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MicroCT Analysis demonstrates OPG mitigates loss of spaceflight OSTEOPENIA IN proximal humerus of mice.  J.R. Milstead¹, A.M. Miesse¹, P.J. Kostenuik², S. Morony², V.L. Ferguson³, S.J. Simske³, D.L. Lacey², T.A. Bateman¹. ¹Dept. of Bioengineering, Clemson Univ., Clemson, SC. ²Amgen Inc., Thousand Oaks, CA. ³BioServe Space Tech., Univ. of Colorado, Boulder.

   Mice treated with or without osteoprotegerin (OPG) were investigated to determine the effects of spaceflight (SF) on trabecular bone. C57BL/6J mice (n=12/group) were given an injection of OPG (20mg/kg, subcutaneously) or a placebo 24 hours prior to spending 12 days in orbit on Space Shuttle flight STS-108. Ground control (GC) mice (age and mass matched) were housed in either AEM or vivarium (VIV) caging, receiving similar treatments beginning 2 days post-launch.
   Trabecular bone of the proximal humerus was analyzed using micro computed tomography (Scanco), allowing bone structure and micro- architecture to be imaged at 15 micron resolution. SF had a significant effect on the properties of trabecular bone. SF trabecular thickness was less than both VIV and AEM controls, 8.5 (p<0.001) and 8.0% (p<0.001), respectively. SF also resulted in a 6.3% (p<0.05) decrease in trabecular number.
   OPG had a significant effect on both SF and GC groups. SF animals treated with OPG had a 39.9% (p<0.001) increase in trabecular density over SF/Placebo, while a 33.3% (p<0.001) and 64.8% (p<0.001) increase in trabecular density was observed for OPG/AEM and OPG/VIV groups over placebo groups, respectively. SF/OPG also had a 39.9% (p<0.05) increase in connective density as well as a 16.1% (p<0.001) increase in trabecular thickness over SF/Placebo groups. OPG GC group results were similar, with the AEM group exhibiting a 52.1% (p<0.05) increase in connective density, 8.2% (p<0.001) increase in trabecular thickness, and 9.9% (p<0.05) increase in trabecular number. OPG/VIV groups demonstrated a 122.6% (p<0.05) increase in connective density, 6.2% (p<0.001) increase in trabecular thickness, and a 20.0% (p<0.05) increase in trabecular number over VIV/placebo groups. This experiment demonstrates that OPG is effective at mitigating the deleterious effects of spaceflight on the mouse skeleton. (NASA/SC EPSCoR, Amgen, Inc.)