Bone matrix development in steroid-induced osteoporosis is associated with a consistently reduced fibrillar stiffness linked to altered bone mineral quality

DOI: 10.1016/j.actbio.2018.05.053

Authors: L. Xi (Queen Mary University of London; North Carolina State University) , P. De Falco (Queen Mary University of London) , E. Barbieri (Queen Mary University of London; Yokohama Institute for Earth Sciences) , A. Karunaratne (University of Moratuwa) , L. Bentley (MRC Mammalian Genetics Unit and Mary Lyon Centre) , C. T. Esapa (MRC Mammalian Genetics Unit and Mary Lyon Centre; University of Oxford) , N. J. Terrill (Diamond Light Source) , S. D. M. Brown (MRC Mammalian Genetics Unit and Mary Lyon Centre) , R. D. Cox (MRC Mammalian Genetics Unit and Mary Lyon Centre) , G. R. Davis (Queen Mary University of London) , N. M. Pugno (University of Trento; Queen Mary University of London; Italian Space Agency) , R. V. Thakker (MRC Mammalian Genetics Unit and Mary Lyon Centre; University of Oxford) , H. S. Gupta (Queen Mary, University of London)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Acta Biomaterialia

State: Published (Approved)
Published: June 2018
Diamond Proposal Number(s): 9893 , 11806 , 12483

Abstract: Glucocorticoid-induced osteoporosis (GIOP) is a major secondary form of osteoporosis, with the fracture risk significantly elevated – at similar levels of bone mineral density – in patients taking glucocorticoids compared with non-users. The adverse bone structural changes at multiple hierarchical levels in GIOP, and their mechanistic consequences leading to reduced load-bearing capacity, are not clearly understood. Here we combine experimental X-ray nanoscale mechanical imaging with analytical modelling of the bone matrix mechanics to determine mechanisms causing bone material quality deterioration during development of GIOP. In situ synchrotron small-angle X-ray diffraction combined with tensile testing was used to measure nanoscale deformation mechanisms in a murine model of GIOP, due to a corticotrophin-releasing hormone promoter mutation, at multiple ages (8-, 12-, 24- and 36 weeks), complemented by quantitative micro-computed tomography and backscattered electron imaging to determine mineral concentrations. We develop a two-level hierarchical model of the bone matrix (mineralized fibril and lamella) to predict fibrillar mechanical response as a function of architectural parameters of the mineralized matrix. The fibrillar elastic modulus of GIOP-bone is lower than healthy bone throughout development, and nearly constant in time, in contrast to the progressively increasing stiffness in healthy bone. The lower mineral platelet aspect ratio value for GIOP compared to healthy bone in the multiscale model can explain the fibrillar deformation. Consistent with this result, independent measurement of mineral platelet lengths from wide-angle X-ray diffraction finds a shorter mineral platelet length in GIOP. Our results show how lowered mineralization combined with altered mineral nanostructure in GIOP leads to lowered mechanical competence.

Journal Keywords: Glucocorticoid induced osteoporosis; Synchrotron X-ray nanomechanical imaging; Nanoscale deformation mechanisms; Multiscale mechanical modelling

Subject Areas: Biology and Bio-materials


Instruments: I22-Small angle scattering & Diffraction

Documents:
1-s2.0-S1742706118303325-main.pdf