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Rodents provide a useful analog for understanding the effects of spaceflight on the human body, offering opportunities for investigations into the relationship between microgravity and the musculoskeletal system. In particular, rodents have often been utilized to improve our understanding of the effects of spaceflight on the spine, including intervertebral disc and vertebral body health. However, there are a number of experimental factors that differ between existing works, including mission duration, animal housing, and anatomical location of interest, making it difficult to draw holistic conclusions. Additionally, the quadrupedal nature of the murine spine results in different biomechanical loading than in a bipedal organism. Thus, the objective of this study was to more fully define the bulk properties of the murine lumbar spine model after 28 days of spaceflight. Additionally, the proximal tibia was analyzed to provide insight into the skeletal site-specificity of gravitational unloading in space. Results indicated that the effects of spaceflight on vertebral body bone microarchitecture, intervertebral disc biochemistry, and intervertebral disc joint mechanics were statistically insignificant, while large and significant bone loss was observed in the proximal tibia of the same animals. We hypothesize that this may be due to site-specific loading changes in space.  Specifically, vigorous ambulatory behaviors observed in this experiment after initial acclimation to spaceflight may increase axial load-bearing in the lumbar spine, while maintaining microgravity induced mechanical unloading in the tibia. In total, this work shows that the rodent spine, unlike the weight bearing …