Sponsors: National Aeronautics and Space Administration (NASA) NASA Goddard Space Flight Center (GSFC) NASA Goddard Institute for Space Studies (GISS) NASA New York City Research Initiative (NYCRI) Stony Brook University, Department of Biomedical Engineering Contributors: Dr. Judex, Principal Investigator Shikha Gupta, Post-Doc INTRODUCTION Bone is a dynamic and adaptive tissue that responds to mechanical signaling induced by weight bearing. Bone tissue is very sensitive to stimuli, allowing it to constantly remodel itself to adapt to the load placed upon it [1]. Cellular activities involve a constant homeostatic interaction between bone formation and resorption, which maintain the quantity and quality of bone tissue [2]. During osteoporosis and unloading, this equilibrium is disrupted to favor bone resorption, thus leading to a net loss of bone [3]. After space flight missions, many astronauts are put at risk for osteoporosis and osteopenia. The microgravity in space produces a catabolic effect on bone by inhibiting bone matrix mineralization [4]. The goal of this research was to test the differential effects of frequency and duration of periods of simulated weightlessness (hindlimb unloading) on bone remodeling in mouse model. We hypothesized that a single long exposure to HLU would cause more bone loss than multiple short exposures. This study specifically focuses on bone loss of cortical tissue in the femoral mid-diaphysis because bone reduction, induced by loss of weight-bearing, is very site-specific within a given bone [5,6]. The Effect of Simulated Microgravity on Bone Quantity and Quality in the Mid-Diaphysis of the Mouse Femur Lisa Tan*, Shikha Gupta, Stefan Judex Biomedical Engineering, State University of New York, Stony Brook *Ward Melville High School, InSTAR Science Research Program MATERIALS AND METHODS Suspension Apparatus A mouse hindlimb-suspension apparatus was used to mimic the microgravity conditions in space and to test the effect on bone loss. BALB/cByJ x C3H/HeJ F2 mouse generation (gender-divided) Mice were tested from the age of 16 (mature adult) to 32 weeks (1 wk HLU, 3 wk RA) (2 wk HLU, 6 wk RA) 4+12 (4 wk HLU, 6 wk RA) In vivo µCT Bone loss was studied using an in vivo Micro CT Scanner (vivaCT 40; SCANCO Medical). From the scans from in vivo Micro CT, a 3-D evaluation was reconstructed. The following morphological indices in the mid-diaphyseal region of the mouse femur were determined from the evaluations: cortical thickness (Ct.Th), tissue mineral density, and endosteal area. An automatic IPL Image Processing Language script was used to recreate 3-D images of these scanned frames. These parameters were calculated at baseline and after one week of suspension. The measurements were taken for both the male and females F2 mice. REFERENCES 1.Judex, S. et al.(2009) Orthod Craniofac Res. 2. Judex, S. et al.(2002) FASEB J. 3. Squire, M. et al.(2008) Bone 4. Burger, E.H. & Klein-Nulend, J. (1998) J Bone Miner. Res. 5. Judex, S. et al.(2004) J Bone and Miner. Res. 6. Judex, S. et al.(2004) J Bone and Miner. Res. RESULTS There was a significant difference only in cortical thickness between males and females both at baseline and after 1wk of HLU. No significant difference in cortical thickness (Figure 3), endosteal area (Figure 4), or tissue mineral density (Figure 5) were observed after 1wk of HLU for both males and females. DISCUSSION The extent of bone loss and changes in cortical bone quantity and quality are affected by different regimes of unloading. Though no significant change in the mid-diaphysis were noted after 1wk of HLU, we hypothesize that changes in cellular remodeling activities had been initiated but that the changes were not yet manifest in the morphology of the mid-diaphysis. We anticipated that more pronounced changes will occur after 2wk or 4wk of HLU. Figure 2. 3-D reconstructions of the mid-diaphysis in a male F2 mouse from the 1wk HLU group at (a) baseline and (b) after 1wk of HLU. a b Figure 3. Changes in the mid- diaphyseal cortical thickness between baseline (16wk age) and 1 wk of HLU in male and females. Figure 5. Changes in the mid-diaphyseal tissue mineral density between baseline (16wk age) and 1 wk of HLU in male and females. Figure 4. Changes in the mid- diaphyseal endosteal area between baseline (16wk age) and 1 wk of HLU in male and females. Figure 1. A picutre of the hindlimb suspension device. The lack of weight-bearing on the hindlimbs mimics the conditions in space and causes similar responses in bone tissue.