Aims. Postoperative malalignment of the femur is one of the main complications in distal femur fractures. Few papers have investigated the impact of intraoperative malalignment on postoperative function and bone healing outcomes. The aim of this study was to investigate how intraoperative fracture malalignment affects postoperative bone healing and functional outcomes. Methods. In total, 140 patients were retrospectively identified from data obtained from a database of hospitals participating in a trauma research group. We divided them into two groups according to coronal plane malalignment of more than 5°: 108 had satisfactory fracture alignment (< 5°, group S), and 32 had unsatisfactory alignment (> 5°, group U). Patient characteristics and injury-related factors were recorded. We compared the rates of nonunion, implant failure, and reoperation as healing outcomes and Knee Society Score (KSS) at three, six, and 12 months as functional outcomes. We also performed a sub-analysis to assess the effect of fracture malalignment by plates and nails on postoperative outcomes. Results. The rates of nonunion and reoperation in group U were worse than those in group S (25.0% vs 14.3%; 15.6% vs 5.6%), but the differences were not significant (p = 0.180 and p = 0.126, respectively). Mean KSS in group U at all follow-up periods was significantly worse that in group S (75.7 (SD 18.8) vs 86.0 (SD 8.7); p < 0.001; 78.9 (SD 17.2) vs 89.1 (SD 9.8); p < 0.001; 85.0 (SD 11.9) vs 91.1 (SD 7.2); p = 0.002, respectively). In the sub-analysis of plates, mean KSS was significantly worse in group U at three and six months. In the sub-analysis of nails, the rate of reoperation was significantly higher in group U (28.6% vs 5.8%; p = 0.025), and mean KSS at six and 12 months was significantly worse in Group U. Conclusion. To obtain good postoperative functional results, intraoperative alignment of the coronal plane should be accurately restored to less than 5°. Cite this article: Bone Jt Open 2022;3(2):165–172

Aims. This study evaluates the quality of patient-reported outcome measures (PROMs) reported in childhood fracture trials and recommends outcome measures to assess and report physical function, functional capacity, and quality of life using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) standards. Methods. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant systematic review of OVID Medline, Embase, and Cochrane CENTRAL was performed to identify all PROMs reported in trials. A search of OVID Medline, Embase, and PsycINFO was performed to identify all PROMs with validation studies in childhood fractures. Development studies were identified through hand-searching. Data extraction was undertaken by two reviewers. Study quality and risk of bias was evaluated by COSMIN guidelines and recorded on standardized checklists. Results. Searches yielded 13,672 studies, which were screened to identify 124 trials and two validation studies. Review of the 124 trials identified 16 reported PROMs, of which two had validation studies. The development papers were retrieved for all PROMs. The quality of the original development studies was adequate for Patient-Reported Outcomes Measurement Information System (PROMIS) Mobility and Upper Extremity and doubtful for the EuroQol Five Dimension Youth questionnaire (EQ-5D-Y). All other PROMs were found to have inadequate development studies. No content validity studies were identified. Reviewer-rated content validity was acceptable for six PROMs: Activity Scale for Kids (ASK), Childhood Health Assessment Questionnaire, PROMIS Upper Extremity, PROMIS Mobility, EQ-5D-Y, and Pediatric Quality of Life Inventory (PedsQL4.0). The Modified Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire was shown to have indeterminate reliability and convergence validity in one study and PROMIS Upper Extremity had insufficient convergence validity in one study. Conclusion. There is insufficient evidence to recommend strongly the use of any single PROM to assess and report physical function or quality of life following childhood fractures. There is a need to conduct validation studies for PROMs. In the absence of these studies, we cautiously recommend the use of the PROMIS or ASK-P for physical function and the PedsQL4.0 or EQ-5D-Y for quality of life. Cite this article: Bone Joint J 2020;102-B(12):1599–1607

Aims

The aim of this study was to describe and compare joint-specific and generic health-related quality of life outcomes of the first versus second knee in patients undergoing staged bilateral total knee arthroplasty (BTKA) for osteoarthritis.

Aims. We performed a meta-analysis investigating the association between preoperative psychological distress and postoperative pain and function after total knee arthroplasty (TKA). Materials and Methods. Pubmed/Medline, Embase, PsycINFO, and the Cochrane library were searched for studies on the influence of preoperative psychological distress on postoperative pain and physical function after TKA. Two blinded reviewers screened for eligibility and assessed the risk of bias and the quality of evidence. We used random effects models to pool data for the meta-analysis. Results. Six prospective cohort studies, with a total of 1525 patients, were included. The random effects models showed significantly poorer outcomes in patients who preoperatively had elevated scores on the pain catastrophizing scale, worse 36-Item Short-Form Health Survey (SF-36) mental health score, symptoms of anxiety and/or depression, and somatization dysfunction. After 12 months, the standard mean difference for pain was −0.74 (95% confidence interval (CI) −1.04 to −0.44) and −0.56 (95% CI −0.80 to −0.32) for function. Conclusion. Preoperative pain catastrophizing, mental distress, symptoms of anxiety and/or depression, and somatoform disorders appear to adversely affect pain and function after TKA. Some patients undergoing TKA may therefore need psychological support to improve the outcome and quality of life

Aims. To assess if older symptomatic children with club foot deformity differ in perceived disability and foot function during gait, depending on initial treatment with Ponseti or surgery, compared to a control group. Second aim was to investigate correlations between foot function during gait and perceived disability in this population. Methods. In all, 73 children with idiopathic club foot were included: 31 children treated with the Ponseti method (mean age 8.3 years; 24 male; 20 bilaterally affected, 13 left and 18 right sides analyzed), and 42 treated with primary surgical correction (mean age 11.6 years; 28 male; 23 bilaterally affected, 18 left and 24 right sides analyzed). Foot function data was collected during walking gait and included Oxford Foot Model kinematics (Foot Profile Score and the range of movement and average position of each part of the foot) and plantar pressure (peak pressure in five areas of the foot). Oxford Ankle Foot Questionnaire, Disease Specific Index for club foot, Paediatric Quality of Life Inventory 4.0 were also collected. The gait data were compared between the two club foot groups and compared to control data. The gait data were also correlated with the data extracted from the questionnaires. Results. Our findings suggest that symptomatic children with club foot deformity present with similar degrees of gait deviations and perceived disability regardless of whether they had previously been treated with the Ponseti Method or surgery. The presence of sagittal and coronal plane hindfoot deformity and coronal plane forefoot deformity were associated with higher levels of perceived disability, regardless of their initial treatment. Conclusion. This is the first paper to compare outcomes between Ponseti and surgery in a symptomatic older club foot population seeking further treatment. It is also the first paper to correlate foot function during gait and perceived disability to establish a link between deformity and subjective outcomes. Cite this article: Bone Joint Open 2020;1-7:384–391

Aims. The aim of this study was to examine whether tourniquet use can improve perioperative blood loss, early function recovery, and pain after primary total knee arthroplasty (TKA) in the setting of multiple-dose intravenous tranexamic acid. Methods. This was a prospective, randomized clinical trial including 180 patients undergoing TKA with multiple doses of intravenous tranexamic acid. One group was treated with a tourniquet during the entire procedure, the second group received a tourniquet during cementing, and the third group did not receive a tourniquet. All patients received the same protocol of intravenous tranexamic acid (20 mg/kg) before skin incision, and three and six hours later (10 mg/kg). The primary outcome measure was perioperative blood loss. Secondary outcome measures were creatine kinase (CK), CRP, interleukin-6 (IL-6), visual analogue scale (VAS) pain score, limb swelling ratio, quadriceps strength, straight leg raising, range of motion (ROM), American Knee Society Score (KSS), and adverse events. Results. The mean total blood loss was lowest in the no-tourniquet group at 867.32 ml (SD 201.11), increased in the limited-tourniquet group at 1024.35 ml (SD 176.35), and was highest in the tourniquet group at 1,213.00 ml (SD 211.48). The hidden blood loss was lowest in the no-tourniquet group (both p < 0.001). There was less mean intraoperative blood loss in the tourniquet group (77.48 ml (SD 24.82)) than in the limited-tourniquet group (137.04 ml (SD 26.96)) and the no-tourniquet group (212.99 ml (SD 56.35); both p < 0.001). Patients in the tourniquet group showed significantly higher levels of muscle damage and inflammation biomarkers such as CK, CRP, and IL-6 than the other two groups (p < 0.05). Outcomes for VAS pain scores, limb swelling ratio, quadriceps strength, straight leg raising, ROM, and KSS were significantly better in the no-tourniquet group at three weeks postoperatively (p < 0.05), but there were no significant differences at three months. No significant differences were observed among the three groups with respect to transfusion rate, thrombotic events, or the length of hospital stay. Conclusion. Patients who underwent TKA with multiple doses of intravenous tranexamic acid but without a tourniquet presented lower total blood loss and hidden blood loss, and they showed less postoperative inflammation reaction, less muscle damage, lower VAS pain score, and better early knee function. Our results argue for not using a tourniquet during TKA. Cite this article: Bone Joint Res 2020;9(6):322–332

Objectives. Patient function after arthroplasty should ideally quickly improve. It is not known which peri-operative function assessments predict length of stay (LOS) and short-term functional recovery. The objective of this study was to identify peri-operative functions assessments predictive of hospital LOS and short-term function after hospital discharge in hip or knee arthroplasty patients. Methods. In total, 108 patients were assessed peri-operatively with the timed-up-and-go (TUG), Iowa level of assistance scale, post-operative quality of recovery scale, readiness for hospital discharge scale, and the Western Ontario and McMaster Osteoarthritis Index (WOMAC). The older Americans resources and services activities of daily living (ADL) questionnaire (OARS) was used to assess function two weeks after discharge. . Results. Following multiple regressions, the pre- and post-operative day two TUG was significantly associated with LOS and OARS score, while the pre-operative WOMAC function subscale was associated with the OARS score. Pre-operatively, a cut-off TUG time of 11.7 seconds for LOS and 10.3 seconds for short-term recovery yielded the highest sensitivity and specificity, while a cut-off WOMAC function score of 48.5/100 yielded the highest sensitivity and specificity. Post-operatively, a cut-off day two TUG time of 31.5 seconds for LOS and 30.9 seconds for short-term function yielded the highest sensitivity and specificity. . Conclusions. The pre- and post-operative day two TUG can indicate hospital LOS and short-term functional capacities, while the pre-operative WOMAC function subscale can indicate short-term functional capacities. Cite this article: Bone Joint Res 2015;4:145–151

Aims. There are comparatively few randomized studies evaluating knee arthroplasty prostheses, and fewer still that report longer-term functional outcomes. The aim of this study was to evaluate mid-term outcomes of an existing implant trial cohort to document changing patient function over time following total knee arthroplasty using longitudinal analytical techniques and to determine whether implant design chosen at time of surgery influenced these outcomes. Methods. A mid-term follow-up of the remaining 125 patients from a randomized cohort of total knee arthroplasty patients (initially comprising 212 recruited patients), comparing modern (Triathlon) and traditional (Kinemax) prostheses was undertaken. Functional outcomes were assessed with the Oxford Knee Score (OKS), knee range of movement, pain numerical rating scales, lower limb power output, timed functional assessment battery, and satisfaction survey. Data were linked to earlier assessment timepoints, and analyzed by repeated measures analysis of variance (ANOVA) mixed models, incorporating longitudinal change over all assessment timepoints. Results. The mean follow-up of the 125 patients was 8.12 years (7.3 to 9.4). There was a reduction in all assessment parameters relative to earlier assessments. Longitudinal models highlight changes over time in all parameters and demonstrate large effect sizes. Significant between-group differences were seen in measures of knee flexion (medium-effect size), lower limb power output (large-effect size), and report of worst daily pain experienced (large-effect size) favouring the Triathlon group. No longitudinal between-group differences were observed in mean OKS, average daily pain report, or timed performance test. Satisfaction with outcome in surviving patients at eight years was 90.5% (57/63) in the Triathlon group and 82.8% (48/58) in the Kinemax group, with no statistical difference between groups (p = 0.321). Conclusion. At a mean 8.12 years, this mid-term follow-up of a randomized controlled trial cohort highlights a general reduction in measures of patient function with patient age and follow-up duration, and a comparative preservation of function based on implant received at time of surgery. Cite this article: Bone Joint J 2020;102-B(4):434–441

Aims. The aims of this study is to report the clinical and radiological outcomes after pre-, central-, and postaxial polydactyly resection in children from a tertiary referral centre. Methods. All children who underwent resection of a supernumerary toe between 2001 and 2013 were prospectively enrolled and invited for a single re-assessment. Clinical parameters and several dedicated outcome scores (visual analogue scale (VAS), Paediatric Outcomes Data Collection Instrument (PODCI), Activities Scale for Kids (ASK), and American Orthopaedic Foot and Ankle Society Score (AOFAS)) were obtained, as were radiographs of the operated and non-operated feet along with pedobarographs. Results. In all, 39 children (52 feet) with a mean follow-up of 7.2 years (3.1 to 13.0) were included in the study. Resection of a duplicated great toe was performed in ten children, central polydactyly in four, and postaxial polydactyly in 26. The mean postoperative VAS (0.7; 0 to 7), ASK (93.7; 64.2 to 100), and AOFAS range (85.9 to 89.0) indicated excellent outcomes among this cohort and the PODCI global functioning scale (95.7; 75.5 to 100) was satisfactory. No significant differences were found regarding outcomes of pre- versus postaxial patients, nor radiological toe alignment between the operated and non-operated sides. Minor complications were observed in six children (15%). There were seven surgical revisions (18%), six of whom were in preaxial patients. In both groups, below the operation area, a reduced mean and maximum force was observed. Changes in the hindfoot region were detected based on the prolonged contact time and reduced force in the preaxial group. Conclusion. Excellent mid-term results can be expected after foot polydactyly resection in childhood. However, parents and those who care for these children need to be counselled regarding the higher risk of subsequent revision surgery in the preaxial patients. Also, within the study period, the plantar pressure distribution below the operated part of the foot did not return to completely normal. Cite this article: Bone Joint J 2021;103-B(2):415–420

Aims

To investigate whether idiopathic osteonecrosis of the femoral head (ONFH) is related to impaired osteoblast activities.

Aims. The aim of this study was to evaluate health-related quality of life (HRQoL) and joint function in tenosynovial giant cell tumour (TGCT) patients before and after surgical treatment. Patients and Methods. This prospective cohort study run in two Dutch referral centres assessed patient-reported outcome measures (PROMs; 36-Item Short-Form Health Survey (SF-36), visual analogue scale (VAS) for pain, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)) in 359 consecutive patients with localized- and diffuse-type TGCT of large joints. Patients with recurrent disease (n = 121) and a wait-and-see policy (n = 32) were excluded. Collected data were analyzed at specified time intervals preoperatively (baseline) and/or postoperatively up to five years. Results. A total of 206 TGCT patients, 108 localized- and 98 diffuse-type, were analyzed. Median age at diagnosis of localized- and diffuse-type was 41 years (interquartile range (IQR) 29 to 49) and 37 years (IQR 27 to 47), respectively. SF-36 analyses showed statistically significant and clinically relevant deteriorated preoperative and immediate postoperative scores compared with general Dutch population means, depending on subscale and TGCT subtype. After three to six months of follow-up, these scores improved to general population means and continued to be fairly stable over the following years. VAS scores, for both subtypes, showed no statistically significant or clinically relevant differences pre- or postoperatively. In diffuse-type patients, the improvement in median WOMAC score was statistically significant and clinically relevant preoperatively versus six to 24 months postoperatively, and remained up to five years’ follow-up. Conclusion. Patients with TGCT report a better HRQoL and joint function after surgery. Pain scores, which vary hugely between patients and in patients over time, did not improve. A disease-specific PROM would help to decipher the impact of TGCT on patients’ daily life and functioning in more detail. Cite this article: Bone Joint J 2019;101-B:272–280

Aims. The aims of this study were to evaluate the abductor function in moderate and severe slipped capital femoral epiphysis (SCFE), comparing the results of a corrective osteotomy at the base of the femoral neck and osteoplasty with 1) in situ epiphysiodesis for mild SCFE, 2) contralateral unaffected hips, and 3) hips from healthy individuals. Patients and Methods. A total of 24 patients (mean age 14.9 years (. sd. 1.6); 17 male and seven female patients) with moderate or severe SCFE (28 hips) underwent base of neck osteotomy and osteoplasty between 2012 and 2015. In situ epiphysiodesis was performed in seven contralateral hips with mild slip. A control cohort was composed of 15 healthy individuals (mean age 16.5 years (. sd. 2.5); six male and nine female patients). The abductor function was assessed using isokinetic dynamometry and range of abduction, with a minimum one-year follow-up. Results. We found no differences in mean peak abductor torque between the hips that underwent osteotomy and those that received in situ epiphysiodesis (p = 0.63), but the torque was inferior in comparison with contralateral hips without a slip (p < 0.01) and hips from control individuals (p < 0.001). The abduction strength was positively correlated with the range of hip abduction (R = 0.36; p < 0.001). Conclusion. Although the abductor strength was not restored to normal levels, moderate and severe SCFE treated with osteotomy at the base of the femoral neck and osteoplasty showed abductor function similar to in situ epiphysiodesis in hips with less severe displacement. Cite this article: Bone Joint J 2018;100-B:1524–32

Aims. The primary aim of this prognostic study was to identify baseline factors associated with physical health-related quality of life (HRQL) in patients after a femoral neck fracture. The secondary aims were to identify baseline factors associated with mental HRQL, hip function, and health utility. Patients and Methods. Patients who were enrolled in the Fixation using Alternative Implants for the Treatment of Hip Fractures (FAITH) trial completed the 12-item Short Form Health Survey (SF-12), Western Ontario and McMaster Universities Arthritis Index, and EuroQol 5-Dimension at regular intervals for 24 months. We conducted multilevel mixed models to identify factors potentially associated with HRQL. . Results. The following were associated with lower physical HRQL: older age (-1.42 for every ten-year increase, 95% confidence interval (CI) -2.17 to -0.67, p < 0.001); female gender (-1.52, 95% CI -3.00 to -0.05, p = 0.04); higher body mass index (-0.69 for every five-point increase, 95% CI -1.36 to -0.02, p = 0.04); American Society of Anesthesiologists class III (versus class I) (-3.19, 95% CI -5.73 to -0.66, p = 0.01); and sustaining a displaced fracture (-2.18, 95% CI -3.88 to -0.49, p = 0.01). Additional factors were associated with mental HRQL, hip function, and health utility. . Conclusion. We identified several baseline factors associated with lower HRQL, hip function, and utility after a femoral neck fracture. These findings may be used by clinicians to inform treatment and outcomes. Cite this article: Bone Joint J 2018;100-B:361–9

Aims. Advances in arthroscopic techniques for rotator cuff repair have made the mini-open approach less popular. However, the mini-open approach remains an important technique for repair for many surgeons. The aims of this study were to compare the integrity of the repair, the function of the shoulder and satisfaction post-operatively using these two techniques in patients aged > 50 years. Patients and Methods. We identified 22 patients treated with mini-open and 128 patients treated with arthroscopic rotator cuff repair of July 2007 and June 2011. The mean follow-up was two years (1 to 5). Outcome was assessed using the American Shoulder and Elbow Surgeons (ASES) and Simple Shoulder Test (SST) scores, and satisfaction. The integrity of the repair was assessed using ultrasonography. A power analysis ensured sufficient enrolment. Results. There was no statistically significant difference between the age, function, satisfaction, or pain scores (p > 0.05) of the two groups. The integrity of the repair and the mean SST scores were significantly better in the mini-open group (91% of mini-open repairs were intact versus 60% of arthroscopic repairs, p = 0.023; mean SST score 10.9 (standard deviation (. sd. ) 1.3) in the mini-open group; 8.9 (. sd. 3.5) in arthroscopic group; p = 0.003). The ASES scores were also higher in the mini-open group (mean ASES score 91.0 (. sd. 10.5) in mini-open group; mean 82.70 (. sd. 19.8) in the arthroscopic group; p = 0.048). Conclusion. The integrity of the repair and function of the shoulder were better after a mini-open repair than after arthroscopic repair of a rotator cuff tear in these patients. The functional difference did not translate into a difference in satisfaction. Mini-open rotator cuff repair remains a useful technique despite advances in arthroscopy. Cite this article: Bone Joint J 2017;99-B:245–9

Cardiac disease in patients with ankylosing spondylitis (AS) has previously been studied but not in patients with a kyphosis or in those who have undergone an operation to correct it. . The aim of this study was to measure the post-operative changes in cardiac function of patients with an AS kyphosis after pedicle subtraction osteotomy (PSO). The original cohort consisted of 39 patients (33 men, six women). Of these, four patients (two men, two women) were lost to follow-up leaving 35 patients (31 men, four women) to study. The mean age of the remaining patients was 37.4 years (22.3 to 47.8) and their mean duration of AS was 17.0 years (4.6 to 26.4). Echocardiographic measurements, resting heart rate (RHR), physical function score (PFS), and full-length standing spinal radiographs were obtained before surgery and at the two-year follow-up. The mean pre-operative RHR was 80.2 bpm (60.6 to 112.3) which dropped to a mean of 73.7 bpm (60.7 to 90.6) at the two-year follow-up (p = 0.0000). Of 15 patients with normal ventricular function pre-operatively, two developed mild left ventricular diastolic dysfunction (LVDD) at the two-year follow-up. Of 20 patients with mild LVDD pre-operatively only five had this post-operatively. Overall, 15 patients had normal LV diastolic function before their operation and 28 patients had normal LV function at the two-year follow-up. The clinical improvement was 15 out of 20 (75.0%): cardiac function in patients with AS whose kyphosis was treated by PSO was significantly improved. Cite this article: Bone Joint J 2015;97-B:1405–10

Patients who have limb amputation for musculoskeletal tumours are a rare group of cancer survivors. This was a prospective cross-sectional survey of patients from five specialist centres for sarcoma surgery in England. Physical function, pain and quality of life (QOL) outcomes were collected after lower extremity amputation for bone or soft-tissue tumours to evaluate the survivorship experience and inform service provision. Of 250 patients, 105 (42%) responded between September 2012 and June 2013. From these, completed questionnaires were received from 100 patients with a mean age of 53.6 years (19 to 91). In total 60 (62%) were male and 37 (38%) were female (three not specified). The diagnosis was primary bone sarcoma in 63 and soft-tissue tumour in 37. A total of 20 tumours were located in the hip or pelvis, 31 above the knee, 32 between the knee and ankle and 17 in the ankle or foot. In total 22 had hemipelvectomy, nine hip disarticulation, 35 transfemoral amputation, one knee disarticulation, 30 transtibial amputation, two toe amputations and one rotationplasty. The Toronto Extremity Salvage Score (TESS) differed by amputation level, with poorer scores at higher levels (p < 0.001). Many reported significant pain. In addition, TESS was negatively associated with increasing age, and pain interference scores. QOL for Cancer Survivors was significantly correlated with TESS (p < 0.001). This relationship appeared driven by pain interference scores. . This unprecedented national survey confirms amputation level is linked to physical function, but not QOL or pain measures. Pain and physical function significantly impact on QOL. These results are helpful in managing the expectations of patients about treatment and addressing their complex needs. Cite this article: Bone Joint J 2015;97-B:1284–90

Hand function in 33 patients with myelomeningocele, aged from 4 to 17 years, was investigated by clinical examination and formal tests of co-ordination and dexterity. The average score for hand function was 59% of normal and only two children had clinically normal upper limbs. Twenty-eight patients (85%) had cerebellar ataxia, either alone or combined with other abnormal signs, most commonly upper motor neuron lesions. Hand function was significantly better in children of 11 years and older, in children under 11 with milder degrees of hydrocephalus, and in the younger children who were right-handed. Function was not shown to be better in those with lesions lower in the spine, nor in those with stable spines as has been previously reported. When co-ordination of the upper limb, manual dexterity and simultaneous movements of both arms were examined separately, these three were affected equally. Some abnormalities of hand function could be overcome by encouraging affected children to sit up and to practise skillful use of their hands as early in life as possible

Aims

Accumulated evidence indicates that local cell origins may ingrain differences in the phenotypic activity of human osteoblasts. We hypothesized that these differences may also exist in osteoblasts harvested from the same bone type at periarticular sites, including those adjacent to the fixation sites for total joint implant components.

Objectives. Ubiquitin E3 ligase-mediated protein degradation regulates osteoblast function. Itch, an E3 ligase, affects numerous cell functions by regulating ubiquitination and proteasomal degradation of related proteins. However, the Itch-related cellular and molecular mechanisms by which osteoblast differentiation and function are elevated during bone fracture repair are as yet unknown. Methods. We examined the expression levels of E3 ligases and NF-κB members in callus samples during bone fracture repair by quantitative polymerase chain reaction (qPCR) and the total amount of ubiquitinated proteins by Western blot analysis in wild-type (WT) mice. The expression levels of osteoblast-associated genes in fracture callus from Itch knockout (KO) mice and their WT littermates were examined by qPCR. The effect of NF-κB on Itch expression in C2C12 osteoblast cells was determined by a chromatin immunoprecipitation (ChIP) assay. Results. The expression levels of WW Domain Containing E3 Ubiquitin Protein Ligase 1 (Wwp1), SMAD Specific E3 Ubiquitin Protein Ligase 1 (Smurf1), SMAD Specific E3 Ubiquitin Protein Ligase 2 (Smurf2) and Itch were all significantly increased in the fracture callus of WT mice, which was associated with elevated expression of NF-κB members and total ubiquitinated proteins. Callus tissue isolated from Itch KO mice expressed higher levels of osteoblast-associated genes, including Runx2, a positive regulator of osteoblast differentiation, but osteoclast-associated genes were not increased. Both NF-κB RelA and RelB proteins were found to bind to the NF-κB binding site in the mouse Itch promoter. Conclusions. Our findings indicate that Itch depletion may have a strong positive effect on osteoblast differentiation in fracture callus. Thus, ubiquitin E3 ligase Itch could be a potential target for enhancing bone fracture healing. Cite this article: J. Liu, X. Li, H. Zhang, R. Gu, Z. Wang, Z. Gao, L. Xing. Ubiquitin E3 ligase Itch negatively regulates osteoblast function by promoting proteasome degradation of osteogenic proteins. Bone Joint Res 2017;6:154–161. DOI: 10.1302/2046-3758.63.BJR-2016-0237.R1

We evaluated the long-term functional outcome in 118 patients treated for osteosarcoma or Ewing’s sarcoma in the extremities a minimum of five years after treatment. We also examined if impaired function influenced their quality of life and ability to work. The function was evaluated according to the Musculoskeletal Tumor Society (MSTS) score and the Toronto Extremity Salvage Score (TESS). Quality of life was assessed by using the Short Form-36 (SF-36). The mean age at follow-up was 31 years (15 to 57) and the mean follow-up was for 13 years (6 to 22). A total of 67 patients (57%) initially had limb-sparing surgery, but four had a secondary amputation. The median MSTS score was 70% (17% to 100%) and the median TESS was 89% (43% to 100%). The amputees had a significantly lower MSTS score than those with limb-sparing surgery (p < 0.001), but there was no difference for the TESS. Tumour localisation above knee level resulted in significantly lower MSTS scores and TESS (p = 0.003 and p = 0.02, respectively). There were no significant differences in quality of life between amputees and those with limb-sparing surgery except in physical functioning. Of the patients 11% (13) did not work or study. In multivariate analysis, amputation, tumour location above the knee and having muscular pain were associated with low physical function. We conclude that most of the bone tumour survivors managed well after adjustment to their physical limitations. A total of 105 are able to work and have an overall good quality of life