Jumping Exercise and Sclerostin Antibody as Countermeasures for Simulated Microgravity in the Adult Rat Skeleton
Abstract
Astronauts undergo significant bone loss during spaceflight. The lack of gravitational loading increases bone resorption and decreases bone formation in weightbearing bones, resulting in a net loss of bone.
NASA traditionally counteracts bone loss by returning loading to astronauts’ bones with daily resistance exercise. However, recent data suggest that exercise alone does not completely protect astronauts.
To supplement resistance exercise, NASA has previously investigated pharmaceutical countermeasures. A promising osteoporosis medication, anti-sclerostin antibody (Scl-Ab), could provide a viable treatment for spaceflight-induced bone loss.
This study investigated exercise and Scl-Ab as preventive countermeasures to microgravity-induced bone loss. To do this, we used the well-established hindlimb unloading rat model, and we administered Scl-Ab or a voluntary jumping protocol before hindlimb unloading.
First, we characterized loading from our jumping protocol. We found that ground reaction forces were on average 2.8 times body weight in our rats. These greatly elevated loads were osteogenic in forelimbs and hindlimbs. We found elevated bone formation rate, decreased osteoclast surface, and elevated cortical bone mineral density in jumping animals compared to untreated controls. Thus, we believe our jumping model is a physiologically relevant bone model for anabolic resistance exercise in humans.
Next, we assessed the impact of jumping, Scl-Ab, and unloading on bone integrity, and we directly compared the effectiveness of Scl-Ab and jumping exercise. Both preventive countermeasures were effective through four weeks of disuse. Bone architecture and mechanical properties in both treatment groups were improved after four weeks of unloading compared to untreated unloading controls. However, Scl-Ab was much more effective in the especially vulnerable cancellous compartment. Scl-Ab doubled bone volume fraction and tripled yield stress and elastic modulus of cancellous bone compared to unloading controls. Scl-Ab is an especially strong candidate for a pharmaceutical countermeasure to spaceflight bone loss.
Finally, we conducted finite element modeling of compression of cancellous rat bone. These simulations did not reflect findings from µCT and physical compression of the same bone volume. Despite these seemingly erroneous results, we have identified a number of procedural improvements, and we believe that these simulations will become a valuable and routine outcome for our lab.
Subject
BoneMicrogravity
Rat Hindlimb Unloading
Sclerostin Antibody
Jumping Exercise
Ground Reaction Forces
Bone Quality
Finite Element Method
Citation
Elizondo, Jon Paul (2021). Jumping Exercise and Sclerostin Antibody as Countermeasures for Simulated Microgravity in the Adult Rat Skeleton. Doctoral dissertation, Texas A&M University. Available electronically from https : / /hdl .handle .net /1969 .1 /195797.