1. Bisphosphonate Pretreatments Protect Cancellous Bone Density and Strength in Unloaded Adult Rats
J.P. Elizondo1, J. M. Black, J. L. Kosniewski, J. E. Brezicha, S. E. Lenfest, S. A. Bloomfield, M. R. Allen, H. A. Hogan
1Texas A&M University, Dept. of Mechanical Engineering, College Station, TX
LSMCE 2017, Indianapolis, IN
October 7, 2017

2. NASA wants to go to mars by 2030s
Bone loss is an issue

3. Cancellous Bone Loss in Space
Bone adapts to loads placed on it
No load on astronauts’ bones → rapid resorption
Increased fracture risk
Cancellous (“spongy”) is resorbed more than cortical[1]
Normal ISS missions are about 6 mo.
Mission to Mars would be at least two to three years (6-months each way)
Buzz Aldrin suggested 10 years  (Dunn, Marcia (27 August 2015). "Buzz Aldrin joins university, forming 'master plan' for Mars". AP News. Retrieved 30 August 2015.)
[1]A. Leblanc, V. Schneider, L. Shackelford, S. West, V. Oganov, A. Bakulin, L. Voronin, Bone Mineral and Lean Tissue Loss After Long-Duration Spaceflight, J. of Musculoskeletal Neuronal Interaction, 1 (2000)
Image from
Human Femur Cross Section

4. BP incorporated in bone mineral
Bisphosphonates
Are most commonly administered osteoporosis drug
Work by stopping resorption
Have been used in astronauts[2]
Affect bone for years after treatment
Makes pretreatment a possibility X
BP incorporated in bone mineral
Nausea bad in space, some astronauts stopped taking ALN because of it
Stay in human bone for ??? years
[2]Leblanc, A., et al. "Bisphosphonates as a supplement to exercise to protect bone during long-duration spaceflight." Osteoporosis International 24.7 (2013):

5. Rat Model for Microgravity
Hindlimb unloading (HU) model
Load removed from hindlimbs
Analog for unloaded limbs of astronauts
Hindlimb Unloaded Rat

6. Research Question
Will bisphosphonate pretreatment protect from disuse-induced bone loss in the HU rat model?

7. Study Design Administered bisphosphonate pretreatment (4 weeks)
Risedronate (RIS) and Alendronate (ALN)
Put rats through HU protocol (4 weeks)
Four groups: ambulatory control (AC), HU control, ALN+HU, RIS+HU
Acclimation
Drug Pretreat
Unloading
Recovery
Euthanasia
Day 0
Day 28
Day 56
Day 112
Get drugs from collaborators at Indiana Universtiy
Clinical equivalent doses:
ALN: 2.4ug/kg 3x/wk
RIS: 1.2 ug/kg 3x/wk
6 mo old at day 0

8. Data Collection
Ex Vivo peripheral quantitative computed tomography (pQCT)
Reduced platen compression (RPC) mechanical testing
Two cancellous-rich bone sites
Proximal Tibia Metaphysis (PTM)
Distal Femur Metaphysis (DFM)
RPC Testing
pQCT is basically an x-ray that computes BMD

9. pQCT Results HU

10. pQCT Results HU AC
HUC
RIS
ALN

11. RPC Results HU

12. RPC Results HU

13. Conclusion
Bisphosphonate pretreatment could be a viable alternative to concurrent treatment.

14. Acknowledgments All co-authors LSMCE organizers
TAMUS LSAMP BTD (NSF Grant Award No. HRD )
NASA Space Biology grant #NNX13AM43G
NSBRI grant NCC9-58 (funded co-authors JEB and SEL)

15. Questions?

16. Supplemental pQCT ResultsHU

17. Supplemental pQCT ResultsHU

18. Supplemental RPC ResultsHU

19. Supplemental RPC ResultsHU

20. Alendronate in Human Astronauts
Statistical Significance
1 = % change different from 0
2 = % change different from pre-ARED
3 = % change different from ARED
Figure from Leblanc, A., et al. "Bisphosphonates as a supplement to exercise to protect bone during long-duration spaceflight." Osteoporosis International 24.7 (2013):