Skeletal Effects of Bisphosphonate Treatment and Jumping Resistance Exercise on Adult Rats Exposed to Simulated Microgravity
Abstract
The purpose of our study was to investigate the effects of a single period of bisphosphonate (BP) treatment on bone loss resulting from multiple periods of simulated microgravity. We hypothesized that the protective effects of BP treatment would extend through two periods of hindlimb unloading (HU) and an intervening recovery period, and that the BP zoledronate (ZOL) would outperform the BP alendronate (ALN) at preserving bone strength and quality due to ZOL’s higher binding affinity and antiresorptive potency. Male Sprague-Dawley rats (6-months-old) were given either a single injection of ZOL (HU+ZOL), ALN injections three times per week for 5 weeks (HU+ALN), or assigned to aging control (AC) or HU control (HU) groups. HU groups were then exposed to 28 days of HU, followed by 56 days of recovery and a second 28- day HU period. The first and second HU periods resulted in significant declines in total (-5.05%, -0.25%) and cancellous (-18.4%, -9.98%) volumetric bone mineral density (vBMD) at the proximal tibia metaphysis (PTM). BP treatment protected (ALN) or overprotected (ZOL) against losses in bone density and microarchitecture.
Additionally, we aimed to develop a model of voluntary jumping exercise (VJE) that employs positive reinforcement-based training and validate its efficacy as a countermeasure to simulated microgravity. We hypothesized that VJE pre-treatment would effectively preserve bone strength and quality during a subsequent HU period, but that these beneficial effects would not extend to the recovery period following unloading. Male Sprague-Dawley rats (6-months-old) performed VJE for 4 weeks (HU+VJE) and were subsequently exposed to 28 days of HU, followed by 56 days of recovery. HU+VJE had significantly higher total vBMD at the PTM (+8.95%), distal femur metaphysis (+7.57%), and femoral neck (+6.03%) compared to AC at the end of the exercise period. VJE pre-treatment also prevented losses in bone strength and quality measures due to HU and promoted recovery at certain bone sites. These results indicate that BP treatment may be a successful countermeasure against spaceflight bone loss, and that positive reinforcement-based VJE pre-treatment is a useful model of rodent exercise and an effective countermeasure against HU-induced bone loss.
Subject
bonehindlimb unloading
bisphosphonates
alendronate
zoledronate, voluntary jumping exercise
rats
hindlimb suspension
simulated microgravity
Citation
Lenfest, Scott Edward (2020). Skeletal Effects of Bisphosphonate Treatment and Jumping Resistance Exercise on Adult Rats Exposed to Simulated Microgravity. Doctoral dissertation, Texas A&M University. Available electronically from https : / /hdl .handle .net /1969 .1 /191737.