Severe Hemorrhagic Shock Leads to a Delayed Fracture Healing and Decreased Bone Callus Strength in a Mouse Model

Bundkirchen, Katrin; Macke, Christian; Reifenrath, Janin; Schäck, Luisa Marilena; Noack, Sandra; Relja, Borna; Naber, Philipp; Welke, Bastian; Fehr, Michael; Krettek, Christian; Neunaber, Claudia

doi:10.1007/s11999-017-5473-8

Cited by 20 publications

(27 citation statements)

References 22 publications

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“…Most severely injured patients with poor outcomes suffer from a “multiple trauma” consisting of injuries to different systems and compartments. The most common in vivo models imply mainly two insults, with the focus on HS, which is frequently combined with blunt chest trauma or fracture 9–13,24,33–35 . Also combining HS with TBI is commonly applied 24,36–38 .…”

Section: Discussionmentioning

confidence: 99%

“…Male C57BL/6NCrl mice aged 12 weeks were purchased from Charles River Laboratories (Sulzfeld, Germany). Animals were housed and fed under standardized conditions 13 . All mice undergoing surgery received inhalational isoflurane anesthesia (Baxter Deutschland GmbH, Unterschleißheim, Germany) and 1% prilocainhydrochlorid (Xylonest® AstraZeneca GmbH., Wedel, Germany) for local anesthesia.…”

Section: Methodsmentioning

confidence: 99%

“…Hemorrhagic shock was induced as described previously 13 . Briefly, the femoral artery was cannulated with polyethylene tubing (Becton Dickinson and Company, Sparks, MD, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Afterwards, the vastus lateralis biceps femoris muscles were split bluntly, and the full length of the femur was exposed. A standardized external fixator system (MouseExFix simple L 100%, RISystem AG, Davos, Switzerland) was attached to the femur to stabilize the following osteotomy 13 . Osteotomy at the middle of the femur was induced by a 0.44 mm Gigli wire saw (RISystem AG).…”

Section: Methodsmentioning

confidence: 99%

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Traumatic injury pattern is of equal relevance as injury severity for experimental (poly)trauma modeling

Yang

Bundkirchen

Krettek

et al. 2019

Sci Rep

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This study aims to elaborate the relevance of trauma severity and traumatic injury pattern in different multiple and/or polytrauma models by comparing five singular trauma to two different polytrauma (PT) models with high and one multiple trauma (MT) model with low injury-severity score (ISS). The aim is to provide a baseline for reducing animal harm according to 3Rs by providing less injury as possible in polytrauma modeling. Mice were randomly assigned to 10 groups: controls (Ctrl; n = 15), Sham (n = 15); monotrauma groups: hemorrhagic shock (HS; n = 15), thoracic trauma (TxT; n = 18), osteotomy with external fixation (Fx; n = 16), bilateral soft tissue trauma (bSTT; n = 16) or laparotomy (Lap; n = 16); two PT groups: PT I (TxT + HS + Fx; ISS = 18; n = 18), PT II (TxT + HS + Fx + Lap; ISS = 22; n = 18), and a MT group (TxT + HS + bSTT + Lap, ISS = 13; n = 18). Activity and mortality were assessed. Blood gas analyses and organ damage markers were determined after 6 h. Significant mortality occurred in TxT, PT and MT (11.7%). Activity decreased significantly in TxT, HS, both polytrauma and MT vs . Ctrl/Sham. PT-groups and MT had significantly decreased activity vs . bsTT, Lap or Fx. MT had significantly lower pCO 2 vs . Ctrl/Sham, Lap or bsTT. Transaminases increased significantly in PT-groups and MT vs . Ctrl, Sham or monotrauma. Traumatic injury pattern is of comparable relevance as injury severity for experimental multiple or (poly)trauma modeling.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Hemorrhagic shock was induced as described previously 13 . Briefly, the femoral artery was cannulated with polyethylene tubing (Becton Dickinson and Company, Sparks, MD, USA).…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Traumatic injury pattern is of equal relevance as injury severity for experimental (poly)trauma modeling

Yang

Bundkirchen

Krettek

et al. 2019

Sci Rep

Self Cite

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“…To what extent hemorrhage influences fracture healing is not clear, yet. While hemorrhagic shock retards fracture healing during the early phase of the fracture healing process in an experimental mouse model [34], others could not evidence any difference in fracture healing of goats with and without additional hemorrhagic shock [35]. Nonetheless, larger callus with evidence of delayed bone remodeling could be observed in a rabbit model examining the impact of hemorrhage on fracture healing [36].…”

Section: Discussionmentioning

confidence: 99%

Do Systemic Factors Influence the Fate of Nonunions to Become Atrophic? A Retrospective Analysis of 162 Cases

Rupp

Kern

Khassawna

et al. 2019

BioMed Research International

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Introduction. Nonunions are a challenge for orthopedic surgeons. In hypertrophic nonunions, improvement of mechanical stability usually is the satisfactory treatment, whereas in atrophic nonunions improvement of the biological environment is most important. However, scientific evidence revealed that “avital” nonunions are not avascular and fibrous tissue contains cells with osteogenic potential. To find out if systemic factors suppress this intrinsic potential in atrophic nonunions, this study compares characteristics of hypertrophic with atrophic nonunion patients. Methods. We analyzed medical records of 162 surgically treated patients suffering from aseptic long bone nonunions. Atrophic and hypertrophic nonunions were distinguished by absence or presence of callus and calcification in the fracture gap. Mechanical implant loosening and patient characteristics such as age, gender, and body mass index were assessed. Fracture classification according to AO/OTA, open and closed fractures, and osteosynthesis were recorded. In addition, comorbidities and allergies between both groups were compared. Results. A higher number of hypertrophic nonunion patients were male with often allergies. Hypertrophic nonunion occurred more often after intramedullary nailing compared to atrophic nonunions. Atrophic nonunion patients being nonallergic were significantly older than nonallergic patients suffering from hypertrophic nonunions. In both atrophic and hypertrophic nonunion patients, age was lower in patients with accompanying injuries compared with age of patients with isolated fractures. Conclusion. Systemic factors influence development of nonunion types. In nonallergic patients, atrophic nonunions occur more often in the elderly. This manuscript is a first step to identify different factors which might influence the nature of nonunion. To enable nonunion treatment which is tailored to individual patient characteristics, further prospective studies with more sophisticated research methods are necessary.

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Aging Influences Fracture Healing on the Cellular Level and Alters Systemic RANKL and OPG Concentrations in a Murine Model

Zhang,

Neunaber,

et al. 2024

Advanced Biology

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Clinical complications frequently follow polytrauma and bleeding fractures, increasing the risk of delayed fracture healing and nonunions, especially in aged patients. Therefore, this study examines age's impact on fracture repair with and without severe bleeding in mice. Young (17–26 weeks) and aged (64–72 weeks) male C57BL/6J mice (n = 72 in total, n = 6 per group) are allocated into 3 groups: the fracture group (Fx) undergoes femur osteotomy stabilized via external fixator, the combined trauma group (THFx) additionally receives pressure‐controlled trauma hemorrhage (TH) and Sham animals are implanted with catheter and fixator without blood loss or osteotomy. Femoral bones are evaluated histologically 24 h and 3 weeks post‐trauma, while RANKL/OPG and β‐CTx are measured systemically via ELISA after 3 weeks. Aging results in less mineralized bone and fewer osteoclasts within the fracture of aged mice in contrast to young groups after three weeks. Systemically, aged animals exhibit increased RANKL and OPG levels after fracture compared to their young counterparts. The RANKL/OPG ratio rises in aged Fx animals compared to young mice, with a similar trend in THFx groups. In conclusion, age has an effect during the later course of fracture healing on the cellular and systemic levels.

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Severe Hemorrhagic Shock Leads to a Delayed Fracture Healing and Decreased Bone Callus Strength in a Mouse Model

Abstract: A severe hemorrhagic shock in patients could result in initial delayed fracture healing and needs special attention. We plan to conduct a prospective, observational clinical research study to analyze if delayed fracture healing occurs in patients after severe blood loss.

Cited by 20 publications

References 22 publications

Traumatic injury pattern is of equal relevance as injury severity for experimental (poly)trauma modeling

Traumatic injury pattern is of equal relevance as injury severity for experimental (poly)trauma modeling

Do Systemic Factors Influence the Fate of Nonunions to Become Atrophic? A Retrospective Analysis of 162 Cases

Aging Influences Fracture Healing on the Cellular Level and Alters Systemic RANKL and OPG Concentrations in a Murine Model

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