Aims

Several previously identified patient-, injury-, and treatment-related factors are associated with the development of nonunion in distal femur fractures. However, the predictive value of these factors is not well defined. We aimed to assess the predictive ability of previously identified risk factors in the development of nonunion leading to secondary surgery in distal femur fractures.

Objectives. A successful outcome following treatment of nonunion requires the correct identification of all of the underlying cause(s) and addressing them appropriately. The aim of this study was to assess the distribution and frequency of causative factors in a consecutive cohort of nonunion patients in order to optimise the management strategy for individual patients presenting with nonunion. Methods. Causes of the nonunion were divided into four categories: mechanical; infection; dead bone with a gap; and host. Prospective and retrospective data of 100 consecutive patients who had undergone surgery for long bone fracture nonunion were analysed. Results. A total of 31% of patients had a single attributable cause, 55% had two causes, 14% had three causes and 1% had all four. Of those (31%) with only a single attributable cause, half were due to a mechanical factor and a quarter had dead bone with a gap. Mechanical causation was found in 59% of all patients, dead bone and a gap was present in 47%, host factors in 43% and infection was a causative factor in 38% of patients. In all, three of 58 patients (5%) thought to be aseptic and two of nine (22%) suspected of possible infection were found to be infected. A total of 100% of previously treated patients no longer considered to have ongoing infection, had multiple positive microbiology results. Conclusion. Two thirds of patients had multiple contributing factors for their nonunion and 5% had entirely unexpected infection. This study highlights the importance of identifying all of the aetiological factors and routinely testing tissue for infection in treating nonunion. It raises key points regarding the inadequacy of a purely radiographic nonunion classification system and the variety of different definitions for atrophic nonunion in the current mainstream classifications used for nonunion. Cite this article: L. Mills, J. Tsang, G. Hopper, G. Keenan, A. H. R. W. Simpson. The multifactorial aetiology of fracture nonunion and the importance of searching for latent infection. Bone Joint Res 2016;5:512–519. DOI: 10.1302/2046-3758.510.BJR-2016-0138

Introduction. Many surgeons assess biological activity of fracture nonunion by the presence or absence of callus using radiograph. However, it is difficult to assess biological activity only by radiographic appearance. Bone scintigraphy reflects blood supply and bone metabolism and is possibly useful to assess biological activity in nonunion cases. Hypothesis. We hypothesized that poor callus visualization did not always mean lack of biological activity. Materials & Methods. Retrospective assessment and comparison of radiographs and Tc-99m bone scintigraphy of 44 patients with uninfected nonunion was done. Results. Uptake was observed at or around the nonunion site in all cases. Three patterns of uptake were noted; Spot type (S): intense uniform uptake, Uneven type (U): uptake with distribution from cold to hot, and Cleft type (C): decreased uptake surrounded by significant uptake on both sides. All 9 cases of hypertrophic nonunion demonstrated the S type. In 21 cases of oligotrophic nonunion, there were 12 S, 5 U and 4 C. In 3 cases of comminuted nonunion, there were 1 U and 2 C. In 5 cases of defect nonunion, there were 1 U and 4 C. In 6 cases of atrophic nonunion, there were 2 U and 4 C. Discussion & Conclusions. Our results suggest that poor callus visualization does not always mean lack of biological activity. The distribution of uptake and the cleft with decreased uptake are helpful findings to assess the necessity of bone graft or other supplementation in nonunion surgery

Introduction

Non-union is an unfortunate outcome of the fracture healing process for some patients; with an estimated annual incidence of 17.4- 18.9 per 100,00. The management of these patients depicts a significant clinical challenge for surgeons and financial burden to health services. External ultrasound stimulation devices (Exogen^TM) have been highlighted as a novel non invasive therapy to achieve union in cases of delayed and non-union. The aim of the current study was to assess the rate of union in patients using Exogen^TM therapy for delayed fracture union in a district general hospital.

Introduction

Non-union is debilitating, costly and affects 2–8% of intramedullary fixed fractures. Clinical data suggest that percutaneous interfragmentary screws offer a less invasive alternative to exchange nailing. This study aimed to assess their efficiency with biomechanical analyses.

Aims

Impaired fracture repair in patients with type 2 diabetes mellitus (T2DM) is not fully understood. In this study, we aimed to characterize the local changes in gene expression (GE) associated with diabetic fracture. We used an unbiased approach to compare GE in the fracture callus of Zucker diabetic fatty (ZDF) rats relative to wild-type (WT) littermates at three weeks following femoral osteotomy.

Background

Humerus fracture non-union is a challenge for which a wide range of treatments exist. We present our experience of managing these by hybrid Ilizarov frame fixation, without bone graft or debridement of the non-union site.

We present a case of multifocal infection involving the left total hip replacement and the right total knee replacement of a patient, further complicated by an infected non-union of a periprosthetic fracture of the right knee. This required the unique simultaneous management of both infection eradication and fracture stabilization in the knee.

Both sites were treated with a 2-stage procedure, including the novel use of a stemmed articulating spacer for the right knee. This spacer was made combining a retrograde humeral nail, coated with antibiotic-impregnated cement, and a pre-formed articulating cement spacer. The patient was able to weight-bear on this spacer. The fracture went on to unite, and a second stage was performed with the use of stemmed prosthesis and augments. She remains infection free 2 years after the second stage operation.

The use of a stemmed articulating knee spacer can facilitate infection eradication and fracture stabilization while preserving some motion and weight-bearing ability in the 2 stage management of an infected periprosthetic fracture of the knee.

Introduction

Nonunion is a common and costly fracture outcome. Intricate reciprocity between angiogenesis and osteogenesis means vascular cell-based therapy offers a novel approach to stimulating bone regeneration.

Aims. Fractures of the humeral shaft represent 3% to 5% of all fractures. The most common treatment for isolated humeral diaphysis fractures in the UK is non-operative using functional bracing, which carries a low risk of complications, but is associated with a longer healing time and a greater risk of nonunion than surgery. There is an increasing trend to surgical treatment, which may lead to quicker functional recovery and lower rates of fracture nonunion than functional bracing. However, surgery carries inherent risk, including infection, bleeding, and nerve damage. The aim of this trial is to evaluate the clinical and cost-effectiveness of functional bracing compared to surgical fixation for the treatment of humeral shaft fractures. Methods. The HUmeral SHaft (HUSH) fracture study is a multicentre, prospective randomized superiority trial of surgical versus non-surgical interventions for humeral shaft fractures in adult patients. Participants will be randomized to receive either functional bracing or surgery. With 334 participants, the trial will have 90% power to detect a clinically important difference for the Disabilities of the Arm, Shoulder and Hand questionnaire score, assuming 20% loss to follow-up. Secondary outcomes will include function, pain, quality of life, complications, cost-effectiveness, time off work, and ability to drive. Discussion. The results of this trial will provide evidence regarding clinical and cost-effectiveness between surgical and non-surgical treatment of humeral shaft fractures. Ethical approval has been obtained from East of England – Cambridge Central Research Ethics Committee. Publication is anticipated to occur in 2024. Cite this article: Bone Jt Open 2024;5(4):343–349

Fracture nonunion is a severe clinical problem for the patient, as well as for the clinician. About 5-20% of fractures does not heal properly after more than six months, with a 19% nonunion rate for tibia, 12% for femur and 13% for humerus, leading to patient morbidity, prolonged hospitalization, and high costs. The standard treatment with iliac crest-derived autologous bone filling the nonunion site may cause pain or hematoma to the patient, as well as major complications such as infection. The application of mesenchymal autologous cells (MSC) to improve bone formation calls for randomized, open, two-arm clinical studies to verify safety and efficacy. The ORTHOUNION * project (ORTHOpedic randomized clinical trial with expanded bone marrow MSC and bioceramics versus autograft in long bone nonUNIONs) is a multicentric, open, randomized, comparative phase II clinical trial, approved in the framework of the H2020 funding programme, under the coordination of Enrique Gòmez Barrena of the Hospital La Paz (Madrid, Spain). Starting from January 2017, patients with nonunion of femur, tibia or humerus have been actively enrolled in Spain, France, Germany, and Italy. The study protocol encompasses two experimental arms, i.e., autologous bone marrow-derived mesenchymal cells after expansion (‘high dose’ or ‘low dose’ MSC) combined to ceramic granules (MBCP™, Biomatlante), and iliac crest-derived autologous trabecular bone (ICAG) as active comparator arm, with a 2-year follow-up after surgery. Despite the COVID 19 pandemic with several lockdown periods in the four countries, the trial was continued, leading to 42 patients treated out of 51 included, with 11 receiving the bone graft (G1 arm), 15 the ‘high dose’ MSC (200x10. 6. , G2a arm) and 16 the ‘low dose’ MSC (100x10. 6. , G2b arm). The Rizzoli Orthopaedic Institute has functioned as coordinator of the Italian clinical centres (Bologna, Milano, Brescia) and the Biomedical Science and Technologies and Nanobiotechnology Lab of the RIT Dept. has enrolled six patients with the collaboration of the Rizzoli’ 3rd Orthopaedic and Traumatological Clinic prevalently Oncologic. Moreover, the IOR Lab has collected and analysed the blood samples from all the patients treated to monitor the changes of the bone turnover markers following the surgical treatment with G1, G2a or G2b protocols. The clinical and biochemical results of the study, still under evaluation, are presented. * ORTHOUNION Horizon 2020 GA 733288

Aims. Our objective was to conduct a systematic review and meta-analysis, to establish whether differences arise in clinical outcomes between autologous and synthetic bone grafts in the operative management of tibial plateau fractures. Methods. A structured search of MEDLINE, EMBASE, the online archives of Bone & Joint Publishing, and CENTRAL databases from inception until 28 July 2021 was performed. Randomized, controlled, clinical trials that compared autologous and synthetic bone grafts in tibial plateau fractures were included. Preclinical studies, clinical studies in paediatric patients, pathological fractures, fracture nonunion, or chondral defects were excluded. Outcome data were assessed using the Risk of Bias 2 (ROB2) framework and synthesized in random-effect meta-analysis. The Preferred Reported Items for Systematic Review and Meta-Analyses guidance was followed throughout. Results. Six studies involving 353 fractures were identified from 3,078 records. Following ROB2 assessment, five studies (representing 338 fractures) were appropriate for meta-analysis. Primary outcomes showed non-significant reductions in articular depression at immediate postoperative (mean difference -0.45 mm, p = 0.25, 95%confidence interval (CI) -1.21 to 0.31, I. 2. = 0%) and long-term (> six months, standard mean difference -0.56, p = 0.09, 95% CI -1.20 to 0.08, I. 2. = 73%) follow-up in synthetic bone grafts. Secondary outcomes included mechanical alignment, limb functionality, and defect site pain at long-term follow-up, perioperative blood loss, duration of surgery, occurrence of surgical site infections, and secondary surgery. Mean blood loss was lower (90.08 ml, p < 0.001, 95% CI 41.49 to 138.67) and surgery was shorter (16.17 minutes, p = 0.04, 95% CI 0.39 to 31.94) in synthetic treatment groups. All other secondary measures were statistically comparable. Conclusion. All studies reported similar methodologies and patient populations; however, imprecision may have arisen through performance variation. These findings supersede previous literature and indicate that, despite perceived biological advantages, autologous bone grafting does not demonstrate superiority to synthetic grafts. When selecting a void filler, surgeons should consider patient comorbidity, environmental and societal factors in provision, and perioperative and postoperative care provision. Cite this article: Bone Jt Open 2022;3(3):218–228

Aims. Rotator cuff (RC) tears are common musculoskeletal injuries which often require surgical intervention. Noninvasive pulsed electromagnetic field (PEMF) devices have been approved for treatment of long-bone fracture nonunions and as an adjunct to lumbar and cervical spine fusion surgery. This study aimed to assess the effect of continuous PEMF on postoperative RC healing in a rat RC repair model. Methods. A total of 30 Wistar rats underwent acute bilateral supraspinatus tear and repair. A miniaturized electromagnetic device (MED) was implanted at the right shoulder and generated focused PEMF therapy. The animals’ left shoulders served as controls. Biomechanical, histological, and bone properties were assessed at three and six weeks. Results. Extension of the tendon from preload to the maximum load to failure was significantly better in the PEMF-treated shoulders at three weeks compared to controls (p = 0.038). The percentage strain was significantly higher in the PEMF group at both timepoints (p = 0.037). Collagen organization was significantly better (p = 0.034) as was tissue mineral density in the PEMF-treated group at three weeks (p = 0.028). Tendon immunohistochemistry revealed a prominent increase in type I collagen at the repair site at three weeks following continuous PEMF treatment compared with controls. None of the other tested parameters differed between the groups. Conclusion. MED-generated PEMF may enhance early postoperative tendon-to-bone healing in an acute rat supraspinatus detachment and repair model. Superior biomechanical elasticity parameters together with better collagen organization suggest improved RC healing. Cite this article: Bone Joint Res 2021;10(5):298–306

Aims. The primary aim of this study was to identify independent predictors associated with nonunion and delayed union of tibial diaphyseal fractures treated with intramedullary nailing. The secondary aim was to assess the Radiological Union Scale for Tibial fractures (RUST) score as an early predictor of tibial fracture nonunion. Methods. A consecutive series of 647 patients who underwent intramedullary nailing for tibial diaphyseal fractures were identified from a trauma database. Demographic data, comorbidities, smoking status, alcohol consumption, use of non-steroidal anti-inflammatory drugs (NSAIDs), and steroid use were documented. Details regarding mechanism of injury, fracture classification, complications, and further surgery were recorded. Nonunion was defined as the requirement for revision surgery to achieve union. Delayed union was defined as a RUST score < 10 at six months postoperatively. Results. There were 41 nonunions (6.3%), of which 13 were infected (31.7%), and 77 delayed unions (11.9%). There were 127 open fractures (19.6%). Adjusting for confounding variables, NSAID use (odds ratio (OR) 3.50; p = 0.042), superficial infection (OR 3.00; p = 0.026), open fractures (OR 5.44; p < 0.001), and high-energy mechanism (OR 2.51; p = 0.040) were independently associated with nonunion. Smoking (OR 1.76; p = 0.034), open fracture (OR 2.82; p = 0.001), and high-energy mechanism (OR 1.81; p = 0.030) were independent predictors associated with delayed union. The RUST score at six-week follow-up was highly predictive of nonunion (sensitivity and specificity of 75%). Conclusion. NSAID use, high-energy mechanisms, open fractures, and superficial infection were independently associated with nonunion in patients with tibial diaphyseal fractures treated with intramedullary nailing. The six-week RUST score may be useful in identifying patients at risk of nonunion. Cite this article: Bone Jt Open 2021;2(4):227–235

Aims. Biofilm formation is one of the primary reasons for the difficulty in treating implant-related infections (IRIs). Focused high-energy extracorporeal shockwave therapy (fhESWT), which is a treatment modality for fracture nonunions, has been shown to have a direct antibacterial effect on planktonic bacteria. The goal of the present study was to investigate the effect of fhESWT on Staphylococcus aureus biofilms in vitro in the presence and absence of antibiotic agents. Methods. S. aureus biofilms were grown on titanium discs (13 mm × 4 mm) in a bioreactor for 48 hours. Shockwaves were applied with either 250, 500, or 1,000 impulses onto the discs surrounded by either phosphate-buffered saline or antibiotic (rifampin alone or in combination with nafcillin). The number of viable bacteria was determined by quantitative culture after sonication. Representative samples were taken for scanning electron microscopy. Results. The application of fhESWT led to a ten-fold reduction in bacterial counts on the metal discs for all impulse numbers compared to the control (p < 0.001). Increasing the number of impulses did not further reduce bacterial counts in the absence of antibiotics (all p > 0.289). Antibiotics alone reduced the number of bacteria on the discs; however, the combined application of the fhESWT and antibiotic administration further reduced the bacterial count compared to the antibiotic treatment only (p = 0.032). Conclusion. The use of fhESWT significantly reduced the colony-forming unit (CFU) count of a S. aureus biofilm in our model independently, and in combination with antibiotics. Therefore, the supplementary application of fhESWT could be a helpful tool in the treatment of IFIs in certain cases, including infected nonunions. Cite this article: Bone Joint Res 2021;10(1):77–84

Aims. The modified Radiological Union Scale for Tibia (mRUST) fractures score was developed in order to assess progress to union and define a numerical assessment of fracture healing of metadiaphyseal fractures. This score has been shown to be valuable in predicting radiological union; however, there is no information on the sensitivity, specificity, and accuracy of this index for various cut-off scores. The aim of this study is to evaluate sensitivity, specificity, accuracy, and cut-off points of the mRUST score for the diagnosis of metadiaphyseal fractures healing. Methods. A cohort of 146 distal femur fractures were retrospectively identified at our institution. After excluding AO/OTA type B fractures, nonunions, follow-up less than 12 weeks, and patients aged less than 16 years, 104 sets of radiographs were included for analysis. Anteroposterior and lateral femur radiographs at six weeks, 12 weeks, 24 weeks, and final follow-up were separately scored by three surgeons using the mRUST score. The sensitivity and specificity of mean mRUST score were calculated using clinical and further radiological findings as a gold standard for ultimate fracture healing. A receiver operating characteristic curve was also performed to determine the cut-off points at each time point. Results. The mean mRUST score of ten at 24 weeks revealed a 91.9% sensitivity, 100% specificity, and 92.6% accuracy of predicting ultimate fracture healing. A cut-off point of 13 points revealed 41.9% sensitivity, 100% specificity, and 46.9% accuracy at the same time point. Conclusion. The mRUST score of ten points at 24 weeks can be used as a viable screening method with the highest sensitivity, specificity, and accuracy for healing of metadiaphyseal femur fractures. However, the cut-off point of 13 increases the specificity to 100%, but decreases sensitivity. Furthermore, the mRUST score should not be used at six weeks, as results show an inability to accurately predict eventual fracture healing at this time point. Cite this article: Bone Jt Open 2021;2(10):796–805

Introduction. Classical fixation using a circular frame involves two rings per segment and in many units this remains the norm whether using ilizarov or hexapod type frames. We present the results of two ring circular frame at King's College Hospital. Materials & Methods. A prospective database has been maintained of all frames applied since 2007. Radiographs from frames applied prior to July 2022 were examined. Clinic letters were then used to identify complications. Included: two ring hexapod for fracture, malunion, nonunion, arthrodesis or deformity correction in the lower limb. Excluded: patients under 16 years old, diabetic feet, Charcot joints, soft tissue contractures, arthrodiastasis, correction of the mid/forefoot, plate fixation augmentation, fixation off a third ring. Results. 518 two ring hexapods were identified. Mean age was 46 (16–89). 55% were for fracture, 18% for malunion, 11% for nonunion. Mean frame time was 7 months (2–29 months). All clinic letters from 384 patients showed 203 patients (52%) had at least one pin site infection, 27 nonunions (7%), 16 frame revisions (4%), 25 bone grafting procedures (7%), 5 cases of septic arthritis (1%), 3 periprosthetic fractures (0.8%),), 12 malunions (3%), 4 Amputations (1%). Conclusions. These results demonstrate the efficacy of a two ring hexapod for patients requiring reconstruction of the lower limb

The primary aim was to identify patient and injury factors independently associated with humeral diaphyseal fracture nonunion after non-operative management. The secondary aim was to determine the effect of management (operative/non-operative) on nonunion. Over a ten-year period, 734 humeral diaphyseal fractures (732 consecutive patients) were retrospectively identified from a trauma database. Follow-up was available for 663 fractures (662 patients; median age 57yrs [16–96], 54% female [n=359/662]) which formed the study cohort. Patient and injury characteristics were recorded. There were 523 patients (79%) managed non-operatively and 139 (21%) managed operatively. Outcome (union/nonunion) was determined from medical records and radiographs. Median follow-up was five months (1.2–74). Nonunion occurred in 22.7% of non-operatively managed injuries (n=119/524). Multivariate analysis demonstrated pre-injury NSAIDs (adjusted OR [AOR] 40.8, 95% CI 2.6–632.3; p=0.008), being underweight (BMI <18.5kg/m2; AOR 7.3, 95% CI 1.3 to 40.2; p=0.022), overweight (BMI 25–29.9kg/m2; AOR 2.5, 95% CI 1.1 to 5.9; p=0.034) and class II obesity (BMI 35–39.9kg/m2; AOR 4.5, 95% CI 1.4 to 15.5; p=0.014) were independently associated with an increased risk of nonunion. Operative fixation was independently associated with a lower risk of nonunion (2.9%, n=4/139) than non-operative management (AOR for non-operative/operative 11.0, 95% CI 2.8 to 43.6; p=0.001). Based upon these results, five patients would need to undergo operative fixation to avoid one nonunion. Pre-injury NSAIDs and BMI were independently associated with nonunion following non-operative management of a humeral diaphyseal fracture. Operative fixation was the independent factor most strongly associated with a lower risk of nonunion

Objectives. The objective of this study was to investigate the therapeutic effect of peripheral blood mononuclear cells (PBMNCs) treated with quality and quantity control culture (QQ-culture) to expand and fortify angiogenic cells on the acceleration of fracture healing. Methods. Human PBMNCs were cultured for seven days with the QQ-culture method using a serum-free medium containing five specific cytokines and growth factors. The QQ-cultured PBMNCs (QQMNCs) obtained were counted and characterised by flow cytometry and real-time polymerase chain reaction (RT-PCR). Angiogenic and osteo-inductive potentials were evaluated using tube formation assays and co-culture with mesenchymal stem cells with osteo-inductive medium in vitro. In order to evaluate the therapeutic potential of QQMNCs, cells were transplanted into an immunodeficient rat femur nonunion model. The rats were randomised into three groups: control; PBMNCs; and QQMNCs. The fracture healing was evaluated radiographically and histologically. Results. The total number of PBMNCs was decreased after QQ-culture, however, the number of CD34+ and CD206+ cells were found to have increased as assessed by flow cytometry analysis. In addition, gene expression of angiogenic factors was upregulated in QQMNCs. In the animal model, the rate of bone union was higher in the QQMNC group than in the other groups. Radiographic scores and bone volume were significantly associated with the enhancement of angiogenesis in the QQMNC group. Conclusion. We have demonstrated that QQMNCs have superior potential to accelerate fracture healing compared with PBMNCs. The QQMNCs could be a promising option for fracture nonunion. Cite this article: K. Mifuji, M. Ishikawa, N. Kamei, R. Tanaka, K. Arita, H. Mizuno, T. Asahara, N. Adachi, M. Ochi. Angiogenic conditioning of peripheral blood mononuclear cells promotes fracture healing. Bone Joint Res 2017;6: 489–498. DOI: 10.1302/2046-3758.68.BJR-2016-0338.R1

Background. Scaphoid fractures with displacement have a higher incidence of nonunion and unite in a humpback position that can cause pain and reduced movement, strength and function. The aim of this study is to review the evidence available and establish the risk of nonunion associated with management of displaced scaphoid fractures in a plaster cast. Methods. Electronic databases were searched using the MeSH (Medical Subject Headings) controlled vocabulary (scaphoid fractures, AND'd with explode displaced, or explode nonunion, or explode non-healing or explode cast immobilisation, or explode plaster, or explode surgery). As no randomised or controlled studies were identified, the search was limited to observational studies based on consecutive cases with displaced scaphoid fractures treated in a plaster cast. The criterion for displacement was limited to gap or step of more than 1mm. The ‘random effects’ calculation was used to allow for the possibility that the results from the separate studies differ more than would be expected by chance. Results. Of the 27 articles identified, seven studies were eligible for the meta-analysis with a total of 1401 scaphoids. 93% (1311 scaphoids) of these scaphoid fractures healed in a plaster cast. 207 (15%) of all scaphoid fractures showed displacement of at least 1mm (Gap/step) between fracture fragments. Nonunion was identified in 18% (37/207) of displaced scaphoid fractures treated in a plaster cast. The pooled odds ratio of fracture nonunion between the displaced and undisplaced groups was five times higher with fracture displacement (pooled odds ratio: 5.5, 95%CI: 2.5–12.3; p=0.00, I. 2. =54.6%). The pooled relative risk of fracture nonunion was 4.4 (95%CI: 2.3–8.7; p=0.00 I. 2. =54.3%). Conclusions. Displaced fractures of scaphoid have a four times higher risk of nonunion when treated in a plaster cast and the patients should be advised of this potential risk