1. K. Alice Matthews Jonathon Gali Kellen Sakala Advisors: Dr. Jeffrey Nyman and Dr. Daniel Perrien

2.  Mechanosensitivity of bone is lost with osteoporosis, which affects over 25 million Americans with a total cost of $16.9 billion in 2005. Understanding the signaling that leads to bone adaptation while under mechanical loading can lead to insight into a new target for therapy.  Bone fractures are costly, but understanding the structural strength of the femoral neck in normal and diseased mice can lead to providing insight into its role in osteoporotic fractures

3. 1. Design a dynamic tibial-loading system for live mice that will aid in studying the consequences of deleting the Sirtuin-1gene in osteocytes 2. Design a potting apparatus for loading an excised murine femur to test femoral neck strength in mice suffering from Perthes disease

4. Tibia Loading System: Live subjects  How to design testing fixtures that will allow us to mechanically load a very small bone in a physiological manner Femur System: Excised Bone  Simulate the boundary conditions in a finite element model of the bone, derived from micro-Ct.

5.  Design a loading and potting apparatus that can test femoral neck strength of multiple femurs in the same orientation, and allows femur to be scanned by Micro-CT Jamisa, 1998

6.  Manufacture and calibrate an apparatus for dynamic axial loading of the tibia of live mice.

7. Tibia System  Tibial loading cups should provide support during testing and effectively minimize injury/discomfort to mouse. Femur System  Potted murine femur capable of being transitioned from loading apparatus to micro-ct tube for imaging and subsequent finite element modeling and analysis. Lanyon, 2008

8.  Solid Works drawing of femur loading apparatus (Femur)  Tibial loading cups and platform to hold live mice designed and assembled (Tibia)  IACUC training in hazard, lab, and animal safety performed by all members of the group (Both)  Test and wrote protocol for strain gage amp (Tibia) Strain Gage picture

9.  Find materials and build femoral loading fixture (Femur)  Create protocol in Instron control software and test on ex-vivo tibia (Tibia)  Run finite element analysis (Femur)  Conduct 3 week test loading study to establish complete protocol for repeat loading of in-vivo loading of tibia (Tibia)

10.  Jamsa T et al. Femoral neck strength of mouse in two loading configurations: Method evaluation and fracture characteristics. Journal of Biomechanics, April 1998.  Leanne Kaye Saxon and Lance Edward Lanyon. Methods in Molecular Biology, Chapter 21: Assessment of the In Vivo Adaptive Response to Mechanical Loading. May 2008  Jamsa T et al. Femoral Neck Is a Sensitive Indicator of Bone Loss in Immobilized Hind Limb of Mouse. Journal of Bone and Mineral Research, November 1999.  Willinghamm et al. Age-related changes in bone structure and strength in female and male BALB/c mice. Calcified Tissue International, June 2010