title: Altered lacunar and vascular porosity in osteogenesis imperfecta mouse bone as revealed by synchrotron tomography contributes to bone fragility.
abstract: Osteogenesis imperfecta (brittle bone disease) is caused by mutations in the collagen genes and results in skeletal fragility. Changes in bone porosity at the tissue level indicate changes in bone metabolism and alter bone mechanical integrity. We investigated the cortical bone tissue porosity of a mouse model of the disease, oim, in comparison to a wild type (WT-C57BL/6), and examined the influence of canal architecture on bone mechanical performance. High-resolution 3D representations of the posterior tibial and the lateral humeral mid-diaphysis of the bones were acquired for both mouse groups using synchrotron radiation-based computed tomography at a nominal resolution of 700nm. Volumetric morphometric indices were determined for cortical bone, canal network and osteocyte lacunae. The influence of canal porosity architecture on bone mechanics was investigated using microarchitectural finite element (μFE) models of the cortical bone. Bright-field microscopy of stained sections was used to determine if canals were vascular. Although total cortical porosity was comparable between oim and WT bone, oim bone had more numerous and more branched canals (p<0.001), and more osteocyte lacunae per unit volume compared to WT (p<0.001). Lacunae in oim were more spherical in shape compared to the ellipsoidal WT lacunae (p<0.001). Histology revealed blood vessels in all WT and oim canals. μFE models of cortical bone revealed that small and branched canals, typical of oim bone, increase the risk of bone failure. These results portray a state of compromised bone quality in oim bone at the tissue level, which contributes to its deficient mechanical properties.
authors.affiliation: Department of Bioengineering, Imperial College London, UK; Institute for Biomechanics, ETH Zürich, Switzerland. Electronic address: a.carriero@imperial.ac.uk.
authors.forename: A
authors.initials: A
authors.lastname: Carriero
authors.affiliation: Department of Bioengineering, Imperial College London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Doube
authors.affiliation: Department of Bioengineering, Imperial College London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Vogt
authors.affiliation: Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Busse
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Zustin
authors.affiliation: Institute for Biomechanics, ETH Zürich, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Levchuk
authors.affiliation: Institute for Biomechanics, ETH Zürich, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Schneider
authors.affiliation: Institute for Biomechanics, ETH Zürich, Switzerland.
authors.forename: R
authors.initials: R
authors.lastname: Müller
authors.affiliation: Department of Bioengineering, Imperial College London, UK.
authors.forename: S J
authors.initials: SJ
authors.lastname: Shefelbine
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000473:pathology*; D004195:Disease Models, Animal; D021621:Imaging, Three-Dimensional / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010013:Osteogenesis Imperfecta / Q000000981:diagnostic imaging* / Q000473:pathology*; D016062:Porosity; D014057:Tomography, X-Ray Computed / Q000379:methods*
keywords: Bone; Canal; Oim; Osteocyte lacunae; Osteogenesis imperfecta; Porosity