{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T14:50:12Z","timestamp":1787755812704,"version":"build-2784847793"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"16","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,8,20]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Researchers employ murine fracture models to study bone healing, but the temporal relationship between mouse and human fracture healing is poorly understood. The hypothesis of this study was that it was possible to quantify specific post-fracture time frames corresponding to the stages of endochondral ossification in both mice and humans.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Radiographs of mice and human femoral fractures treated with intramedullary stabilization were reviewed. The study included 330 human femoral fractures (OTA\/AO 32A, B, or C injuries) that ultimately healed without complications in patients aged 18 to 55 years and 309 surgically created midshaft femoral fractures in 3-month-old C57BL6\/J mice. Multiple orthopaedic surgeons assessed the radiographs using the Modified Radiographic Union Score for Tibia (mRUST). A 4-parameter log-logistic curve was fit to describe fracture healing over time, with 3 parameters allowed to vary: Y\n                      <jats:sub>\u221e<\/jats:sub>\n                      (mRUST score at time = \u221e), k (healing rate in [1\/log(time)]), and X\n                      <jats:sub>0.5<\/jats:sub>\n                      (time to half-healing).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      The values (and 95% confidence interval) for the mice were Y\n                      <jats:sub>\u221e<\/jats:sub>\n                      = 14.70 (14.54 to 14.87), k = 4.54\/log(days) (4.30 to 4.77), and X\n                      <jats:sub>0.5<\/jats:sub>\n                      = 11.77 days (11.56 to 11.98). For the humans, the values were Y\n                      <jats:sub>\u221e<\/jats:sub>\n                      = 16.78 (16.21 to 17.36), k = 1.37\/log(days) (1.28 to 1.45), and X\n                      <jats:sub>0.5<\/jats:sub>\n                      = 91 days (83 to 99). All parameters differed significantly between the mice and humans (p &lt; 0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Using mRUST scoring and mathematical modeling, we were able to quantify and compare the temporal progression of fracture healing in mice and humans.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Relevance:<\/jats:title>\n                    <jats:p>These data are relevant for designing and\/or interpreting fracture healing studies of mice and humans to promote rational translation of fracture research between species.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2106\/jbjs.24.01304","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T18:02:11Z","timestamp":1752170531000},"page":"1841-1847","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":3,"title":["Of Mice and Men: Temporal Comparison of Femoral Shaft Fracture Healing After Intramedullary Nailing"],"prefix":"10.2106","volume":"107","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1394-7378","authenticated-orcid":false,"given":"Yohan","family":"Jang","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4735-2818","authenticated-orcid":false,"given":"Luke A.","family":"Lopas","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3923-566X","authenticated-orcid":false,"given":"David P.","family":"Foley","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6354-7685","authenticated-orcid":false,"given":"Todd O.","family":"McKinley","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, Indiana"},{"name":"Indiana Center for Musculoskeletal Health (ICMH), Indiana University School of Medicine, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5750-2533","authenticated-orcid":false,"given":"Brian H.","family":"Mullis","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, Indiana"},{"name":"Indiana Center for Musculoskeletal Health (ICMH), Indiana University School of Medicine, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2639-4290","authenticated-orcid":false,"given":"Christopher D.","family":"Collier","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, Indiana"},{"name":"Indiana Center for Musculoskeletal Health (ICMH), Indiana University School of Medicine, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8312-6608","authenticated-orcid":false,"given":"Ziyue","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Health Data Science, School of Public Health, Indiana University, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7293-0088","authenticated-orcid":false,"given":"Melissa A.","family":"Kacena","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, Indiana"},{"name":"Indiana Center for Musculoskeletal Health (ICMH), Indiana University School of Medicine, Indianapolis, Indiana"},{"name":"Richard L. Roudebush VA Medical Center, Department of Veterans Affairs, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4182-3244","authenticated-orcid":false,"given":"Roman M.","family":"Natoli","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, Indiana"},{"name":"Indiana Center for Musculoskeletal Health (ICMH), Indiana University School of Medicine, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,7,10]]},"reference":[{"issue":"3","key":"bib1-20250822","first-page":"201","article-title":"A brief history of animal modeling","volume":"110","author":"Ericsson","year":"2013","journal-title":"Mo Med."},{"key":"bib2-20250822","doi-asserted-by":"crossref","first-page":"1","DOI":"10.22203\/eCM.v013a01","article-title":"Animal models for implant biomaterial research in bone: a review","volume":"13","author":"Pearce","year":"2007","journal-title":"Eur Cell Mater."},{"issue":"2","key":"bib3-20250822","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1007\/s11914-022-00770-7","article-title":"Clinical Assessments of Fracture Healing and Basic Science Correlates: Is There Room for Convergence?","volume":"21","author":"Lopas","year":"2023","journal-title":"Curr Osteoporos Rep."},{"issue":"7","key":"bib4-20250822","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1016\/j.injury.2020.04.011","article-title":"A comprehensive review of mouse diaphyseal femur fracture models","volume":"51","author":"Gunderson","year":"2020","journal-title":"Injury."},{"key":"bib5-20250822","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2022.911058","article-title":"Validation of the modified radiographic union score for tibia fractures (mRUST) in murine femoral fractures","volume":"13","author":"Alentado","year":"2022","journal-title":"Front Endocrinol (Lausanne)."},{"issue":"4","key":"bib6-20250822","doi-asserted-by":"crossref","first-page":"e143","DOI":"10.1097\/BOT.0000000000002518","article-title":"Reliability of the Modified Radiographic Union Score for Tibia Fractures (mRUST) for Femoral Shaft Fractures","volume":"37","author":"Schmidt","year":"2023","journal-title":"J Orthop Trauma."},{"key":"bib7-20250822","article-title":"Characterization of a reproducible model of fracture healing in mice using an open femoral osteotomy","volume":"12","author":"Collier","year":"2020","journal-title":"Bone Rep."},{"issue":"Suppl 1","key":"bib8-20250822","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1097\/BOT.0000000000001063","article-title":"Fracture and Dislocation Classification Compendium-2018","volume":"32","author":"Meinberg","year":"2018","journal-title":"J Orthop Trauma."},{"issue":"1","key":"bib9-20250822","doi-asserted-by":"crossref","first-page":"10254","DOI":"10.1038\/s41598-018-28228-w","article-title":"Knee Joint Tissues Effectively Separate Mixed Sized Molecules Delivered in a Single Bolus to the Heart","volume":"8","author":"Ngo","year":"2018","journal-title":"Sci Rep."},{"issue":"11","key":"bib11-20250822","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1097\/CORR.0000000000000446","article-title":"Early Maturity as the New Normal: A Century-long Study of Bone Age","volume":"476","author":"Boeyer","year":"2018","journal-title":"Clin Orthop Relat Res."},{"key":"bib13-20250822","doi-asserted-by":"crossref","first-page":"116978","DOI":"10.1016\/j.bone.2023.116978","article-title":"Intramedullary implant stability affects patterns of fracture healing in mice with morphologically different bone phenotypes","volume":"179","author":"Glatt","year":"2024","journal-title":"Bone."},{"issue":"6","key":"bib14-20250822","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1007\/s00223-008-9144-3","article-title":"Comparison of fracture healing among different inbred mouse strains","volume":"82","author":"Manigrasso","year":"2008","journal-title":"Calcif Tissue Int."},{"issue":"8","key":"bib15-20250822","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1359\/jbmr.080317","article-title":"Genetic variation in the patterns of skeletal progenitor cell differentiation and progression during endochondral bone formation affects the rate of fracture healing","volume":"23","author":"Jepsen","year":"2008","journal-title":"J Bone Miner Res."},{"issue":"11","key":"bib16-20250822","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1369\/jhc.6A6959.2006","article-title":"Three-dimensional reconstruction of fracture callus morphogenesis","volume":"54","author":"Gerstenfeld","year":"2006","journal-title":"J Histochem Cytochem."},{"issue":"8","key":"bib17-20250822","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1016\/j.jbiomech.2008.03.010","article-title":"A new technique for internal fixation of femoral fractures in mice: impact of stability on fracture healing","volume":"41","author":"Garcia","year":"2008","journal-title":"J Biomech."},{"issue":"1","key":"bib18-20250822","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.jbiomech.2005.10.034","article-title":"Development of a locking femur nail for mice","volume":"40","author":"Holstein","year":"2007","journal-title":"J Biomech."},{"issue":"1","key":"bib19-20250822","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.jss.2008.02.042","article-title":"Development of a stable closed femoral fracture model in mice","volume":"153","author":"Holstein","year":"2009","journal-title":"J Surg Res."},{"issue":"3","key":"bib20-20250822","first-page":"629","article-title":"Development of the radiographic union score for tibial fractures for the assessment of tibial fracture healing after intramedullary fixation","volume":"68","author":"Whelan","year":"2010","journal-title":"J Trauma."},{"issue":"11","key":"bib21-20250822","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1097\/BOT.0000000000000390","article-title":"Determination of Radiographic Healing: An Assessment of Consistency Using RUST and Modified RUST in Metadiaphyseal Fractures","volume":"29","author":"Litrenta","year":"2015","journal-title":"J Orthop Trauma."},{"issue":"2","key":"bib22-20250822","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.injury.2022.11.006","article-title":"Small residual fracture gaps delay time to union in length stable femur fractures treated with intrameduallary fixation","volume":"54","author":"Chang","year":"2023","journal-title":"Injury."},{"issue":"4","key":"bib23-20250822","doi-asserted-by":"crossref","first-page":"e154","DOI":"10.1097\/OI9.0000000000000154","article-title":"Weight-bearing status may influence rates of radiographic healing following reamed, intramedullary fixation of diaphyseal femur fractures","volume":"4","author":"Flanagan","year":"2021","journal-title":"OTA Int."},{"issue":"2","key":"bib24-20250822","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1097\/00005131-199702000-00003","article-title":"The treatment of femoral shaft fractures using intramedullary interlocked nails with and without intramedullary reaming: a preliminary report","volume":"11","author":"Tornetta","year":"1997","journal-title":"J Orthop Trauma."},{"issue":"9","key":"bib25-20250822","article-title":"A Scoring System for Predicting Nonunion After Intramedullary Nailing of Femoral Shaft Fractures","volume":"8","author":"Kraus","year":"2024","journal-title":"J Am Acad Orthop Surg Glob Res Rev."},{"issue":"6","key":"bib26-20250822","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1007\/s11999-016-4821-4","article-title":"Will My Tibial Fracture Heal? Predicting Nonunion at the Time of Definitive Fixation Based on Commonly Available Variables","volume":"474","author":"O\u2019Halloran","year":"2016","journal-title":"Clin Orthop Relat Res."},{"issue":"8","key":"bib27-20250822","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1080\/1354750X.2021.1985171","article-title":"Predicting fracture healing with blood biomarkers: the potential to assess patient risk of fracture nonunion","volume":"26","author":"Chitwood","year":"2021","journal-title":"Biomarkers."},{"issue":"4","key":"bib29-20250822","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1111\/j.1474-9726.2012.00832.x","article-title":"Rapamycin slows aging in mice","volume":"11","author":"Wilkinson","year":"2012","journal-title":"Aging Cell."},{"issue":"8039","key":"bib32-20250822","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/s41586-024-08189-z","article-title":"A multi-omic atlas of human embryonic skeletal development","volume":"635","author":"To","year":"2024","journal-title":"Nature."},{"issue":"6","key":"bib33-20250822","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1242\/dev.057547","article-title":"A landmark-free morphometric staging system for the mouse limb bud","volume":"138","author":"Boehm","year":"2011","journal-title":"Development."},{"issue":"3","key":"bib34-20250822","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/S8756-3282(03)00199-6","article-title":"Bone development and age-related bone loss in male C57BL\/6J mice","volume":"33","author":"Ferguson","year":"2003","journal-title":"Bone."},{"issue":"4","key":"bib35-20250822","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1210\/endrev\/bnae004","article-title":"Preclinical Rodent Models for Human Bone Disease, Including a Focus on Cortical Bone","volume":"45","author":"Koh","year":"2024","journal-title":"Endocr Rev."},{"issue":"6","key":"bib36-20250822","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1016\/S0736-0266(03)00099-8","article-title":"Noninvasive fatigue fracture model of the rat ulna","volume":"21","author":"Tami","year":"2003","journal-title":"J Orthop Res."},{"issue":"8","key":"bib37-20250822","doi-asserted-by":"crossref","first-page":"1878","DOI":"10.1016\/j.biomaterials.2012.09.024","article-title":"Solid-supported lipid bilayers to drive stem cell fate and tissue architecture using periosteum derived progenitor cells","volume":"34","author":"Evans","year":"2013","journal-title":"Biomaterials."},{"issue":"11","key":"bib38-20250822","doi-asserted-by":"crossref","first-page":"3523","DOI":"10.1007\/s11999-014-3829-x","article-title":"Fractures in geriatric mice show decreased callus expansion and bone volume","volume":"472","author":"Lopas","year":"2014","journal-title":"Clin Orthop Relat Res."},{"issue":"1","key":"bib39-20250822","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1002\/jor.23652","article-title":"Bone healing in an aged murine fracture model is characterized by sustained callus inflammation and decreased cell proliferation","volume":"36","author":"Hebb","year":"2018","journal-title":"J Orthop Res."},{"key":"bib40-20250822","doi-asserted-by":"crossref","DOI":"10.3389\/fbioe.2021.755964","article-title":"Sex Differences in Mesenchymal Stem Cell Therapy With Gelatin-Based Microribbon Hydrogels in a Murine Long Bone Critical-Size Defect Model","volume":"9","author":"Ueno","year":"2021","journal-title":"Front Bioeng Biotechnol."},{"issue":"Suppl 3","key":"bib41-20250822","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/j.injury.2021.03.063","article-title":"PTH1-34 improves devitalized allogenic bone graft healing in a murine femoral critical size defect","volume":"52","author":"Rocha","year":"2021","journal-title":"Injury."},{"key":"bib42-20250822","doi-asserted-by":"crossref","first-page":"345","DOI":"10.22203\/eCM.v041a22","article-title":"Healing of sub-critical femoral osteotomies in mice is unaffected by tacrolimus and deletion of recombination activating gene 1","volume":"41","author":"Liu","year":"2021","journal-title":"Eur Cell Mater."},{"issue":"97","key":"bib43-20250822","first-page":"52368","article-title":"A simple critical-sized femoral defect model in mice","volume":"52368","author":"Clough","year":"2015","journal-title":"J Vis Exp."},{"issue":"12","key":"bib44-20250822","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1089\/ten.tec.2017.0230","article-title":"* Calvarial Defects: Cell-Based Reconstructive Strategies in the Murine Model","volume":"23","author":"Murphy","year":"2017","journal-title":"Tissue Eng Part C Methods."},{"issue":"1","key":"bib45-20250822","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1097\/BPO.0000000000001068","article-title":"Evaluation of Fracture and Osteotomy Union in the Setting of Osteogenesis Imperfecta: Reliability of the Modified Radiographic Union Score for Tibial Fractures (RUST)","volume":"40","author":"Franzone","year":"2020","journal-title":"J Pediatr Orthop."}],"container-title":["Journal of Bone and Joint Surgery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.2106\/JBJS.24.01304","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T13:53:01Z","timestamp":1787752381000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.2106\/JBJS.24.01304"}},"subtitle":["Retrospective Observational Study of Modified Radiographic Union Scores for Tibia"],"short-title":[],"issued":{"date-parts":[[2025,7,10]]},"references-count":40,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2025]]}},"URL":"https:\/\/doi.org\/10.2106\/jbjs.24.01304","relation":{},"ISSN":["0021-9355","1535-1386"],"issn-type":[{"value":"0021-9355","type":"print"},{"value":"1535-1386","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,10]]}}}