Collaborative Research: Determining the Impacts of Lacunar-Canalicular Remodeling on Bone Fracture Toughness

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This award will support research to study bone fragility in aging, a major unsolved problem. Over 40 percent of women and 25 percent of men over 60 will experience a fragility fracture. The purpose of this research is to improve our understanding of the origins of bone toughness and to test if the loss of bone toughness is explained by the health of bone cells called osteocytes. Osteocytes are strain-sensing cells embedded in bone. These cells are interconnected by an expansive porous network. Osteocytes can remove and replace (that is, remodel) bone tissue surrounding this expansive network. Therefore, osteocytes may have an important but overlooked role in maintaining bone quality, specifically toughness. Because osteocyte health declines in aging and disease, it is important to understand whether interrupting osteocyte health decreases bone toughness. This project will advance the understanding of how, where, and why the osteocyte remodels bone and the impacts of osteocyte bone remodeling on bone toughness. The investigators will recruit and train underrepresented graduate and undergraduate students in the completion of the work. This work will also involve underrepresented undergraduate and high school students in the research and will engage K-12 students and teachers in bone biomechanics and materials science outreach activities. This project partners several novel approaches to investigate the impacts of osteocyte lacunar-canalicular remodeling on bone quality and fracture toughness. First, finite element modeling, histology, and histomorphometry will be used to assess the fraction of osteocytes that are remodeling bone tissue and evaluate whether osteocyte bone remodeling is related to bone tissue strain. Second, Auger electron spectroscopy will be used to produce submicron-resolution maps of bone mineral and matrix composition near osteocyte lacunae. Contact resonance atomic force microscopy maps will deliver an assessment of how bone energy dissipation, which determines bone fracture toughness, varies at the submicrometer-scale. Third, a high dietary fat diet will be used as a novel platform to study how lacunar-canicular remodeling affects bone fracture toughness. These models exploit the detrimental effect of fat on osteocyte health to modulate lacunar-canicular remodeling activities. The key outcomes of the project are (1) the number and location of remodeling osteocytes and determination of whether lacunar-canicular remodeling is related to bone tissue strain, (2) bone composition and mechanical properties at a physiologically-relevant resolution near remodeling and non-remodeling osteocytes, and (3) determination of whether lacunar-canicular remodeling beneficially impacts bone fracture toughness. This project is jointly funded by the Biomechanics and Mechanobiology program and the Established Program to Stimulate Competitive Research (EPSCoR).This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.