ALTERATIONS IN BONE TISSUE PROPERTIES WITH PARATHYROID HORMONE TREATMENT

Abstract

Osteoporosis, an age-related bone disease characterized by low bone mass, is a potential public health problem responsible for over 8.9 million fractures annually. From an engineering perspective to understanding the mechanism of increased fragility with osteoporosis, we applied engineering theory to study this complex composite material, bone. Amount of bone, bone distribution, and tissue material properties are determinants of whole bone strength. Parathyroid hormone (PTH, teriparatide, hPTH [1-34]) is a FDA-approved anabolic osteoporosis treatment. PTH has shown to reduce fracture risk by over 50% and increased bone volume fraction. However, the alterations in material properties and mechanical properties with PTH treatment, and the correlations to bone mechanical failure are unknown. The objectives of this research were to 1) examine alterations in microstructure and tissue properties of both cortical and cancellous bone with PTH treatment using an osteopenia sheep model, and 2) investigate the influence of microstructure and anisotropic material properties on crack propagation in a pre-notched cortical beam under bending. To investigate the alterations in tissue properties across different length scales, a large, multi-level experiment was designed for both cortical and cancellous bone in an osteopenia sheep model. The first study focused on cortical bone and the effect of PTH treatment was greater at the micro- and nanoscale than at the whole bone level. There was no difference with whole-bone strength; however, fatigue life has shown to increase compared to other bisphosphonate-treated samples whereas fracture toughness was decreased in PTH-treated group and osteon density was higher. Furthermore, mineralization increased whereas indentation modulus decreased and hardness reduced with PTH treatment. Millimeter and nano-scale material properties were correlated with whole bone strength, but fatigue properties correlated little to bending strength or fracture toughness. In the second study, cancellous bone was examined. There was no difference in monotonic compressive strength with PTH treatment; however, PTH-treated group preserved mechanical properties during cyclic loading compared to vehicle group. Additionally, PTH increased the volume fraction of rod-type trabeculae and decreased mineralization whereas nanoindentaion and hardness were not different. Correlating tissue composition, microstructure, and mechanical performance, energy dissipation was highly correlated with volume fraction of rods and mineralization. In the third study, fracture behavior in a single pre-notched cortical bone tissue was examined with finite element based simulation software (FRANC2D). The role of anisotropy of fracture toughness and of altered microstructure in crack trajectory and the force needed to propagate a crack was investigated. Cortical bone with more osteons located further away from the applied loads to maximize intact material would withstand more load before propagating cracks and fracturing.