in control mice. HLU resulted in greater bone loss than SF, possibly due to differences in housing conditions. HLU effectively models long-duration effects of SF on the musculoskeletal system, highlighting its utility for studying astronaut health risks and developing countermeasures.