Approach to Tibial Shaft Nonunions: Diagnosis and Management.

The tibia is the most common long bone at risk for nonunion with an annual incidence ranging from 12% to 19%. This topic continues to be an area of research as management techniques constantly evolve. A foundational knowledge of the fundamental concepts, etiology, and risk factors for nonunions is crucial for success. Treatment of tibial shaft nonunions often requires a multidisciplinary effort. This article provides guidance based on the most recent literature that can be used to aid the treating provider in the diagnosis, workup, and management of tibial shaft nonunions.

[Diagnostic and therapeutic work-up of infected tibial nonunion]. / Diagnostik und Therapie der infizierten Tibia-Pseudarthrose.

BACKGROUND: The failure of bone fracture healing is one of the major complications of fracture treatment, especially of the tibia due to its limited soft tissue coverage and high rate of open injuries. Although implant development is constantly progressing and modern surgical techniques are continuously improving, infected tibial nonunion plays a decisive role in terms of its variable clinical presentation. OBJECTIVE: This article provides guidelines for the successful surgical treatment of infected tibial nonunion. MATERIAL AND METHOD: Strategies are presented to identify infection as a cause of failure of fracture healing and to achieve infection and bone healing. RESULTS: A significant amount of tibial nonunions primarily thought to be aseptic ultimately turn out to be infected nonunions. CONCLUSION: The treatment of infected tibial nonunion requires extensive clinical, radiological and laboratory diagnostics as well as a profound biomechanical and biological understanding of the bone situation. This is the only way to achieve rapid osseous healing with as few revision interventions as possible.

[Non-union]. / Non-union.

A non-union is a fracture that fails to heal within the expected time frame and occurs in approximately 3 to 5% of all fractures. Non-union has a negative impact on mental and physical functioning and quality of life. The causes, clinical presentation and treatment for non-union differ strongly on a case-by-case basis. By presenting three cases we aim to give healthcare providers more insight into the clinical scenario of non-union. In addition, we elaborate on characteristics, etiology, diagnostics and treatment of non-union.

Diagnosis of Occult Infection Using Fracture-Related Infection Criteria at the Time of Nonunion Repair.

OBJECTIVES: To apply the recently developed fracture-related infection criteria to patients presenting for repair of fracture nonunion and determine the incidence and associated organisms of occult infection in these patients. DESIGN: Retrospective study. SETTING: Tertiary referral trauma center. PATIENTS AND PARTICIPANTS: Patients presenting with fracture nonunion after operative intervention. MAIN OUTCOME MEASUREMENTS: Demographic variables, injury characteristics, culture results, and physical examination and laboratory values at the time of presentation. RESULTS: A total of 270 nonunion patients were identified. Sixty-eight percent (n = 184) had no clinical or laboratory signs of infection at presentation before nonunion repair. After operative intervention, 7% of these clinically negative patients (n = 12/184) had positive intraoperative cultures indicating occult infection. The most common organisms causing occult infection were low-virulence coagulase-negative Staphylococcu s (83%) and Cutibacterium acnes (17%). Thirty-two percent of patients (n = 86/270) presented with clinical and/or laboratory signs of infection at presentation before nonunion repair, with 19% of these patients (n = 16/86) having negative cultures. The most common organisms in this group of patients with positive clinical signs and intraoperative cultures were methicillin-resistant Staphylococcus Aureus (21%) and gram-negative rods (29%). Patients with nonunion of the tibia were significantly more likely to have high-virulence organism culture results ( P < 0.001). CONCLUSIONS: Based on this analysis, occult infection occurs in 7% of patients presenting with nonunion and no clinical or laboratory signs of infection. We recommend that all patients should be carefully evaluated for infection with intraoperative cultures regardless of presentation. Organisms associated with occult infection at the time of nonunion repair were almost exclusively of low virulence ( CoNS and C. Acnes ) and were more likely to present in the upper extremity. Patients with nonunion of the tibia were more likely to have infection secondary to high-virulence organisms and demonstrate clinical or laboratory signs of infection at the time of presentation. LEVEL OF EVIDENCE: Diagnostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

[Infected nonunion: diagnostic and therapeutic work-up]. / Infizierte Pseudarthrose: diagnostischer und therapeutischer Ablauf.

BACKGROUND: Septic nonunion is one of the major complications in fracture healing. The challenge is to identify the infection as the cause of nonunion first and then to achieve healing of the infection and the bone. OBJECTIVE: Because of the more heterogeneous appearance of an infected nonunion, the prevalence of germ detection in surgical nonunion revision is often underestimated. MATERIAL AND METHODS: In a retrospective study between 2010 and 2017, 86 patients with radiologically confirmed femoral shaft nonunion without clinical evidence and unremarkable medical history of a florid infection as the cause of nonunion, who had undergone primary single-stage surgical nonunion revision were analyzed. At least four intraoperatively obtained samples were evaluated for microbiological diagnosis. A distinction was made between tissue samples with subsequent 48­h short-term incubation and tissue samples with 14-day long-term cultivation. The finding "germ detection" was made if at least two of the samples demonstrated bacterial growth. RESULTS: In 18 of 86 patients with a nonunion preoperatively judged to be aseptic, positive bacterial evidence was obtained after short-term incubation. After long-term cultivation, positive bacterial detection was possible in 38 of 86 patients with a femoral shaft nonunion initially classified as aseptic. Regarding potential risk factors, the two groups demonstrated no relevant differences. In 29 patients, 1 pathogen was isolated from the obtained samples, whereas in the remaining 9 patients, a mixed culture with an average of 2.9 ± 0.5 different bacteria was detected. Identification revealed mainly low-virulence bacteria, most commonly Staphylococcus epidermidis. CONCLUSION: If the preoperative diagnostics including clinical, laboratory and radiological examination as well as a careful anamnesis reveal indications of a possible infectious event, the surgical nonunion revision should be performed in two stages with specimen collection before definitive nonunion revision. For microbiological diagnosis, several representative tissue samples should independently be obtained from the nonunion site and incubated for 14 days. Only in the absence of evidence of septic nonunion is a single-stage procedure suggested.

Bacterial Identification and Visualization of Bacterial Biofilms Adjacent to Fracture Sites After Internal Fixation.

Objectives: The primary aims of this study were to determine if any correlation exists in cases of fracture fixation among: (1) bacterial profiles recovered from the instrumentation and adjacent tissues; (2) the type of orthopedic injury; and (3) the clinical outcome-union versus nonunion. A secondary goal was to compare culture and molecular diagnostics for identifying the bacterial species present following fracture fixation. Design: Single-institution, prospective case-control cohort study. Setting: Single level 1 trauma center. Patients: Forty-nine bony nonunion cases undergoing revision internal fixation and 45 healed fracture controls undergoing removal of hardware. Intervention: Bacterial infection was detected by standard microbial culture methods and by a pan-eubacterial domain, molecular diagnostic (MDx) assay. Confirmation of culture and MDx results was achieved with bacterial ribosomal 16S rRNA fluorescence in situ hybridization (FISH) to visualize bacterial biofilms. Main Outcome Measurements: MDx and microbial culture methods results were the primary study outcomes. Results: Ninety-four percent of the nonunion cohort and 93% of the union cohort had bacteria detected by the MDx. Seventy-eight percent of the nonunion cases and 69% of the controls were culture negative, but MDx positive. Although no significant differences in bacterial composition were observed between the cases and controls, differences were observed when cases were divided by comorbidities. Conclusion: The MDx is more sensitive than microbial culture in detecting bacterial presence. The lack of significantly different findings with regard to bacterial profile identified between the cases and controls suggests that host factors and environmental conditions are largely responsible for determining if bony union will occur. Level of Evidence: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Predicting fracture healing with blood biomarkers: the potential to assess patient risk of fracture nonunion.

Fracture non-union is a significant orthopaedic problem affecting a substantial number of patients yearly. Treatment of nonunions is devastating to patients and costly to the healthcare system. Unfortunately, the diagnosis of non-union is typically made in a reactionary fashion by an orthopaedic surgeon based on clinical assessment and radiographic features several months into treatment. For this reason, investigators have been trying to develop prediction algorithms; however, these have relied on population-based approaches and lack the predictive capability necessary to make individual treatment decisions. There is also a growing body of literature focussed on identifying blood biomarkers that are associated with non-union. This review describes the research that has been done in this area. Further studies of patient-centered, precision medicine approaches will likely improve fracture non-union diagnostic/prognostic capabilities.

Prediction of Nonunion After Nonoperative Treatment of a Proximal Humeral Fracture.

BACKGROUND: The prevalence of nonunion after a proximal humeral fracture (PHF) and the risk factors for its occurrence are poorly defined. We aimed to estimate the rate of nonunion in nonoperatively treated patients and to produce a clinical model for its prediction. METHODS: Two thousand two hundred and thirty adult patients (median age, 72 years [range, 18 to 103 years]; 75.5% were female) with a PHF underwent assessment of fracture union using standard clinical evaluation and conventional radiographs. We assessed the prevalence of nonunion and measured the effect of 19 parameters on healing. Best statistical practices were used to construct a multivariate logistic regression model. The PHF assessment of risk of nonunion model (PHARON) was externally validated in a subsequent prospectively collected population of 735 patients, treated by the same protocol in our institution. RESULTS: Overall, 231 (10.4%) of 2,230 patients developed nonunion. Only 3 (0.8%) of 395 patients with a head-shaft angle (HSA) of >140° developed nonunion; in this cohort, none of the measured candidate variables were independently predictive of nonunion on multivariate logistic regression analysis. In the larger cohort of 1,835 patients with an HSA of ≤140°, 228 (12.4%) developed nonunion. Decreasing HSA, increasing head-shaft translation (HST), and smoking were independently predictive of nonunion on multivariate analysis. The prevalence of nonunion was very low (1%) in the majority with both an HSA of >90° and HST of <50%, whereas the risk was much higher (83.7%) in the 8.3% with an HSA of ≤90° and HST of ≥50%. In both groups, the prevalence of nonunion was much higher in smokers. CONCLUSIONS: The prevalence of nonunion after PHF is higher than previously reported. Most patients have favorable risk-factor estimates and a very low risk of this complication, but a smaller subgroup is at much higher risk. The risk can be accurately estimated with PHARON, using standard clinical assessment tools. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

The risk assessment model of fracture nonunion after intramedullary nailing for subtrochanteric femur fracture.

ABSTRACT: To investigate the influencing factors of fracture nonunion after intramedullary nailing for subtrochanteric fractures and to construct a risk assessment model.Based on the multicenter retrospective analysis of 251 patients, all patients were divided into modeling group and verification group. In the modeling group, postoperative fracture nonunion rate, general data, fracture-related factors, surgical reduction-related factors, mechanical and biological factors were calculated, and the influencing factors of fracture nonunion were screened by univariate analysis. Logistic regression model was used for multifactor analysis to construct the risk assessment model. Based on the logistic regression model, the risk prediction model was constructed by drawing the Nomogram diagram. Through the verification group, the influencing factors were evaluated again, and the differentiation and calibration of the model were evaluated. The calibration degree was evaluated by Hosmer-Lemeshow test, goodness of fit test, and calibration curve. The discriminant degree was evaluated by the receiver operating characteristic curve.Fracture nonunion occurred in 34 of 149 patients in the modeling group. Among the 14 potential influencing factors, univariate analysis and logistic regression analysis showed that postoperative hip varus, intramedullary nail fixation failure, and reduction of fracture with large incision were the risk factors of fracture nonunion. The medial cortex fracture was seen reduced on X-Ray was a protective factor for fracture nonunion, and a regression equation was established. Based on the logistic regression model, the Nomogram diagram is drawn. Twenty-four cases of fracture nonunion occurred in the verification group. The area under the receiver operating characteristic curve was area under curve =0.883 > 0.7, indicating that there was a moderate differentiation to evaluate the occurrence of fracture nonunion after operation. The goodness of fit test: the Hosmers-Lemeshow test (X2 = 2.921, P = .712 > .05) showed that the model had a good calibration.After intramedullary nailing of subtrochanteric fracture, hip varus, failure of intramedullary nail fixation and wide surgical dissection are the risk factors of fracture nonunion, and the postoperative reduction of medial cortex fracture is protective factor.National key research and development projects: 2016YFC0105806.

The AMANDUS Project PART II-Advanced Microperfusion Assessed Non-Union Diagnostics with Contrast-Enhanced Ultrasound (CEUS): A Reliable Diagnostic Tool for the Management and Pre-operative Detection of Infected Upper-Limb Non-unions.

The management of upper-limb non-unions can be challenging, especially when infection is existent. Thus, pre-operative detection of infection plays a relevant role in non-union treatment. This study investigated in a large cohort the diagnostic potential of contrast-enhanced ultrasound (CEUS) as stand-alone method for differentiating between aseptic and infected upper-limb non-unions. Osseous perfusion of 50 upper-extremity non-unions (radius/ulna, n = 20; humerus, n = 22; clavicle, n = 8) was prospectively assessed with CEUS before revision surgery. The perfusion was quantified via time-intensity curves and peak enhancement (in arbitrary units). Significant perfusion differences between aseptic and infected non-unions could be detected (peak enhancement, p < 0.001). The sensitivity and specificity for the detection of infected upper-limb non-unions were 80% and 94.3% (cutoff peak enhancement: 130.8 arbitrary units). CEUS reliably differentiates between aseptic and infected upper-limb non-unions. Consequently, CEUS should be integrated into the daily diagnostic routine algorithm to plan non-union revision surgery more precisely as a single- or multi-step procedure.

Endoscopic resection of scar tissues and bone graft with an intramedullary nail left in situ for distal femoral nonunion after nailing: A case report.

Femoral shaft nonunion after the intramedullary nailing has been successfully treated with advances in surgical technique. Nonetheless, the techniques cause morbidity to periosteum at the fracture site. We report the case of a 67-year-old man who underwent endoscopic surgery for refractory nonunion following the fracture of the distal femoral shaft, despite two fixations using an interlocking nail. In addition, the patient had uncontrolled diabetic mellitus. Endoscopy allowed us to acquire a clear view of the nonunion site, in which the resection of scar tissues and the packing of the cancellous bone were performed. At the final follow-up, bone healing was observed, and the patient was able to return to normal daily and social activity.

The Life of a Fracture: Biologic Progression, Healing Gone Awry, and Evaluation of Union.

New knowledge about the molecular biology of fracture-healing provides opportunities for intervention and reduction of risk for specific phases that are affected by disease and medications. Modifiable and nonmodifiable risk factors can prolong healing, and the informed clinician should optimize each patient to provide the best chance for union. Techniques to monitor progression of fracture-healing have not changed substantially over time; new objective modalities are needed.

Bioinformatic analysis and experimental identification of blood biomarkers for chronic nonunion.

BACKGROUND: Incomplete fracture healing may lead to chronic nonunion; thus, determining fracture healing is the primary issue in the clinical treatment. However, there are no validated early diagnostic biomarkers for assessing chronic nonunion. In this study, bioinformatics analysis combined with an experimental verification strategy was used to identify blood biomarkers for chronic nonunion. METHODS: First, differentially expressed genes in chronic nonunion were identified by microarray data analysis. Second, Dipsaci Radix (DR), a traditional Chinese medicine for fracture treatment, was used to screen the drug target genes. Third, the drug-disease network was determined, and biomarker genes were obtained. Finally, the potential blood biomarkers were verified by ELISA and qPCR methods. RESULTS: Fifty-five patients with open long bone fractures (39 healed and 16 nonunion) were enrolled in this study, and urgent surgical debridement and the severity of soft tissue injury had a significant effect on the prognosis of fracture. After the systems pharmacology analysis, six genes, including QPCT, CA1, LDHB, MMP9, UGCG, and HCAR2, were chosen for experimental validation. We found that all six genes in peripheral blood mononuclear cells (PBMCs) and serum were differentially expressed after injury, and five genes (QPCT, CA1, MMP9, UGCG, and HCAR2) were significantly lower in nonunion patients. Further, CA1, MMP9, and QPCT were markedly increased after DR treatment. CONCLUSION: CA1, MMP9, and QPCT are biomarkers of nonunion patients and DR treatment targets. However, HCAR2 and UGCG are biomarkers of nonunion patients but not DR treatment targets. Therefore, our findings may provide valuable information for nonunion diagnosis and DR treatment. TRIAL REGISTRATION: ISRCTN, ISRCTN13271153. Registered 05 April 2020-Retrospectively registered.

Tibial Fracture Healing Score: A Novel Tool to Predict Tibial Nonunion.

The aim of the study was to investigate the utility of a simple office-based tool in predicting the need for secondary intervention to obtain union in patients with tibial fractures. All patients 18 years and older with isolated tibial shaft fractures (OTA 41A, 42A-C, and 43A) treated with intramedullary nailing from 2013 to 2017 were screened. Eighty-seven patients met enrollment criteria. Surgeon assessment of the following 3 clinical parameters was performed at routine office visits and scored as follows: (1) pain (none/mild/decreased=1, no change/increased=0); (2) function (minimal limp/able to perform a single-leg stance=1, significant limp/unable to perform single-leg stance=0); and (3) examination (no/minimal pain with manipulation=1, pain with manipulation=0). Radiographic healing was assessed by the adjusted radiographic union scale in tibial fractures (aRUST). The tibial fracture healing score (TFHS) is the sum of 3 clinical scores (0 to 3) and aRUST score (1 to 3) at 3 months postoperatively. The overall nonunion rate was 11%. A RUST score of 5 or less and a sum of the 3 clinical scores of less than 2 at 3 months were found be predictive of nonunion. A TFHS of less than 3 at 3 months was more reliable in identifying patients requiring nonunion repair, especially for those with minimal radiographic healing (RUST score 6 or 7) at 3 months. The TFHS is a simple office-based clinical tool that may identify patients at high risk of nonunion (TFHS <3) following isolated tibial shaft fracture more effectively than clinical examination or radiographic assessment alone. [Orthopedics. 2020;43(4);e323-e328.].

Management of nonunion of humeral medial condyle fracture: A case series and review of the literature.

Pediatric humeral medial condyle fracture (HMCF) is a rare condition and is difficult to detect, especially in young children. The management of late presentation of HMCF is challenging and lacks consensus. Herein, we reported four cases of HMCF nonunion received open reduction and internal fixation (ORIF) or supracondyle osteotomy from our institution. In addition, 12 cases of ORIF and 4 cases of osteotomy reported in the previous studies were also reviewed. The HMCF nonunion can heal after ORIF, but the indication and the optimal techniques need to be clarified. Supracondylar osteotomy alone is an effective and safe treatment option to improve the functional and cosmetic outcomes of HMCF nonunion.

Upper endplate nonunion after transcorporeal percutaneous endoscopic cervical discectomy: A case report.

BACKGROUND: Transcorporeal percutaneous endoscopic cervical discectomy (TcPECD) destroys the integrity of the vertebral body. We herein discuss its long-term risks and avoidance measures. Case presentation: A 44-year-old woman underwent TcPECD. Although her upper limb symptoms were relieved after the operation, the bone channel did not heal and the endplate of the segment was altered. She consequently developed chronic neck and shoulder discomfort. CONCLUSION: Careful preoperative planning is needed to avoid non-healing of the bone channel following TcPECD. The diameter of the bony channel should be as small as possible and the channel should be opened at the posterior edge of the upper endplate to avoid collapse.

Rib Plating Offers Favorable Outcomes in Patients With Chronic Nonunion of Prior Rib Fractures.

BACKGROUND: Although open reduction and internal fixation (ORIF) is an accepted treatment for a proportion of acute rib fractures, The literature on its potential to treat chronic, nonunion fractures is scarce. This study evaluates the outcomes and quality of life of patients who underwent ORIF for chronic, symptomatic, nonunion rib fractures. METHODS: Thirty-two patients were explored for possible ORIF of nonunion rib fractures (≥6 months after injury). After excluding non-English-speaking patients (n = 1), those where no instability was noted at surgery (n = 3), and those deceased at the time of study (n = 4), 24 patients were eligible. Telephone interviews were conducted using a previously published rib fracture pain questionnaire. RESULTS: Seventy percent of eligible patients (19/24) consented and completed the questionnaire at a median of 55 months (interquartile range, 24-62) from surgery. Injuries were classified as multisystem trauma (n = 4) or isolated rib fractures (n = 15). The median pain severity (on a scale of 1 [none/mild] to 10 [severe]) significantly decreased from preoperatively (9; interquartile range, 7-10) to postoperatively (1; interquartile range, 0-2; P < .001). Most patients returned to daily activities, were able to work at their preinjury level, were satisfied with their surgery, and would undergo operative management again. CONCLUSIONS: Patients who underwent ORIF reported a significant decrease in fracture-associated symptoms and pain severity postoperatively. Most returned to daily activities, could work at preinjury levels, and were satisfied with surgery. ORIF should be considered as an option to help patients with symptomatic nonunion rib fractures.

Identification of key microRNAs and target genes for the diagnosis of bone nonunion.

A number of recent studies have highlighted the causes of bone nonunion (BN), however, the rate of BN incidence continues to rise and available therapeutic options to treat this condition remain limited. Thus, to prevent disease progression and improve patient prognosis, it is vital that BN, or the risk thereof, be accurately identified in a timely manner. In the present study, bioinformatics analyses were used to screen for the differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) between patients with BN and those with bone union, using data from the Gene Expression Omnibus database. Furthermore, clinical samples were collected and analyzed by reverse transcription­quantitative PCR and western blotting. In vitro and in vivo experiments were carried out to confirm the relationship between BN and the DEGs of interest, in addition to being used to explore the underlying molecular mechanism of BN. Functional enrichment analysis of the downregulated DEGs revealed them to be enriched for genes associated with 'ECM­receptor interactions', 'focal adhesion', 'and the calcium signaling pathway'. When comparing DEM target genes with these DEGs, nine DEGs were identified as putative DEM targets, where hsa­microRNA (miR)­1225­5p­CCNL2, hsa­miR­339­5p­PRCP, and hsa­miR­193a­3p­mitogen­activated protein kinase 10 (MAPK10) were the only three pairs which were associated with decreased gene expression levels. Furthermore, hsa­miR­193a­3p was demonstrated to induce BN by targeting MAPK10. Collectively, the results of the present study suggest that hsa­miR­193a­3p may be a viable biomarker of BN.

Epidemiology, Clinical Assessments, and Current Treatments of Nonunions.

PURPOSE OF REVIEW: The failure of bony union following a fracture, termed a fracture nonunion, has severe patient morbidity and economic consequences. This review describes current consensuses and future directions of investigation for determining why, detecting when, and effective treatment if this complication occurs. RECENT FINDINGS: Current nonunion investigation is emphasizing an expanded understanding of the biology of healing. This has led to assessments of the immune environment, multiple cytokines and morphogenetic factors, and the role of skeletogenic stem cells in the development of nonunion. Detecting biological markers and other objective diagnostic criteria is also a current objective of nonunion research. Treatment approaches in the near future will likely be dominated by the development of specific adjunct therapies to the nonunion surgical management, which will be informed by an expanded mechanistic understanding of nonunion biology. Current consensus among orthopedists is that improved diagnosis and treatment of nonunion hinges first on discoveries at the bench side with later translation to the clinic.