Browsing by Subject "cortical bone"

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    The fracture toughness of small animal cortical bone measured using arc-shaped tension specimens: Effects of bisphosphonate and deproteinization treatments
    (Elsevier, 2017-12) Hunckler, Michael D.; Chu, Ethan D.; Baumann, Andrew P.; Curtis, Tyler E.; Ravosa, Matthew J.; Allen, Matthew R.; Roeder, Ryan K.; Department of Anatomy and Cell Biology, School of Medicine
    Small animal models, and especially transgenic models, have become widespread in the study of bone mechanobiology and metabolic bone disease, but test methods for measuring fracture toughness on multiple replicates or at multiple locations within a single small animal bone are lacking. Therefore, the objective of this study was to develop a method to measure cortical bone fracture toughness in multiple specimens and locations along the diaphysis of small animal bones. Arc-shaped tension specimens were prepared from the mid-diaphysis of rabbit ulnae and loaded to failure to measure the radial fracture toughness in multiple replicates per bone. The test specimen dimensions, crack length, and maximum load met requirements for measuring the plane strain fracture toughness. Experimental groups included a control group, bisphosphonate treatment group, and an ex vivo deproteinization treatment following bisphosphonate treatment (5 rabbits/group and 15 specimens/group). The fracture toughness of ulnar cortical bone from rabbits treated with zoledronic acid for six months exhibited no difference compared with the control group. Partially deproteinized specimens exhibited significantly lower fracture toughness compared with both the control and bisphosphonate treatment groups. The deproteinization treatment increased tissue mineral density (TMD) and resulted in a negative linear correlation between the measured fracture toughness and TMD. Fracture toughness measurements were repeatable with a coefficient of variation of 12–16% within experimental groups. Retrospective power analysis of the control and deproteinization treatment groups indicated a minimum detectable difference of 0.1 MPa·m1/2. Therefore, the overall results of this study suggest that arc-shaped tension specimens offer an advantageous new method for measuring the fracture toughness in small animal bones.
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    In vivo UTE-MRI reveals positive effects of raloxifene on skeletal bound water in skeletally mature beagle dogs
    (Full citation forthcoming. Accepted manuscript., 2015) Allen, Matthew R.; Territo, Paul R.; Lin, Chen; Persohn, Scott; Jiang, Lei; Riley, Amanda A.; McCarthy, Brian P.; Newman, Christopher L.; Burr, David B.; Hutchins, Gary D.
    Raloxifene positively affects mechanical properties of the bone matrix in part through modification of skeletal bound water. The goal of this study was to determine if raloxifene induced alterations in skeletal hydration could be measured in vivo using ultra-short echotime magnetic resonance imaging (UTE-MRI). Twelve skeletally mature female beagle dogs (n=6/group) were treated for 6 months with oral doses of saline vehicle (VEH, 1 ml/kg/day) or raloxifene (RAL, 0.5 mg/kg/day). Following six months of treatment, all animals underwent in vivo UTE-MRI of the proximal tibial cortical bone. UTE-MRI signal intensity versus echotime curves were analyzed by fitting a double exponential to determine the short and long relaxation times of water with the bone (dependent estimations of bound and free water, respectively). Raloxifene-treated animals had significantly higher bound water (+14%; p = 0.05) and lower free water (-20%) compared to vehicle-treated animals. These data provide the first evidence that drug-induced changes in skeletal hydration can be non-invasively assessed using UTE-MRI.
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    Pyk2: Potential Regulator of Post Menopausal Bone Loss
    (2013) Largura, Heather; Liu, Sean S.; Stewart, Kelton T.; Baldwin, James Joseph, 1925-; Allen, Matthew R.; Bruzzaniti, Angela
    Osteoporosis is a pathologic condition of bone, commonly found in post-menopausal women, which occurs from an imbalance between bone formation and resorption. Following menopause, the bone resorbing activity of osteoclasts exceeds bone formation by osteoblasts, resulting in decreased trabecular and cortical bone and a subsequent decrease in bone mass. Reduced bone mass increases the risk of pathologic fracture of bones. Due to adverse effects associated with current treatment protocols for bone loss, alternative treatment modalities with reduced adverse effects are needed. Estrogen plays a role in maintaining balance in the bone remodeling cycle by controlling remodeling activation, osteoblast and osteoclast numbers, and their respective effectiveness in formation and resorption. With declining estrogen levels, this elegantly balanced interaction is altered and bone resorption exceeds bone formation, resulting in bone loss and increased bone fragility. Pyk2 is a protein tyrosine kinase that plays an important role in regulating bone resorption by osteoclasts, as well as osteoblast proliferation and differentiation. Deletion of the Pyk2 gene in mice leads to an increase in bone mass, in part due to dysfunctional osteoclast and osteoblast activity. In this study, we examined the role of Pyk2 in the effects of estrogen on bone mass. We used wild type (WT) and Pyk2 knock-out (KO) mice that had been ovariectomized (OVX) and treated with or without estrogen (E2)-releasing pellets. Control mice included sham OVX surgery receiving placebo pellet. We found that deletion of Pyk2 conferred increased bone mass in sham, OVX and OVX+E2 mice. In addition, Pyk2 KO mice supplemented with 17estradiol exhibited a marked increase in bone volume/trabecular volume, trabecular number, and trabecular thickness, but not cortical bone parameters compared to WT mice. Results of this study provide evidence for the role of Pyk2 in the effects of estrogen on bone mass. Understanding the role of Pyk2 in bone could lead to the development of new pharmaceutical targets for the treatment of bone loss associated with osteoporosis.  
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    Simultaneous visualisation of calcified bone microstructure and intracortical vasculature using synchrotron X-ray phase contrast-enhanced tomography
    (Nature Publishing group, 2017-10-16) Núñez, Juan A.; Goring, Alice; Hesse, Eric; Thurner, Philipp J.; Schneider, Philipp; Clarkin, Claire E.; Anatomy and Cell Biology, School of Medicine
    3D imaging of the bone vasculature is of key importance in the understanding of skeletal disease. As blood vessels in bone are deeply encased in the calcified matrix, imaging techniques that are applicable to soft tissues are generally difficult or impossible to apply to the skeleton. While canals in cortical bone can readily be identified and characterised in X-ray computed tomographic data in 3D, the soft tissue comprising blood vessels that are putatively contained within the canal structures does not provide sufficient image contrast necessary for image segmentation. Here, we report an approach that allows for rapid, simultaneous visualisation of calcified bone tissue and the vasculature within the calcified bone matrix. Using synchrotron X-ray phase contrast-enhanced tomography we show exemplar data with intracortical capillaries uncovered at sub-micrometre level without the need for any staining or contrast agent. Using the tibiofibular junction of 15 week-old C57BL/6 mice post mortem, we show the bone cortical porosity simultaneously along with the soft tissue comprising the vasculature. Validation with histology confirms that we can resolve individual capillaries. This imaging approach could be easily applied to other skeletal sites and transgenic models, and could improve our understanding of the role the vasculature plays in bone disease.