In this thesis, first, a load-controlled feedback loading device was built for in vivo trabecular bone adaptation studies in a rat tail vertebra compression model using histomorphometry and micro-computed tomography (fiCT)-based finite element analysis (FEA). Conversion of the μCT image to an accurate finite element (FE) model was verified by analyzing the effects of three types of image thresholding techniques, a critical step in converting μCT images to FE models. The apparent Young’s moduli were predicted for models of bovine trabecular bone constructed using each thresholding technique and compared with those measured directly by mechanical testing. To further verify the tissue level mechanical environment predicted by FEA, the strain in the cortical bone of the rat tail vertebra was directly measured using strain gage techniques and compared to the predicted results of μCT-based FEA.
With the in vivo rat tail vertebra model, the trabecular bone response to dynamic mechanical loading was quantified. In addition, the effect of parathyroid hormone (PTH) on trabecular bone response was quantified. Daily mechanical loading or PTH administration significantly increased bone formation rate (BFR) compared to animals without any treatment through significant increases in both mineral apposition rate (MAR) and labeled bone surface (LS/BS). PTH, when combined with mechanical loading, enhanced bone formation mainly through a significant increase in MAR after the first week, and through a significant increase in LS/BS after 2 and 4 weeks. Synergistic effects in BFR were present when PTH was combined with mechanical loading, especially after 2 and 4 weeks, where the increase in BFR was sustained. However, when either PTH or mechanical loading was the only stimulus, the bone formation response diminished to the level of control (no surgery, no treatment) animals after 4 weeks. Significant correlations were also observed between the bone formation indices and trabecular bone tissue mechanical microenvironment for 1 and 2 weeks. PTH administration enhanced as well as sustained these correlations into 4 weeks. The synergistic effects of combined PTH and mechanical stimulation on trabecular bone formation suggest a potential benefit for combined PTH administration and exercise in the treatment of osteoporosis.