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Early intra-articular complement activation in ankle fractures.

ABSTRACT: Cytokine regulation possibly influences long term outcome following ankle fractures, but little is known about synovial fracture biochemistry. Eight patients with an ankle dislocation fracture were included in a prospective case series and matched with patients suffering from grade 2 osteochondritis dissecans (OCD) of the ankle. All fractures needed external fixation during which joint effusions were collected. Fluid analysis was done by ELISA measuring aggrecan, bFGF, IL-1 ?, IGF-1, and the complement components C3a, C5a, and C5b-9. The time periods between occurrence of fracture and collection of effusion were only significantly associated with synovial aggrecan and C5b-9 levels (P < 0.001). Furthermore, synovial expressions of both proteins correlated with each other (P < 0.001). Although IL-1 ? expression was relatively low, intra-articular levels correlated with C5a (P < 0.01) and serological C-reactive protein concentrations 2 days after surgery (P < 0.05). Joint effusions were initially dominated by neutrophils, but the portion of monocytes constantly increased reaching 50% at day 6 after fracture (P < 0.02). Whereas aggrecan and IL-1? concentrations were not different in fracture and OCD patients, bFGF, IGF-1, and all complement components were significantly higher concentrated in ankle joints with fractures (P < 0.01). Complement activation and inflammatory cell infiltration characterize the joint biology following acute ankle fractures.

SUBMITTER: Schmal H

PROVIDER: S-EPMC4055461 | biostudies-other | 2014

REPOSITORIES: biostudies-other

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Early intra-articular complement activation in ankle fractures.

Schmal Hagen H Salzmann Gian M GM Niemeyer Philipp P Langenmair Elia E Guo Renfeng R Schneider Conny C Habel Maria M Riedemann Niels N

BioMed research international 20140521

Cytokine regulation possibly influences long term outcome following ankle fractures, but little is known about synovial fracture biochemistry. Eight patients with an ankle dislocation fracture were included in a prospective case series and matched with patients suffering from grade 2 osteochondritis dissecans (OCD) of the ankle. All fractures needed external fixation during which joint effusions were collected. Fluid analysis was done by ELISA measuring aggrecan, bFGF, IL-1 β, IGF-1, and the com ...[more]

PMID: 24967368

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Project description:BackgroundSeveral malreduction criteria have been proposed for ankle surgery, but the criteria of most importance for functional outcome remain undetermined. Furthermore, the acute inflammatory response in the ankle joint after fracture is hypothesized to result in osteoarthritis development, but no study has investigated the correlation between the levels of these inflammatory cytokines and post-surgical functional outcomes. We aimed to identify malreduction criteria and inflammatory cytokines associated with functional outcome after ankle surgery.MethodsDuring surgery, synovial fluid from the fractured and healthy contralateral ankles of 46 patients was collected for chemiluminescence analysis of 22 inflammatory cytokines and metabolic proteins. The quality of fracture reduction was based on 9 criteria on plain X-rays and 5 criteria on weight-bearing computed tomography (WBCT) scans. After 3 and 12 months, we recorded scores on American Orthopedic Foot and Ankle Society (AOFAS) scale, the Danish version of Foot Function Index (FFI-DK), EQ-5D-5L index score, the Kellgren-Lawrence score, and joint space narrowing.ResultsTibiofibular (TF) overlap (p = 0.02) and dime sign (p = 0.008) correlated with FFI-DK. Tibiotalar tilt correlated positively with joint space narrowing at 3 months (p = 0.01) and 12 months (p = 0.03). TF widening correlated with FFI-DK (p = 0.04), AOFAS (p = 0.02), and EQ-5D-5L (p = 0.02). No consistent correlations between synovial cytokine levels and functional outcomes were found at 12 months.ConclusionsMalreduction of TF overlap, TF widening, and tibiotalar tilt were the most important criteria for functional outcome after ankle surgery. Increased inflammatory cytokine levels after fracture did not affect functional outcome at 12 months.Trial registrationThis cohort study is registered the 10th of December 2018 at ClinicalTrials.gov ( NCT03769909 ), was approved by the local committee on health ethics (The Regional Committees on Health Research Ethics for Southern Denmark: J.No. S-20170139), and was reported to the National Danish Data Protection Agency (17/28505).

Project description:IntroductionIntra-articular fractures are the leading etiology for posttraumatic osteoarthritis (PTOA) in the ankle. Elevation of proinflammatory cytokines following intra-articular fracture may lead to synovial catabolism and cartilage degradation. We aimed to compare cytokine levels in injured and healthy ankle joints, examine the longer-term cytokine levels in fractured ankles, and investigate the association between cytokine levels in fractured ankles and plasma.Materials and methodsIn this cross-sectional study, synovial fluid (SF) and plasma of forty-seven patients with acute intra-articular ankle fractures and eight patients undergoing implant removal were collected prior to surgery. We determined concentrations of sixteen inflammatory cytokines, two cartilage degradation proteins, and four metabolic proteins and compared the levels in acutely injured ankles with those of the healthy contralateral side or during metal removal. Cytokine levels in injured ankles were also compared to serum cytokine levels. Nonparametric Wilcoxon rank-sum and Spearman tests were used for statistical analysis, and a p value below 0.05 was considered significant.ResultsCompared to the healthy ankles, the synovial fluid in ankles with acute intra-articular fracture had elevated levels of several proinflammatory cytokines and proteases (IL-1β, IL-2, IL-6, IL-8, IL-12p70, TNF, IFNγ, MMP-1, MMP-3, and MMP-9) and anti-inflammatory cytokines (IL-1RA, IL-4, IL-10, and IL-13). The levels of cartilage degradation products (ACG, CTX-2) and metabolic mediators (TGF-β1 and TGF-β2) were also significantly higher. Synovial concentrations of ACG, IL-12-p70, IFNγ, IL-4, and bFGF correlated with serum levels. While most of the examined synovial cytokines were unchanged after implant removal, IL-4 and IL-6 levels were upregulated.ConclusionsWe show that an acute ankle fracture is followed by an inflammatory reaction and cartilage degeneration. These data contribute to the current understanding of the protein regulation behind the development of PTOA and is a further step towards supplementing the current surgical treatment. This cross-sectional study was "retrospectively registered" on the 31th October 2017 at ClinicalTrials.gov (NCT03769909). The registration was carried out after inclusion of the first patient and prior to finalization of patient recruitment and statistical analyses: https://clinicaltrials.gov/ct2/show/NCT03769909?term=NCT03769909&draw=2&rank=1.

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Early intra-articular complement activation in ankle fractures.

Publications

Early intra-articular complement activation in ankle fractures.

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