Aims. To investigate whether idiopathic osteonecrosis of the femoral head (ONFH) is related to impaired osteoblast activities. Methods. We cultured osteoblasts isolated from trabecular bone explants taken from the femoral head and the intertrochanteric region of patients with idiopathic ONFH, or from the intertrochanteric region of patients with osteoarthritis (OA), and compared their viability, mineralization capacity, and secretion of paracrine factors. Results. Osteoblasts from the intertrochanteric region of patients with ONFH showed lower alkaline phosphatase (ALP) activity and mineralization capacity than osteoblasts from the same skeletal site in age-matched patients with OA, as well as lower messenger RNA (mRNA) levels of genes encoding osteocalcin and bone sialoprotein and higher osteopontin expression. In addition, osteoblasts from patients with ONFH secreted lower osteoprotegerin (OPG) levels than those from patients with OA, resulting in a higher receptor activator of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) ligand (RANKL)-to-OPG ratio. In patients with ONFH, osteoblasts from the femoral head showed reduced viability and mineralized nodule formation compared with osteoblasts from the intertrochanteric region. Notably, the secretion of the pro-resorptive factors interleukin-6 and prostaglandin E. 2. as well as the RANKL-to-OPG ratio were markedly higher in osteoblast cultures from the femoral head than in those from the intertrochanteric region. Conclusion. Idiopathic ONFH is associated with a reduced mineralization capacity of osteoblasts and increased secretion of pro-resorptive factors. Cite this article: Bone Joint Res 2021;10(9):619–628

Aims. Obtaining solid implant fixation is crucial in revision total knee arthroplasty (rTKA) to avoid aseptic loosening, a major reason for re-revision. This study aims to validate a novel grading system that quantifies implant fixation across three anatomical zones (epiphysis, metaphysis, diaphysis). Methods. Based on pre-, intra-, and postoperative assessments, the novel grading system allocates a quantitative score (0, 0.5, or 1 point) for the quality of fixation achieved in each anatomical zone. The criteria used by the algorithm to assign the score include the bone quality, the size of the bone defect, and the type of fixation used. A consecutive cohort of 245 patients undergoing rTKA from 2012 to 2018 were evaluated using the current novel scoring system and followed prospectively. In addition, 100 first-time revision cases were assessed radiologically from the original cohort and graded by three observers to evaluate the intra- and inter-rater reliability of the novel radiological grading system. Results. At a mean follow-up of 90 months (64 to 130), only two out of 245 cases failed due to aseptic loosening. Intraoperative grading yielded mean scores of 1.87 (95% confidence interval (CI) 1.82 to 1.92) for the femur and 1.96 (95% CI 1.92 to 2.0) for the tibia. Only 3.7% of femoral and 1.7% of tibial reconstructions fell below the 1.5-point threshold, which included the two cases of aseptic loosening. Interobserver reliability for postoperative radiological grading was 0.97 for the femur and 0.85 for the tibia. Conclusion. A minimum score of 1.5 points for each skeletal segment appears to be a reasonable cut-off to define sufficient fixation in rTKA. There were no revisions for aseptic loosening at mid-term follow-up when this fixation threshold was achieved or exceeded. When assessing first-time revisions, this novel grading system has shown excellent intra- and interobserver reliability. Cite this article: Bone Joint J 2024;106-B(5):468–474

Aims. Limb salvage for pelvic sarcomas involving the acetabulum is a major surgical challenge. There remains no consensus about what is the optimum type of reconstruction after resection of the tumour. The aim of this study was to evaluate the surgical outcomes in these patients according to the methods of periacetabular reconstruction. Methods. The study involved a consecutive series of 122 patients with a periacetabular bone sarcoma who underwent limb-salvage surgery involving a custom-made prosthesis in 65 (53%), an ice-cream cone prosthesis in 21 (17%), an extracorporeal irradiated autograft in 18 (15%), and nonskeletal reconstruction in 18 (15%). Results. The rates of major complications necessitating further surgery were 62%, 24%, 56%, and 17% for custom-made prostheses, ice-cream cone prostheses, irradiated autografts and nonskeletal reconstructions, respectively (p = 0.001). The ten-year cumulative incidence of failure of the reconstruction was 19%, 9%, 33%, and 0%, respectively. The major cause of failure was deep infection (11%), followed by local recurrence (6%). The mean functional Musculoskeletal Tumour Society (MSTS) scores were 59%, 74%, 64%, and 72%, respectively. The scores were significantly lower in patients with major complications than in those without complications (mean 52% (SD 20%) vs 74% (SD 19%); p < 0.001). For periacetabular resections involving the ilium, the mean score was the highest with custom-made prostheses (82% (SD 10%)) in patients without any major complication; however, nonskeletal reconstruction resulted in the highest mean scores (78% (SD 12%)) in patients who had major complications. For periacetabular resections not involving the ilium, significantly higher mean scores were obtained with ice-cream cone prostheses (79% (SD 17%); p = 0.031). Conclusion. Functional outcome following periacetabular reconstruction is closely associated with the occurrence of complications requiring further surgery. For tumours treated with periacetabular and iliac resection, skeletal reconstruction may result in the best outcomes in the absence of complications, whereas nonskeletal reconstruction is a reasonable option if the risk of complications is high. For tumours requiring periacetabular resection without the ilium, reconstruction using an ice-cream cone prosthesis supported by antibiotic-laden cement is a reliable option. Cite this article: Bone Joint J 2021;103-B(4):795–803

Aims. The aim of this study was to determine the differences in spinal imaging characteristics between subjects with or without lumbar developmental spinal stenosis (DSS) in a population-based cohort. Methods. This was a radiological analysis of 2,387 participants who underwent L1-S1 MRI. Means and ranges were calculated for age, sex, BMI, and MRI measurements. Anteroposterior (AP) vertebral canal diameters were used to differentiate those with DSS from controls. Other imaging parameters included vertebral body dimensions, spinal canal dimensions, disc degeneration scores, and facet joint orientation. Mann-Whitney U and chi-squared tests were conducted to search for measurement differences between those with DSS and controls. In order to identify possible associations between DSS and MRI parameters, those who were statistically significant in the univariate binary logistic regression were included in a multivariate stepwise logistic regression after adjusting for demographics. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported where appropriate. Results. Axial AP vertebral canal diameter (p < 0.001), interpedicular distance (p < 0.001), AP dural sac diameter (p < 0.001), lamina angle (p < 0.001), and sagittal mid-vertebral body height (p < 0.001) were significantly different between those identified as having DSS and controls. Narrower interpedicular distance (OR 0.745 (95% CI 0.618 to 0.900); p = 0.002) and AP dural sac diameter (OR 0.506 (95% CI 0.400 to 0.641); p < 0.001) were associated with DSS. Lamina angle (OR 1.127 (95% CI 1.045 to 1.214); p = 0.002) and right facet joint angulation (OR 0.022 (95% CI 0.002 to 0.247); p = 0.002) were also associated with DSS. No association was observed between disc parameters and DSS. Conclusion. From this large-scale cohort, the canal size is found to be independent of body stature. Other than spinal canal dimensions, abnormal orientations of lamina angle and facet joint angulation may also be a result of developmental variations, leading to increased likelihood of DSS. Other skeletal parameters are spared. There was no relationship between DSS and soft tissue changes of the spinal column, which suggests that DSS is a unique result of bony maldevelopment. These findings require validation in other ethnicities and populations. Level of Evidence: I (diagnostic study). Cite this article: Bone Joint J 2021;103-B(4):725–733

Salter innominate osteotomy is an effective reconstructive procedure for the treatment of developmental dysplasia of the hip (DDH), but some children have a poor outcome at skeletal maturity. In order to investigate factors associated with an unfavourable outcome, we assessed the development of the contralateral hip. We retrospectively reviewed 46 patients who underwent a unilateral Salter osteotomy at between five and seven years of age, with a mean follow-up of 10.3 years (7 to 20). The patients were divided into three groups according to the centre–edge angle (CEA) of the contralateral hip at skeletal maturity: normal (> 25°, 22 patients), borderline (20° to 25°, 17 patients) and dysplastic (<  20°, 7 patients). The CEA of the affected hip was measured pre-operatively, at eight to nine years of age, at 11 to 12 years of age and at skeletal maturity. The CEA of the affected hip was significantly smaller in the borderline and dysplastic groups at 11 and 12 years of age (p = 0.012) and at skeletal maturity (p = 0.017) than in the normal group. Severin group III was seen in two (11.8%) and four hips (57.1%) of the borderline and dysplastic groups, respectively (p < 0.001). . Limited individual development of the acetabulum was associated with an unfavourable outcome following Salter osteotomy. Cite this article: Bone Joint J 2014;96-B:1419–23

The accurate assessment of skeletal maturity is essential in the management of orthopaedic conditions in the growing child. In order to identify the time of peak height velocity (PHV) in adolescents, two systems for assessing skeletal maturity have been described recently; the calcaneal apophyseal ossification method and the Sanders hand scores. . The purpose of this study was to compare these methods in assessing skeletal maturity relative to PHV. We studied the radiographs of a historical group of 94 healthy children (49 females and 45 males), who had been followed longitudinally between the ages of three and 18 years with serial radiographs and physical examination. Radiographs of the foot and hand were undertaken in these children at least annually between the ages of ten and 15 years. We reviewed 738 radiographs of the foot and 694 radiographs of the hand. PHV was calculated from measurements of height taken at the time of the radiographs. . Prior to PHV we observed four of six stages of calcaneal apophyseal ossification and two of eight Sanders stages. Calcaneal stage 3 and Sanders stage 2 was seen to occur about 0.9 years before PHV, while calcaneal stage 4 and Sanders stage 3 occurred approximately 0.5 years after PHV. . The stages of the calcaneal and Sanders systems can be used in combination, offering better assessment of skeletal maturity with respect to PHV than either system alone. . Cite this article: Bone Joint J 2015;97-B:1710–17

Aims. It has been generally accepted that open fractures require early skeletal stabilization and soft-tissue reconstruction. Traditionally, a standard gauze dressing was applied to open wounds. There has been a recent shift in this paradigm towards negative pressure wound therapy (NPWT). The aim of this study was to compare the clinical outcomes in patients with open tibial fractures receiving standard dressing versus NPWT. Methods. This multicentre randomized controlled trial was approved by the ethical review board of a public sector tertiary care institute. Wounds were graded using Gustilo-Anderson (GA) classification, and patients with GA-II to III-C were included in the study. To be eligible, the patient had to present within 72 hours of the injury. The primary outcome of the study was patient-reported Disability Rating Index (DRI) at 12 months. Secondary outcomes included quality of life assessment using 12-Item Short-Form Health Survey questionnaire (SF-12), wound infection rates at six weeks and nonunion rates at 12 months. Logistic regression analysis and independent-samples t-test were applied for secondary outcomes. Analyses of primary and secondary outcomes were performed using SPSS v. 22.0.1 and p-values of < 0.05 were considered significant. Results. A total of 486 patients were randomized between January 2016 and December 2018. Overall 206 (49.04%) patients underwent NPWT, while 214 (50.95%) patients were allocated to the standard dressing group. There was no statistically significant difference in DRI at 12 months between NPWT and standard dressing groups (mean difference 0.5; 95% confidence interval (CI) -0.08 to 1.1; p = 0.581). Regarding SF-12 scores at 12 months follow-up, there was no significant difference at any point from injury until 12 months (mean difference 1.4; 95% CI 0.7 to 1.9; p = 0.781). The 30-day deep infection rate was slightly higher in the standard gauze dressing group. The non-union odds were also comparable (odds ratio (OR) 0.90, 95% CI 0.56 to 1.45; p = 0.685). Conclusion. Our study concludes that NPWT therapy does not confer benefit over standard dressing technique for open fractures. The DRI, SF-12 scores, wound infection, and nonunion rates were analogous in both study groups. We suggest surgeons continue to use cheaper and more readily available standard dressings. Cite this article: Bone Joint J 2020;102-B(7):912–917

The aim of this study was to identify whether there was any difference in patient, tumour, treatment or outcome characteristics between patients with skeletal or extra-skeletal Ewing’s sarcoma. We identified 300 patients with new primary Ewing’s sarcoma diagnosed between 1980 and 2005 from the centres’ local database. There were 253 (84%) with skeletal and 47 (16%) with extra-skeletal Ewing’s sarcomas. Although patients with skeletal Ewing’s were younger (mean age 16.8 years) than those with extra-skeletal Ewing’s sarcoma (mean age 27.5 years), there was little difference between the groups in terms of tumour stage or treatment. Nearly all the patients were treated with chemotherapy and most had surgery. There was no difference in the overall survival of patients with skeletal (64%) and extra-skeletal Ewing’s sarcoma (61%) (p = 0.85), and this was also the case when both groups were split by whether they had metastases or not. This large series has shown that the oncological outcomes of Ewing’s sarcoma are related to tumour characteristics and patient age, and not determined by whether they arise in bone or soft tissue

In vivo animal experimentation has been one of the cornerstones of biological and biomedical research, particularly in the field of clinical medicine and pharmaceuticals. The conventional in vivo model system is invariably associated with high production costs and strict ethical considerations. These limitations led to the evolution of an ex vivo model system which partially or completely surmounted some of the constraints faced in an in vivo model system. The ex vivo rodent bone culture system has been used to elucidate the understanding of skeletal physiology and pathophysiology for more than 90 years. This review attempts to provide a brief summary of the historical evolution of the rodent bone culture system with emphasis on the strengths and limitations of the model. It encompasses the frequency of use of rats and mice for ex vivo bone studies, nutritional requirements in ex vivo bone growth and emerging developments and technologies. This compilation of information could assist researchers in the field of regenerative medicine and bone tissue engineering towards a better understanding of skeletal growth and development for application in general clinical medicine. Cite this article: A. A. Abubakar, M. M. Noordin, T. I. Azmi, U. Kaka, M. Y. Loqman. The use of rats and mice as animal models in ex vivo bone growth and development studies. Bone Joint Res 2016;5:610–618. DOI: 10.1302/2046-3758.512.BJR-2016-0102.R2

Aims. Arthrofibrosis is a relatively common complication after joint injuries and surgery, particularly in the knee. The present study used a previously described and validated rabbit model to assess the biomechanical, histopathological, and molecular effects of the mast cell stabilizer ketotifen on surgically induced knee joint contractures in female rabbits. Methods. A group of 12 skeletally mature rabbits were randomly divided into two groups. One group received subcutaneous (SQ) saline, and a second group received SQ ketotifen injections. Biomechanical data were collected at eight, ten, 16, and 24 weeks. At the time of necropsy, posterior capsule tissue was collected for histopathological and gene expression analyses (messenger RNA (mRNA) and protein). Results. At the 24-week timepoint, there was a statistically significant increase in passive extension among rabbits treated with ketotifen compared to those treated with saline (p = 0.03). However, no difference in capsular stiffness was detected. Histopathological data failed to demonstrate a decrease in the density of fibrous tissue or a decrease in α-smooth muscle actin (α-SMA) staining with ketotifen treatment. In contrast, tryptase and α-SMA protein expression in the ketotifen group were decreased when compared to saline controls (p = 0.007 and p = 0.01, respectively). Furthermore, there was a significant decrease in α-SMA (ACTA2) gene expression in the ketotifen group compared to the control group (p < 0.001). Conclusion. Collectively, these data suggest that ketotifen mitigates the severity of contracture formation in a rabbit model of arthrofibrosis. Cite this article: Bone Joint Res 2020;9(6):302–310

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

In skeletally immature patients, resection of bone tumours and reconstruction of the lower limb often results in leg-length discrepancy. The Stanmore non-invasive extendible endoprosthesis, which uses electromagnetic induction, allows post-operative lengthening without anaesthesia. Between 2002 and 2009, 55 children with a mean age of 11.4 years (5 to 16) underwent reconstruction with this prosthesis; ten patients (18.2%) died of disseminated disease and one child underwent amputation due to infection. We reviewed 44 patients after a mean follow-up of 41.2 months (22 to 104). The mean Musculoskeletal Tumor Society score was 24.7 (8 to 30) and the Toronto Extremity Salvage score was 92.3% (55.2% to 99.0%). There was no local recurrence of tumour. Complications developed in 16 patients (29.1%) and ten (18.2%) underwent revision. The mean length gained per patient was 38.6 mm (3.5 to 161.5), requiring a mean of 11.3 extensions (1 to 40), and ten component exchanges were performed in nine patients (16.4%) after attaining the maximum lengthening capacity of the implant. There were 11 patients (20%) who were skeletally mature at follow-up, ten of whom had equal leg lengths and nine had a full range of movement of the hip and knee. This is the largest reported series using non-invasive extendible endoprostheses after excision of primary bone tumours in skeletally immature patients. The technique produces a good functional outcome, with prevention of limb-length discrepancy at skeletal maturity

Construction of a functional skeleton is accomplished through co-ordination of the developmental processes of chondrogenesis, osteogenesis, and synovial joint formation. Infants whose movement in utero is reduced or restricted and who subsequently suffer from joint dysplasia (including joint contractures) and thin hypo-mineralised bones, demonstrate that embryonic movement is crucial for appropriate skeletogenesis. This has been confirmed in mouse, chick, and zebrafish animal models, where reduced or eliminated movement consistently yields similar malformations and which provide the possibility of experimentation to uncover the precise disturbances and the mechanisms by which movement impacts molecular regulation. Molecular genetic studies have shown the important roles played by cell communication signalling pathways, namely Wnt, Hedgehog, and transforming growth factor-beta/bone morphogenetic protein. These pathways regulate cell behaviours such as proliferation and differentiation to control maturation of the skeletal elements, and are affected when movement is altered. Cell contacts to the extra-cellular matrix as well as the cytoskeleton offer a means of mechanotransduction which could integrate mechanical cues with genetic regulation. Indeed, expression of cytoskeletal genes has been shown to be affected by immobilisation. In addition to furthering our understanding of a fundamental aspect of cell control and differentiation during development, research in this area is applicable to the engineering of stable skeletal tissues from stem cells, which relies on an understanding of developmental mechanisms including genetic and physical criteria. A deeper understanding of how movement affects skeletogenesis therefore has broader implications for regenerative therapeutics for injury or disease, as well as for optimisation of physical therapy regimes for individuals affected by skeletal abnormalities. Cite this article: Bone Joint Res 2015;4:105–116

Aims. Following the introduction of national standards in 2009, most major paediatric trauma is now triaged to specialist units offering combined orthopaedic and plastic surgical expertise. We investigated the management of open tibia fractures at a paediatric trauma centre, primarily reporting the risk of infection and rate of union. Patients and Methods. A retrospective review was performed on 61 children who between 2007 and 2015 presented with an open tibia fracture. Their mean age was nine years (2 to 16) and the median follow-up was ten months (interquartile range 5 to 18). Management involved IV antibiotics, early debridement and combined treatment of the skeletal and soft-tissue injuries in line with standards proposed by the British Orthopaedic Association. Results. There were 36 diaphyseal fractures and 25 distal tibial fractures. Of the distal fractures, eight involved the physis. Motor vehicle collisions accounted for two thirds of the injuries and 38 patients (62%) arrived outside of normal working hours. The initial method of stabilisation comprised: casting in nine cases (15%); elastic nailing in 19 (31%); Kirschner (K)-wiring in 13 (21%); intramedullary nailing in one (2%); open reduction and plate fixation in four (7%); and external fixation in 15 (25%). Wound management comprised: primary wound closure in 24 (39%), delayed primary closure in 11 (18%), split skin graft (SSG) in eight (13%), local flap with SSG in 17 (28%) and a free flap in one. A total of 43 fractures (70%) were Gustilo-Anderson grade III. There were four superficial (6.6%) and three (4.9%) deep infections. Two deep infections occurred following open reduction and plate fixation and the third after K-wire fixation of a distal fracture. No patient who underwent primary wound closure developed an infection. All the fractures united, although nine patients required revision of a mono-lateral to circular frame for delayed union (two) or for altered alignment or length (seven). The mean time to union was two weeks longer in diaphyseal fractures than in distal fractures (13 weeks versus 10.8 weeks, p = 0.016). Children aged > 12 years had a significantly longer time to union than those aged < 12 years (16.3 weeks versus 11.4 weeks, p = 0.045). The length of stay in hospital for patients with a Gustilo-Anderson grade IIIB fracture was twice as long as for less severe injuries. . Conclusion. Fractures in children heal better than those in adults. Based on our experience of deep infection we discourage the use of internal fixation with a plate for open tibial fractures in children. We advocate aggressive initial wound debridement in theatre with early definitive combined orthopaedic and plastic surgery in order to obtain skeletal stabilisation and soft-tissue cover. Cite this article: Bone Joint J 2017;99-B:544–53