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