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Although irradiation can reduce trabecular bone mass, alter trabecular microarchitecture, and increase collagen cross\u2010linking, 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\u2010loading fatigue life, we conducted total\u2010body, acute, gamma\u2010irradiation experiments on skeletally mature (17\u2010week\u2010old) C57BL\/6J male mice (<jats:italic>n<\/jats:italic>\u00a0=\u00a084). Mice were administered doses of either 0\u2009Gy (sham), 1\u2009Gy (motivated by cumulative exposures from a Mars mission), or 5\u2009Gy (motivated by clinical therapy regimens) with retrieval of the lumbar vertebrae at either a short\u2010term (11\u2010day) or long\u2010term (12\u2010week) time point after exposure. Micro\u2010computed 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\u2009days post\u2010exposure, 5\u2009Gy irradiation significantly reduced trabecular mass (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), altered microarchitecture (eg, connectivity density <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), and increased collagen cross\u2010links (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Despite these changes, vertebral strength (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.745) and fatigue life (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.332) remained unaltered. At 12\u2009weeks after 5\u2009Gy exposure, the trends in trabecular bone persisted; in addition, regardless of irradiation, cortical thickness (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01) and fatigue life (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01) decreased. These results demonstrate that the highly significant effects of 5\u2009Gy total\u2010body irradiation on the trabecular bone morphology and collagen cross\u2010links 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\u2010exposure time as a positive control and testing of both failure modalities are needed to determine the cause of increased fracture risk. \u00a9 2021 The Authors. <jats:italic>JBMR Plus<\/jats:italic> 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.<\/jats:p>","DOI":"10.1002\/jbm4.10545","type":"journal-article","created":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T13:06:10Z","timestamp":1630415170000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Relations Between Bone Quantity, Microarchitecture, and Collagen Cross\u2010links on Mechanics Following In Vivo Irradiation in Mice"],"prefix":"10.1093","volume":"5","author":[{"given":"Megan M","family":"Pendleton","sequence":"first","affiliation":[{"name":"Department of Mechanical Engineering University of California  Berkeley CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon R","family":"Emerzian","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering University of California  Berkeley CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saghi","family":"Sadoughi","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering University of California  Berkeley CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred","family":"Li","sequence":"additional","affiliation":[{"name":"Endocrine Research Unit University of California and Veteran Affairs Medical Center  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer W","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Washington University  St. Louis MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon Y","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Washington University  St. Louis MO USA"},{"name":"Department of Biomedical Engineering Washington University  St. Louis MO USA"},{"name":"Department of Mechanical Engineering and Materials Science Washington University  St. Louis MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace D","family":"O'Connell","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering University of California  Berkeley CA USA"},{"name":"Department of Orthopaedic Surgery University of California  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean D","family":"Sibonga","sequence":"additional","affiliation":[{"name":"Biomedical Research and Environmental Sciences Division NASA Johnson Space Center  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6702-6673","authenticated-orcid":false,"given":"Joshua S","family":"Alwood","sequence":"additional","affiliation":[{"name":"Space Biosciences Division NASA Ames Research Center  Moffett Field CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony M","family":"Keaveny","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering University of California  Berkeley CA USA"},{"name":"Department of Bioengineering University of California  Berkeley CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,9,26]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.21873\/invivo.12356"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.32807"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2019.09.012"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.2030"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1259\/bjr.20160885"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2016.01.006"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.3857\/roj.2014.32.4.213"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2009.05.059"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.294.20.2587"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.25994"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01078.2005"},{"issue":"1","key":"e_1_2_7_13_1","first-page":"14","article-title":"Space radiation and bone loss","volume":"25","author":"Willey JS","year":"2011","journal-title":"Gravit Space Biol Bull."},{"key":"e_1_2_7_14_1","unstructured":"National Council on Radiation Protection and Measurements.Radiation protection guidance for activities in low\u2010earth orbit: recommendations of the National Council on Radiation Protection and Measurements. 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