Ulf Sigurdsen

Impact of freezing on immunology and incorporation of bone allograft

With an increasing clinical use of deep frozen allograft for bone reconstruction, it is important to understand the immunological and biological events of allograft incorporation. In this study, we have investigated the impact of deep freezing on immunology and biopotency for incorporation of bone allografts. Deep frozen bone grafts matched or mismatched for major histoscompatibilty complex (MHC) were implanted in an 8‐mm segmental defect in the tibia in rats. The construct was stabilized with intramedullary nailing. The immune response was evaluated by determination of serum antibody against the grafts MHC molecules at day 1 and after 2 and 4 months. Incorporation of the graft was compared with fresh syngeneic grafts and assessed with the use of conventional radiography, biomechanical testing and measurement of bone mineral content and density after 4 months. The analyses revealed no antibody responses in the rats that received grafts from donors differing at histocompatibility loci, and at 4 months the frozen grafts showed an overall reconstruction that was not significantly different from the fresh grafts. This study indicates that in the long run there are no significant consequences; either immunological or biomechanical, of the use of deep frozen allogenous bone as compared to fresh autogenous bone grafts in this animal model.

External fixation compared to intramedullary nailing of tibial fractures in the rat

Background and purpose It is not known whether there is a difference in bone healing after external fixation and after intramedullary nailing. We therefore compared fracture healing in rats after these two procedures. Methods 40 male rats were subjected to a standardized tibial shaft osteotomy and were randomly assigned to 2 treatment groups: external fixation or intramedullary nailing. Evaluation of half of each treatment group at 30 days and the remaining half at 60 days included radiography, dual energy radiographic absorbtiometry, and mechanical testing. Results Radiographically, both treatment groups showed sign of fracture healing with gradual bridging of the fracture line, while with intramedullary nailing the visible collar of callus was increased peripherally, indicative of periosteal healing. At 30 days, densitometric and mechanical properties were similar in the 2 groups. At 60 days, however, the intramedullary nailed bones had more strength, greater callus area, and higher bone mineral content in the callus segment compared to externally fixated fractures. Interpretation Tibial shaft fractures in the rat treated with external fixation and intramedullary nailing show a similar healing pattern in the early phase of fracture healing, while at the time of healing intramedullary nailing provides improved densitometric properties and superior mechanical properties compared to external fixation. Clinical findings indicate that intramedullary nailing in human tibial fractures may be more advantageous for bone healing than external fixation, in a similar way.

Incidence and risk factors for removal of an internal fixation following surgery for ankle fracture: A retrospective cohort study of 997 patients.

BACKGROUND Implant removal in ankle fractures treated by open reduction and fixation is often based on diffuse complaints. This study determined the incidence of implant removal and identified risk factors for two principal causes for removal: complaints and surgical site infection (SSI). METHODS Retrospective cohort study involving 997 patients operated on 2009-2011 with follow-up through to 2013. The incidence of implant removal was analysed using competing risk analysis. Risk factors for implant removal were assessed using cause-specific hazard ratios (HRs) from a Cox regression analysis. RESULTS The mean age at surgery was 51.6 years, 550 (55%) of the patients were female, and 170 patients (17%) had implant removal: 144 due to complaints and 26 due to infection. Multivariable HRs for implant removal due to complaints were 0.70 for male sex (p=0.047), 0.79 for each 10-year increase in age (p<0.001), 0.70 for treatment with a syndesmosis screw (p=0.038), and 1.09 for each 15-min increase in operation duration (p=0.007). HRs for hardware removal due to infection were 1.42 for each 10-year increase in age (p=0.006) and 3.15 for current smoking (p=0.005). CONCLUSION In total 17% of patients had implant removal after open reduction and fixation; the majority because of subjective complaints. The risk factors for implant removal were different for removal due to complaints than for those removed due to infection. This information may be used to inform patients about the risk and risk factors for future implant removal.

The Effect of timing of conversion from external fixation to secondary intramedullary nailing in experimental tibial fractures.

Diaphyseal tibial fractures with initial temporary external fixation (EF) are usually converted to intramedullary nailing (IMN) within 2 weeks, and no consensus on the optimal conversion time point exists. Current clinical practice is mainly based on estimation of the risk of postoperative infection. This is the first investigation of the effect of timing of such conversion on fracture healing. Forty male rats received a standardized tibial shaft osteotomy and EF. The animals were then randomly assigned to conversion to IMN at either 7 (group A, N = 10), 14 (group B, N = 10), or 30 (group C, N = 10) days after initial fixation. Group D (N = 10) served as a control group without conversion. Evaluation at 60 days included X‐ray, DXA, and mechanical testing. Group A had significantly increased bone mineral content and callus area compared to the control group. Groups B and C showed significantly inferior mechanical bending strength and rigidity compared to both group A and the control group (D). The timing of the conversion procedure has a significant effect on fracture healing. Early conversion procedure did not improve healing compared to control, but was advantageous compared to late conversion (at 2 or 4 weeks) with higher mineralization and superior biomechanical properties.

Conversion of External Fixation to Definitive Intramedullary Nailing in Experimental Tibial Fractures

ABSTRACT Background and Purpose: Initial treatment with external fixation of tibial fractures is indicated in severely injuried multitrauma patients. A conversion procedure to secondary nailing is often performed later to enhance fracture repair. The aim of the study was to compare definitive treatment of experimental tibial fractures with external fixation to an early conversion to secondary intramedullary nailing with large and small diameter nails. Methods: Thirty male rats were subject to a standardized tibial shaft osteotomy initially stabilized with external fixation. On day 7, they were assigned to either the control group (group A, N = 10) or conversion to secondary nailing with a small (group B, N = 10) or large diameter nails (group C, N = 10). Evaluation at 60 days included radiography, dual energy radiographic absorptiometry (DXA), and mechanical bending testing. Results: All fractures healed radiographically with bridging of the fracture line and more or less visible periosteal callus formation. Group B demonstrated significantly increased mineralization and callus formation measured as DXA parameters, bone mineral content (BMC), and callus area (CA) compared to both the other two groups. This group also tended to have mechanically stronger bones with higher fracture energy compared to both the other two groups, but no significant difference in mechanical prioperties between the groups was found in our study. Interpretation: In conclusion, we found that conversion from external fixation of leg fractures in rats to intramedullary nailing did not improve bone healing significantly supporting external fixation as definitive fracture management.

Associations of timing of surgery with postoperative length of stay, complications, and functional outcomes 3–6 years after operative fixation of closed ankle fractures

AIMS To evaluate the associations of timing of surgery with postoperative length of stay (LOS), complications, and functional outcomes 3-6 years after open reduction and internal fixation (ORIF) in closed ankle fractures. PATIENTS AND METHODS Historical cohort study by chart review of 1011 patients for postoperative LOS and complications; 959 individuals were invited to participate in a postal survey with functional outcomes questionnaires. Complications were classified as perioperative, early, or late. The associations with time from trauma to surgery (<8h, 8h to 6days, >6days) were assessed with (1) postoperative LOS using multivariable random-effects negative binomial regression, (2) complications using multivariable binary and multinomial logistic regression, and (3) three different functional outcomes using multivariable linear regression. RESULTS The mean patient age was 51.4 (range 18-94) years, 556 (55%) were female, and 567 individuals (59%) responded to the questionnaire. There were no statistically significant associations between time to surgery and either postoperative LOS or complications after adjusting for several patient and fracture characteristics. Patients operated on >6days after the trauma had significantly worse scores on the Olerud and Molander Ankle Score (OMAS) (p=0.039) and somewhat worse, but non-significant, scores on the Lower Extremity Functional Scale (LEFS; p=0.573) and the Self-Reported Foot and Ankle Score (SEFAS) scale (p=0.161) than those operated on <8h after trauma. CONCLUSION In ankle-fracture surgery, there was no apparent association between timing of surgery and postoperative LOS or complications. A delay of surgery for 8h to 6days resulted in similar functional outcomes after 3-6 years suggesting there may be a safe window of time for surgery of up to 6days after trauma that can be used to plan and perform the final ORIF.

The influence of compression on the healing of experimental tibial fractures

PURPOSE Experimental studies of the effects of various mechanical conditions and stimuli on bone healing have disclosed an improvement potential in bone fracture mineralization and biomechanical properties. We therefore evaluated the effect of a clinically practicable application of a mechanical compressive interfragmentary stimulus on the healing of experimental tibial diaphyseal fractures. METHODS Sixty Male rats received a standardized tibial shaft osteotomy stabilized with a unilateral external fixator with a zero interfragmentary distance, and then randomly assigned to the compression (N=20), control (N=20) or distraction (N=20) group. From days 4 to day 14, the external fixator was either tightened (compression group) or loosened (distraction group) once daily to gradually induce a total axial displacement of the external fixator pin clamps of 1.25 mm. Evaluation at 30 and 60 days post-osteotomy included radiography, dual-energy X-ray absorptiometry (DXA), quantitative CT and mechanical testing. RESULTS All fractures healed radiographically with sparse callus. At 60 days, the compression and control groups exhibited significantly less amount of mineralized callus in terms of DXA measured callus area and bone mineral content (BMC) compared to the distraction group. These groups also demonstrated a smaller volume of low-mineralized bone tissue (callus) and a larger volume of highly mineralized bone tissue (cortical bone) measured by QCT than in the distraction group. Both mechanical strength and stiffness was significantly higher in the compression and control groups than in the distraction group at 60 days. DISCUSSION Compression did not enhance fracture healing in terms of mineralization, bending strength, or stiffness at the time of union, compared with the control condition. The compression and control groups exhibited improved healing in terms of mechanical strength and stiffness and a more mature callus mineralization compared with the distraction group.

Functional outcomes following surgical-site infections after operative fixation of closed ankle fractures

BACKGROUND To compare the functional outcomes between patients with and without postoperative surgical-site infection (SSI) after surgical treatment in closed ankle fractures. METHODS Retrospective cohort study with prospective follow-up. Of 1011 treated patients, 959 were eligible for inclusion in a postal survey. Functional outcomes were assessed using three self-reported questionnaires. RESULTS In total 567 patients responded a median of 4.3 years (range 3.1-6.2 years) after surgery. In total 29/567 had an SSI. The mean Olerud and Molander Ankle Score was 19.8 points lower for patients with a deep SSI (p=0.02), the Lower Extremity Functional Scale score was 10.2 points lower (p<0.01) and the Self-Reported Foot & Ankle Questionnaire score was 5.0 points higher (p=0.10) than for those without an SSI, after adjusting for age, sex, smoking status, diabetes, physical status, fracture classification and duration of surgery. CONCLUSIONS Patients with a deep SSI had worse long-term functional outcomes than those without an SSI.

Correlations between strength and quantitative computed tomography measurement of callus mineralization in experimental tibial fractures.

BACKGROUND the evaluation of fracture healing in the clinic has not changed significantly during the past few decades, despite the development of modern tissue-imaging tools. Recent publications have reported significant and interesting associations between biomechanical properties and quantitative computed tomography data of fractures and grafts. We therefore studied the correlations between the strength and segmented quantitative computed tomography data of tibial diaphyseal fractures. METHODS forty male rats received a tibial-shaft osteotomy that was initially stabilized with either intramedullary nailing or external fixation. Evaluation at 30 and 60 days post-osteotomy included X-ray, quantitative computed tomography and bending testing. Quantitative computed tomography data were segmented by voxel density into soft callus (171-539 mg/cm(3)), hard callus (540-1199 mg/cm(3)) and cortical bone (≥ 1200mg/cm(3)), and volumetric bone mineral density was calculated. FINDINGS all fractures demonstrated pronounced formation of soft and hard callus tissues at 30 days post-osteotomy, and at 60 days the cortical bone volume was significantly increased with callus resorption. Bending strength correlated significantly and positively with fracture-site cortical bone volume and volumetric bone mineral density in the intramedullary nailed group in the early phase of healing. INTERPRETATION quantitative computed tomography was used to quantify characteristic secondary healing. The observed correlations indicate that biomechanically important mineralization can be measured by quantitative computed tomography in the early phase of healing in flexibly fixed fractures.

Association of Body Mass Index With the Pattern of Surgically Treated Ankle Fractures Using Two Different Classification Systems

Abstract The present retrospective cohort study assessed the association of body mass index (BMI) with the pattern of ankle fractures using 2 classifications systems. Of the 1011 consecutive patients who underwent surgery for ankle fractures in 2 hospitals from January 2009 to December 2011, 837 had a classifiable fracture according to 1 of 2 classification systems and complete information available for covariates. The association of BMI, adjusted for age, sex, corticosteroid use, diabetes, and smoking status with having a more proximal fibula fracture (Weber class A to C) and an increasing number of malleoli involved (uni‐, bi‐, or trimalleolar) was assessed using multivariable ordered logistic regression analysis. The mean age of the patients was 50.9 ± 16.9 years, and 461 (55%) were female. On multivariable analysis, BMI and male sex were associated with having a more proximal fibula fracture using the Weber classification, with an odds ratio (OR) of 1.07 (95% confidence interval [CI] 1.04 to 1.11; p < .001) per 1 kg/m2 increase and OR of 2.96 (95% CI 2.13 to 4.11; p < .001) compared with female sex, respectively. Age was not associated with this fracture classification. In an analysis of uni‐, bi‐, and trimalleolar fractures, age per 10 years showed higher odds (OR 1.24, 95% CI 1.14 to 1.36; p < .001) and male sex lower odds compared with female sex (OR 0.36, 95% CI 0.27 to 0.48; p < .001) of having trimalleolar fractures than uni‐ or bimalleolar fractures. An increasing BMI did not seem to be a risk factor, although an inverse U‐shaped relationship was seen between quintiles of BMI and the OR of having trimalleolar versus uni‐ or bimalleolar fractures. Corticosteroid use, diabetes, and smoking status were not significantly associated with the pattern of the ankle fractures using either classification system. In conclusion, an increasing BMI and male sex were risk factors for proximal fibula fractures, and female sex and age were risk factors for bi‐ and trimalleolar fractures. &NA; Level of Clinical Evidence: 3