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Item Effects of anti-resorptive treatment on the material properties of individual canine trabeculae in cyclic tensile tests(Elsevier, 2021) Frank, Martin; Grabos, Andreas; Reisinger, Andreas G.; Burr, David B.; Pahr, Dieter H.; Allen, Matthew R.; Thurner, Philipp J.; Anatomy and Cell Biology, School of MedicineOsteoporosis is defined as a decrease of bone mass and strength, as well as an increase in fracture risk. It is conventionally treated with antiresorptive drugs, such as bisphosphonates (BPs) and selective estrogen receptor modulators (SERMs). Although both drug types successfully decrease the risk of bone fractures, their effect on bone mass and strength is different. For instance, BP treatment causes an increase of bone mass, stiffness and strength of whole bones, whereas SERM treatment causes only small (4%) increases of bone mass, but increased bone toughness. Such improved mechanical behavior of whole bones can be potentially related to the bone mass, bone structure or material changes. While bone mass and architecture have already been investigated previously, little is known about the mechanical behavior at the tissue/material level, especially of trabecular bone. As such, the goal of the work presented here was to fill this gap by performing cyclic tensile tests in a wet, close to physiologic environment of individual trabeculae retrieved from the vertebrae of beagle dogs treated with alendronate (a BP), raloxifene (a SERM) or without treatments. Identification of material properties was performed with a previously developed rheological model and of mechanical properties via fitting of envelope curves. Additionally, tissue mineral density (TMD) and microdamage formation were analyzed. Alendronate treatment resulted in a higher trabecular tissue stiffness and strength, associated with higher levels of TMD. In contrast, raloxifene treatment caused a higher trabecular toughness, pre-dominantly in the post-yield region. Microdamage formation during testing was not affected by either anti-resorptive treatment regimens. These findings highlight that the improved mechanical behavior of whole bones after anti-resorptive treatment is at least partly caused by improved material properties, with different mechanisms for alendronate and raloxifene. This study further shows the power of performing a mechanical characterization of trabecular bone at the level of individual trabeculae for better understanding of clinically relevant mechanical behavior of bone.Item Reference point indentation is insufficient for detecting alterations in traditional mechanical properties of bone under common experimental conditions(Elsevier, 2016-06) Krege, John B.; Aref, Mohammad W.; McNerny, Erin; Wallace, Joseph M.; Organ, Jason M.; Allen, Matthew R.; Department of Anatomy and Cell Biology, School of MedicineReference point indentation (RPI) was developed as a novel method to assess mechanical properties of bone in vivo, yet it remains unclear what aspects of bone dictate changes/differences in RPI-based parameters. The main RPI parameter, indentation distance increase (IDI), has been proposed to be inversely related to the ability of bone to form/tolerate damage. The goal of this work was to explore the relationshipre-intervention RPI measurebetween RPI parameters and traditional mechanical properties under varying experimental conditions (drying and ashing bones to increase brittleness, demineralizing bones and soaking in raloxifene to decrease brittleness). Beams were machined from cadaveric bone, pre-tested with RPI, subjected to experimental manipulation, post-tested with RPI, and then subjected to four-point bending to failure. Drying and ashing significantly reduced RPI's IDI, as well as ultimate load (UL), and energy absorption measured from bending tests. Demineralization increased IDI with minimal change to bending properties. Ex vivo soaking in raloxifene had no effect on IDI but tended to enhance post-yield behavior at the structural level. These data challenge the paradigm of an inverse relationship between IDI and bone toughness, both through correlation analyses and in the individual experiments where divergent patterns of altered IDI and mechanical properties were noted. Based on these results, we conclude that RPI measurements alone, as compared to bending tests, are insufficient to reach conclusions regarding mechanical properties of bone. This proves problematic for the potential clinical use of RPI measurements in determining fracture risk for a single patient, as it is not currently clear that there is an IDI, or even a trend of IDI, that can determine clinically relevant changes in tissue properties that may contribute to whole bone fracture resistance.