Housing in the Animal Enclosure Module Spaceflight Hardware Increases Trabecular Bone Mass in Ground-Control Mice

ABSTRACT During spaceflight, mice are housed in specially designed cages called the Animal Enclosure Module (AEM). Utilization of this flight hardware may affect the skeletal properties of housed animals, independent of microgravity considerations. To address this issue, we studied the effect of 13 days of AEM housing versus standard vivarium enclosure on female C57BL/6J mice (n=12/group). The effects of AEM housing were most pronounced in the trabecular compartment. AEM mice had 44% and 144% greater trabecular bone volume fraction and connectivity density, respectively, versus vivarium. A similar response was seen at the proximal humerus. We noted a decrease in proximal tibia osteoclast surface (-65%) and eroded surface (-73%) for AEM versus vivarium, while tibia trabecular mineralizing surface (MS/BS) was nearly three-fold greater. Surprisingly, there was also decreased osteoblast surface, as well as lower osteoid volume, surface, and thickness at this site. The effects of AEM housing on femur cortical bone were modest: there was greater periosteal MS/BS, with no effect at the endocortical surface, and lower femur stiffness. Taken together, we have demonstrated significant effects of AEM housing on ground control mice, particularly in the trabecular bone compartment. These findings suggest that an early increase in bone formation, perhaps due to altered behavior and loading in this unique housing environment, was followed by decreased bone formation and resorption as the animals adapted to their new environment. Characterization of spaceflight animal housing is critical to elucidating the true effects of microgravity on skeletal parameters and for the proper selection of ground-based controls.