Impact of artificial gravity on spaceflight-induced skeletal deterioration in male mice

Spaceflight-induced bone loss may increase the risk of fracture during long-duration missions. Exposure to artificial gravity (AG) of 1 G by centrifugation has been shown to prevent spaceflight-associated bone loss in mice. However, whether lower levels of AG can prevent skeletal deterioration during spaceflight is unknown. Young adult (11 weeks) male C57Bl/6 J mice were exposed to microgravity (µG) or AG (0.33 G, 0.67 G, or 1 G) via centrifugation during a 30-day mission on the International Space Station ( n = 5-6/group). Ground controls were housed in an identical habitat (HGC, n = 12). We used DXA to measure body composition and bone mineral density (BMD) pre- and post-flight in vivo. After necropsy, we measured bone microarchitecture, histomorphometric parameters, and gene expression. Spaceflight led to a marked increase in total body fat mass, which was prevented by AG in a dose-dependent fashion. Mice exposed to 1 G of AG had equivalent bone mass, microarchitecture, and strength compared to HGC, but lower levels of AG only partially mitigated these bone deficits. AG prevented deficits in endocortical bone formation, but only partially preserved periosteal bone formation. Cortical bone transcriptomic patterns were altered in µG and returned to those of HGC with increasing levels of AG. Exposure to levels of AG below 1 G during spaceflight partially mitigates spaceflight-associated bone deficits, though not consistently in a dose-associated manner. 1 G of artificial gravity was necessary to ameliorate most of the microgravity-associated deficits in bone health.