Abstract
Space travel and prolonged bed rest are examples of mechanical unloading that induce significant muscle and bone loss. The compromised structure and function of bone and muscle owing to unloading make the reloading period a high risk for injury. To explore interactions between skeletal bone and muscle during reloading, we hypothesized that acute external mechanical loading of bone in combination with re-ambulation facilitates the proportional recovery of bone and muscle lost during hind limb suspension (HLS) unloading. Adult male C57Bl/6J mice were randomly assigned to a HLS or time-matched ground control (GC) group. After 2-weeks of HLS, separate groups of mice were studied at day 14 (no re-ambulation), day 28 (14 days re-ambulation) and day 56 (42 days re-ambulation); throughout the re-ambulation period, one limb received compressive mechanical loading and the contralateral limb served as an internal control. HLS induced loss of trabecular bone volume (BV/TV; −51 ± 2%) and muscle weight (−15 ± 2%) compared to GC at day 14. At day 28, the left tibia (re-ambulation only) of HLS mice had recovered approximately 20% of BV/TV lost during HLS, while the right tibia (re-ambulation and acute external mechanical loading) recovered to GC values of BV/TV (~100% recovery). At day 56, the right tibia continued to recover bone for some outcomes (trabecular BV/TV, trabecular thickness), while the left limb did not. Cortical bone displayed a delayed response to HLS, with a 10% greater decrease in BV/TV at day 28 compared to day 14. In contrast to bone, acute external mechanical loading during the re-ambulation period did not significantly increase muscle mass or protein synthesis in the gastrocnemius, compared to re-ambulation alone. Our results suggest acute external mechanical loading facilitates the recovery of bone during reloading following HLS unloading, but this does not translate to a concomitant recovery of muscle mass.
Highlights
Space travel, missions to Mars, will expose astronauts to extended periods of mechanical unloading that produce significant bone and muscle loss[1,2,3,4,5]
Our results suggest that acute external mechanical loading, of a duration and load previously shown to induce site-specific increases in mineral content [26], facilitates bone recovery following a period of hind limb suspension (HLS)
At day 14, there was detectable trabecular bone loss in ground control (GC) mice, owing in part to age, but with substantial additional loss observed in HLS mice
Summary
Missions to Mars, will expose astronauts to extended periods of mechanical unloading that produce significant bone and muscle loss[1,2,3,4,5]. Unloading causes a concomitant atrophy of bone and muscle, of equal clinical importance is the subsequent reloading period. Decreased structure and function of the musculoskeletal system associated with osteopenia and sarcopenia following unloading increases risk of injury during re-ambulation[6,7,8,9]. In this study we evaluated the catabolic effects associated with hind limb suspension (HLS) unloading, followed by re-ambulation in the presence or absence of acute external mechanical loading
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