As there is little information on the factors that influence fracture union following intramedullary nailing of the tibia we retrospectively investigated patient-, injury- and treatment-related factors in 161 patients with closed or grade I open fractures of the tibial diaphysis. The patients were reviewed until clinical and radiological evidence of union at a mean of 13.3 months (4 to 60). Multivariate statistical analysis using a Cox proportional hazards model showed that the risk of failure of union increased by 2.38 times for highly comminuted fractures, by 3.14 times when nail dynamisation was applied, and by 1.65 times when the locking screws failed. In fractures with no or only minimal comminution the risk of nonunion increased if the post-reduction gap was ≥ 3 mm.

Aims. There is an increasing concern of osteoporotic fractures in the ageing population. Low-magnitude high-frequency vibration (LMHFV) was shown to significantly enhance osteoporotic fracture healing through alteration of osteocyte lacuno-canalicular network (LCN). Dentin matrix protein 1 (DMP1) in osteocytes is known to be responsible for maintaining the LCN and mineralization. This study aimed to investigate the role of osteocyte-specific DMP1 during osteoporotic fracture healing augmented by LMHFV. Methods. A metaphyseal fracture was created in the distal femur of ovariectomy-induced osteoporotic Sprague Dawley rats. Rats were randomized to five different groups: 1) DMP1 knockdown (KD), 2) DMP1 KD + vibration (VT), 3) Scramble + VT, 4) VT, and 5) control (CT), where KD was performed by injection of short hairpin RNA (shRNA) into marrow cavity; vibration treatment was conducted at 35 Hz, 0.3 g; 20 minutes/day, five days/week). Assessments included radiography, micro-CT, dynamic histomorphometry and immunohistochemistry on DMP1, sclerostin, E11, and fibroblast growth factor 23 (FGF23). In vitro, murine long bone osteocyte-Y4 (MLO-Y4) osteocyte-like cells were randomized as in vivo groupings. DMP1 KD was performed by transfecting cells with shRNA plasmid. Assessments included immunocytochemistry on osteocyte-specific markers as above, and mineralized nodule staining. Results. Healing capacities in DMP1 KD groups were impaired. Results showed that DMP1 KD significantly abolished vibration-enhanced fracture healing at week 6. DMP1 KD significantly altered the expression of osteocyte-specific markers. The lower mineralization rate in DMP1 KD groups indicated that DMP1 knockdown was associated with poor fracture healing process. Conclusion. The blockage of DMP1 would impair healing outcomes and negate LMHFV-induced enhancement on fracture healing. These findings reveal the importance of DMP1 in response to the mechanical signal during osteoporotic fracture healing. Cite this article: Bone Joint Res 2022;11(7):465–476

Aims. The aim of this study was to determine the fracture haematoma (fxH) proteome after multiple trauma using label-free proteomics, comparing two different fracture treatment strategies. Methods. A porcine multiple trauma model was used in which two fracture treatment strategies were compared: early total care (ETC) and damage control orthopaedics (DCO). fxH was harvested and analyzed using liquid chromatography-tandem mass spectrometry. Per group, discriminating proteins were identified and protein interaction analyses were performed to further elucidate key biomolecular pathways in the early fracture healing phase. Results. The early fxH proteome was characterized by immunomodulatory and osteogenic proteins, and proteins involved in the coagulation cascade. Treatment-specific proteome alterations were observed. The fxH proteome of the ETC group showed increased expression of pro-inflammatory proteins related to, among others, activation of the complement system, neutrophil functioning, and macrophage activation, while showing decreased expression of proteins related to osteogenesis and tissue remodelling. Conversely, the fxH proteome of the DCO group contained various upregulated or exclusively detected proteins related to tissue regeneration and remodelling, and proteins related to anti-inflammatory and osteogenic processes. Conclusion. The early fxH proteome of the ETC group was characterized by the expression of immunomodulatory, mainly pro-inflammatory, proteins, whereas the early fxH proteome of the DCO group was more regenerative and osteogenic in nature. These findings match clinical observations, in which enhanced surgical trauma after multiple trauma causes dysbalanced inflammation, potentially leading to reduced tissue regeneration, and gained insights into regulatory mechanisms of fracture healing after severe trauma. Cite this article: Bone Joint Res 2024;13(5):214–225

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

Aims. Fibrinolysis plays a key transition step from haematoma formation to angiogenesis and fracture healing. Low-magnitude high-frequency vibration (LMHFV) is a non-invasive biophysical modality proven to enhance fibrinolytic factors. This study investigates the effect of LMHFV on fibrinolysis in a clinically relevant animal model to accelerate osteoporotic fracture healing. Methods. A total of 144 rats were randomized to four groups: sham control; sham and LMHFV; ovariectomized (OVX); and ovariectomized and LMHFV (OVX-VT). Fibrinolytic potential was evaluated by quantifying fibrin, tissue plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) along with healing outcomes at three days, one week, two weeks, and six weeks post-fracture. Results. All rats achieved healing, and x-ray relative radiopacity for OVX-VT was significantly higher compared to OVX at week 2. Martius Scarlet Blue (MSB) staining revealed a significant decrease of fibrin content in the callus in OVX-VT compared with OVX on day 3 (p = 0.020). Mean tPA from muscle was significantly higher for OVX-VT compared to OVX (p = 0.020) on day 3. Mechanical testing revealed the mean energy to failure was significantly higher for OVX-VT at 37.6 N mm (SD 8.4) and 71.9 N mm (SD 30.7) compared with OVX at 5.76 N mm (SD 7.1) (p = 0.010) and 17.7 N mm (SD 11.5) (p = 0.030) at week 2 and week 6, respectively. Conclusion. Metaphyseal fracture healing is enhanced by LMHFV, and one of the important molecular pathways it acts on is fibrinolysis. LMHFV is a promising intervention for osteoporotic metaphyseal fracture healing. The improved mechanical properties, acceleration of fracture healing, and safety justify its role into translation to future clinical studies. Cite this article: Bone Joint Res 2021;10(1):41–50

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

A balanced inflammatory response is important for successful fracture healing. The response of osteoporotic fracture healing is deranged and an altered inflammatory response can be one underlying cause. The objectives of this review were to compare the inflammatory responses between normal and osteoporotic fractures and to examine the potential effects on different healing outcomes. A systematic literature search was conducted with relevant keywords in PubMed, Embase, and Web of Science independently. Original preclinical studies and clinical studies involving the investigation of inflammatory response in fracture healing in ovariectomized (OVX) animals or osteoporotic/elderly patients with available full text and written in English were included. In total, 14 articles were selected. Various inflammatory factors were reported; of those tumour necrosis factor-α (TNF-α) and interleukin (IL)-6 are two commonly studied markers. Preclinical studies showed that OVX animals generally demonstrated higher systemic inflammatory response and poorer healing outcomes compared to normal controls (SHAM). However, it is inconclusive if the local inflammatory response is higher or lower in OVX animals. As for clinical studies, they mainly examine the temporal changes of the inflammatory stage or perform comparison between osteoporotic/fragility fracture patients and normal subjects without fracture. Our review of these studies emphasizes the lack of understanding that inflammation plays in the altered fracture healing response of osteoporotic/elderly patients. Taken together, it is clear that additional studies, preclinical and clinical, are required to dissect the regulatory role of inflammatory response in osteoporotic fracture healing. Cite this article: Bone Joint Res 2020;9(7):368–385

Aims. Minimally invasive fixation of pelvic fragility fractures is recommended to reduce pain and allow early mobilization. The purpose of this study was to evaluate the outcome of two different stabilization techniques in bilateral fragility fractures of the sacrum (BFFS). Methods. A non-randomized, prospective study was carried out in a level 1 trauma centre. BFFS in 61 patients (mean age 80 years (SD 10); four male, 57 female) were treated surgically with bisegmental transsacral stablization (BTS; n = 41) versus spinopelvic fixation (SP; n = 20). Postoperative full weightbearing was allowed. The outcome was evaluated at two timepoints: discharge from inpatient treatment (TP1; Fitbit tracking, Zebris stance analysis), and ≥ six months (TP2; Fitbit tracking, Zebris analysis, based on modified Oswestry Disability Index (ODI), Majeed Score (MS), and the 12-Item Short Form Survey 12 (SF-12). Fracture healing was assessed by CT. The primary outcome parameter of functional recovery was the per-day step count; the secondary parameter was the subjective outcome assessed by questionnaires. Results. Overall, no baseline differences were observed between the BTS and SP cohorts. In total, 58 (BTS = 19; SP = 39) and 37 patients (BTS = 14; SP = 23) could be recruited at TP1 and TP2, respectively. Mean steps per day at TP1 were median 308 (248 to 434) in the BTS group and 254 (196 to 446) in the SP group. At TP2, median steps per day were 3,759 (2,551 to 3,926) in the BTS group and 3,191 (2,872 to 3,679) in the SP group, each with no significant difference. A significant improvement was observed in each group (p < 0.001) between timepoints. BTS patients obtained better results than SP patients in ODI (p < 0.030), MS (p = 0.007), and SF-12 physical status (p = 0.006). In all cases, CT showed sufficient fracture healing of the posterior ring. Conclusion. Both groups showed significant outcome improvement and sufficient fracture healing. Both techniques can be recommended for BFFS, although BTS was superior with respect to subjective outcome. Step-count tracking represents a reliable method to evaluate the mobility level. Cite this article: Bone Joint J 2021;103-B(3):462–468

Aims. Cigarette smoking has a negative impact on the skeletal system, causes a decrease in bone mass in both young and old patients, and is considered a risk factor for the development of osteoporosis. In addition, it disturbs the bone healing process and prolongs the healing time after fractures. The mechanisms by which cigarette smoking impairs fracture healing are not fully understood. There are few studies reporting the effects of cigarette smoking on new blood vessel formation during the early stage of fracture healing. We tested the hypothesis that cigarette smoke inhalation may suppress angiogenesis and delay fracture healing. Methods. We established a custom-made chamber with airflow for rats to inhale cigarette smoke continuously, and tested our hypothesis using a femoral osteotomy model, radiograph and microCT imaging, and various biomechanical and biological tests. Results. In the smoking group, Western blot analysis and immunohistochemical staining revealed less expression of vascular endothelial growth factor (VEGF) and von Willebrand factor (vWF). The smoking group also had a lower microvessel density than the control group. Image and biochemical analysis also demonstrated delayed bone healing. Conclusion. Cigarette smoke inhalation was associated with decreased expression of angiogenic markers in the early bone healing phase and with impaired bone healing. Cite this article:Bone Joint Res. 2020;9(3):99–107

Objectives. The aim of this study was to review the current evidence and future application for the role of diagnostic and therapeutic ultrasound in fracture management. Methods. A review of relevant literature was undertaken, including articles indexed in PubMed with keywords “ultrasound” or “sonography” combined with “diagnosis”, “fracture healing”, “impaired fracture healing”, “nonunion”, “microbiology”, and “fracture-related infection”. Results. The use of ultrasound in musculoskeletal medicine has expanded rapidly over the last two decades, but the diagnostic use in fracture management is not routinely practised. Early studies have shown the potential of ultrasound as a valid alternative to radiographs to diagnose common paediatric fractures, to detect occult injuries in adults, and for rapid detection of long bone fractures in the resuscitation setting. Ultrasound has also been shown to be advantageous in the early identification of impaired fracture healing; with the advent of 3D image processing, there is potential for wider adoption. Detection of implant-related infection can be improved by ultrasound mediated sonication of microbiology samples. The use of therapeutic ultrasound to promote union in the management of acute fractures is currently a controversial topic. However, there is strong in vitro evidence that ultrasound can stimulate a biological effect with potential clinical benefit in established nonunions, which supports the need for further investigation. Conclusion. Modern ultrasound image processing has the potential to replace traditional imaging modalities in several areas of trauma practice, particularly in the early prediction of impaired fracture healing. Further understanding of the therapeutic application of ultrasound is required to understand and identify the use in promoting fracture healing. Cite this article: J. A. Nicholson, S. T. J. Tsang, T. J. MacGillivray, F. Perks, A. H. R. W. Simpson. What is the role of ultrasound in fracture management? Diagnosis and therapeutic potential for fractures, delayed unions, and fracture-related infection. Bone Joint Res 2019;8:304–312. DOI: 10.1302/2046-3758.87.BJR-2018-0215.R2

Aims. The aim of this study was to assess the safety and clinical outcome of patients with a femoral shaft fracture and a previous complex post-traumatic femoral malunion who were treated with a clamshell osteotomy and fixation with an intramedullary nail (IMN). Methods. The study involved a retrospective analysis of 23 patients. All had a previous, operatively managed, femoral shaft fracture with malunion due to hardware failure. They were treated with a clamshell osteotomy between May 2015 and March 2020. The mean age was 42.6 years (26 to 62) and 15 (65.2%) were male. The mean follow-up was 2.3 years (1 to 5). Details from their medical records were analyzed. Clinical outcomes were assessed using the quality of correction of the deformity, functional recovery, the healing time of the fracture, and complications. Results. The mean length of time between the initial injury and surgery was 4.5 years (3 to 10). The mean operating time was 2.8 hours (2.05 to 4.4)), and the mean blood loss was 850 ml (650 to 1,020). Complications occurred in five patients (21.7%): two with wound necrosis, and three with deep vein thrombosis. The mean coronal deformity was significantly corrected from 17.78° (SD 4.62°) preoperatively to 1.35° (SD 1.72°) postoperatively (p < 0.001), and the mean sagittal deformity was significantly corrected from 20.65° (SD 5.88°) preoperatively to 1.61° (SD 1.95°; p < 0.001) postoperatively. The mean leg length discrepancy was significantly corrected from 3.57 cm (SD 1.27) preoperatively to 1.13 cm (SD 0.76) postoperatively (p < 0.001). All fractures healed at a mean of seven months (4 to 12) postoperatively. The mean Lower Extremity Functional Scale score improved significantly from 45.4 (SD 9.1) preoperatively to 66.2 (SD 5.5) postoperatively (p < 0.001). Partial cortical nonunion in the deformed segment occurred in eight patients (34.8%) and healed at a mean of 2.4 years (2 to 3) postoperatively. Conclusion. A clamshell osteotomy combined with IMN fixation in the treatment of patients with a femoral shaft fracture and a previous post-traumatic femoral malunion achieved excellent outcomes. Partial cortical nonunions in the deformed segment also healed satisfactorily. Cite this article: Bone Joint J 2023;105-B(4):449–454

Aims. Ankle fracture is one of the most common musculoskeletal injuries sustained in the UK. Many patients experience pain and physical impairment, with the consequences of the fracture and its management lasting for several months or even years. The broad aim of ankle fracture treatment is to maintain the alignment of the joint while the fracture heals, and to reduce the risks of problems, such as stiffness. More severe injuries to the ankle are routinely treated surgically. However, even with advances in surgery, there remains a risk of complications; for patients experiencing these, the associated loss of function and quality of life (Qol) is considerable. Non-surgical treatment is an alternative to surgery and involves applying a cast carefully shaped to the patient’s ankle to correct and maintain alignment of the joint with the key benefit being a reduction in the frequency of common complications of surgery. The main potential risk of non-surgical treatment is a loss of alignment with a consequent reduction in ankle function. This study aims to determine whether ankle function, four months after treatment, in patients with unstable ankle fractures treated with close contact casting is not worse than in those treated with surgical intervention, which is the current standard of care. Methods. This trial is a pragmatic, multicentre, randomized non-inferiority clinical trial with an embedded pilot, and with 12 months clinical follow-up and parallel economic analysis. A surveillance study using routinely collected data will be performed annually to five years post-treatment. Adult patients, aged 60 years and younger, with unstable ankle fractures will be identified in daily trauma meetings and fracture clinics and approached for recruitment prior to their treatment. Treatments will be performed in trauma units across the UK by a wide range of surgeons. Details of the surgical treatment, including how the operation is done, implant choice, and the recovery programme afterwards, will be at the discretion of the treating surgeon. The non-surgical treatment will be close-contact casting performed under anaesthetic, a technique which has gained in popularity since the publication of the Ankle Injury Management (AIM) trial. In all, 890 participants (445 per group) will be randomly allocated to surgical or non-surgical treatment. Data regarding ankle function, QoL, complications, and healthcare-related costs will be collected at eight weeks, four and 12 months, and then annually for five years following treatment. The primary outcome measure is patient-reported ankle function at four months from treatment. Anticipated impact. The 12-month results will be presented and published internationally. This is anticipated to be the only pragmatic trial reporting outcomes comparing surgical with non-surgical treatment in unstable ankle fractures in younger adults (aged 60 years and younger), and, as such, will inform the National Institute for Health and Care Excellence (NICE) ‘non-complex fracture’ recommendations at their scheduled update in 2024. A report of long-term outcomes at five years will be produced by January 2027. Cite this article: Bone Jt Open 2024;5(3):184–201

Objectives. Small animal models of fracture repair primarily investigate indirect fracture healing via external callus formation. We present the first described rat model of direct fracture healing. Methods. A rat tibial osteotomy was created and fixed with compression plating similar to that used in patients. The procedure was evaluated in 15 cadaver rats and then in vivo in ten Sprague-Dawley rats. Controls had osteotomies stabilised with a uniaxial external fixator that used the same surgical approach and relied on the same number and diameter of screw holes in bone. Results. Fracture healing occurred without evidence of external callus on plain radiographs. At six weeks after fracture fixation, the mean stress at failure in a four-point bending test was 24.65 N/mm. 2. (. sd. 6.15). Histology revealed ‘cutting-cones’ traversing the fracture site. In controls where a uniaxial external fixator was used, bone healing occurred via external callus formation. Conclusions. A simple, reproducible model of direct fracture healing in rat tibia that mimics clinical practice has been developed for use in future studies of direct fracture healing

Aims. To evaluate if union of clavicle fractures can be predicted at six weeks post-injury by the presence of bridging callus on ultrasound. Methods. Adult patients managed nonoperatively with a displaced mid-shaft clavicle were recruited prospectively. Ultrasound evaluation of the fracture was undertaken to determine if sonographic bridging callus was present. Clinical risk factors at six weeks were used to stratify patients at high risk of nonunion with a combination of Quick Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH) ≥ 40, fracture movement on examination, or absence of callus on radiograph. Results. A total of 112 patients completed follow-up at six months with a nonunion incidence of 16.7% (n = 18/112). Sonographic bridging callus was detected in 62.5% (n = 70/112) of the cohort at six weeks post-injury. If present, union occurred in 98.6% of the fractures (n = 69/70). If absent, nonunion developed in 40.5% of cases (n = 17/42). The sensitivity to predict union with sonographic bridging callus at six weeks was 73.4% and the specificity was 94.4%. Regression analysis found that failure to detect sonographic bridging callus at six weeks was associated with older age, female sex, simple fracture pattern, smoking, and greater fracture displacement (Nagelkerke R. 2. = 0.48). Of the cohort, 30.4% (n = 34/112) had absent sonographic bridging callus in addition to one or more of the clinical risk factors at six weeks that predispose to nonunion. If one was present the nonunion rate was 35%, 60% with two, and 100% when combined with all three. Conclusion. Ultrasound combined with clinical risk factors can accurately predict fracture healing at six weeks following a displaced midshaft clavicle fracture. Cite this article: Bone Joint Res 2021;10(2):113–121

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

Aims. Vancouver type B periprosthetic femoral fractures (PFF) are challenging complications after total hip arthroplasty (THA), and some treatment controversies remain. The objectives of this study were: to evaluate the short-to-mid-term clinical outcomes after treatment of Vancouver type B PFF and to compare postoperative outcome in subgroups according to classifications and treatments; to report the clinical outcomes after conservative treatment; and to identify risk factors for postoperative complications in Vancouver type B PFF. Methods. A total of 97 consecutive PPFs (49 males and 48 females) were included with a mean age of 66 years (standard deviation (SD) 14.9). Of these, 86 patients were treated with surgery and 11 were treated conservatively. All living patients had a minimum two-year follow-up. Patient demographics details, fracture healing, functional scores, and complications were assessed. Clinical outcomes between internal fixation and revisions in patients with or without a stable femoral component were compared. Conservatively treated PPFs were evaluated in terms of mortality and healing status. A logistic regression analysis was performed to identify risk factors for complications. Results. In surgically treated patients, all fractures united and nine complications were identified. The mean postoperative Visual Analogue Scale (VAS) for pain was 1.5 (SD 1.3), mean Parker Mobility Score (PMS) was 6.5 (SD 2.4), and mean Harris Hip Score (HHS) was 79.4 (SD 16.2). Among type B2 and type B3 fractures, patients treated with internal fixation had significantly lower PMS (p = 0.032) and required a longer time to heal (p = 0.012). In conservatively treated patients, one-year mortality rate was 36.4% (4/11), and two patients ultimately progressed to surgery. Young age (p = 0.039) was found to be the only risk factor for complications. Conclusion. The overall clinical outcome among Vancouver type B PFF was satisfactory. However, treatment with internal fixation in type B2 and B3 fractures had a significantly longer time to heal and lower mobility than revision cases. Conservative treatment was associated with high rates of early mortality and, in survivors, nonunion. This probably reflects our selection bias in undertaking surgical intervention. In our whole cohort, younger patient age was a risk factor for postoperative complications in Vancouver type B PFF. Cite this article: Bone Joint J 2020;102-B(3):293–300

Objectives. Healing in cancellous metaphyseal bone might be different from midshaft fracture healing due to different access to mesenchymal stem cells, and because metaphyseal bone often heals without a cartilaginous phase. Inflammation plays an important role in the healing of a shaft fracture, but if metaphyseal injury is different, it is important to clarify if the role of inflammation is also different. The biology of fracture healing is also influenced by the degree of mechanical stability. It is unclear if inflammation interacts with stability-related factors. Methods. We investigated the role of inflammation in three different models: a metaphyseal screw pull-out, a shaft fracture with unstable nailing (IM-nail) and a stable external fixation (ExFix) model. For each, half of the animals received dexamethasone to reduce inflammation, and half received control injections. Mechanical and morphometric evaluation was used. Results. As expected, dexamethasone had a strong inhibitory effect on the healing of unstable, but also stable, shaft fractures. In contrast, dexamethasone tended to increase the mechanical strength of metaphyseal bone regenerated under stable conditions. Conclusions. It seems that dexamethasone has different effects on metaphyseal and diaphyseal bone healing. This could be explained by the different role of inflammation at different sites of injury. Cite this article: Bone Joint Res 2015;4:170–175

Objectives. Up to 10% of fractures result in undesirable outcomes, for which female sex is a risk factor. Cellular sex differences have been implicated in these different healing processes. Better understanding of the mechanisms underlying bone healing and sex differences in this process is key to improved clinical outcomes. This study utilized a macrophage–mesenchymal stem cell (MSC) coculture system to determine: 1) the precise timing of proinflammatory (M1) to anti-inflammatory (M2) macrophage transition for optimal bone formation; and 2) how such immunomodulation was affected by male versus female cocultures. Methods. A primary murine macrophage-MSC coculture system was used to demonstrate the optimal transition time from M1 to M2 (polarized from M1 with interleukin (IL)-4) macrophages to maximize matrix mineralization in male and female MSCs. Outcome variables included Alizarin Red staining, alkaline phosphatase (ALP) activity, and osteocalcin protein secretion. Results. We found that 96 hours of M1 phenotype in male cocultures allowed for maximum matrix mineralization versus 72 hours in female cocultures. ALP activity and osteocalcin secretion were also enhanced with the addition of IL-4 later in male versus female groups. The sex of the cells had a statistically significant effect on the optimal IL-4 addition time to maximize osteogenesis. Conclusion. These results suggest that: 1) a 72- to 96-hour proinflammatory environment is critical for optimal matrix mineralization; and 2) there are immunological differences in this coculture environment due to sex. Optimizing immunomodulation during fracture healing may enhance and expedite the bone regeneration response. These findings provide insight into precise immunomodulation for enhanced bone healing that is sex-specific. Cite this article: K. Nathan, L. Y. Lu, T. Lin, J. Pajarinen, E. Jämsen, J-F. Huang, M. Romero-Lopez, M. Maruyama, Y. Kohno, Z. Yao, S. B. Goodman. Precise immunomodulation of the M1 to M2 macrophage transition enhances mesenchymal stem cell osteogenesis and differs by sex. Bone Joint Res 2019;8:481–488. DOI: 10.1302/2046-3758.810.BJR-2018-0231.R2

Aims. Current American Academy of Orthopaedic Surgeons (AAOS) guidelines for treating femoral fractures in children aged two to six years recommend early spica casting although some individuals have recommended intramedullary stabilization in this age group. The purpose of this study was to compare the treatment and family burden of care of spica casting and flexible intramedullary nailing in this age group. Methods. Patients aged two to six years old with acute, non-pathological femur fractures were prospectively enrolled at one of three tertiary children’s hospitals. Either early closed reduction with spica cast application or flexible intramedullary nailing was accomplished under general anaesthesia. The treatment method was selected after discussion of the options by the surgeon with the family. Data were prospectively collected on patient demographics, fracture characteristics, complications, pain medication, and union. The Impact on Family Scale was obtained at the six-week follow-up visit. In all, 75 patients were included in the study: 39 in the spica group and 36 in the nailing group. The mean age of the spica group was 2.71 (2.0 to 6.9) years and the mean age of the nailing group was 3.16 (2.0 to 6.9) years. Results. All fractures healed without evidence of malunion or more than 2.0 cm of shortening. The mean Impact on Family score was 70.2 for the spica group and 63.2 (55 to 99) for the nailing group, a statistically significant difference (p = 0.024) in a univariate analysis suggesting less impairment of the family in the intramedullary nailing group. There was no significant difference between pain medication requirements in the first 24 hours postoperatively. Two patients in the spica group and one patient in the intramedullary nailing group required additional treatment under anaesthesia. Conclusion. Both early spica casting and intramedullary nailing were effective methods for treating femoral fractures in children two to six years of age. Intramedullary stabilization provides an option in this age group that may be advantageous in some social situations that depend on the child’s mobility. Fracture treatment should be individualized based on factors that extend beyond anatomical and biological factors. Cite this article: Bone Joint J 2020;102-B(8):1056–1061

Objectives. Electromagnetic fields (EMF) are widely used in musculoskeletal disorders. There are indications that EMF might also be effective in the treatment of osteoporosis. To justify clinical follow-up experiments, we examined the effects of EMF on bone micro-architectural changes in osteoporotic and healthy rats. Moreover, we tested the effects of EMF on fracture healing. Methods. EMF (20 Gauss) was examined in rats (aged 20 weeks), which underwent an ovariectomy (OVX; n = 8) or sham-ovariectomy (sham-OVX; n = 8). As a putative positive control, all rats received bilateral fibular osteotomies to examine the effects on fracture healing. Treatment was applied to one proximal lower leg (three hours a day, five days a week); the lower leg was not treated and served as a control. Bone architectural changes of the proximal tibia and bone formation around the osteotomy were evaluated using in vivo microCT scans at start of treatment and after three and six weeks. Results. In both OVX and sham-OVX groups, EMF did not result in cancellous or cortical bone changes during follow-up. Moreover, EMF did not affect the amount of mineralised callus volume around the fibular osteotomy. Conclusions. In this study we were unable to reproduce the strong beneficial findings reported by others. This might indicate that EMF treatment is very sensitive to the specific set-up, which would be a serious hindrance for clinical use. No evidence was found that EMF treatment can influence bone mass for the benefit of osteoporotic patients. Cite this article: Bone Joint Res 2014;3:230–5