Patients (2.7M in EU) with positive cancer prognosis frequently develop metastases (≈1M) in their remaining lifetime. In 30-70% cases, metastases affect the spine, reducing the strength of the affected vertebrae. Fractures occur in ≈30% patients. Clinicians must choose between leaving the patient exposed to a high fracture risk (with dramatic consequences) and operating to stabilise the spine (exposing patients to unnecessary surgeries). Currently, surgeons rely on their sole experience. This often results in to under- or over-treatment. The standard-of-care are scoring systems (e.g. Spine Instability Neoplastic Score) based on medical images, with little consideration of the spine biomechanics, and of the structure of the vertebrae involved. Such scoring systems fail to provide clear indications in ≈60% patients. The HEU-funded METASTRA project is implemented by biomechanicians, modellers, clinicians, experts in verification, validation, uncertainty quantification and certification from 15 partners across Europe. METASTRA aims to improve the stratification of patients with vertebral metastases evaluating their risk of fracture by developing dedicated reliable computational models based on Explainable Artificial Intelligence (AI) and on personalised Physiology-based biomechanical (VPH) models.Introduction
Method
Shoulder arthroplasty (SA) has been performed with different types of implants, each requiring different replacement systems. However, data on previously utilized implant types are not always available before revision surgery, which is paramount to determining the appropriate equipment and procedure. Therefore, this meta-analysis aimed to evaluate the accuracy of the AI models in classifying SA implant types. This systematic review was conducted in Pubmed, Embase, SCOPUS, and Web of Science from inception to December 2023, according to PRISMA guidelines. Peer-reviewed research evaluating the accuracy of AI-based tools on upper-limb X-rays for recognizing and categorizing SA implants was included. In addition to the overall meta-analysis, subgroup analysis was performed according to the type of AI model applied (CNN (Convolutional neural network), non-CNN, or Combination of both) and the similarity of utilized datasets between studies.Introduction
Methods
The recent introduction of Chatbots has provided an interactive medium to answer patient questions. The accuracy of responses with these programs in limb lengthening and reconstruction surgery has not previously been determined. Therefore, the purpose of this study was to assess the accuracy of answers from 3 free AI chatbot platforms to 23 common questions regarding treatment for limb lengthening and reconstruction. We generated a list of 23 common questions asked by parents before their child's limb lengthening and reconstruction surgery. Each question was posed to three different AI chatbots (ChatGPT 3.5 [OpenAI], Google Bard, and Microsoft Copilot [Bing!]) by three different answer retrievers on separate computers between November 17 and November 18, 2023. Responses were only asked one time to each chatbot by each answer retriever. Nine answers (3 answer retrievers × 3 chatbots) were randomized and platform-blinded prior to rating by three orthopedic surgeons. The 4-point rating system reported by Mika et al. was used to grade all responses.Introduction
Method
Cephalomedullary nailing (CMN) is commonly used for unstable pertrochanteric fracture. CMN is relatively safe method although various complications can potentially occur needing revision surgery. Commonly used salvage procedures such as renailing, hemiarthroplasty, conservative treatment or total hip arthroplasty (THA) are viable alternatives. The aim was to investigate the rate of THA after CMN and evaluate the performance on conversion total hip arthroplasty (cTHA) after failure of CMN. Collected data included patients from two orthopedic centers. Data consisted of all cTHAs after CMN between 2014-2020 and primary cementless THA operations between 2013-2023. Primary THA operations were treated as a control group where Oxford Hip Score (OHS) was the main compared variable.Introduction
Method
A recent study to identify clinically meaningful benchmarks for gait improvement after total hip replacement (THA) has shown that the minimum clinically important improvement (MCII) in gait speed after THA is 0.32 m/sec. Currently, it remains to be investigated what preoperative factors link to suboptimal recovery of gait function after THA. This study aimed to identify preoperative lower-limb muscle predictors for gait speed improvement after THA for hip osteoarthritis. This study enrolled 58 patients who underwent unilateral primary THA. Gait speed improvement was evaluated as the subtraction of preoperative speed from postoperative speed at 6 months after THA. Preoperative muscle composition of the glutei medius and minimus (Gmed+min) and the gluteus maximus (Gmax) was evaluated on a single axial computed tomography slice at the bottom end of the sacroiliac joint. Cross-sectional area ratio of individual composition to the total muscle was calculated.Introduction
Method
Bioactive glasses (BGs) promote osteogenic differentiation of bone progenitor cells by releasing therapeutically active ions. The well-described 45S5-BG (in mol%: SiO2 46.13; P2O5 2.60; CaO 26.91; Na2O 24.35) was supplemented with CaF2 and NaF being added to the batch at nominal 5 (F5-BG) and 25 mol% (F25-BG), respectively. While the effect on physical and chemical properties has already been characterized, the biological properties require further studies. This study investigates the effects of fluoride-supplemented BGs on the osteogenic and angiogenic properties of human bone marrow mesenchymal stromal cells (BMSCs) in vitro. BMSCs were co-cultured with melt-derived 45S5-BG, F5-BG, or F25-BG in ascending concentrations (1, 2 and 3 mg/ml). At 7 days, cell number was determined by 4,6-diamidine-2-phenylindole (DAPI) staining and cell viability by fluorescein diacetate (FDA) assay. The osteogenic potential of the BGs was evaluated through alkaline phosphatase (ALP) gene expression and activity, along with bone morphogenetic protein-2 (BMP2) gene expression and protein concentration. Vascular endothelial growth factor (VEGF) gene expression and protein concentration assessed angiogenic potential. As control, BMSCs were cultured without BG exposure.Introduction
Method
Kienböck's disease is generally defined as the collapse of the lunate bone, and this may lead to early wrist osteoarthritis. Replacing the collapsed lunate with an implant has regained renewed interest with the advancing technology of additive manufacturing, enabling the design of patient-specific implants. The aims of this project are (1) to determine how accurate it is to use the contralateral lunate shape as a template for patient-specific lunate implants, and (2) to study the effects of shape variations wrist kinematics using 4D-computed tomography (CT) scanning. A 3D statistical shape model (SSM) of the lunate was built based on bilateral CT scans of 54 individuals. Using SMM, shape variations of the lunate were identified and the intra- and inter-subject shape variations were compared by performing an intraclass correlation analysis. A radiolucent motor-controlled wrist-holder was designed to guide flexion/extension and radial/ulnar deviation of Introduction
Methods
Chondrocytes are enveloped within the pericellular matrix (PCM), a structurally intricate network primarily demarcated by the presence of collagen type VI microfibrils and perlecan, resembling a protective cocoon. The PCM serves pivotal functions in facilitating cell mechanoprotection and mechanotransduction. The progression of osteoarthritis (OA) is associated with alterations in the spatial arrangement of chondrocytes, transitioning from single strings to double strings, small clusters, and eventually coalescing into large clusters in advanced OA stages. Changes in cellular patters coincide with structural degradation of the PCM and loss of biomechanical properties. Here, we systematically studied matrix metalloproteinases (MMPs), their distribution, activity, and involvement in PCM destruction, utilizing chondrocyte arrangement as an OA biomarker. Cartilage specimens were obtained from 149 osteoarthritis (OA) patients, and selected based on the predominant spatial pattern of chondrocytes. Immunoassays were employed to screen for the presence of various MMPs (-1, -2, -3, -7, -8, -9, -10, -12, -13). Subsequently, the presence and activity of elevated MMPs were further investigated through immunolabeling, western blots and zymograms. Enzymatic assays were utilized to demonstrate the direct involvement of the targeted MMPs in the PCM destruction.Introduction
Methods
Within articular cartilage, chondrocytes reside within the pericellular matrix (PCM), collectively constituting the microanatomical entity known as a chondron. The PCM functions as a pivotal protective shield and mediator of biomechanical and biochemical cues. In the context of Osteoarthritis (OA), enzymatic degradation of the PCM is facilitated by matrix metalloproteinases (MMPs). This study delves into the functional implications of PCM structural integrity decline on the biomechanical properties of chondrons and impact on Ca2+ signaling dynamics. Chondrons isolated from human cartilage explants were incubated with activated MMP-2, -3, or -7. Structural degradation of the pericellular matrix (PCM) was assessed by immunolabelling (collagen type VI and perlecan, n=5). Biomechanical properties of chondrons (i.e. elastic modulus (EM)) were analyzed using atomic force microscopy (AFM). A fluorescent calcium indicator (Fluo-4-AM) was used to record and quantify the intracellular Ca2+ influx of chondrons subjected to single cell mechanical loading (500nN) with AFM (n=7).Introduction
Method
Cartilage comprises chondrocytes and extracellular matrix. The matrix contains different collagens, proteoglycans, and growth factors produced by chondroprogenitor cells that differentiate from proliferating to hypertrophic chondrocytes. In vitro chondrocyte growth is challenging due to differences in behaviour between 2D and 3D cultures. Our aim is to establish a murine 3D spheroid culture method using chondrocytes to study the complex interaction of cells on the chondro-osseous border during enchondral ossification. Primary chondrocytes were isolated from the knee of WT new-born mice and used to form 10,000 cell number spheroids. We used the ATDC5-chondrocyte cell line as an alternative cell type. Spheroids were observed for 7, 14, and 21 days before embedding in paraffin for slicing. Alcian blue staining was performed to identify proteoglycan positive areas to prove the formation of extracellular matrix in spheroids. Collagen type 2, and Collagen type X expression were analyzed via quantitative real-time PCR and immunohistochemistry.Introduction
Method
The biomechanical behavior of lumbar spine instrumentation is critical in understanding its efficacy and durability in clinical practice. In this study, we aim to compare the biomechanics of the lumbar spine instrumented with single-level posterior rod and screw systems employing two distinct screw designs: paddle screw versus conventional screw system. A fully cadaveric-validated 3D ligamentous model of the lumbopelvic spine served as the foundation for our comparative biomechanical analysis1. To simulate instrumentation, the intact spine was modified at the L4L5 level, employing either paddle screws or standard pedicle screws (SPS). The implants were composed of Ti-6AL-4V. Fixation at the S1 ensured consistency across loading scenarios. Loading conditions included a 400-N compressive load combined with a 10 N.m pure bending moment at the level of L1, replicating physiological motions of flexion-extension, lateral bending and axial rotation. We extracted data across various scenarios, focusing on the segmental range of motion at both implanted and adjacent levels.Introduction
Method
Transosseous flexion-distraction injuries of the spine typically require surgical intervention by stabilizing the fractured vertebra during healing with a pedicle-screw-rod constructs. As healing is taking place the load shifts from the implant back to the spine. Monitoring the load-induced deflection of the rods over time would allow quantifiable postoperative assessment of healing progress without the need for radiation exposure or frequent hospital visits. This approach, previously demonstrated to be effective in assessing fracture healing in long bones and monitoring posterolateral spinal fusion in sheep, is now being investigated for its potential in evaluating lumbar vertebra transosseous fracture healing. Six human cadaveric spines were instrumented with pedicle-screws and rods spanning L3 vertebra. The spine was loaded in Flexion-Extension (FE), Lateral-Bending (LB) and Axial-Rotation (AR) with an intact L3 vertebra (representing a healed vertebra) and after transosseous disruption, creating an AO type B1 fracture. The implant load on the rod was measured using an implantable strain sensor (Monitor) on one rod and on the contralateral rod by a strain gauge to validate the Monitor's measurements. In parallel the range of motion (ROM) was assessed.Introduction
Method
Bone and joint infection (BJI) is often characterized by severe inflammation and progressive bone destruction. Osteocytes are the most numerous and long-lived bone cell type, and therefore represent a potentially important long-term reservoir of bacterial infection. SaOS2 cells (1 ×104 cells/cm2) were grown to confluence either without differentiation, representing an osteoblast-like (OB) state (SaOS2-OB) or differentiated to an osteocyte-like stage (SaOS2-OY), using established methods. Four Introduction
Methods
Adolescent Idiopathic Scoliosis (AIS) is a three-dimensional deformity of the spine with unclear etiology. Due to the asymmetry of lateral curves, there are differences in the muscle activation between the convex and concave sides. This study utilized a comprehensive thoracic spine and ribcage musculoskeletal model to improve the biomechanical understanding of the development of AIS deformity and approach an explanation of the condition. In this study, we implemented a motion capture model using a generic rigid-body thoracic spine and ribcage model, which is kinematically determinate and controlled by spine posture obtained, for instance, from radiographs. This model is publicly accessible via a GitHub repository. We simulated gait and standing models of two AIS (averaging 15 years old, both with left lumbar curve and right thoracic curve averaging 25 degrees) and one control subject. The marker set included extra markers on the sternum and the thoracic and lumbar spine. The study was approved by the regional Research Ethics Committee (Journal number: H17034237).Introduction
Methods
Understanding the implications of decreased femoral torsion on gait and running in children and adolescents might help orthopaedic surgeons to optimize treatment decisions. To date, there is limited evidence regarding the kinematic gait deviations between children with decreased femoral torsion and typically developing children as well as regarding the implications of the same on the adaptation of walking to running. A three dimensional gait analysis study was undertaken to compare gait deviations during running and walking among patients with decreased femoral torsion (n=15) and typically developing children (n=11). Linear mixed models were utilized to establish comparisons within and between the two groups and investigate the relation between clinical examination, spatial parameters and the difference in hip rotation between running and walking.Introduction
Method
A long nail is often recommended for treatment of complex trochanteric fractures but requires longer surgical and fluoroscopy times. A possible solution could be a nail with an appropriate length which can be locked in a minimally invasive manner by the main aiming device. We aimed to determine if such a nail model* offers similar structural stability on biomechanical testing on artificial bone as a standard long nail when used to treat complex trochanteric fractures. An artificial osteoporotic bone model was chosen. As osteosynthesis material two cephalomedullary nails (CMN) were chosen: a superior locking nail (SL-Nail) which can be implanted with a singular targeting device, and a long nail (long-nail) with distal locking using free-hand technique. AO31-A2.2 fractures were simulated in a standardized manner. The insertion of the nail was strictly in accordance with the IFU and surgical manual of the manufacturer. The nail was locked dynamically proximally and statically distally. Axial height of the construct, varus collapse, and rotational deformity directly after nail insertion were simulated. A Universal Testing Machine was used. Measurements were made with a stereo-optic tracking system. Reactive movements were recorded and evaluated in all six degrees of freedom. A comparative analysis provided information about the stability and deformation of the assemblies to be compared.Introduction
Method
Osteoporosis accounts for a major risk factor of fracture-associated disability or premature death in the elderly. Enhancement of bone anabolism for slowing osteoporosis is highly demanding. Exerkine fibronectin type III domain containing 5 (FNDC5) regulates energy metabolism, inflammation, and aging. This study was aimed to investigate whether Fndc5 signaling in osteoblasts changed estrogen deficiency-mediated bone loss or microarchitecture deterioration. Female osteoblast-specific Fndc5 transgenic mice (Fndc5Tg), which overexpressed Fndc5 under the control of key osteoblast marker osteocalcin promoter, were given bilateral ovariectomy to induce estrogen deficiency-mediated osteoporosis. Bone mass, microstructures, and biomechanical properties were quantified using μCT imaging and material testing. Dynamic bone formation was traced using fluorescence calcein. Osteogenic differentiation and adipocyte formation of bone-marrow mesenchymal cells were investigated using von Kossa staining and Nile red staining, respectively. Serum osteocalcin, CTX-1 and TRAP5b levels were quantified using designated ELISA kits. Mitochondrial respiration was investigated using Seahorse Extracellular Flux Analyzer.Introduction
Method
Cartilage damage is a critical aspect of osteoarthritis progression, but effective imaging strategies remain limited. Consequently, multimodal imaging approaches are receiving increased attention. Gold nanomaterials, renowned for their therapeutic and imaging capabilities, hold promise in drug development. However, their potential for cartilage imaging is rarely discussed. Here, we developed a versatile nanomaterial, AuNC@BSA-Gd-I, for cartilage detection. By leveraging electrostatic interactions with sulfated glycosaminoglycans (sGAG), the AuNC@BSA-Gd-I can effectively penetrate damaged cartilage while accumulating minimally in healthy cartilage. This probe can be visualized or detected using CT, MRI, IVIS, and a gamma counter, providing a comprehensive approach to cartilage imaging. Additionally, we compared the imaging abilities, cartilage visualization capacities, and versatility of currently disclosed multimodal gold nanomaterials with those of AuNC@BSA-Gd-I. The physicochemical properties of nanomaterials were measured. The potential for cartilage visualization of these nanomaterials was assessed using an Introduction
Method
Hip prosthetic joint infection (PJI) is a debilitating complication following joint replacement surgery, with significant impact on patients and healthcare systems. The INFection ORthopaedic Management: Evidence into Practice (INFORM: EP) study, builds upon the 6-year INFORM programme by developing evidence-based guidelines for the identification and management of hip PJI. A panel of 21 expert stakeholders collaborated to develop best practice guidelines based on evidence from the previous INFORM research programme. An expert consensus process was used to refine guidelines using RAND/UCLA criteria. The guidelines were then implemented over a 12-month period through a Learning Collaborative of 24 healthcare professionals from 12 orthopaedic centres in England. Qualitative interviews were conducted with 17 members of the collaborative and findings used to inform the development of an implementation support toolkit. Patient and public involvement contextualised the implementation of the guidelines. The study is registered with the ISCRTN (34710385).Introduction
Methods
Diabetes mellitus type 2 (DMT2) patients often develop Achilles tendon (AS) degeneration. The ZDF rat model is often used to study DMT2. Hence, this study investigated whether tenocytes isolated from diabetic and non diabetic ZDF rats respond differentially to normo- (NG) and hyperglycemic (HG) conditions in the presence of tumor necrosis (TNF)α. AS tenocytes isolated from adult diabetic (fa/fa) or lean (fa/+) Zucker Diabetic Fatty (ZDF) rats were treated with 10 ng/mL TNFα either under NG or HG conditions (1 g/L Introduction
Method
