{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T22:20:06Z","timestamp":1783549206508,"version":"3.55.0"},"reference-count":53,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100001279","name":"OREF","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001279","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bone"],"published-print":{"date-parts":[[2021,6]]},"DOI":"10.1016\/j.bone.2021.115906","type":"journal-article","created":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T23:02:14Z","timestamp":1614639734000},"page":"115906","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":16,"special_numbering":"C","title":["Type 1 diabetic Akita mice have low bone mass and impaired fracture healing"],"prefix":"10.1016","volume":"147","author":[{"given":"Pei","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer A.","family":"McKenzie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan G.","family":"Buettmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Migotsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Gardner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bone.2021.115906_bb0005","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.2353\/ajpath.2009.090148","article-title":"High levels of tumor necrosis factor-alpha contribute to accelerated loss of cartilage in diabetic fracture healing","volume":"175","author":"Alblowi","year":"2009","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.bone.2021.115906_bb0010","doi-asserted-by":"crossref","first-page":"2682","DOI":"10.2337\/db18-0340","article-title":"FOXO1 deletion reverses the effect of diabetic-induced impaired fracture healing","volume":"67","author":"Alharbi","year":"2018","journal-title":"Diabetes"},{"key":"10.1016\/j.bone.2021.115906_bb0015","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1210\/en.2006-1006","article-title":"Bone loss and increased bone adiposity in spontaneous and pharmacologically induced diabetic mice","volume":"148","author":"Botolin","year":"2007","journal-title":"Endocrinology"},{"key":"10.1016\/j.bone.2021.115906_bb0020","doi-asserted-by":"crossref","first-page":"9338","DOI":"10.1002\/jcp.27617","article-title":"Altered bone microarchitecture in a type 1 diabetes mouse model Ins2(Akita)","volume":"234","author":"Carvalho","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"10.1016\/j.bone.2021.115906_bb0025","doi-asserted-by":"crossref","first-page":"2034","DOI":"10.2337\/dc14-1140","article-title":"Type 1 diabetes through the life span: a position statement of the American Diabetes Association","volume":"37","author":"Chiang","year":"2014","journal-title":"Diabetes Care"},{"key":"10.1016\/j.bone.2021.115906_bb0030","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1002\/jcp.24177","article-title":"Both spontaneous Ins2(+\/\u2212) and streptozotocin-induced type I diabetes cause bone loss in young mice","volume":"228","author":"Coe","year":"2013","journal-title":"J. Cell. Physiol."},{"key":"10.1016\/j.bone.2021.115906_bb0035","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1542\/pir.29.11.374","article-title":"Type 1 diabetes mellitus in pediatrics","volume":"29","author":"Cooke","year":"2008","journal-title":"Pediatr Rev"},{"key":"10.1016\/j.bone.2021.115906_bb0040","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1002\/dmrr.537","article-title":"Influence of diabetic metabolic state on fracture healing in spontaneously diabetic rats","volume":"21","author":"Follak","year":"2005","journal-title":"Diabetes Metab. Res. Rev."},{"key":"10.1016\/j.bone.2021.115906_bb0045","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.bone.2011.06.018","article-title":"Novel functions for insulin in bone","volume":"50","author":"Fulzele","year":"2012","journal-title":"Bone"},{"key":"10.1016\/j.bone.2021.115906_bb0050","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1002\/jor.1100180118","article-title":"Biomechanical evaluation of early fracture healing in normal and diabetic rats","volume":"18","author":"Funk","year":"2000","journal-title":"J. Orthop. Res."},{"issue":"Suppl. 1","key":"10.1016\/j.bone.2021.115906_bb0055","doi-asserted-by":"crossref","first-page":"S88","DOI":"10.1016\/j.injury.2008.01.035","article-title":"Growth and differentiation factors for cartilage healing and repair","volume":"39","author":"Gaissmaier","year":"2008","journal-title":"Injury"},{"key":"10.1016\/j.bone.2021.115906_bb0060","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.bone.2005.04.039","article-title":"The effects of local insulin delivery on diabetic fracture healing","volume":"37","author":"Gandhi","year":"2005","journal-title":"Bone"},{"key":"10.1016\/j.bone.2021.115906_bb0065","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1002\/jor.1100030401","article-title":"Bone grafting: role of histocompatibility in transplantation","volume":"3","author":"Goldberg","year":"1985","journal-title":"J. Orthop. Res."},{"key":"10.1016\/j.bone.2021.115906_bb0070","doi-asserted-by":"crossref","first-page":"653","DOI":"10.3109\/17453674.2012.747054","article-title":"Patient-related risk factors for fracture-healing complications in the United Kingdom general practice research database","volume":"83","author":"Hernandez","year":"2012","journal-title":"Acta Orthop."},{"key":"10.1016\/j.bone.2021.115906_bb0075","doi-asserted-by":"crossref","first-page":"R137","DOI":"10.1530\/EJE-16-0652","article-title":"MECHANISMS IN ENDOCRINOLOGY: diabetes mellitus, a state of low bone turnover - a systematic review and meta-analysis","volume":"176","author":"Hygum","year":"2017","journal-title":"Eur. J. Endocrinol."},{"key":"10.1016\/j.bone.2021.115906_bb0080","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.ejphar.2013.05.020","article-title":"Zinc supplementation inhibits the increase in osteoclastogenesis and decrease in osteoblastogenesis in streptozotocin-induced diabetic rats","volume":"714","author":"Iitsuka","year":"2013","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.bone.2021.115906_bb0085","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.2337\/dc06-0440","article-title":"Prospective study of diabetes and risk of hip fracture: the Nurses\u2019 health study","volume":"29","author":"Janghorbani","year":"2006","journal-title":"Diabetes Care"},{"key":"10.1016\/j.bone.2021.115906_bb0090","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1093\/aje\/kwm106","article-title":"Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture","volume":"166","author":"Janghorbani","year":"2007","journal-title":"Am. J. Epidemiol."},{"key":"10.1016\/j.bone.2021.115906_bb0095","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1002\/jbmr.2539","article-title":"Establishing biomechanical mechanisms in mouse models: practical guidelines for systematically evaluating phenotypic changes in the diaphyses of long bones","volume":"30","author":"Jepsen","year":"2015","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.bone.2021.115906_bb0100","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/s11914-015-0286-8","article-title":"Diabetes and its effect on bone and fracture healing","volume":"13","author":"Jiao","year":"2015","journal-title":"Curr Osteoporos Rep"},{"key":"10.1016\/j.bone.2021.115906_bb0105","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.bone.2008.10.042","article-title":"Diabetes causes the accelerated loss of cartilage during fracture repair which is reversed by insulin treatment","volume":"44","author":"Kayal","year":"2009","journal-title":"Bone"},{"key":"10.1016\/j.bone.2021.115906_bb0110","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1002\/jbmr.59","article-title":"TNF-alpha mediates diabetes-enhanced chondrocyte apoptosis during fracture healing and stimulates chondrocyte apoptosis through FOXO1","volume":"25","author":"Kayal","year":"2010","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.bone.2021.115906_bb0115","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1359\/jbmr.070115","article-title":"Diminished bone formation during diabetic fracture healing is related to the premature resorption of cartilage associated with increased osteoclast activity","volume":"22","author":"Kayal","year":"2007","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.bone.2021.115906_bb0120","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1172\/JCI1842","article-title":"Mapping of murine diabetogenic gene mody on chromosome 7 at D7Mit258 and its involvement in pancreatic islet and beta cell development during the perinatal period","volume":"101","author":"Kayo","year":"1998","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.bone.2021.115906_bb0125","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.2337\/dc09-9032","article-title":"Hyperglycemic crises in adult patients with diabetes","volume":"32","author":"Kitabchi","year":"2009","journal-title":"Diabetes Care"},{"key":"10.1016\/j.bone.2021.115906_bb0130","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.bone.2017.02.014","article-title":"TNFalpha contributes to diabetes impaired angiogenesis in fracture healing","volume":"99","author":"Lim","year":"2017","journal-title":"Bone"},{"key":"10.1016\/j.bone.2021.115906_bb0135","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.bone.2017.07.017","article-title":"Exogenous hedgehog antagonist delays but does not prevent fracture healing in young mice","volume":"103","author":"Liu","year":"2017","journal-title":"Bone"},{"key":"10.1016\/j.bone.2021.115906_bb0140","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.bone.2019.03.026","article-title":"Deletion of FOXO1 in chondrocytes rescues the effect of diabetes on mechanical strength in fracture healing","volume":"123","author":"Lu","year":"2019","journal-title":"Bone"},{"key":"10.1016\/j.bone.2021.115906_bb0145","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s00418-007-0308-4","article-title":"Type I diabetic bone phenotype is location but not gender dependent","volume":"128","author":"Martin","year":"2007","journal-title":"Histochem. Cell Biol."},{"key":"10.1016\/j.bone.2021.115906_bb0150","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1002\/jcb.21573","article-title":"Understanding the pathology and mechanisms of type I diabetic bone loss","volume":"102","author":"McCabe","year":"2007","journal-title":"J. Cell. Biochem."},{"key":"10.1016\/j.bone.2021.115906_bb0155","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1002\/jor.24017","article-title":"Activation of hedgehog signaling by systemic agonist improves fracture healing in aged mice","volume":"37","author":"McKenzie","year":"2019","journal-title":"J. Orthop. Res."},{"key":"10.1016\/j.bone.2021.115906_bb0160","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1007\/s12575-009-9000-5","article-title":"Streptozotocin, type I diabetes severity and bone","volume":"11","author":"Motyl","year":"2009","journal-title":"Biol Proced Online"},{"key":"10.1016\/j.bone.2021.115906_bb0165","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1359\/jbmr.080713","article-title":"IGF-1 and IGF-binding proteins and bone mass, geometry, and strength: relation to metabolic control in adolescent girls with type 1 diabetes","volume":"23","author":"Moyer-Mileur","year":"2008","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.bone.2021.115906_bb0170","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/j.bone.2010.12.016","article-title":"Increasing duration of type 1 diabetes perturbs the strength-structure relationship and increases brittleness of bone","volume":"48","author":"Nyman","year":"2011","journal-title":"Bone"},{"key":"10.1016\/j.bone.2021.115906_bb0175","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1016\/j.bone.2008.07.246","article-title":"Molecular basis for affected cartilage formation and bone union in fracture healing of the streptozotocin-induced diabetic rat","volume":"43","author":"Ogasawara","year":"2008","journal-title":"Bone"},{"key":"10.1016\/j.bone.2021.115906_bb0180","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.afos.2019.11.003","article-title":"Effects of teriparatide on bone in autochthonous transgenic model mice for diabetes mellitus (Akita mice)","volume":"5","author":"Ohuchi","year":"2019","journal-title":"Osteoporos Sarcopenia"},{"key":"10.1016\/j.bone.2021.115906_bb0185","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1172\/JCI0214550","article-title":"Targeted disruption of the chop gene delays endoplasmic reticulum stress-mediated diabetes","volume":"109","author":"Oyadomari","year":"2002","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.bone.2021.115906_bb0190","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.bone.2015.07.012","article-title":"Bone\u2019s responses to mechanical loading are impaired in type 1 diabetes","volume":"81","author":"Parajuli","year":"2015","journal-title":"Bone"},{"key":"10.1016\/j.bone.2021.115906_bb0195","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1172\/JCI0215020","article-title":"Proteotoxicity in the endoplasmic reticulum: lessons from the Akita diabetic mouse","volume":"109","author":"Ron","year":"2002","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.bone.2021.115906_bb0200","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.joca.2011.02.004","article-title":"Expression and function of the insulin receptor in normal and osteoarthritic human chondrocytes: modulation of anabolic gene expression, glucose transport and GLUT-1 content by insulin","volume":"19","author":"Rosa","year":"2011","journal-title":"Osteoarthr. Cartil."},{"key":"10.1016\/j.bone.2021.115906_bb0205","doi-asserted-by":"crossref","first-page":"2485","DOI":"10.1073\/pnas.74.6.2485","article-title":"Studies of streptozotocin-induced insulitis and diabetes","volume":"74","author":"Rossini","year":"1977","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.bone.2021.115906_bb0210","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1056\/NEJMp078030","article-title":"Diabetes treatment--bridging the divide","volume":"356","author":"Rother","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.bone.2021.115906_bb0215","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1007\/s00198-006-0155-5","article-title":"Role of collagen enzymatic and glycation induced cross-links as a determinant of bone quality in spontaneously diabetic WBN\/Kob rats","volume":"17","author":"Saito","year":"2006","journal-title":"Osteoporos. Int."},{"key":"10.1016\/j.bone.2021.115906_bb0220","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1016\/S0140-6736(14)60886-2","article-title":"The global implications of diabetes and cancer","volume":"383","author":"Shi","year":"2014","journal-title":"Lancet"},{"key":"10.1016\/j.bone.2021.115906_bb0225","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1359\/jbmr.090316","article-title":"Type 1 diabetes in young rats leads to progressive trabecular bone loss, cessation of cortical bone growth, and diminished whole bone strength and fatigue life","volume":"24","author":"Silva","year":"2009","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.bone.2021.115906_bb0230","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1002\/jbmr.3648","article-title":"Effects of high-fat diet and body mass on bone morphology and mechanical properties in 1100 advanced intercross mice","volume":"34","author":"Silva","year":"2019","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.bone.2021.115906_bb0235","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1677\/joe.0.1340485","article-title":"The effects of systemic insulin, insulin-like growth factor-I and growth hormone on bone growth and turnover in spontaneously diabetic BB rats","volume":"134","author":"Verhaeghe","year":"1992","journal-title":"J. Endocrinol."},{"key":"10.1016\/j.bone.2021.115906_bb0240","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/s00198-006-0253-4","article-title":"Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes--a meta-analysis","volume":"18","author":"Vestergaard","year":"2007","journal-title":"Osteoporos. Int."},{"key":"10.1016\/j.bone.2021.115906_bb0245","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1172\/JCI4431","article-title":"A mutation in the insulin 2 gene induces diabetes with severe pancreatic beta-cell dysfunction in the Mody mouse","volume":"103","author":"Wang","year":"1999","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.bone.2021.115906_bb0250","doi-asserted-by":"crossref","first-page":"50","DOI":"10.2337\/diab.47.1.50","article-title":"GLUT2 in pancreatic islets: crucial target molecule in diabetes induced with multiple low doses of streptozotocin in mice","volume":"47","author":"Wang","year":"1998","journal-title":"Diabetes"},{"key":"10.1016\/j.bone.2021.115906_bb0255","first-page":"E200","article-title":"Influence of experimental diabetes and insulin on matrix-induced cartilage and bone differentiation","volume":"238","author":"Weiss","year":"1980","journal-title":"Am. J. Phys."},{"key":"10.1016\/j.bone.2021.115906_bb0260","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1097\/01.blo.0000084402.53464.90","article-title":"Open ankle fractures in patients with diabetes mellitus","author":"White","year":"2003","journal-title":"Clin Orthop Relat Res."},{"key":"10.1016\/j.bone.2021.115906_bb0265","doi-asserted-by":"crossref","first-page":"887","DOI":"10.2337\/diab.46.5.887","article-title":"A novel locus, Mody4, distal to D7Mit189 on chromosome 7 determines early-onset NIDDM in nonobese C57BL\/6 (Akita) mutant mice","volume":"46","author":"Yoshioka","year":"1997","journal-title":"Diabetes"}],"container-title":["Bone"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S8756328221000685?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S8756328221000685?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T17:54:30Z","timestamp":1757613270000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S8756328221000685"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6]]},"references-count":53,"alternative-id":["S8756328221000685"],"URL":"https:\/\/doi.org\/10.1016\/j.bone.2021.115906","relation":{},"ISSN":["8756-3282"],"issn-type":[{"value":"8756-3282","type":"print"}],"subject":[],"published":{"date-parts":[[2021,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Type 1 diabetic Akita mice have low bone mass and impaired fracture healing","name":"articletitle","label":"Article Title"},{"value":"Bone","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bone.2021.115906","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"115906"}}