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

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 t...

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Main Authors:	Karunaratne, A., Xi, L., Bentley, L., Sykes, D., Boyde, A., Esapa, C.T., Terrill, N.J., Brown, S.D.M., Cox, R.D., Thakker, R.V., Gupta, H.S.
Format:	Online
Language:	English
Published:	Elsevier Science 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4764652/

id	pubmed-4764652
recordtype	oai_dc
spelling	pubmed-47646522016-03-08 Multiscale alterations in bone matrix quality increased fragility in steroid induced osteoporosis Karunaratne, A. Xi, L. Bentley, L. Sykes, D. Boyde, A. Esapa, C.T. Terrill, N.J. Brown, S.D.M. Cox, R.D. Thakker, R.V. Gupta, H.S. Original Full Length Article 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. Elsevier Science 2016-03 /pmc/articles/PMC4764652/ /pubmed/26657825 http://dx.doi.org/10.1016/j.bone.2015.11.019 Text en © 2015 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Karunaratne, A. Xi, L. Bentley, L. Sykes, D. Boyde, A. Esapa, C.T. Terrill, N.J. Brown, S.D.M. Cox, R.D. Thakker, R.V. Gupta, H.S.
spellingShingle	Karunaratne, A. Xi, L. Bentley, L. Sykes, D. Boyde, A. Esapa, C.T. Terrill, N.J. Brown, S.D.M. Cox, R.D. Thakker, R.V. Gupta, H.S. Multiscale alterations in bone matrix quality increased fragility in steroid induced osteoporosis
author_facet	Karunaratne, A. Xi, L. Bentley, L. Sykes, D. Boyde, A. Esapa, C.T. Terrill, N.J. Brown, S.D.M. Cox, R.D. Thakker, R.V. Gupta, H.S.
author_sort	Karunaratne, A.
title	Multiscale alterations in bone matrix quality increased fragility in steroid induced osteoporosis
title_short	Multiscale alterations in bone matrix quality increased fragility in steroid induced osteoporosis
title_full	Multiscale alterations in bone matrix quality increased fragility in steroid induced osteoporosis
title_fullStr	Multiscale alterations in bone matrix quality increased fragility in steroid induced osteoporosis
title_full_unstemmed	Multiscale alterations in bone matrix quality increased fragility in steroid induced osteoporosis
title_sort	multiscale alterations in bone matrix quality increased fragility in steroid induced osteoporosis
description	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.
publisher	Elsevier Science
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4764652/
_version_	1613542375664123904

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

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