Bisphosphonates are the most commonly used osteoporosis treatment that has been effective in preventing osteoporotic fractures by suppressing bone turnover. Turnover refers to the resorption and replacement of tissue. Despite the beneficial effects of bisphosphonates, there is accumulating evidence of a potential complication in the form of atypical femoral fracture. The recent reports of possible association of atypical femoral fracture with prolonged bisphosphonate use brought into attention the possibility of adverse mechanical modifications in bone due to extensive suppression of bone turnover. The overall goal of this award is to advance the understanding of the changes in material composition, organization, and fracture resistance of bone due to suppressed bone turnover via multiscale computational modeling. This project will have a broad and major impact on the society as it will provide timely information on a significant potential public health problem associated with the most commonly used drug therapy for osteoporosis. The results of the project will provide new knowledge that will establish a better understanding of the effects of osteoporosis treatments on bone quality and will help determine patients under risk of atypical femoral fracture. In addition, the research plan will integrate an active educational and outreach component that will broaden the participation of underrepresented groups in engineering.
This research project will significantly improve the current understanding of the changes in fundamental fracture mechanisms in bone as a result of alterations in material composition and organization due to suppressed bone turnover. The project will utilize a new fracture mechanics-based finite element modeling approach and will perform systematic and controlled evaluations at multiple scales to quantify the critical levels of material property changes that will impair the fracture resistance of bone. Specifically, the study will determine the effect of bone mineral and matrix heterogeneity on crack growth, quantify the influence of increased mineralization and accumulation of advanced glycation end products on crack propagation, and identify the critical level of microcrack accumulation in bone that will adversely affect the fracture toughening mechanisms in bone. The novel and innovative computational evaluation approach in this research project will provide unique information that cannot be measured by experiments.
