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SPACEFLIGHT-INDUCED CHANGES IN MOUSE BONE AND OSTEOPROTEGERIN THERAPY.  T.A. Bateman¹, S. Morony², V.L. Ferguson¹, S.J. Simske¹, D.L. Lacey², K.S. Warmington², C.R. Dunstan², L.S. Stodieck¹ and P.J. Kostenuik².  ¹BioServe Space Technologies, University of Colorado, Boulder.  ²Amgen Inc., Thousand Oaks, CA. 

   This experiment characterized the effects of spaceflight (SF) on the skeleton of mice treated with or without OPG, a protein that blocks bone resorption by osteoclasts.  10-week-old female C57BL/6J mice (n=12/group) received a single injection (SC, 24 h pre-launch) of either OPG (20mg/kg) or vehicle (VEH) and spent 12-days in orbit on Space Shuttle flight STS-108.  Mass and age-matched ground control (GC) mice had similar treatments on a 48-hour delay. 

   Upon landing, SF/VEH femur dry mass was lower compared to GC/VEH mice.  OPG significantly increased femoral dry mass in both SF and GC conditions.  Femur whole bone mineral mass (Min-M) and percent mineral composition (%Min) were lower in SF/VEH mice compared to GC/VEH.  SF/OPG had a greater Min-M and %Min than SF/VEH.  SF reduced elastic strength at the femoral midshaft in VEH mice, while OPG increased elastic strength in SF mice.  pQCT analysis of the lumbar vertebra (L5) and proximal tibia revealed a deficit in BMD of SF/VEH mice compared to GC/VEH, indicating a systemic decline in bone mass.  OPG blocked these SF-induced BMD changes.

   Serum and mRNA (humeral diaphysis) analyses suggest changes in both bone formation and resorption contributed to the SF-induced osteopenia. A significant decline in mRNA expression of osteocalcin combined with a decline in serum alkaline phosphotase levels indicate a reduction in bone formation.  Additionally, SF reduced periosteal and endocortical bone formation rates in the femoral diaphysis.  Increased bone resorption in SF mice was suggested by a trend towards increased mRNA expression of the pro-resorptive cytokine RANK ligand and significantly elevated serum TRAP levels.  OPG treatment reduced osteoclast surfaces in the proximal tibia by >95% in all groups.  .  This experiment demonstrates that the mouse is an appropriate model for SF-induced ostepenia, and that OPG is an effective countermeasure.  (Supported by Amgen Inc. and NASA CA# NCC8-242)

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