Browsing by Author "Bart, Zachary R."

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    Microcomputed Tomography Applications in Bone and Mineral Research
    (2013-09) Bart, Zachary R.; Wallace, Joseph M.
    Microcomputed tomography (μCT) has evolved as a development of simple X-ray imaging into an indispensable technique used in both laboratory research and clinical diagnostics. Commercially available systems are capable of creating images at sub-micrometer resolutions to map out the complex web of trabecular bone in small animals, and offer an accurate measurement of bone mineral density for patients at risk of osteoporotic fractures. This review describes the development of μCT, its ability to analyze bone, and how it can be used alongside other clinical and laboratory techniques. μCT offers a non-destructive alternative for imaging mineralized tissues with no required preparation and can also be utilized with living specimen to track skeletal development.
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    Multi-scale Analysis of Bone Chemistry, Morphology and Mechanics in the oim Model of Osteogenesis Imperfecta
    (2014-08) Bart, Zachary R.; Hammond, Max A.; Wallace, Joseph M.
    Osteogenesis imperfecta is a congenital disease commonly characterized by brittle bones and caused by mutations in the genes encoding Type I collagen, the single most abundant protein produced by the body. The oim model has a natural collagen mutation, converting its heterotrimeric structure (two α1 and one α2 chains) into α1 homotrimers. This mutation in collagen may impact formation of the mineral, creating a brittle bone phenotype in animals. Femurs from male wild type (WT) and homozygous (oim/oim) mice, all at 12 weeks of age, were assessed using assays at multiple length scales with minimal sample processing to ensure a near-physiological state. Atomic force microscopy (AFM) demonstrated detectable differences in the organization of collagen at the nanoscale that may partially contribute to alterations in material and structural behavior obtained through mechanical testing and reference point indentation (RPI). Changes in geometric and chemical structure obtained from µ-Computed Tomography and Raman spectroscopy indicate a smaller bone with reduced trabecular architecture and altered chemical composition. Decreased tissue material properties in oim/oim mice are likely driven by changes in collagen fibril structure, decreasing space available for mineral nucleation and growth, as supported by a reduction in mineral crystallinity. Multi-scale analyses of this nature offer much in assessing how molecular changes compound to create a degraded, brittle bone phenotype.
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    Raloxifene reduces skeletal fractures in an animal model of osteogenesis imperfecta
    (Elsevier, 2016) Berman, Alycia G.; Wallace, Joseph M.; Bart, Zachary R.; Allen, Matthew R.; Anatomy and Cell Biology, School of Medicine
    Osteogenesis imperfecta (OI) is a genetic disease of Type I collagen and collagen-associated pathways that results in brittle bone behavior characterized by fracture and reduced mechanical properties. Based on previous work in our laboratory showing that raloxifene (RAL) can significantly improve bone mechanical properties through non-cellular mechanisms, we hypothesized that raloxifene would improve the mechanical properties of OI bone. In experiment 1, tibiae from female wild type (WT) and homozygous oim mice were subjected to in vitro soaking in RAL followed by mechanical tests. RAL soaking resulted in significantly higher post-yield displacement (+75% in WT, +472% in oim; p<0.004), with no effect on ultimate load or stiffness, in both WT and oim animals. In experiment 2, eight-week old WT and oim male mice were treated for eight weeks with saline vehicle (VEH) or RAL. Endpoint measures included assessment of in vivo skeletal fractures, bone density/geometry and mechanical properties. In vivo skeletal fractures of the femora, assessed by micro CT imaging, were significantly lower in oim-RAL (20%) compared to oim-VEH (48%, p=0.047). RAL led to significantly higher DXA-based BMD (p<0.01) and CT-based trabecular BV/TV in both WT and oim animals compared to those treated with VEH. Fracture toughness of the femora was lower in oim mice compared to WT and improved with RAL in both genotypes. These results suggest that raloxifene reduces the incidence of fracture in this mouse model of oim. Furthermore, they suggest that raloxifene's effects may be the result of both cellular (increased bone mass) and non-cellular (presumably changes in hydration) mechanisms, raising the possibility of using raloxifene, or related compounds, as a new approach for treating bone fragility associated with OI.