{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T02:24:22Z","timestamp":1783995862438,"version":"3.55.0"},"reference-count":65,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,3]]},"DOI":"10.1097\/bot.0000000000000489","type":"journal-article","created":{"date-parts":[[2015,11,25]],"date-time":"2015-11-25T16:38:12Z","timestamp":1448469492000},"page":"104-112","source":"Crossref","is-referenced-by-count":27,"title":["Is There an Impact of Concomitant Injuries and Timing of Fixation of Major Fractures on Fracture Healing? A Focused Review of Clinical and Experimental Evidence"],"prefix":"10.1097","volume":"30","author":[{"given":"Frank","family":"Hildebrand","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martijn","family":"van Griensven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Huber-Lang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie B.","family":"Flohe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hagen","family":"Andruszkow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingo","family":"Marzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Christoph","family":"Pape","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-2-20210212","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/j.injury.2004.03.004","article-title":". Damage control: extremities.","volume":"35","author":"Hildebrand","year":"2004","journal-title":"Injury"},{"key":"R2-2-20210212","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1016\/S0140-6736(12)60991-X","article-title":". Advances and future directions for management of trauma patients with musculoskeletal injuries.","volume":"380","author":"Balogh","year":"2012","journal-title":"Lancet"},{"key":"R3-2-20210212","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.injury.2006.08.055","article-title":"Health economics: a cost analysis of treatment of persistent fracture non-unions using bone morphogenetic protein-7.","volume":"38","author":"Dahabreh","year":"2007","journal-title":"Injury"},{"key":"R5-2-20210212","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1002\/jor.20264","article-title":". Ischemia leads to delayed union during fracture healing: a mouse model.","volume":"25","author":"Lu","year":"2007","journal-title":"J Orthop Res"},{"key":"R6-2-20210212","first-page":"1384","article-title":". Prognostic significance of lower extremity long bone fractures after automobile versus pedestrian injuries.","volume":"67","author":"Hannon","year":"2009","journal-title":"J Trauma"},{"key":"R7-2-20210212","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.injury.2014.12.018","article-title":". Individual risk factors for deep infection and compromised fracture healing after intramedullary nailing of tibial shaft fractures: a single centre experience of 480 patients.","volume":"46","author":"Metsemakers","year":"2015","journal-title":"Injury"},{"key":"R8-2-20210212","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1007\/s004020000252","article-title":". The influence of fracture etiology and type on fracture healing: a review of 104 consecutive tibial shaft fractures.","volume":"121","author":"Karladani","year":"2001","journal-title":"Arch Orthop Trauma Surg"},{"key":"R9-2-20210212","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1080\/17453670610046037","article-title":". Compression plating versus intramedullary nailing of humeral shaft fracturesa meta-analysis.","volume":"77","author":"Bhandari","year":"2006","journal-title":"Acta Orthop"},{"key":"R10-2-20210212","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/nrrheum.2012.1","article-title":"Fracture healing under healthy and inflammatory conditions.","volume":"8","author":"Claes","year":"2012","journal-title":"Nat Rev Rheumatol"},{"key":"R11-2-20210212","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1189\/jlb.0606365","article-title":". Roles of neutrophil-mediated inflammatory response in the bony repair of injured growth plate cartilage in young rats.","volume":"80","author":"Chung","year":"2006","journal-title":"J Leukoc Biol"},{"key":"R12-2-20210212","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1097\/TA.0b013e318278956d","article-title":". Systemic inflammation induced by a thoracic trauma alters the cellular composition of the early fracture callus.","volume":"74","author":"Recknagel","year":"2013","journal-title":"J Trauma Acute Care Surg"},{"key":"R13-2-20210212","doi-asserted-by":"crossref","first-page":"462","DOI":"10.3109\/17453679408995493","article-title":". Inflammatory cells in normal human fracture healing.","volume":"65","author":"Andrew","year":"1994","journal-title":"Acta Orthop Scand"},{"key":"R14-2-20210212","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1189\/jlb.0810446","article-title":". Systemic inflammation and fracture healing.","volume":"89","author":"Bastian","year":"2011","journal-title":"J Leukoc Biol"},{"key":"R15-2-20210212","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1160\/TH08-11-0720","article-title":"Neutrophils launch monocyte extravasation by release of granule proteins.","volume":"102","author":"Soehnlein","year":"2009","journal-title":"Thromb Haemost"},{"key":"R16-2-20210212","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1189\/jlb.69.5.698","article-title":". Phenotypic and functional change of cytokine-activated neutrophils: inflammatory neutrophils are heterogeneous and enhance adaptive immune responses.","volume":"69","author":"Yamashiro","year":"2001","journal-title":"J Leukoc Biol"},{"key":"R17-2-20210212","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1242\/dmm.003186","article-title":". Multiple roles for CCR2 during fracture healing.","volume":"3","author":"Xing","year":"2010","journal-title":"Dis Model Mech"},{"key":"R18-2-20210212","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1002\/jbmr.354","article-title":". Osteal macrophages promote in vivo intramembranous bone healing in a mouse tibial injury model.","volume":"26","author":"Alexander","year":"2011","journal-title":"J Bone Miner Res"},{"key":"R19-2-20210212","doi-asserted-by":"crossref","first-page":"2594","DOI":"10.1002\/jcb.23186","article-title":". Complement C3a and C5a modulate osteoclast formation and inflammatory response of osteoblasts in synergism with IL-1beta.","volume":"112","author":"Ignatius","year":"2011","journal-title":"J Cell Biochem"},{"key":"R20-2-20210212","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1097\/00005131-200511101-00002","article-title":"The science of fracture healing.","volume":"19","author":"Einhorn","year":"2005","journal-title":"J Orthop Trauma"},{"key":"R21-2-20210212","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1002\/jbmr.5650100818","article-title":". The expression of cytokine activity by fracture callus.","volume":"10","author":"Einhorn","year":"1995","journal-title":"J Bone Miner Res"},{"key":"R22-2-20210212","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nature01658","article-title":"Osteoclast differentiation and activation.","volume":"423","author":"Boyle","year":"2003","journal-title":"Nature"},{"key":"R23-2-20210212","doi-asserted-by":"crossref","first-page":"784","DOI":"10.2353\/ajpath.2006.060010","article-title":". Kupffer cells and their mediators: the culprits in producing distant organ damage after trauma-hemorrhage.","volume":"169","author":"Hildebrand","year":"2006","journal-title":"Am J Pathol"},{"key":"R24-2-20210212","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1002\/jor.22242","article-title":". Conversion from external fixator to intramedullary nail causes a second hit and impairs fracture healing in a severe trauma model.","volume":"31","author":"Recknagel","year":"2013","journal-title":"J Orthop Res"},{"key":"R25-2-20210212","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1016\/j.injury.2013.05.011","article-title":". Differentiation of osteoprogenitor cells is affected by trauma-haemorrhage.","volume":"44","author":"Neunaber","year":"2013","journal-title":"Injury"},{"key":"R27-2-20210212","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/s00423-003-0405-3","article-title":". Influence of haemorrhagic shock on fracture healing.","volume":"388","author":"Bumann","year":"2003","journal-title":"Langenbecks Arch Surg"},{"key":"R28-2-20210212","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1097\/00005373-199610000-00006","article-title":". Depressed osteoblast activity and increased osteocyte necrosis after closed bone fracture and hemorrhagic shock.","volume":"41","author":"Wichmann","year":"1996","journal-title":"J Trauma"},{"key":"R29-2-20210212","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1097\/00005131-200204000-00006","article-title":". The effect of hemorrhagic shock in a caprine tibial fracture model.","volume":"16","author":"Starr","year":"2002","journal-title":"J Orthop Trauma"},{"key":"R30-2-20210212","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1002\/jor.21299","article-title":". Experimental blunt chest trauma impairs fracture healing in rats.","volume":"29","author":"Recknagel","year":"2011","journal-title":"J Orthop Res"},{"key":"R31-2-20210212","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1002\/jor.20173","article-title":". Moderate soft tissue trauma delays new bone formation only in the early phase of fracture healing.","volume":"24","author":"Claes","year":"2006","journal-title":"J Orthop Res"},{"key":"R32-2-20210212","doi-asserted-by":"crossref","first-page":"223","DOI":"10.3109\/17453674.2011.570677","article-title":". The effect of both a thoracic trauma and a soft-tissue trauma on fracture healing in a rat model.","volume":"82","author":"Claes","year":"2011","journal-title":"Acta Orthop"},{"key":"R33-2-20210212","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1097\/00005131-200307000-00007","article-title":". Influence of extensive muscle injury on fracture healing in rat tibia.","volume":"17","author":"Utvag","year":"2003","journal-title":"J Orthop Trauma"},{"key":"R34-2-20210212","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/s00402-007-0395-7","article-title":". The effect of zymosan and the protective effect of various antioxidants on fracture healing in rats.","volume":"127","author":"Duygulu","year":"2007","journal-title":"Arch Orthop Trauma Surg"},{"key":"R35-2-20210212","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1097\/shk.0b013e3180556a0b","article-title":". The role of C5a in the innate immune response after experimental blunt chest trauma.","volume":"29","author":"Flierl","year":"2008","journal-title":"Shock"},{"key":"R36-2-20210212","first-page":"268","article-title":"The polymorphonuclear leukocyte: has it a role in fracture healing Arch Orthop Trauma Surg.","volume":"109","author":"Grogaard","year":"1990","journal-title":""},{"key":"R37-2-20210212","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/S0736-0266(00)00044-9","article-title":". Alteration of fracture stability influences chondrogenesis, osteogenesis and immigration of macrophages.","volume":"19","author":"Hankemeier","year":"2001","journal-title":"J Orthop Res"},{"key":"R38-2-20210212","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1080\/17453670510045327","article-title":". Lipopolysaccharide impairs fracture healing: an experimental study in rats.","volume":"76","author":"Reikeras","year":"2005","journal-title":"Acta Orthop"},{"key":"R39-2-20210212","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/s007760050159","article-title":"Effects of macrophage activation on bone healing.","volume":"5","author":"Grundnes","year":"2000","journal-title":"J Orthop Sci"},{"key":"R40-2-20210212","doi-asserted-by":"crossref","first-page":"3551","DOI":"10.1002\/art.22175","article-title":". Impaired skeletal development in interleukin-6-transgenic mice: a model for the impact of chronic inflammation on the growing skeletal system.","volume":"54","author":"De Benedetti","year":"2006","journal-title":"Arthritis Rheum"},{"key":"R41-2-20210212","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1016\/j.bone.2007.07.022","article-title":". Callus mineralization and maturation are delayed during fracture healing in interleukin-6 knockout mice.","volume":"41","author":"Yang","year":"2007","journal-title":"Bone"},{"key":"R42-2-20210212","first-page":"189","article-title":". Inflammatory alterations in a novel combination model of blunt chest trauma and hemorrhagic shock.","volume":"70","author":"Seitz","year":"2011","journal-title":"J Trauma"},{"key":"R43-2-20210212","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s00402-004-0768-0","article-title":". External fixation versus locked intramedullary nailing in tibial shaft fractures: a prospective, randomised study of 78 patients.","volume":"125","author":"Braten","year":"2005","journal-title":"Arch Orthop Trauma Surg"},{"key":"R44-2-20210212","doi-asserted-by":"crossref","first-page":"781","DOI":"10.2106\/00004623-200006000-00004","article-title":". Conversion of external fixation to intramedullary nailing for fractures of the shaft of the femur in multiply injured patients.","volume":"82","author":"Nowotarski","year":"2000","journal-title":"J Bone Joint Surg Am"},{"key":"R45-2-20210212","first-page":"39","article-title":". External fixation of femoral fractures in multiply injured intensive care unit patients.","volume":"72","author":"Kazakos","year":"2006","journal-title":"Acta Orthop Belg"},{"key":"R46-2-20210212","first-page":"88","article-title":"External fixation of femoral fractures. Indications and limitations.","volume":"83-","author":"Alonso","year":"1989","journal-title":"Clin Orthop Relat Res"},{"key":"R47-2-20210212","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1097\/00005131-199003000-00012","article-title":". External fixation of femoral fractures: experience with 15 cases.","volume":"4","author":"Rooser","year":"1990","journal-title":"J Orthop Trauma"},{"key":"R48-2-20210212","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/S0002-9610(02)00865-6","article-title":"The timing of fracture treatment in polytrauma patients: relevance of damage control orthopedic surgery.","volume":"183","author":"Pape","year":"2002","journal-title":"Am J Surg"},{"key":"R49-2-20210212","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1097\/01.bot.0000161712.87129.80","article-title":". Timing of fixation of major fractures in blunt polytrauma: role of conventional indicators in clinical decision making.","volume":"19","author":"Pape","year":"2005","journal-title":"J Orthop Trauma"},{"key":"R51-2-20210212","first-page":"674","article-title":"Our experiences with change of osteosynthesis from external fixator to internal fixation in fractures of the lower limb in German.","volume":"128","author":"Schuh","year":"2003","journal-title":"Zentralbl Chir"},{"key":"R52-2-20210212","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1007\/s001040050781","article-title":". Optimal timing for secondary surgery in polytrauma patients: an evaluation of 4,314 serious-injury cases in German.","volume":"70","author":"Pape","year":"1999","journal-title":"Chirurg"},{"key":"R53-2-20210212","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1097\/00005131-200502000-00012","article-title":". Intramedullary nailing following external fixation in femoral and tibial shaft fractures.","volume":"19","author":"Bhandari","year":"2005","journal-title":"J Orthop Trauma"},{"key":"R54-2-20210212","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1302\/0301-620X.76B1.8300656","article-title":". Treatment of grade-IIIb open tibial fractures. A prospective randomised comparison of external fixation and non-reamed locked nailing.","volume":"76","author":"Tornetta","year":"1994","journal-title":"J Bone Joint Surg Br"},{"key":"R55-2-20210212","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1302\/0301-620X.79B3.0790433","article-title":". External fixation and secondary intramedullary nailing of open tibial fractures. A randomised, prospective trial.","volume":"79","author":"Antich-Adrover","year":"1997","journal-title":"J Bone Joint Surg Br"},{"key":"R56-2-20210212","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1097\/00000658-198509000-00003","article-title":". Blunt multiple trauma (ISS 36), femur traction, and the pulmonary failure-septic state.","volume":"202","author":"Seibel","year":"1985","journal-title":"Ann Surg"},{"key":"R57-2-20210212","doi-asserted-by":"crossref","first-page":"S131","DOI":"10.5435\/00124635-200600001-00030","article-title":"External fixation versus conversion to intramedullary nailing for definitive management of closed fractures of the femoral and tibial shaft.","volume":"14","author":"Della Rocca","year":"2006","journal-title":"J Am Acad Orthop Surg"},{"key":"R58-2-20210212","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/0020-1383(92)90010-P","article-title":"Primary external fixation and secondary intramedullary nailing in the treatment of tibial fractures.","volume":"23","author":"Wheelwright","year":"1992","journal-title":"Injury"},{"key":"R59-2-20210212","doi-asserted-by":"crossref","first-page":"e332","DOI":"10.3928\/01477447-20140401-52","article-title":". A meta-analysis of reamed versus unreamed intramedullary nailing for the treatment of closed tibial fractures.","volume":"37","author":"Xia","year":"2014","journal-title":"Orthopedics"},{"key":"R60-2-20210212","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1007\/s00264-009-0895-x","article-title":". Reamed and unreamed intramedullary nailing for the treatment of open and closed tibial fractures: a subgroup analysis of randomised trials.","volume":"34","author":"Xue","year":"2010","journal-title":"Int Orthop"},{"key":"R61-2-20210212","doi-asserted-by":"crossref","first-page":"375","DOI":"10.3109\/17453670903035567","article-title":"External fixation compared to intramedullary nailing of tibial fractures in the rat.","volume":"80","author":"Sigurdsen","year":"2009","journal-title":"Acta Orthop"},{"key":"R62-2-20210212","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1016\/j.orthres.2004.02.006","article-title":". Comparison of unreamed nailing and external fixation of tibial diastasesmechanical conditions during healing and biological outcome.","volume":"22","author":"Klein","year":"2004","journal-title":"J Orthop Res"},{"key":"R63-2-20210212","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1002\/jor.21182","article-title":"The Effect of timing of conversion from external fixation to secondary intramedullary nailing in experimental tibial fractures.","volume":"29","author":"Sigurdsen","year":"2011","journal-title":"J Orthop Res"},{"key":"R64-2-20210212","doi-asserted-by":"crossref","first-page":"142","DOI":"10.3109\/08941930903564118","article-title":"Conversion of external fixation to definitive intramedullary nailing in experimental tibial fractures.","volume":"23","author":"Sigurdsen","year":"2010","journal-title":"J Invest Surg"},{"key":"R65-2-20210212","first-page":"1379","article-title":". Systemic inflammatory response after extremity or truncal fracture operations.","volume":"65","author":"Pape","year":"2008","journal-title":"J Trauma"},{"key":"R66-2-20210212","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/S0736-0266(00)00006-1","article-title":". Molecular aspects of healing in stabilized and non-stabilized fractures.","volume":"19","author":"Le","year":"2001","journal-title":"J Orthop Res"},{"key":"R67-2-20210212","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1016\/j.bone.2005.10.023","article-title":". Instability prolongs the chondral phase during bone healing in sheep.","volume":"38","author":"Epari","year":"2006","journal-title":"Bone"},{"key":"R68-2-20210212","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1007\/s00441-011-1205-7","article-title":". Inflammatory phase of bone healing initiates the regenerative healing cascade.","volume":"347","author":"Schmidt-Bleek","year":"2012","journal-title":"Cell Tissue Res"}],"container-title":["Journal of Orthopaedic Trauma"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/10.1097\/BOT.0000000000000489","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T17:52:06Z","timestamp":1718214726000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/00005131-201603000-00002"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,3]]},"references-count":65,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2016]]}},"URL":"https:\/\/doi.org\/10.1097\/bot.0000000000000489","relation":{},"ISSN":["0890-5339"],"issn-type":[{"value":"0890-5339","type":"print"}],"subject":[],"published":{"date-parts":[[2016,3]]}}}