Background

The molecular mechanisms underlying non-union bone fractures largely remain elusive. Recently, spatial transcriptomics approaches for musculoskeletal tissue samples have been developed requiring direct placement of histology sections on barcoded slides. However, Formalin-Fixed-Paraffin-Embedded (FFPE) bone sections have been associated with limited RNA quality and read depth compared to soft tissue. Here, we test spatial transcriptomics workflows based on transcriptomic probe transfer to characterize molecular features discriminating non-union and union bone fractures in mice.

Objectives. To explore the therapeutic potential of combining bone marrow-derived mesenchymal stem cells (BM-MSCs) and hydroxyapatite (HA) granules to treat nonunion of the long bone. Methods. Ten patients with an atrophic nonunion of a long bone fracture were selectively divided into two groups. Five subjects in the treatment group were treated with the combination of 15 million autologous BM-MSCs, 5g/cm. 3. (HA) granules and internal fixation. Control subjects were treated with iliac crest autograft, 5g/cm. 3. HA granules and internal fixation. The outcomes measured were post-operative pain (visual analogue scale), level of functionality (LEFS and DASH), and radiograph assessment. Results. Post-operative pain evaluation showed no significant differences between the two groups. The treatment group demonstrated faster initial radiographic and functional improvements. Statistically significant differences in functional scores were present during the first (p = 0.002), second (p = 0.005) and third (p = 0.01) month. Both groups achieved similar outcomes by the end of one-year follow-up. No immunologic or neoplastic side effects were reported. Conclusions. All cases of nonunion of a long bone presented in this study were successfully treated using autologous BM-MSCs. The combination of autologous BM-MSCs and HA granules is a safe method for treating nonunion. Patients treated with BM-MSCs had faster initial radiographic and functional improvements. By the end of 12 months, both groups had similar outcomes. Cite this article: H.D. Ismail, P. Phedy, E. Kholinne, Y. P. Djaja, Y. Kusnadi, M. Merlina, N. D. Yulisa. Mesenchymal stem cell implantation in atrophic nonunion of the long bones: A translational study. Bone Joint Res 2016;5:287–293. DOI: 10.1302/2046-3758.57.2000587

Aims. A number of anti-retroviral therapies (ART) have been implicated in potentially contributing to HIV-associated bone disease. The aim of this study was to evaluate the effect of combination ART on the fracture healing process. Methods. A total of 16 adult male Wistar rats were randomly divided into two groups (n = eight each): Group 1 was given a combination of Tenfovir 30 mg, Lamivudine 30 mg, and Efavirenz 60 mg per day orally, whereas Group 2 was used as a control. After one week of medication preload, all rats underwent a standardized surgical procedure of mid-shaft tibial osteotomy fixed by intramedullary nail with no gap at the fracture site. Progress in fracture healing was monitored regularly for eight weeks. Further evaluations were carried out after euthanasia by micro-CT, mechanically and histologically. Two blinded orthopaedic surgeons used the Radiological Union Scoring system for the Tibia (RUST) to determine fracture healing. Results. The fracture healing process was different between the two groups at week 4 after surgery; only two out of eight rats showed full healing in Group 1 (ART-treated), while seven out of eight rats had bone union in Group 2 (control) (p = 0.040). However, at week eight postoperatively, there was no statistical difference in bone healing; seven out of eight progressed to full union in both groups. Conclusion. This study demonstrated that combination ART resulted in delayed fracture healing at week 4 after surgery in rats, but did not result in the development of nonunion. Cite this article: Bone Joint Res 2022;11(8):585–593

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. Methods. We conducted a retrospective cohort study of adult patients with traumatic distal femur fracture treated with lateral locking plate between 2009 and 2018. The patients who underwent secondary surgery due to fracture healing problem or plate failure were considered having nonunion. Background knowledge of risk factors of distal femur fracture nonunion based on previous literature was used to form an initial set of variables. A logistic regression model was used with previously identified patient- and injury-related variables (age, sex, BMI, diabetes, smoking, periprosthetic fracture, open fracture, trauma energy, fracture zone length, fracture comminution, medial side comminution) in the first analysis and with treatment-related variables (different surgeon-controlled factors, e.g. plate length, screw placement, and proximal fixation) in the second analysis to predict the nonunion leading to secondary surgery in distal femur fractures. Results. We were able to include 299 fractures in 291 patients. Altogether, 31/299 fractures (10%) developed nonunion. In the first analysis, pseudo-R. 2. was 0.27 and area under the receiver operating characteristic curve (AUC) was 0.81. BMI was the most important variable in the prediction. In the second analysis, pseudo-R. 2. was 0.06 and AUC was 0.67. Plate length was the most important variable in the prediction. Conclusion. The model including patient- and injury-related factors had moderate fit and predictive ability in the prediction of distal femur fracture nonunion leading to secondary surgery. BMI was the most important variable in prediction of nonunion. Surgeon-controlled factors had a minor role in prediction of nonunion. Cite this article: Bone Jt Open 2023;4(8):584–593

Aims. Excision of chronic osteomyelitic bone creates a dead space which must be managed to avoid early recurrence of infection. Systemic antibiotics cannot penetrate this space in high concentrations, so local treatment has become an attractive adjunct to surgery. The aim of this study was to present the mid- to long-term results of local treatment with gentamicin in a bioabsorbable ceramic carrier. Methods. A prospective series of 100 patients with Cierny-Mader Types III and IV chronic ostemyelitis, affecting 105 bones, were treated with a single-stage procedure including debridement, deep tissue sampling, local and systemic antibiotics, stabilization, and immediate skin closure. Chronic osteomyelitis was confirmed using strict diagnostic criteria. The mean follow-up was 6.05 years (4.2 to 8.4). Results. At final follow-up, six patients (six bones) had recurrent infection; thus 94% were infection-free. Three infections recurred in the first year, two in the second year, and one 4.5 years postoperatively. Recurrence was not significantly related to the physiological class of the patient (1/20 Class A (5%) vs 5/80 Class B (6.25%); p = 0.833), nor was it significantly related to the aetiology of the infection, the organisms which were cultured or the presence of nonunion before surgery (1/10 with nonunion (10%) vs 5/90 without nonunion (5.6%); p = 0.570). Organisms with intermediate or high-grade resistance to gentamicin were significantly more likely in polymicrobial infections (9/21; 42.8%) compared with monobacterial osteomyelitis (7/79 (8.9%); p < 0.001). However, recurrence was not significantly more frequent when a resistant organism was present (1/16 for resistant cases (6.25%) vs 5/84 in those with a microbiologically sensitive infection (5.95%); p = 0.958). Conclusion. We found that a single-stage protocol, including the use of a high-delivery local antibiotic ceramic carrier, was effective over a period of several years. The method can be used in a wide range of patients, including those with significant comorbidities and an infected nonunion. Cite this article: Bone Joint J 2022;104-B(9):1095–1100

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 management of fractures of the medial epicondyle is one of the greatest controversies in paediatric fracture care, with uncertainty concerning the need for surgery. The British Society of Children’s Orthopaedic Surgery prioritized this as their most important research question in paediatric trauma. This is the protocol for a randomized controlled, multicentre, prospective superiority trial of operative fixation versus nonoperative treatment for displaced medial epicondyle fractures: the Surgery or Cast of the EpicoNdyle in Children’s Elbows (SCIENCE) trial.

Aims

Olecranon fractures are usually caused by falling directly on to the olecranon or following a fall on to an outstretched arm. Displaced fractures of the olecranon with a stable ulnohumeral joint are commonly managed by open reduction and internal fixation. The current predominant method of management of simple displaced fractures with ulnohumeral stability (Mayo grade IIA) in the UK and internationally is a low-cost technique using tension band wiring. Suture or suture anchor techniques have been described with the aim of reducing the hardware related complications and reoperation. An all-suture technique has been developed to fix the fracture using strong synthetic sutures alone. The aim of this trial is to investigate the clinical and cost-effectiveness of tension suture repair versus traditional tension band wiring for the surgical fixation of Mayo grade IIA fractures of the olecranon.

Aims

Giant cell tumour of bone (GCTB) treatment changed since the introduction of denosumab from purely surgical towards a multidisciplinary approach, with recent concerns of higher recurrence rates after denosumab. We evaluated oncological, surgical, and functional outcomes for distal radius GCTB, with a critically appraised systematic literature review.

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.

Purpose: Management of septic nonunion of long bones is a difficult challenge requiring a multidisciplinary approach. The purpose of this study was to report our results with a two-stage technique using a spacer (Masquelet technique). Material and methods: Between June 1997 and July 2001, eleven patients were treated for septic nonunion (n=7) or suspected septic nonunion (n= =4). There were seven men and four women: mean age 38 years (26–51). Nonunion involved the humerus (n=1), the femur (n=1), and the tibia (n=9). The same surgical technique was used in all cases: “carcinologic” debridement with gap filling using antibiotic cement and osteosynthesis when necessary, followed by a second procedure two months later to remove the spacer and insert an autologous bone graft when laboratory results had returned to normal. Results: Mean follow-up was three years (1–5). All patients achieved per primam bone healing within 4.5 months (3–6) despite a mean bone gap of 55 mm (15–100) after avivement. Intraoperative samples taken during the second procedure were negative and there was no recurrent infection or need for revision. Discussion: This two-phase technique has provided encouraging results in terms of “infectious cure” and bone healing. A standardised approach to the treatment of septic nonunion of long bones as used in our centre should provide data validating this technique

Thirty patients of infected nonunion of long bones were treated with radical resection of the necrotic bone and bone transport or compression/distraction osteosynthesis. Nonunion, infection, deformity, bone gap and shortening were all addressed simultaneously using the Ilizarov principles. There were 15 cases with bone loss ranging from 4 to 12cm (median bone gap of 7 cm), 10 cases of stiff non-union (6 of which had an associated deformity) and 5 cases of mobile non-union. The median time in Ilizarov frame was 150 days. Median follow up after frame removal was 33.5 months. Bone grafting at docking site was required in only 3 cases(10%). There were 3 cases of refracture(10%) and 3 cases of recurrence of infection (10%). The bone result was excellent in 21 patients (70%), good in 3(10%), fair in none (0%) and poor in 6 (20%). The functional results were excellent in 8 patients (26.7%), good in 12 (40%), fair in3 (10%) and poor in 7 (23.3%). It is difficult to precisely define the indications for preservation and reconstruction of severe injuries. The surgical team has to appreciate the length, disability, complications and cost of treatment. Patients must be aware of the limitations of functional results and the possible difficulty of return to work despite the reconstructive attempt

Aims

This observational cross-sectional study aimed to answer the following questions: 1) how has nonunion incidence developed from 2009 to 2019 in a nationwide cohort; 2) what is the age and sex distribution of nonunions for distinct anatomical nonunion localizations; and 3) how high were the costs for surgical nonunion treatment in a level 1 trauma centre in Germany?

Bone is one of the most highly adaptive tissues in the body, possessing the capability to alter its morphology and function in response to stimuli in its surrounding environment. The ability of bone to sense and convert external mechanical stimuli into a biochemical response, which ultimately alters the phenotype and function of the cell, is described as mechanotransduction. This review aims to describe the fundamental physiology and biomechanisms that occur to induce osteogenic adaptation of a cell following application of a physical stimulus. Considerable developments have been made in recent years in our understanding of how cells orchestrate this complex interplay of processes, and have become the focus of research in osteogenesis. We will discuss current areas of preclinical and clinical research exploring the harnessing of mechanotransductive properties of cells and applying them therapeutically, both in the context of fracture healing and de novo bone formation in situations such as nonunion. Cite this article: Bone Joint Res 2019;9(1):1–14

Purpose of the study: Nonunion, which is a biological failure, requires revision, usually an aggressive operation. Haematopoietic bone marrow contains colony forming unit fibroblasts (CFU-F) which could favour bone healing. The purpose of this work was to determine whether a minimally invasive procedure, injection of CFU-F into the nonunion space, could favour bone healing without further procedure. Material and methods: Our series included 43 patients: 36 male and 7 female, mean age 39.9 years. Forty-seven atrophic and aseptic nonunions of long bones were treated with percutaneous injection of concentrated autologous bone marrow: 27 tibias, 17 femurs, 3 humeri. Bone marrow was harvested from the posterior iliac crests (346 ml) then centrifuged to keep the leuko-platelet fraction (78 ml). This concentrate was injection into the nonunion space under radioscopic guidance. Efficacy was assessed on the basis of clinical criteria (complete pain-free weight-bearing, absence of contention, absence of mobility) and on radiographic criteria (healing of 3/4 corticals). Results: Thirty nonunions healed: 19 tibias (70%, 11 femurs (65%) and 0 humerus. Mean time to healing was 5.9 months (2.4–15.6). Factors of poor prognosis were: smoking, alcohol, diabetes, corticosteroids, radiotherapy, history of sepsis (p=0.01). Early grafting increased the chances of success (p=0.04). Age, initial skin opening, type of fixation did not have a significant impact on healing. The number of CFU-F had an effect on the rate of healing. Discussion: This technique is effective for the treatment of nonunion of the lower limb, allowing bone healing in two thirds of the cases with a minimally aggressive procedure. The method is easy to perform but requires a rigorous technique for the different phases of puncture, concentration and reinjection. Nonunions unresponsive to conventional methods, and thus corresponding to multifactorial problems, probably constitute the limitation of this method. Cell expansion or differentiation techniques could be helpful in improving the success rate but at the present time the osteogenic potential of these cells remains to be elucidated as a function of their stage of maturation. Conclusion: Percutaneous grafts of concentrated autologous bone marrow can be a useful contribution to the therapeutic armamentarium for nonunion. Morbidity is low and the method does not compromise future options. It can be proposed as a first-intention solution for the treatment of long bone nonunion

Shortness of an extremity due to different causes is an issue that may adversely affect human life functional and psychologically. In this study, in the light of previous studies, it is aimed to develop a new expandable intramedullary system, providing lengthening in order to remove previous problems and complications and to annihilate leg length discrepancies at present and future without second surgical intervention as far as possibble by lenghtening the intramedullary nail. To this end, a new electromechanically activated intramedullary nail has been designed and generated. The intramedullary nail was designed to perform extremity lengthening electro-mechanically. The 3D design of the system is performed with computer software and the rapid and metal prototype of the system has been produced. The intramedullary nail system is comprised of three main units; Mechanical transmission unit, Electronic unit, Lengthening unit. The nail system is designed to function both mechanically and electronically complying with the requirement. This also provides an advantage that if any one (mechanic or electronic) fails, the lengthening process can continue with the other. Compression tests are applied in order to evaluate the strength of the system. The deformation values of the parts are recorded and stress values of each parts were calculated. The new system needs only 300N loading for mechanical lengthening. When 800N is considered as average human weight, the implant must withstand minumum 2400N load. Considering the safety conditions, we applied 4000N load on the new system. At 4000N, the whole system shows only 1.465 mm deformation which is less than the gap between the two bone parts. Also, when the system is implanted inside the bone, the loads are distributed proportionally between the bone and the implant. So, except for extraordinary conditions, the newly developed system is highly rigid and safe. In each applied method, lots of complications whether general or method-specific are seen. When the methods like Albizzia, ISKD and FITBONE avaliable and widely used today are examined separately, complications specific to these methods can be clearly observed [1–12]. Bliskunov Nail, Albizzia Nail and ISKD [13–18] have mechanical working principles and in these systems, lengthening process is obtained by rotational movement of the extremity. This rotational movement causes complications like pain, dislocation and uncontrolled lengthening [11,13,16,19–21]. In our newly developed system, only axial stimulation is needed for the activation of the mechanism. This is one of the advantages of our system. Both the mechanical unit and the electronical units are designed to be extended 0.1 mm at each activation. This means that the optimal amount of distraction (1mm/day) can be achieved in a controlled way. In other systems, the distraction amount can not be fully controlled and complications seen on other systems [1, 6, 8–10], like distruption of callus due to the excessive distraction and nonunion of the bone can be encountered. The success of the system at practice will be examined with in-vivo animal experiments and according to the results, it will be ready for use on human by performing necessary restorations

Autogenous cancellous bone is the most effective material in stimulating osteogenic response and the standard graft augmentation for patients with nonunions or bone defects. However it may not be available in sufficient quantity and bone harvesting may give rise to morbidity. Allograft does not have the osteogenic potential of autogenous bone and may be complicated by immunological reaction and transmission of infections. The search of bone substitutes has led to study several growth factors capable of inducing bone formation. Bone morphogenetic proteins (BMPs) have been shown to have a central role in endochondral and intramembranous bone formation and are thought to promote normal bone healing process. Recent studies demonstrated that platelet-rich plasma (PRP) provides several growth factors and stimulates osteogenesis. The aim of the study was the evaluation of rhBMP-7 (rhOP-1) and PRP effects on the different cells detected at the site of nonunion, such as osteoblast-like cells, fibroblast-like cells and mesenchymal cells. During the surgical treatment of seven nonunion cases, cancellous bone and nonunion tissue were harvested. Osteoblast-like cells and fibroblast-like cells were isolated and characterized. Mesenchymal cells were obtained from bone marrow samples of the same patients. Each cell type was incubated with rhBMP-7 and PRP at different concentrations. Proliferation rate and alkaline phosphatase (ALP) activity were assessed at 3, 7, 15, and 30 days. cytochemical and immunocytochemical analysis were performed at 15 and 30 days. Proliferation rate was higher in osteoblast-like cells and mesenchymal cells than in fibroblast-like cells. Growth factors induced mesenchymal cells to express osteoblast phenotype markers. The results show that fibroblast-like cells at the site of nonunion are responsive to growth factors stimulation, though their low osteoblastic differentiation rate, even at highest concentration of growth factors. These data suggest that the use of growth factors in nonunion treatment should be combined with autologous cancellous bone and/or bone marrow graft, sources of target cells, in order to enhance osteogenic response

Aims

In contrast to operations performed for other fractures, there is a high incidence rate of surgical site infection (SSI) post-open reduction and internal fixation (ORIF) done for tibial plateau fractures (TPFs). This study investigates the effect of induced membrane technique combined with internal fixation for managing SSI in TPF patients who underwent ORIF.

Aims

Distraction osteogenesis (DO) is a useful orthopaedic procedure employed to lengthen and reshape bones by stimulating bone formation through controlled slow stretching force. Despite its promising applications, difficulties are still encountered. Our previous study demonstrated that pulsed electromagnetic field (PEMF) treatment significantly enhances bone mineralization and neovascularization, suggesting its potential application. The current study compared a new, high slew rate (HSR) PEMF signal, with different treatment durations, with the standard Food and Drug Administration (FDA)-approved signal, to determine if HSR PEMF is a better alternative for bone formation augmentation.