Indiana University-Purdue University Indianapolis (IUPUI) / Although the in vivo tibial loading model has been used to study the bone forma- tion response of mice to exercise, little emphasis has been placed on the translation of architectural and compositional modifications to changes in mechanical behaviour. The goals of the studies discussed below were to investigate the mechanical response in both healthy and osteolathrytic mice to this loading model and to determine the dose-depended effects of strain level on these properties. In two separately designed studies, strain levels ranging from 1700 to 2400 were applied to the right tibiae of 8 week old female C57BL/6 mice, while the left tibiae were used as non-loaded control. The first study consisted of loading both PBS- and BAPN-injected mice to 1750 microstrain which resulted in little bone formation but some tissue-level changes in mechanical analyses and an improvement in fatigue-resistance in terms of microdamage accumulation. The second study loaded healthy mice to three strain levels (1700, 2050, and 2400). Results indicated that the low end of the strain range did not engender a robust formation response, while the high end of the strain range resulted in a woven bone response in half of the animals in that group. Future studies will focus on the mid-strain level of 2050 which induced both significant architectural and mechanical improvements.

Indiana University-Purdue University Indianapolis (IUPUI) / Skeletal fractures due to bone disease impact an estimated 1.5 million Americans per year, creating a large economic burden on our society. Treatment of bone diseases prior to fracture often involves bisphosphonates (current gold-standard in osteoporosis care and prevention). Although bisphosphonates decrease fracture incidence, they often improve bone mass without regard for bone quality. Thus, although bisphosphonates increase the amount of bone present, the inherent bone material strength often decreases, creating a trade-off that increases the risk of atypical fractures after long-term use. This trade-off demonstrates the need for a treatment that targets both bone quality AND quantity. Although bone quality is important, the components of bone that contribute to bone quality are incompletely understood, making it difficult to create new pharmacological agents. With this in mind, my particular area of interest is in understanding how mechanical stimuli protects the formation of bone, leading to improved bone quality. Initially, this area was explored through use of tibial loading in a disease mouse model (osteolathyrism, induced by injection of beta-aminoproprionitrile) as a means of assessing how the body is able to compensate for decreased bone quality. The results of the BAPN and tibial loading studies indicated that injecting mice with BAPN may not be the ideal method to induce osteolathyrism. However, other intriguing results from the BAPN studies then led us into an exploration of how tibial loading itself contributes to bone quality.