Abstract. Introduction. Total knee replacement (TKR) in patients with skeletal dysplasia is technically challenging surgery due to deformity, joint contracture, and associated co-morbidities. The aim of this study is to follow up patients with skeletal dysplasia following a TKR. Methodology. We retrospectively reviewed 22 patients with skeletal dysplasia who underwent 31 TKRs at our institution between 2006 and 2022. Clinical notes, operative records and radiographic data were reviewed. Results. Achondroplasia was the most common skeletal dysplasia (8), followed by Chondrodysplasia punctata (7) and Spondyloepiphyseal dysplasia (5). There were fourteen men and eight women with mean age of 51 years (28 to 73). The average height of patients was 1.4 metres (1.16–1.75) and the mean weight was 64.8 Kg (34.3–100). The mean follow up duration was 68.32 months (1–161). Three patients died during follow up. Custom implants were required in twelve patients (38.71%). Custom jigs were utilised in six patients and two patients underwent robotic assisted surgery. Hinged TKR was used in seventeen patients (54.84%), posterior stabilised TKR in nine patients (29.03%), and cruciate retaining TKR in five patients (16.13%). One patient underwent a patella resurfacing for persistent anterior knee pain and another had an intra-operative medial tibial plateau fracture which was managed with fixation. No revisions occurred during the follow up period. Conclusion. Despite the technical challenges and complexity of TKR within this unique patient group, we demonstrate good implant survivorship during the study period. Cross sectional imaging is recommended preoperatively for precise planning and templating

Aims. The aim of this study was to compare outcomes after growth-friendly treatment for early-onset scoliosis (EOS) between patients with skeletal dysplasias versus those with other syndromes. Methods. We retrospectively identified 20 patients with skeletal dysplasias and 292 with other syndromes (control group) who had completed surgical growth-friendly EOS treatment between 1 January 2000 and 31 December 2018. We compared radiological parameters, complications, and health-related quality of life (HRQoL) at mean follow-up of 8.6 years (SD 3.3) in the dysplasia group and 6.6 years (SD 2.6) in the control group. Results. Mean major curve correction per patient did not differ significantly between the dysplasia group (43%) and the control group (28%; p = 0.087). Mean annual spinal height increase was less in the dysplasia group (9.3 mm (SD 5.1) than in the control group (16 mm (SD 9.2); p < 0.001). Mean annual spinal growth adjusted to patient preoperative standing height during the distraction period was 11% in the dysplasia group and 14% in the control group (p = 0.070). The complication rate was 1.6 times higher (95% confidence interval (CI) 1.3 to 2.0) in the dysplasia group. The following complications were more frequent in the dysplasia group: neurological injury (rate ratio (RR) 5.1 (95% CI 2.3 to 11)), deep surgical site infection (RR 2.2 (95% CI 1.2 to 4.1)), implant-related complications (RR 2.0 (95% CI 1.5 to 2.7)), and unplanned revision (RR 1.8 (95% CI 1.3 to 2.5)). Final fusion did not provide additional spinal height compared with watchful waiting (p = 0.054). There were no significant differences in HRQoL scores between the groups. Conclusion. After growth-friendly EOS treatment, patients with skeletal dysplasias experienced a higher incidence of complications compared to those with other syndromes. Surgical growth-friendly treatment for skeletal dysplasia-associated EOS should be reserved for patients with severe, progressive deformities that are refractory to nonoperative treatment. Cite this article: Bone Joint J 2024;106-B(6):596–602

Aims. The aim of this study was to compare the surgical and quality-of-life outcomes of children with skeletal dysplasia to those in children with idiopathic early-onset scoliosis (EOS) undergoing growth-friendly management. Patients and Methods. A retrospective review of two prospective multicentre EOS databases identified 33 children with skeletal dysplasia and EOS (major curve ≥ 30°) who were treated with growth-friendly instrumentation at younger than ten years of age, had a minimum two years of postoperative follow-up, and had undergone three or more lengthening procedures. From the same registries, 33 matched controls with idiopathic EOS were identified. A total of 20 children in both groups were treated with growing rods and 13 children were treated with vertical expandable prosthetic titanium rib (VEPTR) instrumentation. Results. Mean preoperative major curves were 76° (34° to 115°) in the skeletal dysplasia group and 75° (51° to 113°) in the idiopathic group (p = 0.55), which were corrected at final follow-up to 49° (13° to 113°) and 46° (12° to 112°; p = 0.68), respectively. T1-S1 height increased by a mean of 36 mm (0 to 105) in the skeletal dysplasia group and 38 mm (7 to 104) in the idiopathic group at the index surgery (p = 0.40), and by 21 mm (1 to 68) and 46 mm (7 to 157), respectively, during the distraction period (p = 0.0085). The skeletal dysplasia group had significantly worse scores in the physical function, daily living, financial impact, and parent satisfaction preoperatively, as well as on financial impact and child satisfaction at final follow-up, than the idiopathic group (all p < 0.05). The domains of the 24-Item Early-Onset Scoliosis Questionnaire (EOSQ24) remained at the same level from preoperative to final follow-up in the skeletal dysplasia group (all p > 0.10). Conclusion. Children with skeletal dysplasia gained significantly less spinal growth during growth-friendly management of their EOS and their health-related quality of life was significantly lower both preoperatively and at final follow-up than in children with idiopathic EOS. Cite this article: Bone Joint J 2019;101-B:1563–1569

Novel immersive virtual reality (IVR) technologies are revolutionizing medical education. Virtual anatomy education using head-mounted displays allows users to interact with virtual anatomical objects, move within the virtual rooms, and interact with other virtual users. While IVR has been shown to be more effective than textbook learning and 3D computer models presented in 2D screens, the effectiveness of IVR compared to cadaveric models in anatomy education is currently unknown. In this study, we aim to compare the effectiveness of IVR with direct cadaveric bone models in teaching upper and lower limb anatomy for first-year medical students. A randomized, double-blind crossover non-inferiority trial was conducted. Participants were first-year medical students from a single University. Exclusion criteria included students who undertook prior undergraduate or graduate degrees in anatomy. In the first stage of the study, students were randomized in a 1:1 ratio to IVR or cadaveric bone groups studying upper limb skeletal anatomy. All students were then crossed over and used cadaveric bone or IVR to study lower limb skeletal anatomy. All students in both groups completed a pre-and post-intervention knowledge test. The educational content was based on the University of Toronto Medical Anatomy Curriculum. The Oculus Quest 2 Headsets (Meta Technologies) and PrecisionOS Anatomy application (PrecisionOS Technology) were utilized for the virtual reality component. The primary endpoint of the study was student performance on the pre-and post-intervention knowledge tests. We hypothesized that student performance in the IVR groups would be comparable to the cadaveric bone group. 50 first-year medical students met inclusion criteria and were computer randomized (1:1 ratio) to IVR and cadaveric bone group for upper limb skeletal anatomy education. Forty-six students attended the study, 21 completed the upper limb modules, and 19 completed the lower limb modules. Among all students, average score on the pre-intervention knowledge test was 14.6% (Standard Deviation (SD)=18.2%) and 25.0% (SD=17%) for upper and lower limbs, respectively. Percentage increase in students’ scores between pre-and post-intervention knowledge test, in the upper limb for IVR, was 15 % and 16.7% for cadaveric bones (p = 0. 2861), and for the lower limb score increase was 22.6% in the IVR and 22.5% in the cadaveric bone group (p = 0.9356). In this non-inferiority crossover randomized controlled trial, we found no significant difference between student performance in knowledge tests after using IVR or cadaveric bones. Immersive virtual reality and cadaveric bones were equally effective in skeletal anatomy education. Going forward, with advances in VR technologies and anatomy applications, we can expect to see further improvements in the effectiveness of these technologies in anatomy and surgical education. These findings have implications for medical schools having challenges in acquiring cadavers and cadaveric parts

Novel immersive virtual reality (IVR) technologies are revolutionizing medical education. Virtual anatomy education using head-mounted displays allows users to interact with virtual anatomical objects, move within the virtual rooms, and interact with other virtual users. While IVR has been shown to be more effective than textbook learning and 3D computer models presented in 2D screens, the effectiveness of IVR compared to cadaveric models in anatomy education is currently unknown. In this study, we aim to compare the effectiveness of IVR with direct cadaveric bone models in teaching upper and lower limb anatomy for first-year medical students. A randomized, double-blind crossover non-inferiority trial was conducted. Participants were first-year medical students from a single University. Exclusion criteria included students who undertook prior undergraduate or graduate degrees in anatomy. In the first stage of the study, students were randomized in a 1:1 ratio to IVR or cadaveric bone groups studying upper limb skeletal anatomy. All students were then crossed over and used cadaveric bone or IVR to study lower limb skeletal anatomy. All students in both groups completed a pre-and post-intervention knowledge test. The educational content was based on the University of Toronto Medical Anatomy Curriculum. The Oculus Quest 2 Headsets (Meta Technologies) and PrecisionOS Anatomy application (PrecisionOS Technology) were utilized for the virtual reality component. The primary endpoint of the study was student performance on the pre-and post-intervention knowledge tests. We hypothesized that student performance in the IVR groups would be comparable to the cadaveric bone group. 50 first-year medical students met inclusion criteria and were computer randomized (1:1 ratio) to IVR and cadaveric bone group for upper limb skeletal anatomy education. Forty-six students attended the study, 21 completed the upper limb modules, and 19 completed the lower limb modules. Among all students, average score on the pre-intervention knowledge test was 14.6% (Standard Deviation (SD)=18.2%) and 25.0% (SD=17%) for upper and lower limbs, respectively. Percentage increase in students’ scores between pre-and post-intervention knowledge test, in the upper limb for IVR, was 15 % and 16.7% for cadaveric bones (p = 0. 2861), and for the lower limb score increase was 22.6% in the IVR and 22.5% in the cadaveric bone group (p = 0.9356). In this non-inferiority crossover randomized controlled trial, we found no significant difference between student performance in knowledge tests after using IVR or cadaveric bones. Immersive virtual reality and cadaveric bones were equally effective in skeletal anatomy education. Going forward, with advances in VR technologies and anatomy applications, we can expect to see further improvements in the effectiveness of these technologies in anatomy and surgical education. These findings have implications for medical schools having challenges in acquiring cadavers and cadaveric parts

Bone marrow stem cells (BMSCs) represent a collection of different cell types exhibiting stem cell characteristics but with notable heterogeneity. Among these, Skeletal Stem Cells (SSCs) represent a distinct matrix subgroup within BMSC and demonstrate a specialized capacity to facilitate bone formation, recruit chondrocytes, and contribute to hematopoiesis. SSCs play a pivotal role in orchestrating the functions of skeletal organs. Local ischemia has a significant impact on cell survival and function. We hypothesize that bone ischemia induces alterations in the differentiation potential of SSCs, consequently influencing changes in bone structure. We mechanically dissected tissue from the necrotic segment in the femoral head and more normal appearing areas from the femoral neck of specimens from 5 patients diagnosed with osteonecrosis of the femoral head (ONFH). These tissues were enzymatically broken down into individual cell suspensions. Utilizing fluorescence-activated cell sorting (FACS) based on specific surface markers indicative of human skeletal stem cells (hSSC), namely CD45- CD235a- CD31- TIE2- Podoplanin (PDPN)+ CD146- CD73+ CD164+, we isolated a distinct cell population. Subsequent in vitro evaluations, focusing on clonogenicity, osteogenesis, and chondrogenesis were conducted to assess the functional prowess of these SSCs. Moreover, we introduced BMP2 at a concentration of 50ng/ml to SSCs extracted from necrotic regions to potentially reinstate their osteogenic capabilities. We effectively isolated SSCs from both Necrotic and Non-necrotic Zones. We observed an augmented clonal formation capacity and chondrogenesis ability of SSCs isolated from the necrotic region, accompanied by a significant decline in osteogenic ability (P＜0.01), an effect not reversible even with the addition of BMP2. Ischemia adversely affects the proliferation and function of SSCs, resulting in a diminished osteogenic capacity and an insensitivity to BMP2, ultimately leading to structural alterations in bone tissue

Introduction. The purpose of this study is to evaluate the radiological and clinical outcomes in Northern Ireland of free vascularised fibular bone grafting for the treatment of humeral bone loss secondary to osteomyelitis. Upper limb skeletal bone loss due to osteomyelitis is a devastating and challenging complication to manage for both surgeon and patient. Patients can be left with life altering disability and functional impairment. This limb threatening complication raises the question of salvage versus amputation and the associated risk and benefits of each. Free vascularised fibula grafting is a recognised treatment option for large skeletal defects in long bones but is not without significant risk. The benefit of vascularised over non-vascularised fibula grafts include preservation of blood supply lending itself to improved remodeling and osteointegration. Materials & Methods. Sixteen patients in Northern Ireland had free vascularised fibula grafting. Inclusion criteria included grafting to humeral defects secondary to osteomyelitis. Six patients were included in this study. Patients were contacted to complete DASH (Disabilities of the Arm, Shoulder and Hand) questionnaires as our primary outcome measure. Secondary outcome measures included radiological evaluation of osteointegration and associated operative complications. Complications were assessed via review of Electronic Care Record outpatient and in-patient documents

Background. Replacing bone lost as a consequence of trauma or disease is a major challenge in the treatment of musculoskeletal disorders. Tissue engineering strategies seek to harness the potential of stem cells to regenerate lost or damaged tissue. Bone marrow aspirate (BMA) provides a promising autologous source of skeletal stem cells (SSCs) however, previous studies have demonstrated that the concentration of SSCs required for robust tissue regeneration is below levels present in iliac crest BMA, emphasising the need for cell enrichment strategies prior to clinical application. Aims. To develop a novel strategy to enrich skeletal stem cells (SSCs) from human BMA, clinically applicable for intra-operative orthopaedic use. Methods. Iliac crest BMA was purchased from commercial suppliers and femoral canal BMA was obtained with informed consent from older patients undergoing total hip replacement. 5 to 40ml of BMA was processed to obtain 2–8 fold volume reductions. SSC function was assessed by assays for fibroblastic colony-forming units (CFU-F). Cell viability and seeding efficiency of processed and unprocessed aspirates applied to allograft was assessed. Results. Iliac crest BMA from 15 patients was enriched for SSCs in a processing time of only 15 minutes. Femoral BMA from 15 patients in the elderly cohort was concentrated up to 5-fold with a corresponding enrichment of viable, functional SSCs as confirmed by flow cytometry, CFU-F assays and histological analysis. The SSC enrichment of bone marrow aspirate significantly enhanced cell seeding efficiency onto allograft confirming the utility of this approach for application to bone regeneration. Conclusion. The ability to rapidly enrich BMA demonstrates the potential of this strategy for intra-operative application to enhance bone healing. The development of this device offers immediate potential for clinical application to reduce morbidity in many scenarios associated with local bone stock loss. Further analysis in vivo is ongoing prior to clinical tests

Genetic skeletal disorders constitute a rare and heterogeneous bone diseases often leading to poor quality of life. Several surgical options are available. The surgeon must deal with specific features (bone deformity, previous procedures, abnormal bone quality, stiffness or instability, muscle weakness). The questions concern the feasibility of the procedures and the surgical strategy. 55 patients (26 W, 29 M) were reviewed between 2016 and 2022. The mean age of the patients was 35 years (17–71). The diagnosis included 9 hereditary multiple exostoses, 8 osteogenesis imperfecta, 6 multiple epiphyseal dysplasia congenita, 6 achondroplasia, 4 osteopetrosis, 3 pycnodysostosis, 3 hypophosphatemic rickets, 3 fibrous dysplasia, 2 mucopolysaccharidosis, and 10 miscellaneous. 25 patients were referred for hip problems (40 hips). 4 patients (7 hips) requiring a THA have not been operated (4 planned). 4 patients (6 hips) had a proximal femoral fixation (2 osteotomies, 4 fracture fixations). 17 patients (27 hips) sustained a THA (25 primary, 2 revisions). All of them were operated by one operator, using a posterolateral approach and standard implants (including 7 dysplastic and 2 short stems). No customized implant has been used. As regard the 27 THAs, the mean follow up was 4.2 years (1–12). The early complications included 2 femoral cracks and 1 femur fracture. There were 2 revisions (1 cup loosening at 2 years, 1 stem loosening at 4 years). No infection nor dislocation occurred. All the patients were satisfied with their treatment and regain some autonomy. 3 THA were considered as unfeasible. Constitutional bone diseases need a multidisciplinary program of care. The indication for surgery is based on a mutual trust patient/surgeon, a careful evaluation of benefits/risks, and an accurate imaging to anticipate the difficulties. The expected results are a better function and quality of life, and a stability over time

Cigarette smoking has a negative impact on the skeletal system by reducing bone mass and increasing the risk of fractures through its direct or indirect effects on bone remodeling. Recent evidence shows that smoking causes an imbalance in bone turnover, making bone vulnerable to osteoporosis and fragility fractures. In addition, cigarette smoking is known to have deleterious effects on fracture healing, as a positive correlation has been shown between the daily number of cigarettes smoked and years of exposure to smoking, although the underlying mechanisms are not fully understood. Smoking is also known to cause several medical and surgical complications responsible for longer hospital stays and a consequent increase in resource consumption. Smoking cessation is, therefore, highly advisable to prevent the onset of metabolic bone disease. However, some of the consequences appear to continue for decades. Based on this evidence, the aim of our work was to assess the impact of smoking on the skeletal system, particularly bone fractures, and to identify the pathophysiological mechanisms responsible for the impairment of fracture healing. Because smoking represents a major public health problem, understanding the association between cigarette smoking and the occurrence of bone disease is necessary in order to identify potential new targets for intervention

Aims. Different methods of anterior cruciate ligament (ACL) reconstruction have been described for skeletally immature patients before closure of the growth plates. However, the outcome and complications following this treatment remain unclear. The aim of this systematic review was to analyse the outcome and complications of different techniques which may be used for reconstruction of the ACL in these patients. Materials and Methods. We performed a systematic review of the literature according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. This involved a comprehensive search of PubMed, Medline, CINAHL, Cochrane, Embase and Google Scholar databases using the following combinations of keywords, “knee”, “anterior cruciate ligament”, “reconstruction”, “injury”, “children”, “adolescent”, “skeletally immature”, “open physis” and “surgery”. Results. A total of 53 studies met the inclusion criteria and were included for analysis. The overall rate of disturbance of growth after ACL reconstruction was 2.6%, with no statistical difference between transphyseal and physeal-sparing techniques. Physeal-sparing techniques had a lower rate of post-operative complications compared with transphyseal techniques (p = 0.0045). Outcomes assessed were Lysholm score, International Knee Documentation Committee (IKDC) score, the IKDC grade, the Tegner score and the KT-1000. Both techniques had similar clinical outcomes. Conclusions. This review reveals low rates of disturbance of growth after ACL reconstruction in skeletally immature patients. Although limited, the available evidence did not support any particular surgical technique when considering disturbance of growth or clinical outcome. Further randomised controlled trials are needed to investigate the efficacy of differing surgical techniques on outcomes in skeletally immature patients. Cite this article: Bone Joint J 2017;99-B:1053–60

Background. In 2012, the National Joint Registry recorded 86,488 primary total hip replacements (THR) and 9,678 revisions (1). To date aseptic loosening remains the most common cause of revision in hip and knee arthroplasty, accounting for 40% and 32% of all cases respectively and emphasising the need to optimise osseointegration in order to reduce revisions. Clinically, osseointegration results in asymptomatic stable durable fixation of orthopaedic implants. Osseointegration is a complex process involving a number of distinct mechanisms affected by the implant surface topography, which is defined by surface orientation and surface roughness. Micro- and nano-topography levels have discrete effects on implant osseointegration and yet the role on cell function and subsequent bone implant function is unknown. Nanotopography such as collagen banding is a critical component influencing the SSC niche in vivo and has been shown to influence a range of cell behaviours in vitro (2,3). We have used unique fabricated nanotopographical pillar substrates to examine the function of human bone stem cells on titanium surfaces. Aim. To investigate the effect of nanotopographical cues on adult skeletal stem cell (SSC) fate, phenotype and function within in-vitro environments. Materials and methods. Adult human skeleltal stem cells (SSCs) were immunoselected and enriched using STRO-1 antibody and cultured on tissue culture plastic (TCP) and titanium-coated nanotopgraphical substrates (illustrated in Figure 1). Following culture, metabolic activity of SSCs on TCP and Ti substrates was compared. Subsequently, osteoinductive potential was analysed under basal and osteogenic conditions (four groups: TCP in basal media, TCP in osteogenic media, Ti planar substrates basal and Ti pillar substrates basal). Results. At 7 days, cell metabolic activity was significantly enhanced on Ti substrates, specifically on Ti pillars of defined height in comparison to TCP (Figure 2). Following culture on defined topographies for 21 days, expression of the bone matrix protein, osteopontin, on Ti pillars was significantly enhanced when compared to TCP or Ti planar (Figure 3). Conclusion. We demonstrate the ability of discrete raised nanopillars to modualte adult SSC populations in the absence of any chemical cues. These results indicate the potential of discrete and defined nanopillar constructs to stimulate SSC function, an effect not observed on planar Ti constructs. These findings herald exciting opportunities to improve the bioactivity of implant design and, ultimately, osseointegration with clinical implications therein

Advances in our understanding of skeletal stem cells and their role in bone development and repair, offer the potential to open new frontiers in bone regeneration. However, the ability to harness these cells to replace or restore the function of traumatised or lost skeletal tissue as a consequence of age or disease remains a significant challenge. We have developed protocols for the isolation, expansion and translational application of skeletal cell populations with cues from developmental biology informed by in vitro and ex vivo models as well as, nanoscale architecture and biomimetic niche development informing our skeletal tissue engineering approaches. We demonstrate the importance of biomimetic cues and delivery strategies to directly modulate differentiation of human adult skeletal cells and, central to clinical application, translational studies to examine the efficacy of skeletal stem and cell populations in innovative scaffold compositions for orthopaedics. While a number of challenges remain multidisciplinary approaches that integrate developmental and engineering processes as well as cell, molecular and clinical techniques for skeletal tissue engineering offer significant promise. Harnessing such approaches across the hard tissue interface will ultimately improve the quality of life of an increasing ageing population

Introduction. This is a report of the outcome of management of congenital pseudoarthrosis of the tibia (CPT) at skeletal maturity. Materials and Methods. Retrospective study. Inclusion criteria:. CPT Crawford IV. Skeletally maturity. Availability of radiographs and medical records. Outcome: union rate, healing time, residual deformities, ablation and refracture. Results. 23 patients who reached maturity were analysed. Time to union was 7.6 months. Union rate 70%. External fixation group: 7 patients, age 6.1 years, all united, 1 needed Bone graft. Average union time 8.2 months, no residual mal-alignment, no amputations, 2/7 needed corrective osteotomies and residual LLD in 2/7 < 1 cm. Numbers of surgery was 3. Vascularized fibular graft was done in 3 cases; all had failed previous attempts. Union time was 7 months. 2/3 united, 1 had amputation due to extensive disease. All patients had residual mal-alignment. Rodding group included 13 patients, age 3.2 years, union rate 61%, union time 8.3 months. Average LLD 1 cm with 1 patient LLD > 2 cm. Residual knee mal-alignment in 2/13, 4 had procurvatum and 55% of patients had ankle valgus. Fibula pseudoarthrosis. Refracture was reported in 53% of the rodding group. The causes of refracture were mal-alignment in 3, traumatic in 2 and idiopathic in 2. Total surgeries no 5. 2 patients had amputations after an unsuccessful 1. st. attempt. Our current trend of treatment was applied on 8 patients. They are not skeletally mature yet. the treatment combined excision of hamartoma, tibial rodding, wrapped periosteal graft with/out neutralization frame, and fibular fixation. Average age 3.8 years, union time was 10 months, Union rate 80%, no residual deformities. Conclusions. Our study shows the evolution of the treatment of CPT with increasing union rate, fewer residual deformities, and numbers of surgeries with more recent techniques

Recent approaches have sought to harness the potential of stem cells to regenerate bone lost as a consequence of trauma or disease. Bone marrow aspirate (BMA) provides an autologous source of skeletal stem cells (SSCs) for such applications, however previous studies have demonstrated that the concentration of SSCs present in iliac crest BMA is below that required for robust bone regeneration. Here we present a novel acoustic-facilitated filtration strategy to concentrate BMA for SSCs, clinically applicable for intra-operative orthopaedic use. The aim of this study was to demonstrate the efficacy of this strategy in concentrating SSCs from iliac crest bone marrow, as well as femoral canal BMA from older patients. Iliac crest BMA (Lonza, Rockville, MD, USA) and femoral canal BMA was obtained with informed consent from older patients during total hip replacement. 5 to 40ml of BMA was processed via the acoustically-aided exclusion filtration process to obtain 2-8 fold volume reductions. SSC concentration and function was assessed by flow-cytometry, assays for fibroblastic colony-forming units (CFU-F) and multi-lineage differentiation along chondrogenic, osteogenic and adipogenic pathways examined. Seeding efficiency of enriched and unprocessed BMA (normalised to cell number) onto allograft was assessed. Iliac crest BMA from 15 patients was enriched for SSCs in a processing time of only 15 minutes. Femoral BMA from 15 patients in the elderly cohort was concentrated up to 5-fold with a corresponding enrichment of viable and functional SSCs, confirmed by flow cytometry and assays for CFU-F. Enhanced osteogenic (P<0.05) and chondrogenic (P<0.001) differentiation was observed using concentrated aspirate, as evidenced by biochemical assay and semi-quantitative histological analysis. Furthermore, enhanced cell seeding efficiency onto allograft was seen as an effect of SSC concentration per ml of aspirate (P<0.001), confirming the utility of this approach for application to bone regeneration. The ability to rapidly enrich BMA demonstrates potential for intra-operative application to enhance bone healing and offers immediate capacity for clinical application to treat many scenarios associated with local bone stock loss. Further in vivo analysis is ongoing prior to clinical tests

Lung cancer is the most common cancer diagnosed, the leading cause of cancer-related deaths, and bone metastases occurs in 20–40% of lung cancer patients. They often present symptomatically with pain or skeletal related events (SREs), which are independently associated with decreased survival. Bone modifying agents (BMAs) such as Denosumab or bisphosphonates are routinely used, however no specific guidelines exist from the National Comprehensive Cancer Center or the European Society of Medical Oncologists. Perhaps preventing the formation of guidelines is the lack of a high-quality quantitative synthesis of randomized controlled trial (RCT) data to determine the optimal treatment for the patient important outcomes of 1) Overall survival (OS), 2) Time to SRE, 3) SRE incidence, and 4) Pain Resolution. The objective of this study was to perform the first systematic review and network meta-analysis (NMA) to assess the best BMA for treatment of metastatic lung cancer to bone. We conducted our study in accordance to the PRISMA protocol. We performed a librarian assisted search of MEDLINE, PubMed, EMBASE, and Cochrane Library and Chinese databases including CNKI and Wanfang Data. We included studies that are RCTs reporting outcomes specifically for lung cancer patients treated with a bisphosphonate or Denosumab. Screening, data extraction, risk of bias and GRADE were performed in duplicate. The NMA was performed using a Bayesian probability model with R. Results are reported as relative risks, odds ratios or mean differences, and the I2 value is reported for heterogeneity. We assessed all included articles for risk of bias and applied the novel GRADE framework for NMAs to rate the quality of evidence supporting each outcome. We included 132 RCTs comprising 11,161 patients with skeletal metastases from lung cancer. For OS, denosumab was ranked above zoledronic acid (ZA) and estimated to confer an average of 3.7 months (95%CI: −0.5 – 7.6) increased survival compared to untreated patients. For time to SRE, denosumab was ranked first with an average of 9.1 additional SRE-free months (95%CI: 4.0 – 14.0) compared to untreated patients, while ZA conferred an additional 4.8 SRE-free months (2.4 – 7.0). Patients treated with the combination of Ibandronate and systemic therapy were 2.3 times (95%CI: 1.7 – 3.2) more likely to obtain successful pain resolution, compared to untreated. Meta-regression showed no effect of heterogeneity length of follow-up or pain scales on the observed treatment effects. Heterogeneity in the network was considered moderate for overall survival and time to SRE, mild for SRE incidence, and low for pain resolution. While a generally high risk of bias was observed across studies, whether they were from Western or Chinese databases. The overall GRADE for the evidence underlying our results is High for Pain control and SRE incidence, and Moderate for OS and time to SRE. This study represents the most comprehensive synthesis of the best available evidence guiding pharmacological treatment of bone metastases from lung cancer. Denosumab is ranked above ZA for both overall survival and time to SRE, but both treatments are superior to no treatment. ZA was first among all bisphosphonates assessed for odds of reducing SRE incidence, while the combination of Ibandronate and radionuclide therapy was most effective at significantly reducing pain from metastases. Clinicians and policy makers may use this synthesis of all available RCT data as support for the use of a BMA in MBD for lung cancer

Intermittently administered parathyroid hormone (PTH 1-34) has been shown to promote bone formation in both human and animal studies. The hormone and its analogues stimulate both bone formation and resorption, and as such at low doses are now in clinical use for the treatment of severe osteoporosis. By varying the duration of exposure, parathyroid hormone can modulate genes leading to increased bone formation within a so-called ‘anabolic window’. The osteogenic mechanisms involved are multiple, affecting the stimulation of osteoprogenitor cells, osteoblasts, osteocytes and the stem cell niche, and ultimately leading to increased osteoblast activation, reduced osteoblast apoptosis, upregulation of Wnt/β-catenin signalling, increased stem cell mobilisation, and mediation of the RANKL/OPG pathway. Ongoing investigation into their effect on bone formation through ‘coupled’ and ‘uncoupled’ mechanisms further underlines the impact of intermittent PTH on both cortical and cancellous bone. Given the principally catabolic actions of continuous PTH, this article reviews the skeletal actions of intermittent PTH 1-34 and the mechanisms underlying its effect. Cite this article: L. Osagie-Clouard, A. Sanghani, M. Coathup, T. Briggs, M. Bostrom, G. Blunn. Parathyroid hormone 1-34 and skeletal anabolic action: The use of parathyroid hormone in bone formation. Bone Joint Res 2017;6:14–21. DOI: 10.1302/2046-3758.61.BJR-2016-0085.R1

The ideal treatment for traumatic anterior dislocation of the shoulder in the skeletally immature patient is controversial. The aim of this study is to evaluate the outcomes after either conservative and/or surgical treatment using the Latarjet technique. A retrospective series of 49 out of 80 patients were reviewed. We found no significant differences between either treatment method regarding functional scores and pain levels. Although not statistically significant, post-surgical patients showed better signs of shoulder stability than others who have a higher rate of recurrence. Further, 92% of the post-surgical group had returned to the same level of activity versus 52% in the non-surgically treated group. We found no contraindications to operate on a skeletally immature patient. Cite this article: Bone Joint J 2014;96-B:354–9

Introduction and Objective. Calcium phosphates are among the most commonly used bone graft substitute materials. Compositions containing predominantly monetite (∼84.7%) with smaller additions of beta-tricalcium phosphate (β-TCP; ∼8.3%) and calcium pyrophosphate (Ca-PP; ∼6.8%) have previously been demonstrated to exhibit osteoinductive properties. Such a multi-component calcium phosphate bioceramic was fashioned in the form of hollowed-out, dome-shaped devices (15 mm diameter, 4 mm height), each reinforced with a 3D printed Ti6Al4V ELI frame. With the aim to induce bone formation beyond the skeletal envelope, these devices were investigated in vivo using a sheep (Ovis aries) occipital bone model. Materials and Methods. The bioceramic composition was prepared from a mixture of β-TCP/dicalcium pyrophosphate and monocalcium phosphate monohydrate powders mixed with glycerol. The Ti6Al4V ELI frame was positioned into a dome-shaped mould and bioceramic paste was poured over the frame and allowed to set, in sterile water, prior to removal from the mould. In adult female sheep (n=7), the devices were positioned directly over the bone and stabilised using self-drilling screws. After 52 weeks, the devices were retrieved, resin embedded, and used for X-ray micro-computed tomography (micro-CT), histology, backscattered electron scanning electron microscopy (BSE-SEM), energy dispersive X-ray spectroscopy (EDX), micro-Raman spectroscopy, and Fourier transform infrared spectroscopy (FTIR). Results. The bioceramic composition (Ca/P: ∼0.85 at. %) transforms to carbonated apatite (Ca/P: ∼1.2 at. %, Mg/Ca: ∼0.03 at. %), in vivo, largely at the expense of monetite and Ca-PP whereas β-TCP remains detectable. Discrete particles of Ca-PP are identified by correlative BSE-SEM and micro-Raman spectroscopy. Together with chemical transformation, physical degradation is evident within the bulk of the bioceramic. Beyond the confines of the skeletal envelope, de novo bone occupies ∼53–84% (∼73 ± 11%; mean ± standard deviation) of the hollowed-out space. Low porosity and the arrangement of remodelled bone into a concentric lamellar pattern is indicative of cortical-like structure. Such areas are typically surrounded by yet unremodelled, and microstructurally disordered, woven bone that stains intensely with blue cationic dyes, owing to relatively higher acid phosphate content. This pattern indicates a recurring sequence of woven bone formation followed by remodelling. Bone formation is also visible within the bioceramic. Recently remodelled and areas of ongoing remodelling are identified by relatively lower mineral density than the surrounding woven bone. Dendritic extensions of osteocytes appear to extend into the bioceramic surface. Both micro-Raman spectroscopy and FTIR reveal little, if any, detectable difference between the mineral and organic phases of the extracellular matrix, between de novo and native bone. Conclusions. The bioceramic composition undergoes physical degradation, but remains largely intact by 52 weeks in vivo, and only partially transforms to carbonated apatite. In addition to very high bone volume within the hollowed-out bioceramic device, the overall composition and microstructure of de novo bone are similar to native bone. Notably, the mineral phase of bone in response to, and in direct contact with the β-TCP, monetite, and Ca-PP, remains exclusively carbonated apatite

The term “skeletal skew” recognises the oblique positioning or slanting of two similar halves of the body. It is preferred to asymmetry which describes a disproportion between two quantities with no common measure. In 1982 69 babies with skeletal skew were described in relation to the abduction contracture which affects the hip and leg on which the body lies in persistent sidelying. The skeletal skew was evident at birth in 24 cases, but only became obvious at 4–6 months of age in the remaining 45 cases. The adducted, uppermost hip looks spuriously dysplastic but the proximal femoral ossification centre is usually equal to the opposite side and the ultrasound scan is within normal limits. Associated skewing affects the skull (plagiocephaly) the neck (torticollis), thorax, pelvis and feet in a proportion of these squint babies. When the pelvic radiograph is assessed confusion is avoided if the ischial lower border is set horizontally; this corrects the apparent, increased acetabular inclination (angle) on the adducted side. The concomitant rotational artefact can be appreciated by reviewing differences in the widths of the iliac wings and obturator foramina, sacral-symphysial alignment and femoropelvic overlap. Of the 45 cases with pronounced skeletal skew manifesting at 3–4 months of age, the oblique positioning corrected during early walking age, as shown by calculating the difference between the abduction arcs of the two hips. The plagiocephaly, with flattening of the brow on the upper side, may persist until skeletal maturity. Follow up at 18 years was achieved in 41 of the 45 cases. There was one case of mild bilateral hip dysplasia and one case of a leg length discrepancy of 1.5 cm. In 40 cases the hips were normal clinically and radiographically although 5 had persistence of increased femoral anteversion. No splintage or stretching of the adducted hip had been undertaken during infancy and hence the great majority of cases with skeletal skew correct. Ultrasound assessment is advised in borderline cases for this relatively common condition which results in a referral rate of 5.3 per 1000 live births, compared to the Edinburgh neonatal splintage rate for hip instability of 3.8 per 1000 live births

Tissue engineering is a promising approach to regenerate damaged skeletal tissues. In particular, the use of injectable hydrogels alleviates common issues of poor cell viability and engraftment. However, uncontrolled cell fate, resulting from unphysiological environments and degradation rates, still remain a hurdle and impedes tissue healing. We thus aim at developing a new platform of injectable hyaluronic acid (HA) hydrogels with a large panel of properties (stiffness, degradation…) matching those of skeletal tissues. Hence, HA with different molecular weights were functionalized with silylated moieties. Upon injection, these hydrogels formed through a sol-gel chemistry within 5 to 20 minutes in physiological conditions, as demonstrated by rheological characterization. By varying the crosslinking density and concentration, we obtained hydrogels spanning a large range of elastic moduli (E = 0.1–20 kPa), similar to those of native ECMs, with tunable biodegradation rates (from 24 hours to > 50 days) and swelling ratios (500 to 5000% (w/w)). Cell viability was confirmed by Live/Dead assays and will be completed by in vivo subcutaneous implantations in mice to study the foreign body reaction and degradation rate. We further developed hybrid HA/biphasic calcium phosphate granules hydrogels and demonstrated a strong mechanical reinforcement (E = 0.1 MPa) and a faster relaxation behaviour (τ. 1/2. < 400s), with similar degradation rates. Ongoing in vitro differentiation assays and in vivo implantations in a rabbit femur model will further assess their ability to drive bone regeneration. Collectively, these results suggest that this hydrogel platform offers promising outcomes for improved strategies in skeletal tissue engineering

The atlas of Greulich and Pyle for skeletal maturity and epiphyseal closure is widely used in many countries to assess skeletal age and to plan orthopaedic surgery. The data used to compile the atlas were collected from institutionalised American children in the 1950s. In order to determine whether the atlas was relevant to subSaharan Africa, we compared skeletal age, according to the atlas, with chronological age in 139 skeletally immature Malawian children and young adults with an age range from 1 year 11 months to 28 years 5 months. The height and weight of each patient were also measured in order to calculate the body mass index. The skeletal age of 119 patients (85.6%) was lower than the chronological age. The mean difference was 20.0 ± 24.1 months (t-test, p = 0.0049), and the greatest difference 100 months. The atlas is thus inaccurate for this group of children. The body mass index in 131 patients was below the normal range of 20 to 25 kg/m. 2. . The reasons for the low skeletal age in this group of children are discussed. Poor nutrition and chronic diseases such as malaria and diarrhoea which are endemic in Malawi are likely to be contributing factors. We did not find any correlation between the reduction in body mass index in our patients and the degree of retardation of skeletal age

Patients with skeletal dysplasia are prone to developing advanced osteoarthritis of the knee requiring total knee replacement (TKR) at a younger age than the general population. TKR in this unique group of patients is a technically demanding procedure owing to the deformity, flexion contracture, generalised hypotonia and ligamentous laxity. We retrospectively reviewed the outcome of 11 TKRs performed in eight patients with skeletal dysplasia at our institution using the Stanmore Modular Individualised Lower Extremity System (SMILES) custom-made rotating-hinge TKR. There were three men and five women with mean age of 57 years (41 to 79). Patients were followed clinically and radiologically for a mean of seven years (3 to 11.5). The mean Knee Society clinical and function scores improved from 24 (14 to 36) and 20 (5 to 40) pre-operatively, respectively, to 68 (28 to 80) and 50 (22 to 74), respectively, at final follow-up. Four complications were recorded, including a patellar fracture following a fall, a tibial peri-prosthetic fracture, persistent anterior knee pain, and aseptic loosening of a femoral component requiring revision. Our results demonstrate that custom primary rotating-hinge TKR in patients with skeletal dysplasia is effective at relieving pain, with a satisfactory range of movement and improved function. It compensates for bony deformity and ligament deficiency and reduces the likelihood of corrective osteotomy. Patellofemoral joint complications are frequent and functional outcome is worse than with primary TKR in the general population

Aims

The gluteus minimus (GMin) and gluteus medius (GMed) have unique structural and functional segments that may be affected to varying degrees, by end-stage osteoarthritis (OA) and normal ageing. We used data from patients with end-stage OA and matched healthy controls to 1) quantify the atrophy of the GMin and GMed in the two groups and 2) describe the distinct patterns of the fatty infiltration in the different segments of the GMin and GMed in the two groups.

Skeletal scintigraphy, which has now been established as a useful and accurate method of detecting early skeletal metastases and assessing their response to treatment, has been investigated for its pathological basis. Histological examination of several hundred necropsy specimens, from sixty-eight patients who died from malignant disease, showed a significant increase of osteoid and immature woven bone in the presence of metastatic cancer. Tumour-cell suspensions of the VX2 carcinoma were injected into the medullary cavity or on to the periosteal surface of the ilia or tibiae of New Zealand white rabbits. A combination of bone destruction and new bone formation, similar to the autopsy material, was seen. There were at least two mechanisms for the new bone production. Initially, intramembranous ossification was seen in the fibrous stroma surrounding the tumour. Once the cortex was involved and cortical bone destruction had occurred, large amounts of woven bone resembling fracture callus were laid down. The new bone had a markedly increased avidity for boneseeking isotopes, indicating why skeletal scintigraphy was useful. A further twenty rabbits, in whose ilia the VX2 carcinoma was growing, were treated by local irradiation. When treatment was successful the tumour was destroyed, the production of new bone ceased, and the lesion lost its increased avidity for bone-seeking isotopes, indicating that skeletal scintigraphy could be used to assess the response of skeletal metastases to therapy

TGF-beta signaling has a well established role not only in adult organ homeostasis but also in skeletal development. Follistatin-like 3 (FSTL3), related to follistatin, is an inhibitor of TGF-beta ligands, with an established role in glucose and fat metabolism. However it has not previously been studied in skeletal development. Using a FSTL3 knock-out (KO) mouse model we have studied both embryonic skeletal development and adult bone phenotypes. Staining for skeletal and cartilage markers during development shows acceleration of skeletal tissue differentiation, with an eventual normalization at E18.5 (which is just prior to birth). Acceleration of bone mineralization occurs during both endochondral and intramembranous ossification. Use of micro-CT imaging highlighted the development of a scoliosis in the KO animals, along with abnormal shape of cranium and cranial sutures. Further investigation of the cranial phenotype in adult KO mice reveals craniosynastosis, with atypical fusion of the frontal suture. These mice have a change in overall cranial shape with shortening of the anterior head and a compensatory expansion of the posterior cranial bones, in a similar fashion to brachyencephaly. Our study therefore highlights a significant role of FSTL3 in skeletal tissue development and mineralization, as well as the development of clinically significant skeletal developmental disorders such as scoliosis, craniosynastosis and brachyencephaly

Skeletal metastases from hepatocellular carcinoma are highly destructive vascular lesions which severely reduce the quality of life. Pre-existing liver cirrhosis presents unique challenges during the surgical management of such lesions. We carried out a retrospective study of 42 patients who had been managed surgically for skeletal metastases from hepatocellular carcinoma affecting the appendicular skeleton between January 2000 and December 2006. There were 38 men and four women with a mean age of 60.2 years (46 to 77). Surgery for a pathological fracture was undertaken in 30 patients and because of a high risk of fracture in 12. An intralesional surgical margin was achieved in 36 and a wide margin in six. Factors influencing survival were determined by univariate and multivariate analyses. The survival rates at one, two and three years after surgery were 42.2%, 25.8% and 19.8%, respectively. The median survival time was ten months (95% confidence interval 6.29 to 13.71). The number of skeletal metastases and the Child-Pugh grade were identified as independent prognostic factors by Cox regression analysis. The method of management of the hepatocellular carcinoma, its status in the liver, the surgical margin for skeletal metastases, the presence of a pathological fracture and adjuvant radiotherapy were not found to be significantly related to the survival of the patient, which was affected by hepatic function, as represented by the Child-Pugh grade

Femoral lengthening using the Intramedullary Skeletal Kinetic Distractor is a new technique. However, with intramedullary distraction the surgeon has less control over the lengthening process. Therefore, 33 femora lengthened with this device were assessed to evaluate the effect of operative variables under the surgeon’s control on the course of lengthening. The desired lengthening was achieved in 32 of 33 limbs. Problems encountered included difficulty in achieving length in eight femora (24%) and uncontrolled lengthening in seven (21%). Uncontrolled lengthening was more likely if the osteotomy was placed with less than 80 mm of the thick portion of the nail in the distal fragment (p = 0.052), and a failure to lengthen was more likely if there was over 125 mm in the distal fragment (p = 0.008). The latter problem was reduced with over-reaming by 2.5 mm to 3 mm. Previous intramedullary nailing also predisposed to uncontrolled lengthening (p = 0.042), and these patients required less reaming. Using the Intramedullary Skeletal Kinetic Distractor, good outcomes were obtained; problems were minimised by optimising the position of the osteotomy and the amount of over-reaming performed

The case histories of these Black Notley patients show that no serious harmful effects have been caused by pregnancies going to full term. Most of the patients had normal confinements; Caesarian sections were few and were usually done for obstetric reasons, not for fear of reactivation of the disease. This experience bears out a remark made to me by Marcel Galland. When asked if Caesarian sections were required for women who became pregnant after treatment at Berck for skeletal tuberculosis, he replied: "Jarnais! Tout passe!". Two patients in the series had artificial abortions, and one aborted spontaneously. Two of these three patients did not do as well as other patients whose pregnancies went to full term. Quite another question is whether the onset of skeletal tuberculosis sooii after pregnancy may be attributed to the pregnancy. In a group of women of child-bearing age, it would be difficult to distinguish between post hoc and propter hoc in considering this question. One patient of this series, H. Q. (Case 25), was admitted eight months pregnant with active tuberculosis of the knee; but pain in the joint had started fifteen months before admission, and the onset of disease no doubt preceded the pregnancy. Some of the patients admitted to Black Notley were mothers of young children hut there is no note of any pregnancy having preceded the onset of tuberculosis by a short interval. The follow-up reports of the married patients compare favourably with those of the unmarried. Further, it may be argued that pregnancy increases resistance to tuberculosis. Such a belief was current from the time of Hippocrates until the middle of the nineteenth century, and clinical evidence can be quoted in favour of such a view. In America, Lyman (1943) followed up 1,818 women who had been treated for tuberculosis in a sanatorium; many had married despite medical advice to the contrary. Lyman found that the late results of treatment were four times as good in the married patients as in the single women. Lyman says, "When we consider that the married group established this record in spite of the fact that 192 out of 315 gave histories of pregnancies (averaging 2·25 children each), it is clear that some factor not yet accounted for has exerted a profound influence in their cases.". I have speculated elsewhere as to what this factor may be (Wilkinson 1949). But it seems clear that increased sterol circulation in the body is associated with increased reticulo-endothelial activity (Fraser 1935). Thus reticulo-endothelial proliferation has been observed in the lesions of lupus following the administration of calciferol (Dowling, Gauvain and Macrae 1948). An increase of blood cholesterol is found during pregnancy. The sex hormones are sterols and might be expected to be raised in the marital state; it is perhaps significant that marital contacts form a group relatively immune to tuberculosis. There would appear to be good grounds for reassuring the married woman who has suffered from skeletal tuberculosis regarding the prospect of normal pregnancy. Many letters received from patients in a follow-up of this sort are poignant documents. There is no doubt that the majority of these women desire children as ardently as normal women, and that a safe confinement following skeletal tuberculosis is an excellent form of rehabilitation

Introduction: The natural history of idiopathic scoliosis is not well understood. Previous reports focused on characteristics of curve progression pre-defined at 5–6 degrees. However, the absolute curve magnitude at skeletal maturity is more predictive of long-term curve behavior rather than progression of defined magnitude over shorter periods of growth. It is generally agreed that curves < 30 degrees are unlikely to progress after skeletal maturity. Hence, defining factors that influence curve progression to an absolute magnitude of ≥30 degrees at skeletal maturity significantly aids clinical decision-making. Methods: Of 279 patients with idiopathic scoliosis detected by school screening of 72,699 adolescents, 186 fulfilled the study criteria and were followed up to skeletal maturity. Initial age, gender, pubertal status and initial curve magnitude were used as predictive factors for curve progression to ≥30 degrees at skeletal maturity. Uni and multivariate, logistic regression and receiver operating characteristic (ROC) analysis was performed. Results: Curve magnitude at first presentation was the most important predictive factor for curve progression to ≥30 degrees at skeletal maturity. An initial curve of 25 degrees had the best ROC of 0.8 with a positive predictive value of 68% and a negative predictive value of 92% for progression to ≥30 degrees at skeletal maturity. The highest risk was a pre-pubertal female < 12 years of age with a Cobb of ≥25 degrees at presentation; with an 82% chance of progression to a Cobb of ≥30 degrees. Probability of progression to ≥30 degrees was defined by 1/(1 + exp (−z)). [z = −3.709 + 0.931(Gender) + 0.825(Puberty) + 3.314(Cobb) + 0.171(Age)]. Conclusions: Initial curve magnitude is the most important independent predictor of long-term curve progression past skeletal maturity. An initial Cobb of 25 degrees is an important threshold. Combined with other factors, we identify patient profiles with high or low risk for progression

Assessment of skeletal age is important in children’s orthopaedics. We compared two simplified methods used in the assessment of skeletal age. Both methods have been described previously with one based on the appearance of the epiphysis at the olecranon and the other on the digital epiphyses. We also investigated the influence of assessor experience on applying these two methods. Our investigation was based on the anteroposterior left hand and lateral elbow radiographs of 44 boys (mean: 14.4; 12.4 to 16.1 ) and 78 girls (mean: 13.0; 11.1 to14.9) obtained during the pubertal growth spurt. A total of nine observers examined the radiographs with the observers assigned to three groups based on their experience (experienced, intermediate and novice). These raters were required to determined skeletal ages twice at six-week intervals. The correlation between the two methods was determined per assessment and per observer groups. Interclass correlation coefficients (ICC) evaluated the reproducibility of the two methods. The overall correlation between the two methods was r = 0.83 for boys and r = 0.84 for girls. The correlation was equal between first and second assessment, and between the observer groups (r ≥ 0.82). There was an equally strong ICC for the assessment effect (ICC ≤ 0.4%) and observer effect (ICC ≤ 3%) for each method. There was no significant (p < 0.05) difference between the levels of experience. The two methods are equally reliable in assessing skeletal maturity. The olecranon method offers detailed information during the pubertal growth spurt, while the digital method is as accurate but less detailed, making it more useful after the pubertal growth spurt once the olecranon has ossified. Cite this article: Bone Joint J 2014;3:1556–60

Introduction:. With the arrival of the 21. st. century, there were clear expectations that cementless fixation in total joint replacements (TJR), and the translational animal protocols for introducing new coatings and surface treatments clinically, had been established. Despite the extensive literature in the 1980s and 1990s demonstrating a translational pathway for predicting skeletal attachment, there remain clinical reports of mechanical implant loosening in both cementless total hip acetabular and total knee components. Before screening a new porous coating or surface treatment, it is important to note that there has been only one experimental translational load-bearing model that has had human (1–3), sheep (4–5), clinical (6–8), and implant retrieval verification confirming skeletal attachment in these types of components, the intracondylar model (1–5,8). What makes the intracondular model predictive of coating or surface treatments for implant attachment is the ability of the model to replicate the healing response of cancellous bone, the main attachment bone tissue to THR acetabular and TKA implants. A lot of the confusion rests with a lack of understanding of the bone response differences between the intracondylar and transcortical animal models. The goal of this study was to test the hypothesis that the intracondylar model can provide positive and negative surface attachment data, whereas, the transcortical model can only provide positive and false positive attachment data. Methods:. Five skeletally mature sheep will have been implanted with two 13×8 mm plugs (500 mm larger than the 7.5 mm drilled holes) two plugs transcortically and two intracondylarly. One plug will be titanium with CP porous coating. Another plug is made of petrified dinosaur poop with similar dimensions (see Figure 1). Another five sheep will also be implanted transcortically and intracondylarly using plugs with 500 mm inset of the same materials and dimensions. Again, two implants at each site. Results:. The goal will be to demonstrate that the fracture healing response at the transcortical site will allow attachment to both material and structural types. The intracondylar plugs should demonstrate only attachment to the Ti porous coated device with the proud CP titanium coating, showing the false positive nature of the transcortical model attachment to dinosaur poop and inset porous coated plugs. The results should provide data for using only the intracondylar model for predicting skeletal attachment of components intended for total joint replacement

Aims. We wished to examine the effectiveness of tibial lengthening using a two ring Ilizarov frame in skeletally immature patients. This is a potentially biomechanically unstable construct which risks the loss of axial control. Patients and Methods. We retrospectively reviewed a consecutive series of 24 boys and 26 girls, with a mean age of 8.6 years (4 to 14), who underwent 52 tibial lengthening procedures with a mean follow-up of 4.3 years (4.0 to 16.9). Tibial alignment was measured before and after treatment using joint orientation lines from the knee and a calculation of the oblique plane axis. Results. The mean percentage length gain was 20% (13 to 31) with a mean bone-healing index (BHI) of 34 days per centimetre (20 to 54). Age at surgery and location of the osteotomy site showed a strong relationship as the location of the osteotomy migrated more proximally with age. However, no significant correlation was found between BHI and the position of the osteotomy. The coronal and sagittal joint orientation of the lengthened tibias were within the normal range in 67% and 92% of cases, respectively. The oblique plane angulation calculation revealed a statistically significant change pre- to post-operatively in both magnitude (p < 0.05) and direction (p < 0.01), but without clinical consequence. The majority of complications were minor (n = 40 in 27 patients; 1.48 complications per segment lengthened) with no residual disability reported. Conclusion. Two-ring tibial lengthening is effective in maintaining segmental alignment, efficient in callous production and relatively comfortable for the patient with few significant complications. Cite this article: Bone Joint J 2016;98-B:1276–82

Between 1992 and 1999, we treated 350 patients with skeletal metastases. A multivariable analysis of the patients was conducted using the Cox proportional hazards model. We identified five significant prognostic factors for survival, namely, the site of the primary lesion, the performance status (Eastern Cooperative Oncology Group status 3 or 4), the presence of visceral or cerebral metastases, any previous chemotherapy, and multiple skeletal metastases. The score for each significant factor was derived from the corresponding estimated regression coefficients (natural logarithm of the hazard ratio). The prognostic score was calculated by adding all the scores for individual factors. The rate of survival was 31% at six months and 11% at one year for the patients with a prognostic score of 6 or more. By contrast, patients with a prognostic score of 2 or less had a rate of survival of 98% at six months and 89% at one year. This scoring system can be used to determine the optimal treatment for patients with pathological fractures or epidural compression

Skeletal age was estimated by examination of radiographs of the carpus in 182 children suffering from Perthes' disease after the reliability of the Greulich and Pyle Atlas had been checked for a control group of British children. A striking tendency to delayed skeletal maturation was shown in the children with Perthes' disease. This trait was also found in ninety-three unaffected siblings of the patients. The velocity of skeletal ageing as the disease progressed was estimated. In some patients the carpal skeleton failed to mature at all for periods of up to three years and the term "skeletal standstill" is applied to this phenomenon. The significance of these findings is discussed and it is suggested that the maturation defect may have aetiological significance

To determine the usefulness of isotope bone scintigraphy in investigating skeletal pain in children, we reviewed the bone scans, plain radiographs and clinical notes of consecutive children under 16 years of age presenting to children’s orthopaedic surgeons at two teaching hospitals in one city. There were 229 patients, of which 87 were boys and 142 girls. They had an average age of 11 years. 139 were investigated for back pain and 90 for skeletal pain in the appendicular skeleton. They were investigated for a variety of conditions including idiopathic back and skeletal pain, scoliosis, Scheuermann’s disease, spondylolysis, osteomyelitis and postoperative pain. There were positive scans in 4 out of 78 patients with idiopathic back pain, and 13 out of 64 with idiopathic skeletal pain. Overall the positive scan rate for all conditions was 10% for back conditions and 22% for pain in the appendicular skeleton. Of all patients with back pain the management was altered in only 3 children. Of all those investigated for appendicular skeletal pain, the management was altered in 6 children. Isotope bone scanning is a low yield and non-specific investigation that imparts a significant dose of radiation to the patient. It should not be used as a first line investigation for idiopathic back or skeletal pain in children. Other tools such as MRI should be considered initially. It still has a role in the investigation of children with obvious abnormality on radiographs, with spondylolysis and probably where there are worrying clinical features to the pain such as night pain and recent onset. The role of bone scanning in the investigation of skeletal pain should be re-evaluated in the investigation of skeletal pain

We undertook a review of bone scans requested for children to determine the usefulness of isotope bone scintigraphy in investigating skeletal pain in this population. We reviewed the bone scans, plain radiographs and clinical notes of consecutive children under 16 years of age presenting to children’s orthopaedic surgeons at two teaching hospitals in one city. There were 229 patients, of which 40% were boys and 60% girls. They had and average age of 11 years. 139 were investigated for back pain and 90 for skeletal pain in the appendicular skeleton. They were investigated for a variety of conditions including idiopathic back and skeletal pain, scoliosis, Scheuermann’s disease, spondylolysis and stress fractures, osteomyelitis and post-operative pain. There were positive scans in 4 out of 78 patients with idiopathic back pain, 1 of 25 patients with scoliosis and 1 out of 5 with spondylolysis and 11 out of 70 with idiopathic skeletal pain. Of all patients with back pain the management was altered in only 3 children. Of all those investigated for appendicular skeletal pain the management was altered in 6 children. Conclusion: Isotope bone scanning is a low yield, and non-specific investigation that imparts a significant dose of radiation to the patient. It should not be used as a first line investigation for idiopathic back or skeletal pain in children. Other tools such as MRI should be considered initially. The role of isotope bone scanning in the investigation of skeletal and joint pain in children should be reevaluated

This study evaluated the effect of limb lengthening on longitudinal growth in patients with achondroplasia. Growth of the lower extremity was assessed retrospectively by serial radiographs in 35 skeletally immature patients with achondroplasia who underwent bilateral limb lengthening (Group 1), and in 12 skeletally immature patients with achondroplasia who did not (Group 2). In Group 1, 23 patients underwent only tibial lengthening (Group 1a) and 12 patients underwent tibial and femoral lengthening sequentially (Group 1b). The mean lengthening in the tibia was 9.2 cm (59.5%) in Group 1a, and 9.0 cm (58.2%) in the tibia and 10.2 cm (54.3%) in the femur in Group 1b. The mean follow-up was 9.3 years (8.6 to 10.3). The final mean total length of lower extremity in Group 1a was 526.6 mm (501.3 to 552.9) at the time of skeletal maturity and 610.1 mm (577.6 to 638.6) in Group 1b, compared with 457.0 mm (411.7 to 502.3) in Group 2. However, the mean actual length, representing the length solely grown from the physis without the length of distraction, showed that there was a significant disturbance of growth after limb lengthening. In Group 1a, a mean decrease of 22.4 mm (21.3 to 23.1) (4.9%) was observed in the actual limb length when compared with Group 2, and a greater mean decrease of 38.9 mm (37.2 to 40.8) (8.5%) was observed in Group 1b when compared with Group 2 at skeletal maturity. In Group 1, the mean actual limb length was 16.5 mm (15.8 to 17.2) (3.6%) shorter in Group 1b when compared with Group 1a at the time of skeletal maturity. Premature physeal closure was seen mostly in the proximal tibia and the distal femur with relative preservation of proximal femur and distal tibia. We suggest that significant disturbance of growth can occur after extensive limb lengthening in patients with achondroplasia, and therefore, this should be included in pre-operative counselling of these patients and their parents

This study aimed to define the rates of lower limb angular correction using temporary hemiepiphysiodesis in differing skeletal pathologies. A retrospective review of 61 children (36M:25F) with angular deformities about the knee who underwent 8-plate hemiepiphysiodesis (mean age 10.8y) was undertaken. The children were divided into 9 groups based on their underlying pathology (lower limb hypoplasia, Blount's disease, skeletal dysplasia, rickets, metabolic disease, acquired growth disturbance, vascular malformation, steroid use and complex genetic disorders). Radiographic measurements of each limb segment was undertaken using the TraumaCad® digital templating software based on standing long-leg radiographs - mechanical lateral distal femoral angle (mLDFA) and mechanical medial proximal tibial angle (mMPTA). The rate of correction of each parameter was calculated as a function of the time lapse between the operation date and first radiographic evidence of full correction of the mechanical axis (zone 1). A total of 144 limb segments (80 distal femoral, 64 proximal tibial physes) were analysed. 62.5% of children had mechanical axes outside the knee joint at the time of operation; 63.2% achieved full correction. The rate of angular correction at the distal femur (mLDFA) was quickest in those with acquired growth disturbance (1.15°/month), complex genetic disorders (1.12°/month) and rickets (0.93°/month). It was slowest in those with vascular malformation (0.40°/month), lower extremity hypoplasia (0.44°/month) and metabolic disease (0.49°/month). At the proximal tibia, mMPTA correction was quickest in those with acquired growth disturbance (0.77°/month) and skeletal dysplasia (0.57°/month); whilst being slowest in those with metabolic disease (0.22°/month) and Blount's disease (0.29°/month). The rate of angular correction about the knee varies with the underlying pathology with correction rates varying up to 3-fold. This study demonstrated the differential rate of correction of angular deformities in children with different skeletal pathologies, which would help guide the timing of hemiepiphysiodesis

The purpose of this study was to compare 2 different strategies of management for ACL rupture in skeletally immature patient. In group 1, patients were treated in a children hospital by ACL reconstruction with open physis. In group 2, patients were treated in an adult hospital by delayed reconstruction at skeletal maturity assessed radiologically. Fifty six consecutive patients were included in this retrospective study. Mean time from injury to surgery in group 1 and 2, was 13.5 and 30 months, respectively. In the overall series, a long time from injury to surgery increased the number of medial meniscal tear (p< 0.0001), but had no influence in the number of lateral meniscal tear (p=0.696). Patients in group 2 exhibited a higher rate of medial meniscal tears (41%) compared to group 1 (16%) (p=0.01). Both groups had the same rate of lateral meniscal tears (p=1). Despite there was no difference between the 2 studied groups in type and location of menisci lesion, patients in group 2 underwent more partial menisectomy (63%) than patients in group 1 (16%) (p=0,014). One temporary tibial valgus deformity was reported and spontaneously resolved. No definitive growth disturbance was noticed. At 27 months mean follow-up, patients in group 1 expressed better subjective IKDC than in group 2. Objective IKDC and radiological results were similar in both groups. Early ACL reconstruction in skeletally immature patient, especially if the patient is more than one year to be skeletally mature, has to be promoted despite of growth disturbance risk. This strategy will decrease medial meniscus lesions and partial meniscectomies which occurred more frequently when ACL reconstruction had been delayed until skeletal maturity

Introduction: Total knee arthroplasty (TKA) in patients with skeletal dysplasia is challenging due to the anatomic variances and deformities. The purpose of this review is to understand the technical issues involved in treating these patients. Methods: Clinical notes, operative reports, and radiographs were retrospectively reviewed of 12 knees in 8 patients: 3 achondroplasia patients (one with bilateral 10° varus deformities, one with a 30° varus deformity in one knee and 25° varus deformity in the other knee, one with a 14° varus deformity); 3 multiple hereditary exostosis patients (one with bilateral 45° valgus deformities, one with a 45° valgus deformity in one knee and 15° valgus deformity in the other, one with a 11° valgus deformity); and 2 osteogenesis imperfecta patients (one with a 25° varus deformity, one with a 17° valgus deformity). Results: Surgical exposure required preoperative placement of soft-tissue expanders to avoid wound complications (1 knee), quadriceps snip (2 knees), and hardware removal (1 knee). Intraoperative balancing of the knee was more complex requiring a lateral epicondylar osteotomy (3 knees), medial release (6 knees), lateral retinacular release (6 knees), and proximal realignment to improve patellar tracking (1 knee). 5 knees required a constrained insert, 2 required tibial augments, one required use of cement and screw technique, and one required modification of an all-polyethylene tibia to accommodate the deformed tibial anatomy. 2 knees required custom tibial components. Complications included 2 peroneal nerve palsies which resolved 3 months postoperatively. Range of motion preoperatively averaged 103° (range 45 to 130°) and 100° postoperatively (range 85 to 120°). All patients were pain-free at their last followup (average follow-up 3.9 years). Conclusion: Special considerations must be made regarding surgical exposure, ligament balancing, implant selection, and anticipation of complications due to the unusual deformities when performing TKA in skeletal dysplasia patients

Skeletal tuberculosis is an indolent disease whose diagnosis is often delayed. Evidence of pulmonary tuberculosis is present in less than 50% of cases. We present our experience from a small inner city district hospital of the difficulties managing patients with skeletal tuberculosis. During the period 1988 to 1998 a total of 38 patients with tuberculous osteomyelitis confirmed microbiologically by tissue culture or histologically on material gained at biopsy presented to our inner city hospital serving 250 000 patients. Two groups of patients were identified in our series. There was an acute group that tended to affect the appendicular skeleton and who responded to local treatment plus chemotherapy with restoration of normal function. In contrast the second group, who were difficult to diagnose, had axial skeleton involvement, deteriorated before treatment and had a poor outcome despite treatment. Failure of admitting medical teams to examine the axial skeleton in their confused patients led to a delay in diagnosis of skeletal tuberculosis in this second group with profound consequences. All health professionals will be encountering skeletal tuberculosis more frequently with the recent resurgence of pulmonary tuberculosis. They may have little experience with the management of this condition and may overlook the diagnosis with consequent catastrophic results. A high index of suspicion is required for prompt diagnosis with early referral to an orthopaedic surgeon improving outcome. Survival in the wake of hindquarter amputation and oncological treatment is improving; the hindquarter amputee population is increasing. Some amputees function well others do not. To assess quality of life and function of hindquarter amputees. 21 amputees (10 females and 11 males) consented to take part in the study. Ethics approval was sought. Assessment was performed using postal questionnaires; SF36 for quality of life; TESS (Toronto Extremity Salvage Score) for physical function and mobility; IEFF( International Index for Erectile Function) for male sexual function; a prosthetics questionnaire to assess prosthetic use. Mean age of the group was 55 with the mean survival of 7 years post amputation. Quality of life results were compared to normal subjects and patients for long tern illness. Amputees had a significant reduction in quality of life concerning physical function and pain. Social function, mental health and energy levels were equivalent to patients with long term illness. The mean TESS result was 56.9 with females having a mean score of 61.7 and male of 48. 50% of the group considered themselves as severely to completely disabled; 50% considered themselves moderately disabled. Five were in full time employment. Six males responded to the sexual function questionnaire. Impotence was universally experienced. Only five amputees used their prosthesis regularly. All amputees have experienced and 20 continue to experience phantom pain. This study illustrates that hindquarter amputees have poor physical function and a low quality of life. Phantom pain is universally experienced. Male amputees experience impotence. Addressing these areas would improve the life of current and future hindquarter amputees

Side shift exercise was originally described by Mehta. Since 1986, we adopted it for the treatment of idiopathic scoliosis. Outcome of the side shift exercise for the patients with idiopathic scoliosis after skeletal maturity was evaluated retrospectively. Fifty-three patients with idiopathic scoliosis whose curve was greater than 20 degrees by the Cobb’s method were included in the study. All the patients were treated only by the side shift exercise and their treatment was started after skeletal maturity. Skeletal maturity was diagnosed by Risser’s method as either grade IV or grade V. The study comprised five men and forty-eight women. Twenty-six patients had thoracic curve, eight had thoracolumbar curve, and nineteen had double major curve. Patients were instructed to shift their trunk to the concavity of the curve repetitively while they were standing and to maintain the side shift position while they were sitting. In double major curve, larger curve was the subject of the treatment. The average age at the beginning of the treatment was 16.3 years (range, 13 to 27 years), and the average age at final follow-up was 19.8 years (range, 14 to 33 years). The average follow-up period was 3.5 years (range, one to 11 years). The average Cobb angle at the beginning of the treatment was 33.3 degrees (range, 20 to 74 degrees), and the average Cobb angle at final follow-up was 32.2 degrees (range, 10 to 73 degrees). Curves of four patients decreased 10 degrees or more. Most of long term follow-up studies reported that untreated idiopathic scoliosis progressed even after skeletal maturity. Although the follow-up period was much shorter, results of the present study suggested that the side shift exercise was a useful treatment option for the management of idiopathic scoliosis after skeletal maturity

Aims

The epiphyseal approach to a chondroblastoma of the intercondylar notch of a child’s distal femur does not provide adequate exposure, thereby necessitating the removal of a substantial amount of unaffected bone to expose the lesion. In this study, we compared the functional outcomes, local recurrence, and surgical complications of treating a chondroblastoma of the distal femoral epiphysis by either an intercondylar or an epiphyseal approach.

The purpose of this study is to introduce our treatment by skeletal traction in brace and to report the safety and easiness of this method and low incidence of cubitus varus. In 1980 we developed a specially designed brace for treating the supracondylar fracture, along with a technique of spontaneous reduction by skeletal traction to develop an easy and safe treatment. The brace is made of plastics and aluminum alloy that are radiolucent. The humeral slide bar with attached axillary pad can be moved up and down to adjust the height of the upper arm for each patient. From 1980 to 1999 we have treated 190 children with displaced supracondylar fracture of the humerus. Their ages ranged from 2 to 14 years old and average of age was 7 years old. The fractures occurred most frequently between the ages of 5 to 6. More boys than girls were injured and the left elbow were more often than the right. Among 190 cases, severely displaced cases were most common. (64%) and moderate case 20%, mild case 16%. The period of follow up was 6 months to 11 years, mean 4 years. Placing the arm in the brace with the elbow flexed at right angle, unstable fracture site will be stabilized first. Skeletal traction is performed by a spring through the winged screw. The traction is maintained for three to four weeks. Spontaneous reduction of the displaced fragment can be expected and we emphasize that any manipulative technique is not performed during the treatment at all. Among 190 patients, cubitus varus occurred in only 3 (1.6%) cases because of technical failure. All patients except one obtained excellent functional results, one had 25 degrees of limitation of the elbow flexion. There were no vascular problems or Volkmann’s contracture and ectopic ossification. The results were satisfactory. Our treatment utilizing the brace and skeletal traction for supracondylar fracture of the humerus in children is safe and effective in preventing cubitus varus

Osteoporosis affects millions globally and current anti-catabolic treatments are limited by significant side-effects. Osteoporosis arises when skeletal stem cells (SSC) no longer sufficiently replenish osteoblasts, leading to net bone loss. A key regulator of SSC behaviour is physical loading, yet the mechanisms by which SSCs sense and respond to changes in their mechanical environment are virtually unknown. Primary cilia are nearly ubiquitous ‘antennae-like’ cellular organelles that have very recently emerged as extracellular chemo/mechano-sensors and thus, are strong candidates to play an important role in regulating SSC responses in bone. This paper will demonstrate that the SSC primary cilium plays an important role in loading-induced bone formation via initial chemosensation and transduction of the potent chemokine TGFβ1 regulating SSC recruitment to the bone surface and secondly it will be shown that the primary cilium is a cAMP responsive mechanosensor directly regulating SSC mechanotransduction via localisation of adenylyl cyclase 6 to the ciliary microdomain. Finally, it will be shown that targeting the cilium therapeutically can be an effective approach to enhance both biochemical and biophysically induced SSC osteogenesis contributing to bone formation, demonstrating a novel anabolic therapy for bone loss diseases such as osteoporosis

When investigating orthopaedic biomaterials and tissue engineered devices, biological investigations by means of in vitro and in vivo tests are mandatory to obtain a overall picture of biocompatibility and therapeutic efficacy. However, various aspects requiring careful consideration should be kept in mind and can explain the complex situations encountered by researchers when the skeletal tissue is involved. This presentation aimed to summarize some useful information in improving in vivo methodology to test present and future therapies for orthopaedic surgery. Some in vivo biological tests to study innovative reconstructive surgical techniques are summarized on the basis of the experience of the Experimental Surgery Department –IOR. After in vitro and in vivo biocompatibility tests, for the study of bone defect healing and of biomaterial osteo-inductive properties the subcutaneous and intramuscular implants are usually performed in laboratory animals while osteoconduction and bone healing evaluation require the development of “nonunions” (sites that never achieve functional bone continuity) and “critical size defects” (the smallest defect that will heal with less than 10% bony growth) models. Biomaterial osteointegration properties are investigated by means of metaphyseal, diaphyseal and intramedullary implantation. The use of pathological animals is also recommended to take into account the clinical situation where biomaterials are often implanted in aged and osteoporotic patients. As far as articular cartilage pathology is concerned, chondral and osteochondral “critical size defects” may be performed and the development of osteoarthritic animals could be also useful. At different experimental times post-explantation evaluations by means of radiology, histology, histomorphometry and biomechanics provide a complete characterization of biomaterials and biotechnologies showing their potential therapeutic efficacy for skeletal reconstruction. In vivo studies provide important pre-clinical information on new biomaterials and biotechnologies for the skeletal reconstruction Among the factors that are increasingly improving the reliability of in vivo testing are the continuous improvement in knowledge on bone biology and comparative science between humans and animals, the awareness that animal suffering should be reduced as much as possible, and, finally, the amount and the accuracy of in vivo post-explantation findings

Natural history of AIS >30° in skeletally mature patients is poorly defined. Studies reporting rates and risk factors for progression are predominantly of large curves in immature patients. Our aim was to determine the rate of curve progression in AIS following skeletal maturity, any associated changes in SRS-22 scores, and identify any potential predictors of curve progression. Patients enrolled in a prospective, longitudinal, multicentre non-surgical AIS database were evaluated. All patients had minimum 2 year follow-up, idiopathic scoliosis >30°, and were skeletally mature. SRS-22 functional outcome scores and radiographic data were compared at baseline and 2-year follow-up. Patients were divided into 3 groups based on curve size: A=30°-39°, B=40°-49°, C= >50°. Curve progression was defined as any change in curve magnitude. There were 80 patients, majority females (93.8%) with a mean age of 16.5+/−0.16. Mean BMI was 21+/−0.31 with 15.1% overweight. Mean major cobb at baseline was 38.3°+/−0.88°. At 2 year follow-up 46.3% of curves had progressed an average 3.4°+/−0.38°. Of curves that progressed, patients in group A had the largest mean rate of progression followed by group B. SRS-22 scores on average declined significantly over 2 years in this cohort (4.23 to 4.08; p=0.002). Patients who progressed had on average a more significant decline in SRS outcome scores compared to those that did not (p=0.018, p=0.041 respectively), with the most significant change noted in the Self-Image domain (p=0.03). There was no significant difference in the change in SRS scores over 2 years based on curve size. Univariate analysis did not identify any factors predictive of curve progression in this cohort. Skeletally mature patients with AIS >30°may continue to have a risk of progression at a mean rate of 1.7°/yr and significant decline in SRS-22 outcome scores, in particular Pain and Self-Image, over time

We have previously shown that cytological diagnosis based on fine-needle aspiration biopsy (FNAB) is a safe and efficient method for the discrimination between benign, primary malignant and metastatic bony lesions. We have now studied metastatic lesions to assess the diagnostic accuracy and to ascertain whether FNAB allows identification of the primary lesion. Between 1990 and 1997, 447 patients were referred for diagnosis of skeletal lesions of unknown type. Of these 119 proved to have metastatic disease, either myeloma or lymphoma. Nine were excluded leaving 110 consecutive patients with metastatic carcinoma (80), myeloma (16) or lymphoma (14). FNAB gave a correct diagnosis in 102 of the 110 patients (93%). In eight it was inconclusive. It correctly diagnosed 15 of 16 patients with myeloma, 12 of 14 with lymphoma, and 75 of 80 with metastatic carcinoma. Furthermore, the site and type of malignancy were correctly suggested in two-thirds of patients with metastatic carcinoma. Overall, only seven open biopsies were carried out. We conclude that time-consuming and costly investigations can be reduced by choosing FNAB as the initial diagnostic method for skeletal lesions of unknown origin. The choice of radiological examinations, laboratory tests and surgical biopsies can be determined by using FNAB

Aims: To determine the usefulness of isotope bone scintography in investigating skeletal pain in children. Methods: We reviewed bone scans, notes and radiographs requested for children under 16 years presenting to two teaching hospitals in the city. Results: There were 229 patients with and average age of 11 years. 139 were investigated for back pain and 90 for skeletal pain in the appendicular skeleton. There were positive scans in 13 patients with back pain and 22 with pain elsewhere. The management was altered in only 3 children with back pain and 6 with other skeletal pain. Conclusions: Isotope bone scintigraphy is a low yield, and non-speciþc investigation that imparts a signiþcant dose of radiation. Its role in the investigation of skeletal pain should be re-evaluated

We reviewed 277 patients with soft-tissue sarcoma (STS) treated between 1975 and 1995 to study the incidence, distribution, time of appearance, and radiological findings of skeletal metastases. Of these, 28 (10.1%) had metastases within a mean period of 18.6 months after admission. The incidence of skeletal metastases differed among the histological subtypes of sarcoma; alveolar soft-part sarcoma, dedifferentiated liposarcoma, angiosarcoma, and rhabdomyosarcoma tended to show higher incidences. The regional bones close to the primary tumour were affected in 13 (46.4%) of the 28 patients, and the axial bones in 18 (64.3%). Radiologically, the metastatic bony lesions predominantly showed osteolytic changes, and there were pathological fractures in 21 of 44 lesions

The purpose of this study was to assess the Interobserver Reliability of the Sauvegrain Skeletal Age Assessment. Elbow radiographs requested to exclude injury were anonymised. Sixteen examinations were assessed by ten independent orthopaedic specialist registrars or consultants. The Sauvegrain method as modified by Dimeglio was used to score the radiographs. The observations made were then assessed for interobserver reliability by means of a multiple observer Kappa score and the total scores by intra-class correlation coefficient. Kappa scores for the components of the score were 0.403 for the lateral condyle; 0.492 for the trochlea; 0.354 for the proximal radius and 0.508 for the olecranon. Adding item scores to produce a modified Sauvegrain score had an intraclass reliability of 0.858 (95% CI 0.758 to 0.935). Methods of identifying skeletal maturation and predicting future growth generally depend on the use of an atlas of hand radiographs. Difficulties with poor interobserver reliability associated with these methods has led to a move towards assessments that do not depend upon bone age estimations. Unfortunately plans based on ratios of growth or average patterns produce errors when unusual types of growth disturbance are present. We conclude that use of a scoring system for maturation assessed by elbow radiographs offers a significant advantage when substituted into the straight line method of growth prediction. The Sauvegrain method as modified by Dimeglio1 has demonstrated an excellent level of inter observer reliability. We have used Sauvegrain scores to improve the accuracy of timing when using the Mosely straight line method

Osteoarthritis is characterised by the loss and damage of cartilage in synovial joints. Whilst joint replacement is the gold standard for end stage disease, repair or regenerative strategies aim to slow disease progression, maintain joint function and defer the need for joint replacement. One approach seeks to target endogenous repair after drilling or microfracture (a type of trauma induced repair) in the area of cartilage loss – connecting the defect to the underlying bone marrow niche. The rationale of this approach is that cells delivered to the defect site, from the bone marrow, will bring about cartilage repair. Bone marrow contains multipotent cells, including stem and stromal populations, of both the haematopoietic and skeletal systems. Bone marrow mesenchymal stromal cells (BMSCs) are characterised by tri-lineage differentiation (bone, cartilage and adipose tissue) and contribute to the formation of the bone marrow niche, which maintains haematopoietic stem cell quiescence. This quiescence ensures life-long haematopoiesis and the supply of mature blood cells to the haematopoietic system. In this study we investigate the interactions between haematopoietic and BMSCs (in both human and mouse cultures) specifically to understand the consequences on BMSCs during tissue repair. A murine MSC cell-line model was co-cultured with enriched fractions of primary murine haematopoietic progenitor cells isolated based on c-Kit, Sca-1, and lineage markers. Similarly, human bone marrow derived MSCs were co-cultured with primary bone marrow haematopoietic fractions isolated based on CD34, CD38 and lineage markers. Using confocal microscopy, we demonstrated that the two cell populations directly interact through cell-cell contact with haematopoietic cells located above and below the MSC monolayer. Cultures were then pushed to differentiate down the osteogenic lineage. Results indicate that MSCs co-cultured with haematopoietic cells exhibited significant inhibition of osteogenesis when analysed by functional assay of matrix mineralisation and gene expression analysis for transcripts including Runx2, Osterix and type I collagen. These data support the hypothesis that hematopoietic progenitor cells influence both the local homeostasis of the bone marrow as well as the repair potential of stromal cells. Such interactions could be important for the resolution of injury after trauma induced repair. Furthermore, manipulation of these interactions, such as the administration of haematopoietic cell stimulating agents, could be used to improve treatment outcomes

Osteoporosis (OP) and osteoarthritis (OA) are leading causes of musculoskeletal dysfunction in elderly, with chondrocyte senescence, inflammation, oxidative stress, subcellular organelle dysfunction, and genomic instability as prominent features. Age-related intestinal disorders and gut dysbiosis contribute to host tissue inflammation and oxidative stress by affecting host immune responses and cell metabolism. Not surprisingly, the development of OP and OA correlate with dysregulations of the gut microflora in rodents and humans. Intestinal microorganisms produce metabolites, including short-chain fatty acids, bile acids, trimethylamine N-oxide, and liposaccharides, affecting mitochondrial function, metabolism, biogenesis, autophagy, and redox reactions in chondrocytes to regulate joint homeostasis. Modulating the abundance of specific gut bacteria, like Lactobacillus and Bifidobacterium, by probiotics or fecal microbiota transplantation appears to suppress age-induced chronic inflammation and oxidative damage in musculoskeletal tissue and holds potential to slow down OP development. The talk will highlight treatment options with probiotics or metabolites for modulating the progression of OA and OP.

1. A case of fibrous dysplasia in a woman aged fifty, with unilateral skeletal lesions, cutaneous pigmentation and possibly accelerated skeletal growth, is described. 2. At necropsy, the bony changes were found to be complicated by many of the changes of lipoid granulomatosis. Disseminated plaques of demyelinisation were found in the central nervous system. 3. The implications of the case are discussed

Patients with skeletal dysplasia are prone to developing advanced degenerative knee disease requiring total knee replacement (TKR) at a younger age than the general population. TKR in this unique group of patients is a technically demanding procedure due to the bone deformity, flexion contracture, generalised hypotonia and ligamentous laxity. We set out to retrospectively review the outcome of 11 TKR's performed in eight patients with skeletal dysplasia at our institution using the SMILES custom-made rotating-hinge total knee system. There were 3 males and 5 females with mean age 57 years (range, 41–79 years), mean height 138 cm (range, 122–155 cm) and mean weight 56 kg (range, 40–102 kg). Preoperative diagnoses included achondroplasia, spondyloepiphyseal dysplasia, pseudoachondroplasia, multiple epiphyseal dysplasia, morquio syndrome, diastrophic dysplasia and Larson's Syndrome. Patients were followed clinically and radiographically for a mean of 7 years (range, 3–11.5 years). Knee pain and function improved in all 11 joints. Mean Knee Society clinical and function scores improved from 24 (range, 14–36) and 20 points (range, 5–40) preoperatively to 68 (range, 28–80) and 50 points (range, 22–74) respectively at final follow-up. Four complications were recorded (36%), including a patellar fracture following a fall, a tibial periprosthetic fracture, persistent anterior knee pain and a femoral component revision for aseptic loosening. Our results suggest that custom rotating-hinge TKR in patients with skeletal dysplasia is effective at relieving pain, optimising movement and improving function. It compensates for bony deformity and ligament deficiency and reduces the need for corrective osteotomy. Patellofemoral joint complications are frequent and functional outcome is worse than primary TKR in the general population. Submission endorsed by Mr Peter Calder, Consultant Orthopaedic Surgeon and Society member

Aim: To assess the Interobserver Reliability of the Sauvegrain Skeletal Age Assessment. Methods and Results: Elbow radiographs requested to exclude injury were anonymised. Sixteen examinations were assessed by ten independent orthopaedic specialist registrars or consultants. The Sauvegrain method as modified by Dimeglio was used to score the radiographs. The observations made were then assessed for interobserver reliability by means of a multiple observer Kappa score and the total scores by intra-class correlation coefficient. Kappa scores for the components of the score were 0.403 for the lateral condyle; 0.492 for the trochlea; 0.354 for the proximal radius and 0.508 for the olecranon. Adding item scores to produce a modified Sauvegrain score had an intra-class reliability of 0.858 (95% CI 0.758 to 0.935). Conclusions: Methods of identifying skeletal maturation and predicting future growth generally depend on the use of an atlas of hand radiographs. Difficulties with poor interobserver reliability associated with these methods have led to a move towards assessments that do not depend upon bone age estimations. Unfortunately plans based on ratios of growth or average patterns produce errors when unusual types of growth disturbance are present. We conclude that use of a scoring system for maturation assessed by elbow radiographs offers a significant advantage when substituted into the straight-line method of growth prediction. The Sauvegrain method as modified by Dimeglio. 1. has demonstrated an excellent level of interobserver reliability. We have used Sauvegrain scores to improve the accuracy of timing when using the Mosely straight-line method. 3.

Adamantinoma is a rare tumour of long bones that occurs most commonly in the tibia. Its pathogenesis is unknown. It is locally aggressive and recurrences are common after resection. Metastases have been reported in 10% to 20% of cases, most commonly in the lungs and rarely in the lymph nodes. We report a patient who developed a skeletal metastasis four years after resection of the primary tumour. There was no evidence of recurrence at the primary site or of secondary deposits in the lungs

Introduction:. 25% of patients with an unknown primary tumour present to the orthopaedic surgeon with skeletal metastases. The onus is on the orthopaedic surgeon to establish the diagnosis, not only to decrease the patient's anxiety but also because the median survival increases from 6–9 months to 23 months when the primary is identified and allows for specific cancer treatment. The diagnostic work up of an unknown primary includes a multitude of special investigations. Since PET/CT has high sensitivity and specificity for detecting the primary tumours, we asked the question: Can you diagnose the unknown primary in patients with skeletal metastases with a PET/CT?. Method:. We included all PET/CT scans done in our institution between 2010 and 2013 for patients with malignancies known to metastasize to bone (melanoma, breast, lung, head and neck, GIT, other) and all scans done in patients with unknown primaries. After reviewing 686 PET/CT scans, 492 showed metastatic disease, with 78 of these having either spinal or skeletal metastases. Results:. Of these 78 patients, 68 primaries could be detected on the PET/CT scan. Thus the PET/CT detected the primary in 87% of cases. This number could possibly be higher as some were melanoma and breast cancer patients who had already undergone surgical resection. The most common primary detected was lung, followed by a group of other and unknown primaries which included cervical, kidney and thyroid carcinoma. Conclusion:. PET/CT scan is a good modality to use when looking for a primary malignancy in patients who present to the orthopaedic surgeon with bone metastases. We postulate that this might be a possible first line investigation when looking for the primary

Introduction:. Skeletal involvement in non-Hodgkin lymphoma in HIV/AIDS is rarely reported. The bone lesions can have a spectrum of radiological features. Aims:. The aim of the study was to review the radiological features of non-Hodgkin lymphoma (NHL) involving the bone in HIV positive patients. Methodology:. All cases of NHL involving bone in HIV positive patients diagnosed histopathologically were recorded retrospectively between September 2002 and December 2013. Clinical manifestations, radiological features and haematological investigations were analysed from the patients' records. Histopathological subtypes were analysed from slides. Results:. 105 Cases of lymphoma involving bone were recorded. Of these, 46 patients met the criteria of being HIV positive and diagnosed with NHL involving bone. The male to female ratio was equal, the age ranged from 14 to 51 years (average 35 years), the absolute CD 4 count ranged from 17 to 307 (average 100). The sites of involvement were:- vertebrae (22), ribs (8), pelvis (6), femur (3), mandible (3), humerus (2), sternum (1) and clavicle (1). Vertebral involvement was multifocal with a large extradural soft tissue mass in 17 cases and solitary in 5 cases. Pathological fractures were seen in 4 cases of long bone involvement. Most patients presented with a high grade large B cell non-Hodgkin lymphoma with CD20 immunopositivity. Conclusion:. Primary bone lymphoma is a rare disease, accounting for approximately 3% of all primary bone malignancies and 4% to 7% of all extranodal lymphomas in the general population. The prevalence of primary and secondary bone lymphoma is very high in HIV positive patients. The disease is very aggressive, presenting in patients with low CD 4 count and the prognosis is poor. The radiologic patterns can be lytic, blastic or subtle changes, solitary or multifocal. The diagnosis of skeletal NHL is made on histopathology

Purpose: Regeneration of skeletal tissue for fracture repair or during morphogenesis involves common phases of cell proliferation and differentiation. Mesenchymatous precursor cells have multiple origins. These cells can be identified in the bone marrow, in the deep layer of the periosteum and in the endosteum. More recently, the presence of circulating multipotent stem cells has been demonstrated in the general circulation. Their contribution to skeletal regeneration processes is suspected. The experiments we report allow visualisation of the multidirectional differentiation phenomena involving mesenchymatous precursor cells in an animal model of skeletal tissue regeneration. Material and methods: An experimental surgical protocol was developed to study the regeneration of skeletal tissue in New Zealand rabbits. Eighteen animals were used. A vascularised periosteum flap was transferred onto the medial aspect of the knee. The flap was fixed in order to be exposed to flexion and extension stress during spontaneous ambulation. The joint was not damaged in any way and the adjacent bone segments were left intact. The animal was allowed to move freely postoperatively. The animal was sacrificed two days to eight weeks later to study standard histological slices taken from the regenerate region and the recipient knee joint. Results: The zone of influence of the flap was recognised early in the environment where it was apposed. This zone involved the marrow of the metaphyseal regions, the neighbouring muscles, the joint cavity, and the menisci. Cell proliferation was noted in each of these sites. It was associated with differentiation of the precursor elements in multiple directions of the mesenchymatous lines. This led to production of cartilaginous, bony, fibrous, and even muscle tissue in the medullary cavity, in the menisci, and in the open joint space. Immunohistochemistry demonstrated the contribution of the mesenchymatous stem cells whose circulating pool was visualised. Discussion: This work is in agreement with the recent demonstration of the contribution of stem cells to general healing phenomena, and the physiological turnover of healthy tissue. Conclusion: The strong potential of multipotent stem cells for tissue reparation and regeneration processes opens important perspectives for cell therapy and tissue engineering. The demonstration of physiological processes operating in vivo which involve participation of the endogenous cell pool is of importance for all fields of medicine and surgery for the treatment of the musculoskeletal system

Tissue engineering regards the generation, regeneration, augmentation or limitation of the structure and function of living tissues by the application of scientific and engineering principles. Skeletal defects resulting from tumor resection, congenital abnormalities or trauma often require surgical intervention to restore the function. Current option for bone replacement include autografts,allografts,metals,ceramic and polymers.However, all these materials have drawbacks, and their selection usually require some compromises. Skeletal tissues are under extensive investigation in tissue engineering research and beside the biological issues, the scaffolds design plays an important role. A number of biodegradable and bioabsorbable materials as well as scaffold designs, have been experimentally and, in some cases clinically studied. An appropriate scaffold should posses highly porous with interconnected pore network for cell growth and flow transport of nutrient and metabolic waste; biocompatible and bioresorbable with a controlled degradation and resorption rate to match cell/ tissue growth, suitable surface chemistry for cell attachment, proliferation and differentiation, and mechanical properties to match those of the implanted tissue. Synthetic biodegradable polymers and inorganic materials are promising as extracellular matrix analogue to facilitated tissue development and growth; these include: polyglycolic acid, poly-l-lactic acid, copolymers, poly-caprolactones, hydroxyapatite, tricalcium phosphates. All these scaffolds are well performing from biological and chemical-physical but they have some limitations from mechanical point of view. To overcome this problem a composite structure made by Polycaprolactone and Hydroxyapatite is studied by mechanical and biological analysis. To obtain a porous structure, the casting and salt leaching technique is implemented. The composite shows mechanical properties in the range of the spongy bone and interesting biological properties with regards to osteoblasts. Injectable gels made of collagen are analysed to carry cells, a preliminary results of collagen gel loaded with MSC cells have been performed and rheological and proliferation study are showing the feasibility to obtain a bioactive materials/cells to be inject in the defined body site defects avoiding massive surgery

We report the results of intramedullary leg lengthening conducted between 2002 and 2009 using the Intramedullary Skeletal Kinetic Distractor in 69 unilateral lengthenings involving 58 femora and 11 tibiae. We identified difficulties that occurred during the treatment and assessed whether they were specifically due to the implant or independent of it. Paley’s classification for evaluating problems, obstacles and complications with external fixators was adopted, and implant-specific difficulties were continuously noted. There were seven failures requiring premature removal of the device, in four due to nail breakage and three for other reasons, and five unsuccessful outcomes after completion of the lengthening. In all, 116 difficulties were noted in 45 patients, with only 24 having problem-free courses. In addition to the difficulties arising from the use of external fixators, there were almost the same number again of implant-specific difficulties. Nevertheless, successful femoral lengthening was achieved in 52 of the 58 patients (90%). However, successful tibial lengthening was only achieved in five of 11 patients (45%)

Between October 2001 and September 2009 we lengthened 242 lower-limb segments in 180 patients using the Intramedullary Skeletal Kinetic Distractor (ISKD). Mechanical failure was defined either as breakage of the ISKD or failure of the internal mechanism to activate. Retrieved nails which failed mechanically were examined by the manufacturer for defects. In all, 15 ISKDs in 12 patients (13 limbs) failed mechanically representing an overall failure rate of 6.2%, with fracture of the device occurring in ten of the 15 failures. Two nails in one patient failed to lengthen and had to be replaced. The manufacturer detected an error in the assembly of the nail, which prompted a wide recall. One nail jammed after being forcefully inserted, and two nails failed to lengthen fully. Lengthening was achieved in all 12 patients, although three required a second operation to exchange a defective nail for a new, functioning device. The ISKD is a complex mechanical device which lengthens by the oscillation of two telescopic sections connected by a threaded rod. The junction between these sections is surrounded by a keyring collar. This keyring collar is the weakest part of the device

Objectives. Regenerative medicine is an emerging field aimed at the repair and regeneration of various tissues. To this end, cytokines (CKs), growth factors (GFs), and stem/progenitor cells have been applied in this field. However, obtaining and preparing these candidates requires invasive, costly, and time-consuming procedures. We hypothesised that skeletal muscle could be a favorable candidate tissue for the concept of a point-of-care approach. The purpose of this study was to characterize and confirm the biological potential of skeletal muscle supernatant for use in regenerative medicine. Methods. Semitendinosus muscle was used after harvesting tendon from patients who underwent anterior cruciate ligament reconstructions. A total of 500 milligrams of stripped muscle was minced and mixed with 1 mL of saline. The collected supernatant was analysed by enzyme-linked immunosorbent assay (ELISA) and flow cytometry. The biological effects of the supernatant on cell proliferation, osteogenesis, and angiogenesis in vitro were evaluated using human mesenchymal stem cells (hMSCs) and human umbilical cord vein endothelial cells (HUVECs). Results. The supernatant contained several GFs/CKs, with especially high levels of basic fibroblast growth factor, and CD34+ cells as the stem/progenitor cell fraction. With regard to biological potential, we confirmed that cell proliferation, osteoinduction, and angiogenesis in hMSCs and HUVECs were enhanced by the supernatant. Conclusions. The current study demonstrates the potential of a new point-of-care strategy for regenerative medicine using skeletal muscle supernatant. This attractive approach and readily-available material could be a promising option for tissue repair/regeneration in the clinical setting. Cite this article: M. Yoshikawa, T. Nakasa, M. Ishikawa, N. Adachi, M. Ochi. Evaluation of autologous skeletal muscle-derived factors for regenerative medicine applications. Bone Joint Res 2017;6:277–283. DOI: 10.1302/2046-3758.65.BJR-2016-0187.R1

Vascular anomalies with skeletal involvement are rare. To ameliorate diagnostics and therapy the classification of the International Society for the Study on Vascular Anomalies (ISSVA) should be applied where proliferating vascular tumours are separated from malformations, which are hereditary and do not change. Furthermore, blood and lymph vessel lesions are distinguished. In addition to isolated local or multifocal bone lesions, involvement of soft tissue and/or other organs can be observed. Here, we report on 6 patients with lymphangiomatosis. Diagnostic workup using whole body MRI is most sensitive to detect all lesions. Localisation was the mandible (n=2), spinal column (n=4), femur (n=1), tibia (n=1), pelvis (n=1), humerus (n=1), scapula (n=1) and rips (n=1). Soft tissue involvement was observed in all patients, 1 patient showed additional lesions in the kidney and spleen, 3 patients in the lung. These 3 patients could be diagnosed with Gorham’s disease, a potentially lethal form of skeletal lymphangiomatosis, with thoracic involvement. Next to the difficulty to find the correct diagnosis, therapy is not standardized. A major problem is the treatment of Gorham’s disease. In the literature, case reports on surgery as well as interferon alpha, chemotherapy, bisphosphonates and radiation therapy can be found. We performed surgery (n=2), radiotherapy (n= 1), polychemotherapy (n=1), bisphosphonates (n=2) and conservative therapy (n=3). One of the patients with Gorham’s disease died because of progressing pulmonary insufficiency. It is still unclear if prophylactic therapy for skeletal involvement should be administered and which therapy is effective. An international register and a multicenter clinical trial are urgently needed

Aims: To study the natural history and treatment of chronic skeletal pelvic pain following childbirth. Methods: 53 patients were studied, of which 13 had surgery to the symphysis pubis (11 fusion, 2 stabilisation). A detailed history was recorded and an examination carried out. Investigations included pelvic X-rays with stress views and MRI of the symphysis pubis in a selected group. Results: Mean age at onset 30.6 years, gestation 39.3 weeks (36–42). 16 of the 17 subsequent pregnancies were associated with recurrence of symptoms. Long term disability showed no relation to type of delivery (p> 0.5). Pain was worse before menstruation. 55% of patients beneþted from conservative management. This did not relate to the site of pain (p> 0.1). Stress views of the symphysis: 39, mean vertical shift 2.2mm. There was no correlation between shift and symptoms. MRI of the symphysis:17, 6 were normal and 11 revealed non-speciþc changes. Surgery:mean age at surgery 34.8 y, time to operation 4.2 y and follow up 23.6 m. Outcome: 7 good, 6 no beneþt. There was a strong reverse correlation between disability and outcome (r=−0.84) while the site of pain had no effect on outcome (p> 0.8). Conclusions: Chronic skeletal pelvic pain following pregnancy is poorly understood and under-diagnosed. It tends to be recurrent and its onset is related to hormonal and mechanical factors in pregnancy. The type of delivery is unlikely to be important although care should be taken with leg and patient positioning. There is no relationship between shift and severity. Conservative treatment is the main standby. Surgery, on the basis of this small study, is useful in those with moderate disability but contraindicated in those with severe disability

In 1980, we developed a specially designed brace for treating supracondylar fractures of the humerus in children, along with an easy and safe technique of reduction by skeletal traction. This method, which takes into consideration only the medial tilting and anterior angulation of the distal fragment, achieves complete reduction, ignoring any lateral, posterior and minor rotational displacements of the fragment. Skeletal traction is applied through a screw inserted into the olecranon and the angulation at the fracture site is reduced regardless of the anatomical position without manipulation. We treated 193 children with displaced supracondylar fractures of the humerus using this method between 1980 and 2001. Only four children (2%) developed cubitus varus. The majority obtained an excellent range of movement at the elbow; one had a 25° limitation of flexion. This technique is an effective and easy method of treating supracondylar fractures of the humerus in children

Activated leukocyte cell adhesion molecule (ALCAM) has been shown to be involved in cell migration and in both homotypic/homophilic adhesion and heterotypic/heterophilic adhesion. It has been shown that a decreased level of ALCAM expression in human breast cancer tissue correlated with a significantly poor prognosis. Aim: Previous studies have looked at nodal and general metastasis; in this analysis using an expanded tumour cohort, we, for the first time, specifically identified patients who went on to develop skeletal metastasis. Primary breast cancer tissues (n=234) and non-neoplastic mammary tissue (n=34) were collected and patients were routinely followed up clinically after surgery. The immunohistochemical distribution and location of ALCAM was assessed in the normal breast tissue and carcinoma and the level of ALCAM transcripts in the frozen tissue was determined using real-time quantitative PCR. The results were analysed against the clinical data looking principally at the levels in patients with skeletal metastasis but also in relation to the nodal involvement, ER status, Nottingham Prognostic Index and survival. The immunohistochemical staining intensity shows that the cytoplasmic staining in normal breast tissue is significantly stronger than that in breast cancer tissue (p=0.023) and also the breast cancer tissue from patients who went onto develop skeletal metastasis (p=0.048). The ALCAM transcript levels were the lowest in patient with skeletal metastasis (p=0.0048) compared to those who were disease free. Significantly lower transcript levels were also found the patients who developed local recurrence (p=0.040), and who died from breast cancer (p= 0.0075). Other indicators of poor prognosis show a significant difference: patients with moderate and poor NPI prognosis lower levels than those with a good prognosis (p=0.05, p=0.0089 respectively); and lower in patients with a positive ER status than those ER negative patients (p=0.043). This study has for the first time shown that the patient who went on to develop skeletal metastasis tended to have the lowest levels of ALCAM transcript in their breast cancers. This fact could be used to provide patient with a more accurate prognosis and identify those who may benefit enhanced monitoring and early medical and orthopaedic treatment

Aim. To determine the rate of recurrence of coronal plane deformity in children treated with ‘guided growth’ using 8-plates, from the time of implant removal to skeletal maturity. Methods. Over a consecutive 5 year period between April 2008 and April 2013 we analysed our results of guided growth treatment using 8-plates to correct coronal plane lower limb deformity. Patients with neuromuscular disorders such as cerebral palsy were excluded. Deformity planning was performed using standardised techniques. Our standard practice is to remove the 8-plate and screws once deformity is corrected both clinically and radiologically. Patients were followed up until either skeletal maturity or recurrence, which necessitated reapplication of the 8-plate. We are aware of no study in which children treated with guided growth using 8-plates are followed up to skeletal maturity. Results. 267 patients were treated with 8-plates in our unit over this 5 year period. Of the patients in whom deformity was corrected and had subsequent plates removed, we identified 41 patients who have either reached skeletal maturity or had recurrence of deformity. Six patients required reapplication of the 8-plates implant. These were young and had skeletal dysplasia. Deformity parameters were analysed both clinically and radiologically in patients who have reached skeletal maturity and showed no recurrence, which necessitated further intervention. Conclusion. A higher proportion of younger patients, especially a sub-group with skeletal dysplasia had recurrence of deformity necessitating reapplication of the 8-plate device. In this group we recommend removal of only the metaphyseal screw once deformity is corrected. This would allow ease of reapplication if recurrence were to reoccur. Level of evidence: III

Bone tissue experiences continued remodelling in response to changes in its biochemical and biophysical environment. Given the finite lifespan of osteoblasts, this continued bone formation requires replenishment from a progenitor population. Although this is largely believed to be from a skeletal stem cell population, given the limitation in in-vivo markers for this cell type, progress in demonstrating this mechanism is limited. Therefore, we characterized the LepR-Cre mouse strain and evaluated whether LepR positive cells are the progenitor population and if they contribute to the osteoblast population over time and in mechanically-induced bone formation in-vivo. Transgenic mouse strains; B6.129(Cg)-Leprtm2(cre)Rck/J to study LepR-expressing cells and B6.Cg-Gt(ROSA)26Sortm9(CAG-tdTomato)Hze/J as a reporter strain were obtained from Jackson Laboratories. Characterization studies were performed on LepR:tdTomato mice at embryonic stage (19.5dpc), 8 and 12 weeks old. Mice (12 weeks old) were subjected to compressive tibia loading with a 11N peak load for 40 cycles, every other day for 2 weeks. Histological analysis reveal that LepR is expressed from the embryonic stage in various organs including bones. LepR positive cells are found around blood vessels and on bone surfaces. Flow cytometry analysis show the amount of LepR positive cells negative for CD45 and Ter-119 markers inside the bone marrow increases over time and following tibial loading. Mechanical loading induces an increase in bone mass and bone parameters. This model allows us to track and evaluate the role of LepR positive cells as bone forming cells, and to decipher the role of these cells in mechanically-induced bone formation

Purpose: The deleterious effects of blocking movement of normal joints has been demonstrated by numerous animal experiments and clinical observations. Conversely, mobilisation of the joints leads to metabolic and trophic effects commonly attributed to changes in the nutritional status of the cartilage. In vitro experiments and mechanobiological studies have however suggested that more fundamental mechanisms are operating, demonstrating the impact of physical factors on biological cell regulation and tissue organisation. The purpose of our experimentation was to study the biological effects of movement on a model of skeletal regeneration from mesenchymatous tissue. The tested hypothesis was that movement crossing a living tissue causes the emission of specific signals which contribute to its anatomic and functional organisation. Material and methods: We used 27 immature rabbits for the model. We transferred a vascularised periosteal flap to the knee region in order to initiate a process of skeletal tissue regeneration. The regenerated tissue was submitted to joint movements caused by the animal’s spontaneous movements. In the first group of animals, the knee was left intact. In the second group, 25 mm of the distal femur was removed, including the condyles. Tissue regeneration was compared with that obtained without joint movement. Results: Qualitative changes in regenerated tissue were found to be influenced by movement. The differentiation of the mesenchymatous precursors was oriented towards production of cartilage and fibrocartilage. In the group with a sectioned femur, a mobile cartilage joint space was obtained at the interface between the regenerated femur and the tibia. A functional neo-joint was formed. Discussion: This model of tissue regeneration, similar to that observed in experimental nonunion, demonstrated the contribution of multipotent stem cells of diverse origins. Joint mobility and its mechanical consequences produced information which were perceived as a modification of the environment. They regulated the differentiation of pluripotent cell elements and thus guided the spatial and temporal organisation of in vivo tissue repair processes. Conclusion: Our results confirm the major influence of mechanical constraints on the organisation of skeletal tissue. The effect is expressed by the remodelling of mature tissues, but is also observed in immature tissues implicated in morphogenesis and skeletal regeneration processes. The transduction mechanisms remain to be described. However, the results obtained for cartilage regeneration demonstrate the practical interest of periosteal arthroplasty. Further improvement of the model to optimise continuous passive movement would open new perspectives for in vivo joint regeneration

1. The skeletal changes in endemic fluorosis are described from an area of the Punjab where the fluorine content of water and soil is very high. 2. A detailed description of a fluorotic skeleton is given, with its various anthropometric measurements. 3. The vertebral changes demonstrated the pathogenesis of the neurological complications observed in this condition

Background. Following endosteal uncemented orthopaedic device implantation, the initial implant/bone interface retains spaces and deficiencies further exacerbated by pressure necrosis and resultant bone resorption. This implant-bone space requires native bone infill through the process of de novo osteogenesis. New appositional bone formation on the implant surface is known as contact osteogenesis and is generated by osteogenic cells, including skeletal stem cells (SSCs), colonising the implant surface and depositing the extracellular bone matrix. Surface nanotopographies provide physical cues capable of triggering SSC differentiation into osteoblasts, thus inducing contact osteogenesis, translated clinically into enhanced osseointegration and attainment of secondary stability. The current study has investigated the in vitro and in vivo effects of unique nanotopographical pillar substrates on SSC phenotype and function. Methods. Adult human SSCs were immunoselected, enriched using STRO-1 antibody and cultured on control and test surfaces for 21 days in vitro. The test groups comprised Ti-coated substrates with planar or modified surfaces with nanopillar. Osteoinductive potential was analysed using qPCR and immunostaining to examine gene expression and protein synthesis. Results. Following in vitro (n=5) culture on nanopillars, the expression of osteogenic genes (ALP, Collagen 1, OPN and OCN) and of Osteopontin protein (a bone matrix protein), on Ti pillars were both significantly enhanced when compared to control or Ti planar surfaces. Conclusions. Discrete raised surface nanopillars modulate adult SSC populations in the absence of any chemical cues and enhance their osteogenic properties, an effect not observed on planar Ti constructs. Hence, these findings herald exciting opportunities to improve the implant surface design, implant osseointegration, and, ultimately, implant survival. Level of evidence. Original experimental study

1. A study of the average rate of growth of the legs and trunk of 202 normal average maturing children is presented. 2. The annual growth of the limbs and trunk was related to the skeletal age of each child, and the increments of growth per skeletal year subjected to statistical analysis. 3. Methods of growth prediction of leg length and mature height have been derived and the practical application of the investigation to orthopaedic surgery is discussed

1. Based on studies in seventy-five patients, a technique is described for body surface activity measurements over localised skeletal lesions up to one month after injection of the λ-emitting isotopes Ca. 47. and Sr. 85. . 2. The activity was high over skeletal lesions like fracture, metastatic cancer, eosinophilic granuloma, chondroma, osteomyelitis and Paget's disease. 3. The high isotope uptake is interpreted as evidence of an increased rate of bone tissue turnover. 4. These findings suggest that external counting of Ca. 47. and Sr. 85. may be used for quantitation of the rate of formation of normal and pathological bone tissue. A special application would be localisation and delineation of metastatic cancer in cases where radiographic evidence is uncertain or non-existent

Angiogenesis and the ability to provide appropriate vascular supply are crucial for skeletal tissue engineering. The aim of this study was to investigate the angiogenic potential of human dental pulp stromal cells (HDPSCs) and stro-1 positive populations as well as their role in tissue regeneration (the clinical reality). HDPSC were isolated from the pulp tissues of human permanent teeth by collagenase digestion. STRO-1 positive cells were enriched using monoclonal anti- STRO-1 and anti- CD45 PE conjugated antibodies together with and fluorescence activated cell sorting (FACS). Cells isolated by FACS were grown to passage4 and cultured as monolayers or on 3D Matrigel scaffold in endothelial cell growth medium-2 (EGM-2) with/without 50ng/mL of vascular endothelial growth factor (VEGF). Cells cultured in alpha MEM supplemented with 10% FCS were used as controls. After 24, 48 and 72 hours angiogenic marker expression (CD31, CD34, vWF and VEGFR-2) was determined by qRT-PCR and immuno-histochemistry. Using three different donors, 0.5-1.5% of total HDPSCs population was characterized as STRO-1+/CD45- cells At each time point cells cultured as monolayer in EGM-2 with VEGF showed up regulation of CD31 and VEGFR-2 expression compared to the control group while expression of CD34 and vWF remained unaffected. However on Matrigel, all four genes were up regulated to different extents. CD31 and VEGFR-2 were up regulated to a greater degree compared to CD34 and vWF. Changes in gene expression in both cell types were time dependent. Immuno-histochemical staining confirmed that the HDPSCs cultured in the test group showed positive staining for the four angiogenic markers (CD31, CD34 vWF and VEGFR-2) when grown in both monolayer and 3D Matrigel culture compared to control cultures. When cultured on Matrigel (but not Monolayer) for 7 days, HDPSC formed tube-like structures in the VEGF treated group. This indicates the potential of use HDPSCs and their STRO-1 positive population for angiogenesis to enhance skeletal tissue repair and/or regeneration toward translational research for clinical benefit

It is generally accepted that children treated for congenital pseudarthrosis of the tibia (CPT) should be followed-up until skeletal maturity, before drawing conclusions about the efficacy of treatment. We undertook this study in order to evaluate the long-term results of treatment of CPT by excision of the pseudarthrosis, intramedullary rodding and onlay cortical bone grafting. Among a total of 46 children with CPT treated by a single surgeon during a 20-year period, 38 had been treated by this technique and 11 of these children have reached skeletal maturity. These eleven cases (nine boys and two girls) formed the basis for this study. The mean age at presentation was 3.1 years (range 0.4–7 years); the mean age at index surgery was 3.2 years (range 0.7–7 years). The mean age at follow-up was 18.4 years (range 16–21.6 years) with a mean interval between surgery and final follow-up of 15.2 years (range 12.8–17.4 years). In all 11 children bone graft was harvested from the contralateral tibial diaphysis. Rods passed from the heel were used in nine children and in two Sheffield telescopic rods were passed from the ankle into the tibia. The fibula was divided in three children to ensure that the tibial fragments were in good contact before placing the graft astride them; the fibula was not touched in the remaining eight instances. To ensure that the intramedullary rod supported the pseudarthrosis site till skeletal maturity, revision rodding was performed as needed when the tip of the rod receded into the distal third. A thermoplastic clamshell orthosis was used till skeletal maturity. At final follow-up the union at the pseudarthrosis site was deemed to be ‘sound’ only if two independent observers concurred that there was definite bony continuity of the cortices on both the anteroposterior and lateral radiographs. Deformities of the tibia and ankle and ranges of motion of the knee, ankle and subtalar joints were noted. The limb lengths were measured with scanograms. The morbidity at the bone graft donor site was recorded. The function of the ankle was assessed by applying the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hind foot Score. Primary union of the tibial pseudarthrosis was achieved in nine of 11 cases with a mean time to union of 6.1 months. Secondary union was achieved in the remaining two cases following further intervention. At final follow-up sound union of the tibial pseudarthrosis was noted in all eleven patients but persistent pseudarthrosis of the fibula was present in 10 of 11 cases. The lateral malleolus was proximally situated in six cases. Ten of eleven children underwent a total of 21 secondary operations on an average of 2.6 years (range 0.5–5.1 years) after initial union was achieved. Six re-fractures were encountered in five patients at a mean of 6.1 years after index surgery. All the re-fractures united following the single episode of intervention. The overall mean shortening at final follow-up was 2.6 cm. At final follow-up, five patients had ankle valgus greater than 10 degrees. All the 11 patients walked without pain. Only two patients had significant motion at the ankle. Despite the ankle stiffness in the remaining children the AOFAS ankle-hindfoot scores ranged between 70 and 98 (mean 83.3). Our long-term results are comparable to the results of other studies in terms of the rate of union, the re-fracture rate, limb length discrepancy, residual deformity and the frequency of surgery

Introduction: The ability to generate bone for skeletal repair, replacement or restoration is a major clinical need. Indeed the paucity of techniques in reconstructive surgery and trauma emphasise the need for alternative bone formation strategies. Natural biological ceramic structures possess arrangements of structural elements that govern and optimise tissue function, nutrition and organisation. The aim of this study was to fabricate biomineral microporous shells with highly complex forms and to examine their ability to interact with human osteoprogenitor cells as cell and growth factor delivery vehicles. Methods: Microporous vaterite shells were generated using a synthetic in-solution mineralisation technique in which mineral is spontaneously deposited around vesicular templates (Walsh and Mann 1999). *. Porous and textured self-organising hollow microspheres (5–20 _m) were generated expressing controlled and uniform shapes. These micropores puncture the surface at high densities and are interconnected throughout the sphere. Primary human bone marrow cells labelled with Cell Tracker Green and ethidium homodimer-1 fluorescent labels and osteoprogenitors transfected with an adenoviral vector expressing Green Fluorescent Protein (AdGFP) were cultured with vaterite shells over three weeks. Results: Cell biocompatibility of these biomimetic spheres was confirmed by confocal fluorescence and light microscopy in primary human bone marrow cultures labelled with CTG and bone marrow cultures transfected with AdGFP. At three weeks microspheres were encapsulated and integrated with osteoprogenitor cells. Histological analysis confirmed expression of alkaline phosphatase, extracellular matrix synthesis and the capacity for extensive mineralisation. Examination by SEM, fluorescent and light microscopy showed that the growth of osteoprogenitors transfected with AdGFP and microspheres in pellet culture showed vaterite spheres were encapsulated and integrated within the osteoprogenitor cell matrix indicating the potential of growth factor delivery. To determine the potential of the spheres to encapsulate selected proteins, microporous spheres were incubated with bovine haemoglobin. FITC microscopic evidence showed haemoglobin could be entrapped inside the spheres and between the biomineral crystal plates during self-assembly. Discussion and Conclusion: These studies demonstrate the development of facile techniques for the generation of porous microsphere sponges that are biocompatible, possess the ability to aid mineralisation and for the delivery of cell and growth factors. These calcium carbonate structures provide a material with widespread application in a range of tissue engineering applications including skeletal tissue regeneration

Purpose: We reviewed our pre-puberty patients whose scoliosis or kyphoscoliosis involved a hemivertebra. The purpose of our work was to evaluate the surgical technique used and evaluate spinal static as well as functional outcome at skeletal maturity. Material and methods: This retrospective analysis included 21 patients who underwent surgery before the age of 10 years and were followed to skeletal maturity. We excluded children with a multiple malformation syndrome or multiple vertebral malformations. The type and localisation of the hemivertebra was noted. Deformation, transversal balance, and radiographic measures were recorded preoperatively. Elements contributing to the indication for surgery, the type of procedure, and complications were also recorded. Events recorded during growth were the clinical course, complementary treatments, and possible surgical revision. Functional and aesthetic outcome was assessed at last follow-up. Spinal deviation was measured and compared with the preoperative angles. Results: Twenty-one children (13 girls, 8 boys), mean age three years ten months (range 10 months – 10 years) met the inclusion criteria. These children had a hemivertebra of the thoracic spine (n=9), the thoracolumbar junction (n=4), the lumbar spine (n=4), or the lumbosacral region (n=4). Surgery was indicated to arrest clinical and radiographic degradation. Several surgical procedures were used: fusion without resection for thoracic vertebrae and resection associated with arthrodesis or epiphysiodesis for other localisations. There were five complications: neurological (n=2), infectious (n=2) and disassembly (n=1). The clinical and radiographic course led to revision in ten children, including two who required a new operation. At mean follow-up of 14 years (9–23 years), the functional outcome was good in 19 patients, poor in one patient with a lumbosacral hemivertebra and in another with a thoracic hemivertebra. The aesthetic result was good in 16 patients. Five of the nine patients with a thoracic hemivertebra remained unsatisfied with the outcome. Mean curvature correction ranged from 26% at the thoracic level to 50% at the thoracolumbar and lumbosacral levels and 75% at the lumbar level. Discussion: The long follow-up of this series is exceptional. Treatment of evolving spinal malformations is a difficult challenge. Early surgery does not guarantee the final outcome and 50% of patients have to be reoperated at the end of growth. The good long-term functional and aesthetic outcome is however encouraging, particularly when hemivertebrectomy can be performed

Background: Deformity of the femoral head after open reduction for developmental dislocation of the hip (DDH) influences the outcome of pelvic osteotomy as a final correction for residual dysplasia to prevent secondary osteoarthritis. The purpose of this study was to review long-term outcomes after open reduction using a medial approach for DDH. The correlation between age at the time of operation and femoral head deformity at skeletal maturity was specifically evaluated. Methods: Forty-two hips in 40 patients with more than 10 years of follow-up were assessed radiologically. The mean age at the time of surgery was 14.3 (range, 6–31) months, and the postoperative follow-up period ranged from 10 to 27 (mean, 15.8) years. The round and enlargement indices of the femoral head were measured on follow-up radiographs to evaluate deformity and enlargement of the femoral head at skeletal maturity. Results: Severin classification was I and II in 16 hips; III, IV, and V in 23; and II at the final follow-up in the 3 hips treated by osteotomy less than 10 years after open reduction. Mean round index at follow-up was 58.3 ± 8.3 (range, 47–79); it showed correlation with age at the time of operation (r = 0.68, p < 0.001). Mean enlargement index at follow-up was 113.4 ± 11.8 (range, 93–137) and showed no correlation with age at the time of operation (r = 0.009, p = 0.96). Conclusions: At more than 10 years’ follow-up, the occurrence of deformity of the femoral head correlated with increased age at the time of operation. Indications for use of a medial approach in the correction of DDH in older patients must take into account the risk of subsequent femoral head deformity at skeletal maturity

Tissue loss, as a result of injury or disease, provides reduced quality of life for many and with an increasingly ageing population there is a greater requirement for skeletal repair strategies. An emerging attractive approach, tissue engineering, is based on the use of an appropriate source of progenitor cells, a scaffold conducive to cell attachment and maintenance of cell function and the delivery of appropriate growth factors. As a cell source, mesenchymal stem cells (MSCs) or marrow stromal cells derived from adult human tissues offer tremendous potential for tissue regeneration. However, to date, the plasticity, multipotentiality and characteristics of potential stem cells from fetal skeletal tissue remain poorly defined. We have examined, in preliminary studies, the multipotentiality and phenotypic properties of cell populations derived from human fetal femurs collected at 8–12 weeks post-conception in comparison to adult-derived mesenchymal stem cell populations including those isolated using STRO-1 immunoselection. Fetal cells were culture expanded from explants in basal media then maintained for periods of up to 28 days in monolayer cultures in adipogenic and osteogenic conditions. Cells were also maintained in chondrogenic conditions via the pellet culture method, maintained in established media conditions including TGF-â3, with cultures taken to 7, 14, 21 and 28 days. Adipocyte formation was confirmed by morphology: large amounts of lipid accumulation were observed by Oil Red O staining and aP2 (FABP-3) immunocytochemistry. Osteogenic differentiation was also confirmed by Type I Collagen immunocytochemistry. The growth of fetal cells on biomimetic scaffolds and their osteogenic activity was confirmed by confocal microscopy and Alkaline Phosphatase staining respectively. In chondrogenic conditions, chondrocytes were embedded within lacunae and extensive matrix deposition was observed using Alcian blue/Sirius red staining. The chondrogenic phenotype was confirmed by positive staining via SOX9 immunocytochemistry. Differentiation and proliferation were accelerated in fetal populations compared to adult-derived immunoselected MSCs. Plasticity of fetal cells has been demonstrated by the formation of large numbers of adipocytes within osteogenic populations. In summary we demonstrate the proliferative and multi-potential properties of fetal-derived chondrocytic cells in direct comparison to adult-derived MSCs including STRO-1 immunoselected populations. Given the demographic challenges and ethical issues surrounding current embryonic cell research, fetal cell populations may also provide a unique half-way model to address stem cell differentiation in comparison to adult cells. Elucidation of immunogenecity and selective differentiation will confirm the potential of these fetal cells as a unique alternate cell source for therapeutic approaches in the restoration of damaged or diseased tissue

Skeletal metastases are an increasing sequaelae for patients with a wide range of neoplastic lesions owing to the increasing incidences of cancer. The diagnosis of a skeletal metastasis is, however, at present a terminal diagnosis representing uncontrolled tumour dissemination. The metastatic destruction of the bone reduces its load bearing capabilities progressing to the principle orthopaedic complication, that of complete loss of cortical integrity. Aim: We examine the population suffering a complication of skeletal metastasis in terms of their mortality and morbidity. We compare patients who underwent surgical stabilization as a result of a fracture through a metastatic lesion against those who underwent prophylactic stabilization. This is a retrospective study of all patients within the Cardiff centre who underwent an operation for a metastatic bone lesion over a 10 year period (n=140). The patients were identified using pathological records created when samples were sent at the time of the operations. The patients were all followed up for a minimum of 24 months. The demographics of the patients were collected and a detailed analysis of the primary tumour, the surgical procedure, the mobility, and survival of the patients was undertaken. The patients data was then cross referenced with the database at the regional cancer centre and the post operative radiotherapy treatment regimen were collected. Patients who underwent prophylactic surgical stabilization had a significant survival advantage compared to those stabilized following a fracture (p=0.002). The morbidity postoperatively, defined by the patients functional mobility, also shows the benefits of prophylactic stabilization with significantly improved mobility when compared to the mobility following fracture stabilization (p=0.033). It has also been shown that there is a significant postoperative survival benefit for those patients who were able to regain mobility (p< 0.01). Our results show a significant survival benefit of prophylactic fixation rather than fixation following fracture which is in line with previous studies We have also, for the first time in a large number study, shown that there is a survival benefit for patients who are able to mobilize following surgery and if prophylactic stabilization was undertaken patients were significantly more mobile postoperatively

1. One hundred and seventy-nine cases of primary malignant bone tumour and giant-cell tumour seen at the Middlesex Hospital since 1925 are reviewed. Tumours arising from non-skeletal tissues in bone have been excluded. 2. The following histological classification is used. Osteosarcoma (osteoblast sarcoma): This tumour is not synonymous with osteogenic (bone-forming) sarcoma. The essential feature is the formation of osteoid tissue by malignant osteoblasts, with no intermediate matrix of cartilage or fibrous tissue. It is the most malignant bone tumour and only four of the thirty-two patients survived three years. Chondrosarcoma: These tumours are composed of cartilage, and some show secondary ossification. The behaviour of this group is related to the degree of cartilaginous differentiation. In general, compared with the osteosarcoma, it is of low-grade malignancy. More than half of the sixty-eight patients survived four years. Fibrosarcoma: The essential feature of this tumour is the production of collagen by malignant fibroblastic tumour cells. Tumours of this type invading the medullary cavity have an average prognosis between that of an osteosarcoma and a chondrosarcoma. Nine of the thirty-four patients survived three years. Spindle-cell sarcoma: These tumours are composed of spindle cells which produce no diagnostic matrix. In spite of the lack of differentiation the outlook is not hopeless. Six of the eleven patients survived for five years or more. Giant-cell tumour: This tumour is composed of a cellular stroma with diagnostic giant cells resembling osteoclasts. It is by no means a benign lesion, for half the tumours recurred after treatment and a quarter of the patients died with metastases. 3. The subdivision of primary malignant skeletal tumours into groups according to the histological pattern appears to be reflected in the behaviour of the individual tumours after treatment. The prognosis of each group has been stated in the appropriate sections

To develop a useful surgical navigation system, accurate determination of bone coordinates and thorough understanding of the knee kinematics are important. In this study, we have verified our algorithm for determination of bone coordinates in a cadaver study using skeletal markers, and at the same time, we also attempted to obtain a better understanding of the knee kinematics. The research was performed at the Medical Simulation Center of Tzu Chi University. Optical measurement system (Polaris® Vicra®, Northern Digital Inc.) was used, and reflective skeletal markers were placed over the iliac crest, femur shaft, and tibia shaft of the same limb. Two methods were used to determine the hip center; one is by circumduction of the femur, assuming it pivoted at the hip center. The other method was to partially expose the head of femur through anterior hip arthrotomy, and to calculate the centre of head from the surface coordinates obtained with a probe. The coordinate system of femur was established by direct probing the bony landmarks of distal femur through arthrotomy of knee joint, including the medial and lateral epicondyle, and the Whiteside line. The tibial axis was determined by the centre of tibia plateau localised via direct probing, and the centre of ankle joint calculated by the midpoint between bilateral malleoli. Repeated passive flexion and extension of knee joint was performed, and the mechanical axis as well as the rotation axis were calculated during knee motion. A very small amount of motion was detected from the iliac crest, and all the data were adjusted at first. There was a discrepancy of about 16.7mm between the two methods in finding the hip centre, and the position found by the first method was located more proximally. When comparing the epicondylar axis to the rotation axis of the tibia around knee joint, there was a difference of 2.46 degrees. The total range of motion for the knee joint measured in this study was 0∼144 degrees. The mechanical axis was found changing in an exponential pattern from 0 degrees to undetermined at 90 degrees of flexion, and then returned to zero again. Taking the value of 5 degrees as an acceptable range of error, the calculated mechanical axis exceeded this value when knee flexion angle was between 60∼120 degrees. The discrepancy between the hip centres calculated from the two methods suggested that the pivoting point of the femur head during hip motion might not be at the center of femur head, and the former location seemed closer to the surface of head at the weight bearing site. Under such circumstances, the mechanical axis obtained through circumduction of the thigh might be 1∼2 degrees different from that obtained through the actual center of femur head. During knee flexion, the mechanical axis also changed gradually, and this could be due to laxity of knee joint, or due to intrinsic valgus/varus alignment. However, the value became unreliable when the knee was at a flexion angle of 60∼120 degrees, and this should be taken into account during navigation surgery

AIM. Avascular necrosis (AVN) of the femoral head is a potentially debilitating disease of the hip in young adults. Impaction bone grafting (IBG) of morcellised fresh frozen allograft is used in a number of orthopaedic conditions. This study has examined the potential of skeletal stem cells (SSC) to augment the mechanical properties of impacted bone graft and we translate these findings into clinical practice. STUDY DESIGN. We have examined the effect of SSC density on augmentation of bone formation. An in vitro model was developed to replicate the surgical IBG process. Plain allograft was used as the control, and the SSC's seeded at a density of 5×103, 5×104 and 2×105 cells per cc of allograft for the experimental groups. All samples were cultured for 2 weeks and mechanically tested to determine shear strength using the Mohr Coulomb failure curve. The approach was translated to 3 patients with early avascular necrosis (AVN) of the femoral head. The patient's bone marrow was concentrated in theatre using a centrifugation device and the concentrated fraction of SSC's were seeded onto milled allograft. The patient's necrotic bone was drilled, curetted and replaced with impacted allograft seeded with SSC's. Osteogenic potential of concentrated and unconcentrated marrow was simultaneously compared in vitro by colony forming unit assays. RESULTS. The mechanical properties of the impacted allograft was significantly improved as a function of increasing SSC density. The difference compared to the control plain allograft was highly significant at the 2×105 level (p=0.001). Autologous SCC's on impacted bone allograft was subsequently applied in 3 patient cases and up to two year follow up demonstrates no deleterious effect. Critically the analysis of concentrated marrow demonstrated a higher SSC count in vitro than plain marrow aspirate. DISCUSSION. We have demonstrated the potential of skeletal stem cells to augment the mechanical properties of impacted bone allograft in a laboratory model and subsequently translated these findings into a new technique for the treatment of AVN of the femoral head. Such an approach provides not only improved mechanical support to the overlying cartilage but critically improved biology for new bone formation. The early clinical results are encouraging and indicate potential use also in fracture non-unions and void filling of bone defects

Introduction: Despite the lack of good clinical evidence post operative radiotherapy is standard practice following non radical surgical treatment of skeletal metastases in long bones There is little in the literature about the size of radiation field and whether the whole bone, the nail or just the area of the metastatic deposit should be covered. Methods: We present two cases where the metastases were treated by intramedullary nailing and were subsequently irradiated. In each case the tip of the intramedullary nail was outside the radiotherapy field. Results: Subsequent second metastasis formation occurred at the tip of the nail compounded by pathological fracture. Salvage surgery was achieved in one case with a total femoral replacement and in the other by bi-columnar plating of the humerus with cement augmentation. Discussion: Intramedullary nailing of a metastasis will seed the tumour to the tip of the nail. It is therefore essential that the tip of the nail be included in the radiotherapy field post-operatively as salvage surgery for subsequent pathological fracture is technically demanding. The aim of any surgery for skeletal metastases is that the reconstruction should outlast the patient. Communication between surgeon and radiation oncologist is essential

A multimodality approach is needed for management of infected joint replacement prostheses and infected skeletal metalwork. We present our results in six patients managed surgically with standard techniques, with the addition of a local antibiotic delivery system using absorbable Calcium Sulphate beads. A retrospective study was undertaken of 6 patients with established musculoskeletal infection in relation to existing metalwork. Two patients had infection in the hip replacement prosthesis, three had infected prosthetic knee joints and one had infection in a femoral locking plate. All were treated with extensive debridement, revision / retention of implants, parenteral antibiotics and local antibiotics. Patients were followed up in clinic for resolution of inflammatory markers and subsidence of signs of infection. Control of infection was achieved in five patients at average 19 months followup. One patient had persistent infection and has undergone further surgery. In this preliminary study, we found local antibiotic delivery using absorbable calcium sulphate beads to be an effective adjuvant to standard debridement, parenteral antibiotics and revision of implants

Vascularised bone grafts have been most commonly applied in reconstructions of the lower extremities. However, the indications for vascularised bone grafts in the upper extremities have now been expanded, as this technique is becoming more widely appreciated. Between 1993 and 2000, 12 patients who had segmental bone defects following trauma of the forearm received vascularised fibular grafts, among them six men and six women. The average age was 39 years (range 16–65 years). The reconstructed sites were the radius in eight patients and the ulna in four. The length of the bone defect ranged from 6 to 13 cm. In four cases the fibular graft was raised as a vascular osteoseptocutaneous fibular graft. For fixation of the grafted fibula, plates were used in ten cases, screws and Kirschner wires in two. In these two cases an external skeletal fixator was used for immobilisation of the extremity. The follow-up period ranged from 93 to 10 months. In 11 patients grafting was successful. There were no instances of fractures of the grafted bone; however, non-union occurred at the proximal site in one case and only one patient required an additional bone graft. No patient showed evidence of resorption of the graft or symptoms related to the donor leg. No recurrence of local infection was encountered in the patients with previous osteomyelitis. The mean period to obtain radiographic bone union was 4.8 months (range 2.5–8 months). With the use of fibular grafts a segment of diaphyseal bone can be transferred that is structurally similar to the radius and ulna and that is of sufficient length for the reconstruction of most skeletal defects in the forearm. A vascularised fibular graft is indicated in patients with intractable non-unions, where conventional bone grafting has failed or for large bone defects (in excess of 6 cm) in the radius or ulna

Fixation by a single screw is considered the current treatment of choice for a slipped capital femoral epiphysis. This approach promotes premature physeal closure. The use of a modified, standard, single, cannulated screw designed to maintain epiphyseal fixation without causing premature closure of the physis was reviewed in ten patients. The nine boys and one girl aged between 10.6 and 12.6 years with unilateral slipped capital femoral epiphysis (SCFE), were markedly skeletally immature (Tanner stage I, bone age 10 to 12.6 years). Clinical and radiological review at a mean follow-up of 44.3 months (36 to 76) showed no difference in the time to physeal closure between the involved and uninvolved side. Measurement of epiphyseal and physeal development showed continued growth and remodelling in all patients. Use of this device provided epiphyseal stability and maintained the capacity for physeal recovery and growth following treatment for both unstable and stable slipped capital femoral epiphysis

Posterolateral spinal fusion is considered one of the most challenging condition for bone graft substitutes since using autogenous bone graft pseudarthrosis have been reported in 30% of cases. MATERIALS AND METHODS.We develop a model of posterolateral spinal fusion in the rabbit based on skeletal stem cells (SSCs) loaded into a coral-hydroxyapatite material (Pro-Osteon 500RTM). 15 rabbits received cell-material constructs, 15 rabbits were sham-operated (decortication of transverse apophyses), 15 rabbits received material alone. The animals were housed for 6 months and radiographically monitored. At sacrifice, the explanted spine was analyzed by conventional and high resolution (Faxitron) radiography, and the outcome judged, blind of histology results, by two orthopedic surgeons. RESULTS: radiographic evaluation showed a fusion rate rate of 90% in animals treated with cell constructs or biomaterial alone, and no fusion in the sham controls. Histology revealed abundant new bone formation directly on the scaffold in the cell construct and biomaterial alone groups, but no evidence of bone formation in the midregion of the interapophyseal space, where poorly vascular, dense fibrous tissue was observed. CONCLUSIONS: The study shows that:. 1) the cell-biomaterial constructs which per se were highly efficient in previous animal studies, used in different absolute quantities but identical ratios were not efficient in the direct preclinical model. 2) Radiography alone is misleading. 3) Once efficient cell and material preparations are obtained, additional consideration must be given to specific circumstances of the pre-clinical and clinical application such as mobility of the graft and its component and vascularization of the graft bed

Introduction: Osteomyelitis and septic arthritis (SA) below the elbow are severe conditions affecting the function and viability of the hand. Factors predisposing to these conditions and parameters affecting prognosis are emphasized. Material and Methods: In a 4 years period, 16 patients with SA (4) or osteomyelitis (12) were treated in a University Orthopaedic Department providing care to a rural population of 1.000.000, Nine had history of trauma in unhygienic environment, 3 had immunodeficiency and in 4 osteomyelitis was iatrogenic [previous fixation of fractures (3) and vein catheterization (1)]. SA was located in the wrist (2) and thumb joints (2) and osteomyelitis involved the radius (3), ulna (1), metacarpals (3) and phalanges (5). Ten patients received oral antibiotics in other centers. The mean delay from onset of symptoms to referral to our center was 22 days. Apart of antibiotics administration, surgical treatment included debridement and irrigation for SA and excision of necrotic bone, stabilization (external fixators), use of antibiotic beads and secondary bridging with bone graft for osteomyelitis. Additional procedures (amputations, arthrodesis) were also required in some cases. Results: Cultures were positive in 9 of 16 cases [Staph. aureus (5) and enterobacter cloacae (3)]. Patients underwent multiple procedures (mean: 3.8) and 4 underwent amputation of a digit (2) and hand (2) due to the rapid extension of infection threatening and finally taking the lives of 2 elderly and immunosuppressed patients. Mean follow-up period of the 12 surviving and non-amputated patients was 18 months. Union was accomplished in all cases. Functional results were excellent or very good in 10 of 12 patients and good in 2 patients. All patients were satisfied and returned to their previous occupations. Conclusions: Osteomyelitis and SA below the elbow was frequent in population living in unhygienic environment or working with soil. All cases received medical treatment with delay. Immunosuppressing conditions favored the extension of infection and threatened patients lives. Delay in treatment in combination to immunosuppression resulted to significant morbidity. Early treatment including surgical drainage, thorough debridement and antibiotic administration is necessary for elimination of skeletal infection and salvage of the hand and patients life

Renal neoplasm is the most frequent cause of metastases, after prostatic and breast carcinoma. Lesions are aggressive and expansive with cortical destruction and soft tissue extension. Pathological fracture is very common, up to 50%. The most frequent localizations are long bones, spine and pelvis. Aim of this work is to evaluate the usefulness of surgical treatment of soft tissue and skeletal metastases in kidney neoplasm. Between 1995 and 2005 66 patients (40 males, 26 females) were submitted to surgical treatment at San Raffaele Hospital, Milano. Most common localizations were femur, humerus, spine, pelvis, metatarsus. We report 3 cases of soft tissue metastases of lower limb. Twenty-five patients had single localization, 10 pathological fracture and in 5 diagnose was bioptical. Surgical treatment was performed with large resection and in 15 patients the lesion was embolized. Twelve patients had local relapse and in 3 we performed a new surgical treatment. We had no infections nor fatal outcome in the post-surgical period

1. Analyses are presented of comparable groups of the two commonest bone-forming tumours—osteochondroma and osteogenic sarcoma—derived from the following sources: Bristol Bone Tumour Register; British Empire Cancer Campaign Annual Report (1949); Stocks and Barrington (1925); Meyerding (1927); and Geschickter and Copeland (1949). 2. From this study, the following features emerge as characteristic and common to both tumours. 1) Both tumours are commoner in the male during the age periods 0-34 years, and over fifty years, with the possible exceptions of tumours of the humerus during early life and tumours of the pelvis. 2) The male preponderance is most marked for the appendicular long bones. 3) The male preponderance is greatest during the age period 15-34 years. 4) In the separate bones, these tumours tend to arise at a somewhat earlier age in the female. 5) In both sexes both tumours tend to arise at an earlier age in the bones of the upper arm and shoulder girdle than in those of the lower limb and pelvis. 6) Both tumours are related to an aberration of endochondral growth in length of bone. 3. The greater growth of the male, and differences in skeletal development in the two sexes, offer a simple and reasonably consistent explanation of these peculiarities and make it possible to discern the interplay of the three factors of age, sex and site of origin of the tumour. 4. From this concept it is possible to make a crude estimate of the factors of time and bulk of tissue which when combined may well account for the observed male preponderance of these tumours, and their anatomical distribution

Introduction: Due to an increase in survival skeletal metastasis becomes a significant factor on life quality in carcinoma patients. Also shown in publications of the last years the surgical approach and the expected prognosis are very much based on the primary. Especially patients with breast carcinoma show very long survival times, which must be considered in choosing the adequate surgical approach. Aim of this study was to proof that on a large collective of consecutively treated patients. Methods: Between 1980 and 2005 115 patients with metastatic disease to the bone due to breast carcinoma had been surgically treated. In 112 female and 3 male the mean age at surgery was 58 years (17–84 years). Retrospectively location and extension of the disease, symptoms, surgical approaches, complications, recurrencies and survival time had been evaluated. Results: The most often peformed procedure was a decompression with or without stabilisation of the spine in 42 cases. Four vertebroplasties had been additionally performed. The proximal femur had to be reconstructed with an endoprotsthetic device in 24 cases, an endoprostehtic reconstruction of the humerus was necessary in 2 patients, of the pelvis in one case. One diaphyseal prothesis was implanted. Two resctions/amputation without any reconstruction had to be performed. In 20 cases a compound osteosynthesis, in 19 cases a biopsy only was done. In most of the cases postsurgical radiation was administered in some cases preoperative radiation had been applied. Follow-up was done 1 to 26 years after surgery (average 11.7 years). Many pateints showed an extented survival despite disseminated disease with a high and quality of life. Radical resection as tried in a few patients did not proof to be beneficial regarding the prognsotic effect. Conclusions: Patients with skeletal manifestations of breast carcinoma showed long survival times despite extented disease. The intralesional surgical approach including radiation therapy showed a better functional outcome in comparison to radical procedures with no disadvantage in survival time or local recurrencies

In a retrospective review of 302 clinically suspected cases of congenital syphilis, bone changes were found in 197. The skeletal manifestations were periostitis (102 cases), osteitis (20), and metaphyseal changes (71). Combinations of more than one lesion were found in 61. Pseudoparalysis was a presenting sign in 34 infants; 12 of these were found to have had pathological fractures and four had dactylitis. Complete radiological healing without residual changes was seen in all 59 cases that were recalled for review. The orthopaedic surgeon should consider the diagnosis of congenital syphilis when destructive lesions of bone are seen in an infant

Introduction and Aims: We studied the outcome of single event multilevel surgery (SEMLS) for the correction of severe crouch gait in spastic diplegia, over a five-year period. It was unknown if gait correction post-SEMLS could be sustained at skeletal maturity. Method: This was a prospective cohort study, utilising validated outcome measures. Presenting symptoms were increasingly abnormal gait, anterior knee pain, patellar fractures and fatigue. SEMLS was based on pre-operative gait analysis: mean of seven procedures (range 5–10), including lengthening of contracted muscle-tendon units (particularly hamstrings and psoas), as well as rotational osteotomies and bony stabilisation procedures to correct lever arm dysfunction. Post-operatively subjects wore Ground Reaction Ankle Foot Orthoses (GRAFOs) and received a community-based rehabilitation program. Post-operative changes were evaluated at five years: technical outcome by 3D kinematics and functional outcome by mobility status. Outcomes were analysed with linear regression with robust standard errors. Results: Eleven children with spastic diplegic cerebral palsy fulfilled the criteria for ‘severe crouch gait’, defined as knee flexion > 30 degrees and ankle dorsiflexion > 15 degrees throughout stance. Ten of 11 subjects had previous Tendo Achilles lengthening. Mean age pre-operatively was 12 years one month (range 8–16) and at follow-up 17 years 10 months (range 16–21). All subjects regained pre-operative mobility levels with improved gait pattern, relief of knee pain and healing of patellar fractures. There was a significant decrease in dependence on assistive devices. Pre- versus five years post-operative kinematics showed clinically and statistically significant increases in knee extension and decreases in ankle dorsiflexion. Improvements were seen in knee extension initial contact (p< 0.001, 95% CI 15°, 31°); maximum knee extension (p< 0.001, 95% CI 16°, 37°), ankle dorsiflexion (p< 0.001, 95% CI 8°, 18°) and plantarflexion 3rd rocker in stance (p=0.03, 95% CI 1°, 17°); knee excursion (p=0.003, 95% CI –24°, −6°), and peak knee flexion timing (p=0.02, 95% CI 2%, 20%). Conclusion: Multilevel surgery for severe crouch gait in spastic diplegia results in consistently marked improvements in dynamic knee and ankle function, but not at the hip and pelvic levels. The results are durable in most patients, after five years and after reaching skeletal maturity

Between 1980 and 1988, displacement bone-marrow transplantation was performed on 25 children with Hurler's syndrome (type-1 mucopolysaccharidosis). We describe the musculoskeletal development of 11 of the 12 surviving children and the orthopaedic procedures undertaken to treat progressive thoracolumbar kyphosis, hip subluxation and carpal tunnel syndrome. We found abnormal bone modelling, focal failures of ossification and an avascular disorder of the femoral head in every patient and offer an explanation for these phenomena. Increasing valgus deformity of the knees and progressive generalised myopathy caused loss of mobility as the children entered adolescence. The benefit of bone-marrow transplantation as a treatment for the skeletal disorders of Hurler's syndrome is limited by the poor penetration of the musculoskeletal tissues by the enzyme derived from the leucocytes

We describe the results of conservative treatment for complete midsubstance tears of the anterior cruciate ligament (ACL) in 18 skeletally immature patients, followed for a minimum of 36 months. Six patients had an ACL reconstruction during the follow-up period and were assessed immediately before their operation. The average time from initial injury to evaluation was 51 months. All patients had symptoms when reviewed. The modified Lysholm knee score showed one excellent result, one good, eight fair, and eight poor with a mean score of 64.3. Only one patient had returned to her preinjury level of athletics. Secondary meniscal tears were confirmed in six patients, and three more had the clinical signs of a tear at follow-up. Radiological evidence of degenerative changes was found in 11 of the 18 patients. We conclude that the results of non-operative treatment for ACL injuries in this age group are poor and not acceptable