Daily Acute Bouts of Weight-bearing During Hindlimb Unloading Mitigate Disuse-Induced Deficits in Cancellous Bone

International Space Station crewmembers experience microgravity, resulting in musculoskeletal losses. It remains unclear how much mechanical loading during disuse is sufficient to mitigate disuse-induced bone loss. We examined 75 minutes of weight-bearing per day on disuse-induced bone loss during hindlimb unloading (HU). Female C57BL/6J mice, 17 weeks (n=10/group), were exposed to HU for 28 days or were ambulatory controls (CC). Half of the HU animals were continuously unloaded while the remainder were removed from tail suspension for ~75 min/day for cage activity weight-bearing (HU+WB). HU and HU+WB led to total body mass and bone mineral density loss. HU+WB mitigated HU-induced losses in total body fat and lean mass and, in the distal femur, prevented losses in μCT measures of cancellous bone volume and microarchitecture. These findings support the robust impact of short durations of normal loading on preventing or mitigating HU-induced bone loss.