Background. In Japan, idiopathic osteonecrosis of the femoral head (ONFH) is designated as a specified rare and intractable disease in patients for whom medical care is subsidized through the Specified Disease Treatment Research Program. Each patient is approved for the subsidy based upon a prefectural governmental review after filing an application together with a clinical research form documenting the patient's medical history, laboratory/clinical findings, and treatment. The purpose of this study was to conduct a fact-finding study of ONFH patients in the Fukuoka Prefecture based on clinical research forms of the Specified Disease Treatment Research Program. Methods. The distribution by gender and age of ONFH patients who filed an application for subsidy under this program between 1999 and 2008 was investigated on the basis of clinical research forms in the Fukuoka Prefecture. For comparative purposes, we also investigated the distribution by gender and age of ONFH patients who had a final diagnosis of ONFH at our institution during the past three years. Results. In the Fukuoka Prefecture, 1,244 ONFH patients (758 men, 61%; and 486 women, 39%) were identified during the 10-year period. The mean age was 48 years for men and 56 years for women. Men showed a normal age distribution with a peak in their fifties, whereas, women displayed a bimodal distribution with peaks in their fifties and seventies. The numbers of patients aged greater than 60 years were 162 (21.4%) for men and 218 (44.9%) for women. At our institution, there were 94 patients (61 men, 64.9%; and 33 women, 35.1%) who had a final diagnosis of ONFH based on radiology and pathology during the 3-year period. The mean age of these patients was 44 years for mrn and 45 years for women. Men showed a bimodal distribution with peaks in their thirties and fifties, whereas, women displayed a unimodal distribution with a peak in their fifties. The numbers of patients aged greater than 60 years were 7 (11.5%) for men and 6 (18.2%) for women. The age distribution of ONFH patients in the Fukuoka Prefecture was significantly higher, particularly for women, compared with patients at our institution. Conclusion. The present study, based on clinical research forms showed that 1,244 patients were identified as having ONFH in the Fukuoka Prefecture during a 10-year period, with a men-to-women ratio of 6:4. For women, approximately half were aged greater than 60 years of age

The interleukin-6/gp130-associated Janus Kinases/STAT3 axis is known to play an important role in mediating inflammatory signals, resulting in production of matrix metalloproteinase-3 (MMP-3). The hip joints with rapidly destructive coxopathy (RDC) demonstrate rapid chondrolysis, probably by increased production of MMP-3 observed in the early stage of RDC. In the recent study, no apparent activation of STAT3 has been shown in the synovial tissues obtained from the osteoarthritic joint at operation. However, no data are currently available on STAT3 activation in the synovial tissues in the early stage of RDC. This study aimed to elucidate STAT3 activation in the synovial tissues in the early stage of RDC. Synovial tissues within 7 months from the disease onset were obtained from four RDC patients with femoral head destruction and high serum levels of MMP-3. RDC synovial tissues showed the synovial lining hyperplasia with an increase of CD68-positive macrophages and CD3-positive T lymphocytes. STAT3 phosphorylation was found in the synovial tissues by immunohistochemistry using anti-phospho-STAT3 antibody. The majority of phospho-STAT3-positive cells were the synovial lining cells and exhibited negative expression of macrophage or T cell marker. Treatment with tofacitinib, a Janus Kinase inhibitor, resulted in a decrease in phospho-STAT3-positive cells, especially with high intensity, indicating effective suppression of STAT3 activation in RDC synovial tissues. Inhibitory effect of tofacitinib could act through the Janus Kinase/STAT3 axis in the synovial tissues in the early stage of RDC. Therefore, STAT3 may be a potential therapeutic target for prevention of joint structural damage in RDC. Acknowledgements: This study was supported by Katakami Foundation for Clinical Research

Osteosarcoma is a highly malignant primary tumor of bone tissue. The 5-year survival rate of patients with metastasis is below 20% and this scenario is unchanged in the last two decades, despite great efforts in pre-clinical and clinical research. Traditional preclinical models of osteosarcoma do not consider the whole complexity of its microenvironment, leading to poor correlation between in vitro/in vivo results and clinical outcomes. Spheroids are a promising in vitro model to mimic osteosarcoma and perform drug-screening tests, as they (i) reproduce the microarchitecture of the tumor, (ii) are characterized by hypoxic regions and necrotic core as the in vivo tumor, (iii) and recapitulate the chemo-resistance phenomena. However, to date, the spheroid model is scarcely used in osteosarcoma research. Our aim is to develop a customized culture dish to grow and characterize spheroids and to perform advanced drug-screening tests. The resulting platform must be adapted to automated image acquisition systems, to overcome the drawbacks of commercial spheroids platforms. To this purpose, we designed and developed a micro-patterned culture dish by casting agarose on a 3D printed mold from a CAD design. We successfully obtained viable and reproducible homotypic osteosarcoma spheroids, with two different cells lines from osteosarcoma (i.e., 143b and MG-63). Using the platform, we performed viability assays and live fluorescent stainings (e.g., Calcein AM) with low reagent consumption. Moreover, the culture dish was validated as drug screening platform, administrating Doxorubicin at different doses, and evaluating its effect on OS spheroids, in terms of morphology and viability. This platform can be considered an attractive alternative to the highly expensive commercial spheroid platforms to obtain homogeneous and reproducible spheroids in a high-throughput and cost effective mode

Low back pain (LBP) is the main cause of disability worldwide and is primarily triggered by intervertebral disc degeneration (IDD). Although several treatment options exist, no therapeutic tool has demonstrated to halt the progressive course of IDD. Therefore, several clinical trials are being conducted to investigate different strategies to regenerate the intervertebral disc, with numerous studies not reaching completion nor being published. The aim of this study was to analyze the publication status of clinical trials on novel regenerative treatments for IDD by funding source and identify critical obstacles preventing their conclusion. Prospective clinical trials investigating regenerative treatments for IDD and registered on . ClinicalTrials.gov. were included. Primary outcomes were publication status and investigational treatment funding. Fisher's exact test was utilized to test the association for categorical variables between groups. 25 clinical trials were identified. Among these, only 6 (24%) have been published. The most common source of funding was university (52%), followed by industry (36%) and private companies (12%). Investigational treatments included autologous (56%) or allogeneic (12%) products alone or in combination with a carrier or delivery system (32%). The latter were more likely utilized in industry or privately funded studies (Fig. 1, p=0.0112). No significant difference was found in terms of funding regarding the publication status of included trials (Table 1, p=0.9104). Most clinical trials investigating regenerative approaches for the treatment of IDD were never completed nor published. This is likely due to multiple factors, including difficult enrollment, high dropout rate, and publication bias. 3. More accurate design and technical support from stakeholders and clinical research organization (CROs) may likely increase the quality of future clinical trials in the field. For any figures or tables, please contact the authors directly

Establishing disease biomarkers has been a long-sought after goal to improve Osteoarthritis (OA) diagnosis, prognosis, clinical and pharmaceutical interventions. Given the role of the synovium in contributing to OA, a meta-analysis was performed to determine significant synovial biomarkers in human OA tissue, compared to non-OA patients. Outcomes will direct future research on marker panels for OA disease modelling in vitro/in vivo, aiding clinical research into OA disease targets. A PRISMA compliant search of databases was performed to identify potential biomarker studies analysing human, OA, synovial samples compared to non-OA/healthy participants. The Risk of Bias In Non-Randomised Studies of Interventions (ROBINS-I) tool assessed methodological quality, with outcome analysed by Grading of Recommendations Assessment, Development and Evaluation (GRADE). Meta-analyses were conducted for individual biomarkers using fixed or random effect models, as appropriate. Where three or more studies included a specific biomarker, Forest Plot comparisons were generated. 3230 studies were screened, resulting in 34 studies encompassing 25 potential biomarkers (1581 OA patients and 695 controls). Significant outcomes were identified for thirteen comparisons. Eleven favoured OA (IL-6, IL-10, IL-13, IP-10, IL-8, CCL4, CCL5, PIICP, TIMP1, Leptin and VEGF), two favoured non-OA controls (BMP-2 and HA). Notably, PIICP showed the largest effect (SMD 6.11 [3.50, 8.72], p <0.00001, I. 2. 99%), and TIMP1 resulted critically important (0.95 [0.65, 1.25], p <0.00001, I. 2. 82%). Leptin and CCL4 showed lower effects (SMD 0.81 [0.33, 1.28], p =0.0009; 0.59 [0.32, 0.86], p <0.0001, respectively). Thirteen significant synovial biomarkers showed links with OA bioprocesses including collagen turnover, inflammatory mediators and ECM components. Limitations arose due to bias risk from incomplete or missing data, publication bias of inconclusive results, and confounding factors from patient criteria. These findings suggest markers of potential clinical viability for OA diagnosis and prognosis that could be correlated with specific disease stages

Critical size bone defects deriving from large bone loss are an unmet clinical challenge1. To account for disadvantages with clinical treatments, researchers focus on designing biological substitutes, which mimic endogenous healing through osteogenic differentiation promotion. Some studies have however suggested that this notion fails to consider the full complexity of native bone with respect to the interplay between osteoclast and osteoblasts, thus leading to the regeneration of less functional tissue2. The objective of this research is to assess the ability of our laboratory's previously developed 6-Bromoindirubin-3’-Oxime (BIO) incorporated guanosine diphosphate crosslinked chitosan scaffold in promoting multilineage differentiation of myoblastic C2C12 cells and monocytes into osteoblasts and osteoclasts1, 3, 4. BIO addition has been previously demonstrated to promote osteogenic differentiation in cell cultures5, but implementation of a co-culture model here is expected to encourage crosstalk thus further supporting differentiation, as well as the secretion of regulatory molecules and cytokines2. Biocompatibility testing of both cell types is performed using AlamarBlue for metabolic activity, and nucleic acid staining for distribution. Osteoblastic differentiation is assessed through quantification of ALP and osteopontin secretion, as well as osteocalcin and mineralization staining. Differentiation into osteoclasts is verified using SEM and TEM, qPCR, and TRAP staining. Cellular viability of C2C12 cells and monocytes was maintained when cultured separately in scaffolds with and without BIO for 21 days. Both scaffold variations showed a characteristic increase in ALP secretion from day 1 to 7, indicating early differentiation but BIO-incorporated sponges yielded higher values compared to controls. SEM and TEM imaging confirmed initial aggregation and fusion of monocytes on the scaffold's surface, but BIO addition appeared to result in smoother cell surfaces indicating a change in morphology. Late-stage differentiation assessment and co-culture work in the scaffold are ongoing, but initial results show promise in the material's ability to support multilineage differentiation. Acknowledgements: The authors would like to acknowledge the financial support of the Collaborative Health Research Program (CHRP) through CIHR and NSERC, as well as Canada Research Chair – Tier 1 in Regenerative Medicine and Nanomedicine, and the FRQ-S

Study aim. There is an ever increasing demand for quality clinical trials in surgery. Surgeons' co-operation and enthusiasm to participate are important, if not crucial in success of such studies, especially if they are multi-centred. Clinician's individual uncertainty (equipoise) about a case has been often cited as an ethical basis for inviting a patient to take part in a clinical trial. This study aims to establish current attitudes of surgeons participating in a national multi-centred randomised controlled trial and explores an on line tool for instant assessment of collective uncertainty (equipoise) for individual clinical cases eligible for a trial. Study design. Surgeons taking part in the UK Heel Fracture Trial were invited to take part. If agreed, they were asked to evaluate treatment prognosis for eligible for the trial anonymised cases of calcaneal fractures online by means of specially designed system. The cases were published on a password protected website on ad-hoc basis during the three years course of the trial. Their responses were submitted instantly on line. Results. 16 out of 24 surgeons agreed to participate. The participating surgeons were emailed links to cases (normally in butches of three) less than once a month. It took them 10-15 min to assess all three cases via interactive interface. Of those who agreed 12 submitted their opinion at least once. 7 voted consistently during the course of the trial. Seventy one cases had been published. The data collected from responses allowed to assess individual and collective uncertainty about clinical cases. 4 surgeons demonstrated tendency towards individual uncertainty, balanced by 4 who did not accept it. However, sufficient collective uncertainty was demonstrated in 84.5% of cases. Discussion. Level of surgeons' enthusiasm towards clinical research appears to be moderate in a selected population of orthopaedic surgeons who already agreed to take part in a randomised clinical trial, despite a very low research time burden of this study. It is important to continue to promote multi-centred studies in order to improve surgeons' attitude towards quality clinical research. Extra efforts by academic clinicians to develop further low research time burden methodologies may increase acceptance and volume of multi-centred clinical research. This study supports previously expressed view that individual uncertainty is a very unreliable and unnecessary justification to offer a subject to take part in a clinical trial. The system used in the study offers surgeons to express their opinions and preferences freely. The instant on line comparison of opinions provides a clear assessment of collective uncertainty, which can be returned to a treating surgeon and a patient him/herself within 48 hours. In absence of collective uncertainty it would be ethical to offer a patient the best treatment according to current opinion. These cases can then be followed up as part of an inclusive trial, if a subject agrees. We believe that using the system may improve decision making process in randomised controlled trials, for example in selected challenging cases

Successful reconstruction of bone defects requires an adequate filling material that supports regeneration and formation of new bone within the treated defect in an optimal fashion. Currently available synthetic bone graft substitutes cannot fulfill all requirements of the highly complex biological processes involved in physiological bone healing. Due their unphysiologically asynchronous biodegradation properties, their specific foreign material-mediated side effects and complications and their relatively modest overall osteogenic potential, their overall clinical performance typically lags behind conventional bone grafts of human origin. However, defect- and pathology specific combination of synthetic bone graft substitutes exhibiting appropriate carrier properties with therapeutic agents and/or conventional bone graft materials allows creation of biologically enhanced composite constructs that can surpass the biological and therapeutic limits even of autologous bone grafts. This presentation introduces a bone defect reconstruction concept based on biological enhancement of optimal therapeutic agent-carrier composites and provides a rationale for an individual, requirement-specific adaptation of a truly patient-specific reconstruction of bone defects. It represents the pinnacle of the bone defect reconstruction pyramid, founded on the basic principles and prerequisites of complete elimination of the underlying pathology, preservation, augmentation or restoration of mechanical stability of the treated bone segment and creation of a biodegradable scaffold with adequate mechanical integrity. It summarises the current body of relevant experimental and clinical research, presents clinical case examples illustrating the various aspects of the proposed concept as well as early clinical results. The author hopes that the theoretical and conceptual framework provided, will help guide future research as well as clinical decision making with respect to this particular field

Introduction. Despite decades of clinical research in artificial joints and underlying failure mechanisms, systematical and reproducible identification of reasons for complications in total knee replacements (TKR) remains difficult. Due to the complex dynamic interaction of implant system and biological situs, malfunction eventually leading to failure is multifactorial and remains not fully understood. The aim of present study was to evaluate different TKR designs and positions with regard to joint kinematics and stability under dynamic conditions by using a robot-based hardware-in-the-loop (HiL) setup. Material & methods. An industrial 6-axis robot with 6-axis force-torque sensor mounted into its end-effector moved and loaded real, commercially available TKR (bicondylar, cruciate-retaining) that were in virtual interaction with a subject-specific computational multibody model representing the anatomical situs of the knee joint while performing passive seated deep knee flexion. The subject-specific musculoskeletal multibody model (MMB) included rigid bones of the lower right extremity. Bone and cartilage geometries were reconstructed from MRT/ CT data sets preserving anatomical landmarks and allowing for the calculation of inertial properties. M. quadriceps femoris was modeled as single passive tensile force elements. Knee ligaments were modelled as elastic spring elements with a nonlinear force-displacement characteristic. Providing the flexion angle, the robot moved and loaded the mounted femoral implant component with respect to the tibial component while being in continuous interaction with the MMB. Several influencing parameters like implant position (internal/external rotation, varus/valgus alignment) and design (fixed vs. mobile bearing, tibia-insert height) as well as ligament insufficiency and joint loading on joint kinematics and stability was systematically analysed. Results. Improper implant positioning caused joint instability, which was demonstrated in higher magnitudes of the relative kinematics. Negative effects by incorrect implant positioning could be partially compensated by a mobile bearing design. However, this was accompanied with an increase in tibiofemoral contact forces. High correlation of tibia-insert height on ligament and contact force was found. After releasing ligament structures, lower tibiofemoral contact forces and joint opening during deep knee flexion were observed. Conclusion. By means of HiL simulation different clinical and technical parameters of TKR were evaluated in a systematical and reproducible fashion under physiological-like boundary conditions with regard to joint kinematics and stability. The proposed HiL test setup combining robot-based testing with MMBs can contribute to deeper understanding of knee joint function and improvement of total knee implant systems. Acknowledgement. The authors would like to thank the Deutsche Forschungsgemeinschaft (grant numbers: WO WO 452/8-1, BA 3347/3-1 and KL 2327/4-1) for supporting the project

Background and objectives. The prevention of osteoporotic fractures is a global problem. Key to this strategy is efficient identification of ‘at risk’ patients in order to address the osteoporosis pandemic, including the identification of previously sustained fractures. GP practices are now integrating touch screens as a method of registering patients' attendance for an appointment, so all ages of patients are becoming familiar with this channel of communication. Our touch screen patient administered questionnaire system intends to provide an effective solution. Methods. The Virtual Research Integration Collaboration (VRIC) framework supports the integration of basic science and clinical research. It enables the management of research lifecycles by integrating scientific approaches with everyday work practice in a virtual research environment (VRE). ‘Catch Before a Fall’ (CBaF) is a clinical research project using VRIC, using a dedicated interface, co-designed by orthopaedic surgeons and basic scientists, adapted for sensory and IT impaired subjects to capture such information, since approximately 75% of registered over 65 year olds visit their GP each year. Results. Established in test sites across the UK, Data analysis is conducted via the VRIC ‘on-line’ portal. The conclusion of the research process is followed up within that tool. Using the validated osteoporosis risk questionnaire augmented by self reporting of height loss to identify missed vertebral fractures, we calculate the patients' risk factor of developing osteoporosis and of having an osteoporosis related fracture within the next 10 years. Patients' data are collected through CBaF (figure 1) and stored in data structures matching the VRIC architecture for automatic importing via a dedicated script and offering direct clinical service provider feedback. Conclusion. Patients recollect a previous fracture including other risk factors, so we are automating the secure data collection process to improve efficiency and save resources. We should see a ‘win’ for the patient who will receive better informed care. CBaF supports the practice who will streamline their pathway for effective osteoporosis management. The insight into personalised care management is a pathfinder, demonstrating improvement of services for our community, should reduce the greater silent population of osteoporosis sufferers worldwide, addressing the acute service burden ‘at source’

Background. Assessment of functional outcome after total hip arthroplasty (THA) often involves subjective patient-reported outcome measures (PROMs) whereas analysis of gait allows more objective assessment. The aims of the study were to compare longitudinal changes of WOMAC function score and ambulatory gait analysis after THA, between patients with low and high self-reported levels of physical function. Methods. Patients undergoing primary THA (n=36; m/f=18/18; mean age=63.9; SD=9.8yrs; BMI=26.3 SD=3.5) were divided in a high and low function group, on their preoperative WOMAC function score. Patients were prospectively measured preoperatively and 3 and 12 months postoperatively. WOMAC function scores 0–100) were compared to inertial sensor based ambulatory gait analysis. Results. WOMAC function scores significantly improved in both low and high groups at 3 months postoperatively whereas gait parameters only improved in with a low pre-operative function. Between 3 and 12 months postoperatively, function scores had not significantly further improved whereas several gait parameters significantly improved in the low function group. WOMAC function scores parameters were only moderately correlated (Spearman's r = 0.33–0.51). Discussion. In routine longitudinal assessment of physical function following THA, ambulatory gait analysis can be supplementary to WOMAC. As gait significantly improved during the first 3 months and following 9 months after THA in patients with a low preoperative level of physical function only, assessment of more demanding tasks than gait may be more sensitive to capture functional improvement in patients with high preoperative function. Acknowledgements. This article presents independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research programme (RP-PG-0407-10070). The views expressed in this article are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The research team acknowledges the support of the NIHR, through the Comprehensive Clinical Research Network

Background. Total hip replacement (THR) and total knee replacement (TKR) are usually effective at relieving pain; however, 7–23% of patients experience chronic post-surgical pain. These trials aimed to investigate the effect of local anaesthetic wound infiltration on pain severity at 12 months after primary THR or TKR for osteoarthritis. Methods. Between November 2009 and February 2012, 322 patients listed for THR and 316 listed for TKR were recruited into a single-centre double-blind randomised controlled trial. Participants were randomly assigned (1:1) to receive local anaesthetic infiltration and standard care or standard care alone. Participants and outcomes assessors were masked to group allocation. The primary outcome was pain severity on the WOMAC Pain scale at 12 months post-surgery. Analyses were conducted using intention-to-treat and per-protocol approaches. Ethics approval was obtained from Southampton and South West Hampshire Research Ethics Committee. Results. In the hip trial, patients in the intervention group had significantly less pain at 12 months post-operative than patients in the standard care group (differences in means 4.74; 95% CI 0.95, 8.54; p=0.015), although the difference was not clinically significant. Post-hoc analysis found that patients in the intervention group were more likely to have none to moderate pain than severe pain at 12 months than those in the standard care group (odds ratio 10.19; 95% CI 2.10, 49.55; p=0.004). In the knee trial, there was no strong evidence that the intervention influenced pain severity at 12 months post-operative (difference in means 3.83; 95% CI −0.83, 8.49; p=0.107). Conclusions. In conclusion, routine use of infiltration could be beneficial in improving long-term pain relief for some patients after THR. Level of evidence. Randomised controlled trial. Funding. This article presents independent research funded by the National Institute for Health Research (NIHR) in England under its Programme Grants for Applied Research programme (RP-PG-0407-10070). The views expressed in this article are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The research team acknowledge the support of the NIHR, through the Comprehensive Clinical Research Network

Mesenchymal stem cells (MSCs) are self-renewing, multipotent cells that could potentially be used to repair injured cartilage in diseases. The objetive was to analyze different sources of human MSCs to find a suitable alternative source for the isolation of MSCs with high chondrogenic potential. Femoral bone marrow, adipose tissue from articular and subcutaneous locations (hip, knee, hand, ankle and elbow) were obtained from 35 patients who undewent different types of orthopedic surgery (21 women, mean age 69.83 ± 13.93 (range 38–91) years. Neoplasic and immunocompromised patients were refused. The Ethical Committee for Clinical Research of the Government of Aragón (CEICA) approved the study and all patients provided informed consent. Cells were conjugated wiith monoclonal antibodies. Cell fluorescence was evaluated by flow cytometry using a FACSCalibur flow cytometer and analysed using CellQuest software (Becton Dickinson). Chondrogenic differentiation of human MSCs from the various tissues at P1 and P3 was induced in a 30-day micropellet culture [Pittenger et al., 1999]. To evaluate the differentiation of cartilaginous pellet cultures, samples were fixed embedded in paraffin and cut into 5- υm-thick slices. The slices were treated with hematoxylin-eosin and safranin O (Sigma-Aldrich). Each sample was graded according to the Bern Histological Grading Scale [Grogan et al., 2006], which is a visual scale that incorporates three parameters indicative of cartilage quality: uniform and dark staining with safranin O, cell density or extent of matrix produced and cellular morphology (overall score 0–9). Stained sections were evaluated and graded by two different researchers under a BX41 dual viewer microscope or a Nikon TE2000-E inverted microscope with the NIS-Elements software. Statistics were calculated using bivariate analysis. Pearson's χ2 or Fisher's exact tests were used to compare the Bern Scores of various tissues. To evaluate the cell proliferation, surface marker expression and tissue type results, ANOVA or Kruskal-Wallis tests were used, depending on the data distribution. Results were considered to be significant when p was < 0.05. MSCs from all tissues analysed had a fibroblastic morphology, but their rates of proliferation varied. Subcutaneous fat derived MSCs proliferated faster than bone marrow. MSCs from Hoffa fat, hip and knee subcutaneous proliferated slower than MSCs from elbow, ankle and hand subcutaneous. Flow cytometry: most of cells lacked expression of CD31, CD34, CD36, CD117 (c-kit), CD133/1 and HLA-DR. At same time 95% of cells expressed CD13, CD44, CD59, CD73, CD90, CD105, CD151 y CD166. Fenotype showed no differences in cells from different anatomic places. Cells from hip and knee subcutaneous showed a worst differentiation to hyaline cartilage. Hoffa fat cells showed high capacity in transforming to hyaline cartilage. Cells from different anatomic places show different chondrogenic potential that has to be considered to choose the cells source

During the past century, orthopaedic surgery has made major advances in many diseases and now has satisfactory treatments available to restore function for most diseases and injuries. However, one problem area that has not advanced as rapidly is osteonecrosis. Despite many years of basic and clinical research, minimal progress has been made in the understanding and treatment of this disease. The barriers to progress and potential solutions that might lead to breakthroughs will be explored and presented. Promising therapeutic pathways will be debated

Objectives. The patient-rated wrist evaluation (PRWE) and the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire are patient-reported outcome measures (PROMs) used for clinical and research purposes. Methodological high-quality clinimetric studies that determine the measurement properties of these PROMs when used in patients with a distal radial fracture are lacking. This study aimed to validate the PRWE and DASH in Dutch patients with a displaced distal radial fracture (DRF). Methods. The intraclass correlation coefficient (ICC) was used for test-retest reliability, between PROMs completed twice with a two-week interval at six to eight months after DRF. Internal consistency was determined using Cronbach’s α for the dimensions found in the factor analysis. The measurement error was expressed by the smallest detectable change (SDC). A semi-structured interview was conducted between eight and 12 weeks after DRF to assess the content validity. Results. A total of 119 patients (mean age 58 years (. sd. 15)), 74% female, completed PROMs at a mean time of six months (. sd. 1) post-fracture. One overall meaningful dimension was found for the PRWE and the DASH. Internal consistency was excellent for both PROMs (Cronbach’s α 0.96 (PRWE) and 0.97 (DASH)). Test-retest reliability was good for the PRWE (ICC 0.87) and excellent for the DASH (ICC 0.91). The SDC was 20 for the PRWE and 14 for the DASH. No floor or ceiling effects were found. The content validity was good for both questionnaires. Conclusion. The PRWE and DASH are valid and reliable PROMs in assessing function and disability in Dutch patients with a displaced DRF. However, due to the high SDC, the PRWE and DASH are less useful for individual patients with a distal radial fracture in clinical practice. Cite this article: Y. V. Kleinlugtenbelt, R. G. Krol, M. Bhandari, J. C. Goslings, R. W. Poolman, V. A. B. Scholtes. Are the patient-rated wrist evaluation (PRWE) and the disabilities of the arm, shoulder and hand (DASH) questionnaire used in distal radial fractures truly valid and reliable? Bone Joint Res 2018;7:36–45. DOI: 10.1302/2046-3758.71.BJR-2017-0081.R1

In approximately 20 years, surgical treatment of femoro-acetabular impingement (FAI) has been widely accepted, and its indications refined. However, the current approach of the disease prevents a good understanding of its pathophysiology, and numerous uncertainties remain. Comprehending inter-individual spine-hip relations (SHRs) can further clarify the pathophysiology of impingement, and explain occasional surprising mismatch between clinical assessment and imaging or intraoperative findings. The rational is simple, the more the spino-pelvic complex is mobile (sagittal ROM) and the more the hip is protected against hip impingement but would probably become at risk of spine-hip syndrome if the spino-pelvic complex comes to degenerate. Grouping patients based on their spine-hip relation can help predict and diagnose hip impingement, and assess the relevance of physiotherapy. With the proposed new classification of FAIs, every patient can be classified in homogeneous groups of complexity of treatment. The primary aim of this paper is to raise awareness of the potential impact that the spine-hip relations have on the hip impingement disease. Two new classifications are proposed, for FAIs and SHRs that can help surgeons in their comprehension, and could be beneficial in clinical and research areas

Introduction. Subtle variations in hip morphology associate with risk of hip osteoarthritis (OA). However, validated accurate methods to quantitate hip morphology using plain radiography are lacking. We have developed a Matlab-based software-tool (SHIPs) that measures 19 OA-associated morphological-parameters of the hip using a PACS pelvic radiograph. In this study we evaluated the accuracy and repeatability of the method. Methods. Software accuracy was assessed by firstly measuring the linear ratio of 2 fixed distances and several angles against a gold-standard test radiograph, and secondly by repeated measurements on a simulated AP radiograph of the pelvis (reformatted from CT-data) that was digitally rotated about 3-axes to determine the error associated with pelvic mal-positioning. Repeatability was assessed using 30-AP Pelvic radiographs analysed twice (intra-observer), by 2 readers (inter-observer), and finally, using 2 pelvic radiographs taken in 23 subjects (n=46 radiographs) taken same day after re-positioning (short-term clinical-practice variability), and was expressed as coefficient of variation (CV%). Results. Software accuracy was 0.1% for linear measurements, and 0.2, 0.4, and 0.1 degrees, for angular measurements of 30, 60, and 90 degrees, respectively. Anterior rotation of the pelvis in the sagittal plane beyond 10 degrees produced a decrease in acetabular-tilt (-11 degrees at 20 degrees rotation) and acetabular-index-of-depth-to-width-ratio (-9.3% at 20 degrees rotation). Conversely, femoral-head-to-neck-ratio increased with both anterior and transverse rotation (+9% to +14% at 20 degrees rotation). The intra-observer CV was between 0.3-6.3%, and inter-observer CV was between 0.7-14.9% for all measurements with the exception of the measurement of horizontal-toit-externa (HTE) that had intra and inter-observer CVs of 33.4 and 29.1%, respectively. Short-term clinical repeatability was between 0.4-8.5%, with the exception of HTE that was 20.7%). Discussion. This software showed good accuracy and precision for the measurement of OA-associated hip morphological-parameters from plain radiographs of the pelvis, and may be useful in clinical research studies quantitating the relationship of these parameters to the development of hip OA. The method is, however, sensitive to large variations in pelvic positioning and use of the HTE measurement is associated with poor repeatability that is likely due to poor definition of the bony landmarks used for this parameter

The current, most popular recommendation for cup orientation, namely the Lewinnek box, dates back to the 70's, that is to say at the stone age of hip arthroplasty. Although Lewinnek's recommendations have been associated with a reduction of dislocation, some complications, either impingement or edge loading related, have not been eliminated. Early dislocations are becoming very rare and most of them probably occur in “outlier” patients with atypical pelvic/hip kinematics. Because singular problems usually need singular treatments, those patients need a more specific personalised planning of the treatment rather than a basic systematic application of Lewinnek recommendations. We aim in this review to define the potential impacts that the spine-hip relations (SHRs) have on hip arthroplasty. We highlight how recent improvements in hip implants technology and knowledge about SHRs can substantially modify the planning of a THR, and make the « Lewinnek recommendations » not relevant anymore. We propose a new classification of the SHRs with specific treatment recommendations for hip arthroplasty whose goal is to help at establishing a personalized planning of a THR. This new classification gives a rationale to optimize the short and long-term patient's outcomes by improving stability and reducing edge loading. We believe this new concept could be beneficial for clinical and research purposes

Introduction. Anteromedial osteoarthritis of the knee (anteromedial gonarthrosis-AMG) is a common form of knee arthritis. In a clinical setting, knee arthritis has always been assessed by plain radiography in conjunction with pain and function assessments. Whilst this is useful for surgical decision making in bone on bone arthritis, plain radiography gives no insight to the earlier stages of disease. In a recent study 82% of patients with painful arthritis had only partial thickness joint space loss on plain radiography. These patients are managed with various surgical treatments; injection, arthroscopy, osteotomy and arthroplasty with varying results. We believe these varying results are in part due to these patients being at different stages of disease, which will respond differently to different treatments. However radiography cannot delineate these stages. We describe the Magnetic Resonance Imaging (MRI) findings of this partial thickness AMG as a way of understanding these earlier stages of the disease. Method. 46 subjects with symptomatic partial thickness AMG underwent MRI assessment with dedicated 3 Tesla sequences. All joint compartments were scored for both partial and full thickness cartilage lesions, osteophytes and bone marrow lesions (BML). Both menisci were assessed for extrusion and tear. Anterior cruciate ligament (ACL) integrity was also assessed. Osteophytes were graded on a four point scale in the intercondylar notch and the lateral margins of the joint compartments. Scoring was performed by a consultant radiologist and clinical research fellow using a validated MRI atlas with consensus reached for disagreements. The results were tabulated and relationships of the interval data assessed with linear by linear Chi2 test and Pearson's Correlation. Results. All cases had medial femoral cartilage loss; 22% partial and 78% full thickness. 79% showed medial tibial loss, however in no cases was there medial tibial loss without femoral loss. 10 cases had lateral compartment partial thickness cartilage loss. Again, there was no tibial loss without femoral loss present. Increasing size of intercondylar notch osteophyte is associated with increasing ACL damage (p=0.001). Independent to this, increasing ACL damage is associated with lateral femoral condyle cartilage loss (p=0.002). Throughout the knee the incidence of BMLs increased with increasing cartilage loss (p=0.025). Only 13% of medial menisci were normal. As meniscal damage increases, so does the incidence of BMLs in the same compartment (p=0.03). Discussion. We describe the MRI findings of early AMG with partial thickness joint space loss. In all cases there was medial femoral loss, either with or without tibial loss. We believe the disease begins on the medial femoral condyle and progresses through the joint in stages. Later stages are associated with damage to the other structures in the knee, such as the meniscus and the ACL. Damage to the ACL is associated with increasing osteophytosis. This description is the first step in describing the stages of early AMG. Description of these stages is important since we believe the outcome of surgical intervention may be dependant on these and they may guide future therapy