A Pronounced Inflammatory Activity Characterizes the Early Fracture Healing Phase in Immunologically Restricted Patients

Hoff, Paula; Gaber, Timo; Strehl, Cindy; Jakstadt, Manuela; Hoff, Holger; Schmidt‐Bleek, Katharina; Lang, Annemarie; Röhner, Eric; Huscher, Dörte; Matziolis, Georg; Burmester, Gerd‐Rüdiger; Schmidmaier, Gerhard; Perka, Carsten; Duda, Georg N.; Buttgereit, Frank

doi:10.3390/ijms18030583

Cited by 43 publications

(43 citation statements)

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“…While pain and limited range of motion are frequently seen in isolated trauma (4,5), previous clinical and experimental studies linked multiple trauma to significantly longer fracture healing times and higher incidences of non-unions in comparison to isolated fractures (7)(8)(9). Overwhelming local and systemic inflammatory responses with an associated negative influence on downstream processes of bone repair are a potential pathomechanism for this impaired fracture healing (10)(11)(12)(13). Despite knowledge about the connectivity between the systemic and local inflammatory responses, information on the impact of trauma severity on systemic and local immunologic interactions and responses is scarce (14).…”

Section: Introductionmentioning

confidence: 99%

Trauma Severity and Its Impact on Local Inflammation in Extremity Injury—Insights From a Combined Trauma Model in Pigs

et al. 2020

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Background: Extremity fracture is frequently seen in multiple traumatized patients. Local post-traumatic inflammatory reactions as well as local and systemic interactions have been described in previous studies. However, trauma severity and its impact on the local immunologic reaction remains unclear. Therefore, fracture-associated local inflammation was investigated in a porcine model of isolated and combined trauma to gain information about the early inflammatory stages. Material and Methods: Polytrauma (PT) consisted of lung contusion, liver laceration, femur fracture, and controlled hemorrhage. Monotrauma (MT) consisted of femur fracture only. The fracture was operatively stabilized and animals were monitored under ICU-standard for 72 h. Blood, fracture hematoma (FH) as well as muscle samples were collected throughout the experimental period. Levels of local and systemic pro-and anti-inflammatory as well as angiogenetic cytokines were measured by ELISA. Results: Both groups showed a significant decrease in pro-inflammatory IL-6 in FH over time. However, concentrations in MT were significantly higher than in PT. The IL-8 concentrations initially decreased in FH, but recovered by the end of the observation period. These dynamics were only statistically significant in MT. Furthermore, concentrations measured in muscle tissue showed inverse kinetics compared to those in FH. The IL-10 did not present statistical resilient dynamics over time, although a slight increase in FH was seen by the end of the observation time in the MT group. Conclusions: Time-dependent dynamics of the local inflammatory response were observed. Trauma severity showed a significant impact, with lower values in pro-as well as angiogenetic mediators. Fracture repair could be altered by these trauma-related changes of the local immunologic milieu, which might serve as a possible explanation for the higher rates of delayed or non-union bone repair in polytraumatised patients.

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Section: Introductionmentioning

confidence: 99%

Trauma Severity and Its Impact on Local Inflammation in Extremity Injury—Insights From a Combined Trauma Model in Pigs

et al. 2020

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“…Similar to our data, increased IL1-beta, IL6 and IL8 (protein levels) were detected early in hematoma [35] while we did not see a clear increase in IL10, IL1R or VEGF early (although at mRNA levels rather than protein). In hematoma (72 h of fracture) from patients with autoimmune conditions, exaggerated expression of the same factor was also reported [36] as well as increased in transcript for osteopontin/SPP1 and HIF1 [37]. This is different in humans, with a massive reduction in ANGPT1 over the overall period studied (0-15 days), while ANGPT2 did not show variation (similar levels to heathy bone).…”

Section: Discussionmentioning

confidence: 76%

Dynamics of Early Signalling Events during Fracture Healing and Potential Serum Biomarkers of Fracture Non-Union in Humans

Burska

Giannoudis

Tan

et al. 2020

JCM

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To characterise the dynamic of events during the early phases of fracture repair in humans, we investigated molecular events using gene expression profiling of bone fragments from the fracture site at different time points after trauma and immune/stromal cells recruitment at the fracture site using flow cytometry. Bone and inflammatory markers were expressed at low levels at homeostasis, while transcripts for bone constituent proteins were consistently detected at higher levels. Early after fracture (range 2–4 days), increased expression of CXCL12, suggested recruitment of immune cells associated with a change in the balance of degradation enzymes and their inhibitors. At intermediate time after fracture (4–8 days), we observed high expression of inflammatory cytokines (IL1-beta, IL6), CCL2, the T-cell activation marker CD69. Late after fracture (8–14 days), high expression of factors co-operating towards the regulation of bone turnover was detected. We identified potential soluble factors and explored circulating levels in patients for whom a union/non-union (U/NU) outcome was known. This showed a clear difference for PlGF (p = 0.003) at day 1. These findings can inform future studies further investigating the cascade of molecular events following fractures and for the prediction of fracture non-union.

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“…No cartilage remains; 28 days: remodeling phase. Histological samples stained with Movat Pentachrome: bone = yellow; bone marrow =purple; cartilage = blue-green, muscle = orange; connective tissue = light blue [2,4,6,15,[34][35][36][37][38][39][40][41][42][43]. Periost has been carefully elevated from the bone and was stained with hematoxylin eosin.…”

Section: Resultsmentioning

confidence: 99%

Research in Fracture Healing and Its Clinical Applications in the Veterinary Practice

Mafamane¹,

Hackenbroich²,

Ellinghaus³

et al. 2017

Journal of Veterinary Science and Animal Husbandry

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A Pronounced Inflammatory Activity Characterizes the Early Fracture Healing Phase in Immunologically Restricted Patients

Cited by 43 publications

References 44 publications

Trauma Severity and Its Impact on Local Inflammation in Extremity Injury—Insights From a Combined Trauma Model in Pigs

Trauma Severity and Its Impact on Local Inflammation in Extremity Injury—Insights From a Combined Trauma Model in Pigs

Dynamics of Early Signalling Events during Fracture Healing and Potential Serum Biomarkers of Fracture Non-Union in Humans

Research in Fracture Healing and Its Clinical Applications in the Veterinary Practice

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