{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:35:25Z","timestamp":1790998525735,"version":"4.1.0"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2014,1,13]],"date-time":"2014-01-13T00:00:00Z","timestamp":1389571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,6,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>\u2003<\/jats:title>\n                  <jats:p>The multiscale hierarchical structure of bone is naturally optimized to resist fractures. In osteogenesis imperfecta, or brittle bone disease, genetic mutations affect the quality and\/or quantity of collagen, dramatically increasing bone fracture risk. Here we reveal how the collagen defect results in bone fragility in a mouse model of osteogenesis imperfecta (oim), which has homotrimeric \u03b11(I) collagen. At the molecular level, we attribute the loss in toughness to a decrease in the stabilizing enzymatic cross-links and an increase in nonenzymatic cross-links, which may break prematurely, inhibiting plasticity. At the tissue level, high vascular canal density reduces the stable crack growth, and extensive woven bone limits the crack-deflection toughening during crack growth. This demonstrates how modifications at the bone molecular level have ramifications at larger length scales affecting the overall mechanical integrity of the bone; thus, treatment strategies have to address multiscale properties in order to regain bone toughness. In this regard, findings from the heterozygous oim bone, where defective as well as normal collagen are present, suggest that increasing the quantity of healthy collagen in these bones helps to recover toughness at the multiple length scales. \u00a9 2014 American Society for Bone and Mineral Research.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.2172","type":"journal-article","created":{"date-parts":[[2014,1,13]],"date-time":"2014-01-13T07:42:49Z","timestamp":1389598969000},"page":"1392-1401","source":"Crossref","is-referenced-by-count":131,"title":["How Tough Is Brittle Bone? Investigating Osteogenesis Imperfecta in Mouse Bone"],"prefix":"10.1093","volume":"29","author":[{"given":"Alessandra","family":"Carriero","sequence":"first","affiliation":[{"name":"Department of Materials Science and EngineeringUniversity of California BerkeleyBerkeleyCAUSA"},{"name":"Materials Sciences DivisionLawrence Berkeley National LaboratoryBerkeleyCAUSA"},{"name":"Department of BioengineeringImperial CollegeLondonUnited Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A","family":"Zimmermann","sequence":"additional","affiliation":[{"name":"Department of Materials Science and EngineeringUniversity of California BerkeleyBerkeleyCAUSA"},{"name":"Materials Sciences DivisionLawrence Berkeley National LaboratoryBerkeleyCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Paluszny","sequence":"additional","affiliation":[{"name":"Department of Earth Science and EngineeringImperial CollegeLondonUnited Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon Y","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic SurgeryUniversity of California San FranciscoSan FranciscoCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hrishikesh","family":"Bale","sequence":"additional","affiliation":[{"name":"Department of Materials Science and EngineeringUniversity of California BerkeleyBerkeleyCAUSA"},{"name":"Materials Sciences DivisionLawrence Berkeley National LaboratoryBerkeleyCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bjorn","family":"Busse","sequence":"additional","affiliation":[{"name":"Department of Materials Science and EngineeringUniversity of California BerkeleyBerkeleyCAUSA"},{"name":"Materials Sciences DivisionLawrence Berkeley National LaboratoryBerkeleyCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Alliston","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic SurgeryUniversity of California San FranciscoSan FranciscoCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galateia","family":"Kazakia","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical ImagingUniversity of California San FranciscoSan FranciscoCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert O","family":"Ritchie","sequence":"additional","affiliation":[{"name":"Department of Materials Science and EngineeringUniversity of California BerkeleyBerkeleyCAUSA"},{"name":"Materials Sciences DivisionLawrence Berkeley National LaboratoryBerkeleyCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra J","family":"Shefelbine","sequence":"additional","affiliation":[{"name":"Department of BioengineeringImperial CollegeLondonUnited Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,1,13]]},"reference":[{"key":"2024020318525607600_jbmr2172-bib-0001","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1038\/nrendo.2011.81","article-title":"New perspectives on osteogenesis imperfecta","volume":"7","author":"Forlino","year":"2011","journal-title":"Nat Rev Endocrinol."},{"key":"2024020318525607600_jbmr2172-bib-0002","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1097\/00003086-199710000-00034","article-title":"The Nicholas Andry Award-1996. 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