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Multiscale alterations in bone matrix quality increased fragility in steroid induced osteoporosis

DOI: 10.1016/j.bone.2015.11.019 DOI Help
PMID: 26657825 PMID Help

Authors: A. Karunaratne (Queen Mary University of London) , L. Xi (Queen Mary University of London) , L. Bentley (Harwell Science and Innovation Campus) , D. Sykes (The Natural History Museum) , A. Boyde (Queen Mary University of London) , C. T. Esapa (Harwell Science and Innovation Campus) , N. J. Terrill (Diamond Light Source) , S. D. M. Brown (Harwell Science and Innovation Campus) , R. D. Cox (Harwell Science and Innovation Campus) , R. V. Thakker (University of Oxford) , H. S. Gupta (Queen Mary, University of London)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Bone

State: Published (Approved)
Published: December 2015

Open Access Open Access

Abstract: A serious adverse clinical effect of glucocorticoid steroid treatment is secondary osteoporosis, enhancing fracture risk in bone. This rapid increase in bone fracture risk is largely independent of bone loss (quantity), and must therefore arise from degradation of the quality of the bone matrix at the micro- and nanoscale. However, we lack an understanding of both the specific alterations in bone quality n steroid-induced osteoporosis as well as the mechanistic effects of these changes. Here we demonstrate alterations in the nanostructural parameters of the mineralized fibrillar collagen matrix, which affect bone quality, and develop a model linking these to increased fracture risk in glucocorticoid induced osteoporosis. Using a mouse model with an N-ethyl-N-nitrosourea (ENU)-induced corticotrophin releasing hormone promoter mutation (Crh-120/+) that developed hypercorticosteronaemia and osteoporosis, we utilized in situ mechanical testing with small angle X-ray diffraction, synchrotron micro-computed tomography and quantitative backscattered electron imaging to link altered nano- and microscale deformation mechanisms in the bone matrix to abnormal macroscopic mechanics. We measure the deformation of the mineralized collagen fibrils, and the nano-mechanical parameters including effective fibril modulus and fibril to tissue strain ratio. A significant reduction (51%) of fibril modulus was found in Crh-120/+ mice. We also find a much larger fibril strain/tissue strain ratio in Crh-120/+ mice (~ 1.5) compared to the wild-type mice (~ 0.5), indicative of a lowered mechanical competence at the nanoscale. Synchrotron microCT show a disruption of intracortical architecture, possibly linked to osteocytic osteolysis. These findings provide a clear quantitative demonstration of how bone quality changes increase macroscopic fragility in secondary osteoporosis.

Journal Keywords: Glucocorticoid Induced Osteoporosis; In Situ Micro Mechanical Testing; Synchrotron Small Angle X-Ray Scattering; Nanoscale Deformation Mechanisms; Multiscale Imaging

Subject Areas: Biology and Bio-materials

Instruments: I13-2-Diamond Manchester Imaging , I22-Small angle scattering & Diffraction