Relations Between Bone Quantity, Microarchitecture, and Collagen Cross‐links on Mechanics Following In Vivo Irradiation in Mice

ABSTRACT Humans are exposed to ionizing radiation via spaceflight or cancer radiotherapy, and exposure from radiotherapy is known to increase risk of skeletal fractures. Although irradiation can reduce trabecular bone mass, alter trabecular microarchitecture, and increase collagen cross‐linking, the...

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Autores principales:	Megan M Pendleton, Shannon R Emerzian, Saghi Sadoughi, Alfred Li, Jennifer W Liu, Simon Y Tang, Grace D O'Connell, Jean D Sibonga, Joshua S Alwood, Tony M Keaveny
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	AGING BONE MECHANICS FATIGUE IONIZING RADIATION RADIOTHERAPY SPACEFLIGHT Orthopedic surgery RD701-811 Diseases of the musculoskeletal system RC925-935
Acceso en línea:	https://doaj.org/article/58ae334e547645b9a909a70b799bcf1b
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spelling	oai:doaj.org-article:58ae334e547645b9a909a70b799bcf1b2021-11-04T12:00:57ZRelations Between Bone Quantity, Microarchitecture, and Collagen Cross‐links on Mechanics Following In Vivo Irradiation in Mice2473-403910.1002/jbm4.10545https://doaj.org/article/58ae334e547645b9a909a70b799bcf1b2021-11-01T00:00:00Zhttps://doi.org/10.1002/jbm4.10545https://doaj.org/toc/2473-4039ABSTRACT Humans are exposed to ionizing radiation via spaceflight or cancer radiotherapy, and exposure from radiotherapy is known to increase risk of skeletal fractures. Although irradiation can reduce trabecular bone mass, alter trabecular microarchitecture, and increase collagen cross‐linking, the relative contributions of these effects to any loss of mechanical integrity remain unclear. To provide insight, while addressing both the monotonic strength and cyclic‐loading fatigue life, we conducted total‐body, acute, gamma‐irradiation experiments on skeletally mature (17‐week‐old) C57BL/6J male mice (n = 84). Mice were administered doses of either 0 Gy (sham), 1 Gy (motivated by cumulative exposures from a Mars mission), or 5 Gy (motivated by clinical therapy regimens) with retrieval of the lumbar vertebrae at either a short‐term (11‐day) or long‐term (12‐week) time point after exposure. Micro‐computed tomography was used to assess trabecular and cortical quantity and architecture, biochemical composition assays were used to assess collagen quality, and mechanical testing was performed to evaluate vertebral compressive strength and fatigue life. At 11 days post‐exposure, 5 Gy irradiation significantly reduced trabecular mass (p < 0.001), altered microarchitecture (eg, connectivity density p < 0.001), and increased collagen cross‐links (p < 0.001). Despite these changes, vertebral strength (p = 0.745) and fatigue life (p = 0.332) remained unaltered. At 12 weeks after 5 Gy exposure, the trends in trabecular bone persisted; in addition, regardless of irradiation, cortical thickness (p < 0.01) and fatigue life (p < 0.01) decreased. These results demonstrate that the highly significant effects of 5 Gy total‐body irradiation on the trabecular bone morphology and collagen cross‐links did not translate into detectable effects on vertebral mechanics. The only mechanical deficits observed were associated with aging. Together, these vertebral results suggest that for spaceflight, irradiation alone will likely not alter failure properties, and for radiotherapy, more investigations that include post‐exposure time as a positive control and testing of both failure modalities are needed to determine the cause of increased fracture risk. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. This article has been contributed to by US Government employees and their work is in the public domain in the USA.Megan M PendletonShannon R EmerzianSaghi SadoughiAlfred LiJennifer W LiuSimon Y TangGrace D O'ConnellJean D SibongaJoshua S AlwoodTony M KeavenyWileyarticleAGINGBONE MECHANICSFATIGUEIONIZING RADIATIONRADIOTHERAPYSPACEFLIGHTOrthopedic surgeryRD701-811Diseases of the musculoskeletal systemRC925-935ENJBMR Plus, Vol 5, Iss 11, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	AGING BONE MECHANICS FATIGUE IONIZING RADIATION RADIOTHERAPY SPACEFLIGHT Orthopedic surgery RD701-811 Diseases of the musculoskeletal system RC925-935
spellingShingle	AGING BONE MECHANICS FATIGUE IONIZING RADIATION RADIOTHERAPY SPACEFLIGHT Orthopedic surgery RD701-811 Diseases of the musculoskeletal system RC925-935 Megan M Pendleton Shannon R Emerzian Saghi Sadoughi Alfred Li Jennifer W Liu Simon Y Tang Grace D O'Connell Jean D Sibonga Joshua S Alwood Tony M Keaveny Relations Between Bone Quantity, Microarchitecture, and Collagen Cross‐links on Mechanics Following In Vivo Irradiation in Mice
description	ABSTRACT Humans are exposed to ionizing radiation via spaceflight or cancer radiotherapy, and exposure from radiotherapy is known to increase risk of skeletal fractures. Although irradiation can reduce trabecular bone mass, alter trabecular microarchitecture, and increase collagen cross‐linking, the relative contributions of these effects to any loss of mechanical integrity remain unclear. To provide insight, while addressing both the monotonic strength and cyclic‐loading fatigue life, we conducted total‐body, acute, gamma‐irradiation experiments on skeletally mature (17‐week‐old) C57BL/6J male mice (n = 84). Mice were administered doses of either 0 Gy (sham), 1 Gy (motivated by cumulative exposures from a Mars mission), or 5 Gy (motivated by clinical therapy regimens) with retrieval of the lumbar vertebrae at either a short‐term (11‐day) or long‐term (12‐week) time point after exposure. Micro‐computed tomography was used to assess trabecular and cortical quantity and architecture, biochemical composition assays were used to assess collagen quality, and mechanical testing was performed to evaluate vertebral compressive strength and fatigue life. At 11 days post‐exposure, 5 Gy irradiation significantly reduced trabecular mass (p < 0.001), altered microarchitecture (eg, connectivity density p < 0.001), and increased collagen cross‐links (p < 0.001). Despite these changes, vertebral strength (p = 0.745) and fatigue life (p = 0.332) remained unaltered. At 12 weeks after 5 Gy exposure, the trends in trabecular bone persisted; in addition, regardless of irradiation, cortical thickness (p < 0.01) and fatigue life (p < 0.01) decreased. These results demonstrate that the highly significant effects of 5 Gy total‐body irradiation on the trabecular bone morphology and collagen cross‐links did not translate into detectable effects on vertebral mechanics. The only mechanical deficits observed were associated with aging. Together, these vertebral results suggest that for spaceflight, irradiation alone will likely not alter failure properties, and for radiotherapy, more investigations that include post‐exposure time as a positive control and testing of both failure modalities are needed to determine the cause of increased fracture risk. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. This article has been contributed to by US Government employees and their work is in the public domain in the USA.
format	article
author	Megan M Pendleton Shannon R Emerzian Saghi Sadoughi Alfred Li Jennifer W Liu Simon Y Tang Grace D O'Connell Jean D Sibonga Joshua S Alwood Tony M Keaveny
author_facet	Megan M Pendleton Shannon R Emerzian Saghi Sadoughi Alfred Li Jennifer W Liu Simon Y Tang Grace D O'Connell Jean D Sibonga Joshua S Alwood Tony M Keaveny
author_sort	Megan M Pendleton
title	Relations Between Bone Quantity, Microarchitecture, and Collagen Cross‐links on Mechanics Following In Vivo Irradiation in Mice
title_short	Relations Between Bone Quantity, Microarchitecture, and Collagen Cross‐links on Mechanics Following In Vivo Irradiation in Mice
title_full	Relations Between Bone Quantity, Microarchitecture, and Collagen Cross‐links on Mechanics Following In Vivo Irradiation in Mice
title_fullStr	Relations Between Bone Quantity, Microarchitecture, and Collagen Cross‐links on Mechanics Following In Vivo Irradiation in Mice
title_full_unstemmed	Relations Between Bone Quantity, Microarchitecture, and Collagen Cross‐links on Mechanics Following In Vivo Irradiation in Mice
title_sort	relations between bone quantity, microarchitecture, and collagen cross‐links on mechanics following in vivo irradiation in mice
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/58ae334e547645b9a909a70b799bcf1b
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_version_	1718444901105926144

Relations Between Bone Quantity, Microarchitecture, and Collagen Cross‐links on Mechanics Following In Vivo Irradiation in Mice

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