A number of classification systems exist for posterior malleolus fractures of the ankle. The reliability of these classification systems remains unclear. The primary aim of this study was to evaluate the reliability of three commonly utilised fracture classification systems of the posterior malleolus. 60 patients across 2 hospitals sustaining an unstable ankle fracture with a posterior malleolus fragment were identified. All patients underwent radiographs and computed tomography of their injured ankle. 9 surgeons including pre-ST3 level, ST3-8 level, and consultant level applied the Haraguchi, Rammelt, and Mason & Molloy classifications to these patients, at two timepoints, at least 4 weeks apart. The order was randomised between assessments. Inter-rater reliability was assessed using Fleiss’ kappa and 95% confidence intervals (CI). Intra-rater reliability was assessed using Cohen's Kappa and standard error (SE). Inter-rater reliability (Fleiss’ Kappa) was calculated for the Haraguchi classification as 0.522 (95% CI 0.490 – 0.553), for the Rammelt classification as 0.626 (95% CI 0.600 – 0.652), and the Mason & Molloy classification as 0.541 (95% CI 0.514 – 0.569). Intra-rater reliability (Cohen's Kappa) was 0.764 (SE 0.034) for the Haraguchi, 0.763 (SE 0.031) for the Rammelt, 0.688 (SE 0.035) for the Mason & Molloy classification. This study reports the inter-rater and intra-rater reliability for three classification systems for posterior malleolus fractures. Based on definitions by Landis & Koch (1977), inter-rater reliability was rated as ‘moderate’ for the Haraguchi and Mason & Molloy classifications; and ‘substantial’ for the Rammelt classification. Similarly, the intra-rater reliability was rated as ‘substantial’ for all three classifications

Virtual mechanical testing is a method for measuring bone healing using finite element models built from computed tomography (CT) scans. Previously, we validated a dual-zone material model for ovine fracture callus that differentiates between mineralized woven bone and soft tissue based on radiodensity. 1. The objective of this study was to translate the dual-zone material model from sheep to two important clinical scenarios: human tibial fractures in early-stage healing and late-stage nonunions. CT scans for N = 19 tibial shaft fractures were obtained prospectively at 12 weeks post-op. A second group of N = 33 tibial nonunions with CT scans were retrospectively identified. The modeling techniques were based on our published method. 2. The dual-zone material model was implemented for humans by performing a cutoff sweep for both the 12-week and nonunion groups. Virtual torsional rigidity (VTR) was calculated as VTR = ML/φ [N-m. 2. /°], where M is the moment reaction, L is the diaphyseal segment length, and φ is the angle of twist. As the soft tissue cutoff was increased, the rigidity of the clinical fractures decreased and soft tissue located within the fracture gaps produced higher strains that are not predicted without the dual zone approach. The structural integrity of the nonunions varied, ranging from very low rigidities in atrophic cases to very high rigidities in highly calcified hypertrophic cases, even with dual-zone material modeling. Human fracture calluses are heterogeneous, comprising of woven bone and interstitial soft tissue. Use of a dual-zone callus material model may be instrumental in identifying delayed unions during early healing when callus formation is minimal and/or predominantly fibrous with little mineralization. ACKNOWLEDGEMENTS:. This work was supported by the National Science Foundation (NSF) grant CMMI-1943287

Odontoid fracture of the second cervical vertebra (C2) is the most common spinal fracture type in elderly patients. However, very little is known about the biomechanical fracture mechanisms, but could play a role in fracture prevention and treatment. This study aimed to investigate the biomechanical competence and fracture characteristics of the odontoid process. A total of 42 human C2 specimens (14 female and 28 male, 71.5 ± 6.5 years) were scanned via quantitative computed tomography, divided in 6 groups (n = 7) and subjected to combined quasi-static loading at a rate of 0.1 mm/s until fracturing at inclinations of −15°, 0° and 15° in sagittal plane, and −50° and 0° in transverse plane. Bone mineral density (BMD), specimen height, fusion state of the ossification centers, stiffness, yield load, ultimate load, and fracture type according to Anderson and d'Alonzo were assessed. While the lowest values for stiffness, yield, and ultimate load were observed at load inclination of 15° in sagittal plane, no statistically significant differences could be observed among the six groups (p = 0.235, p = 0.646, and p = 0.505, respectively). Evaluating specimens with only clearly distinguishable fusion of the ossification centers (n = 26) reveled even less differences among the groups for all mechanical parameters. BMD was positively correlated with yield load (R² = 0.350, p < 0.001), and ultimate load (R² = 0.955, p < 0.001), but not with stiffness (p = 0.070). Type III was the most common fracture type (23.5%). These biomechanical outcomes indicate that load direction plays a subordinate role in traumatic fractures of the odontoid process in contrast to BMD which is a strong determinant of stiffness and strength. Thus, odontoid fractures appear to result from an interaction between load magnitude and bone quality

Cartilage diseases have a significant impact on the patient's quality of life and are a heavy burden for the healthcare system. Better understanding, early detection and proper follow-up could improve quality of life and reduce healthcare related costs. Therefore, the aim of this study was to evaluate if difference between osteoarthritic (OA) and non-osteoarthritic (non-OA) knees can be detected quantitatively on cartilage and subchondral bone levels with advanced but clinical available imaging techniques. Two OA (mean age = 88.3 years) and three non-OA (mean age = 51.0 years) human cadaveric knees were scanned two times. A high-resolution peripheral quantitative computed tomography (HR-pQCT) scan (XtremeCT, Scanco Medical AG, Switzerland) was performed to quantify the bone microstructure. A contrast-enhanced clinical CT scan (GE Revolution Evo, GE Medical Systems AG, Switzerland) was acquired with the contrast agent Visipaque 320 (60 ml) to measure cartilage. Subregions dividing the condyle in four parts were identified semi-automatically and the images were segmented using adaptive thresholding. Microstructural parameters of subchondral bone and cartilage thickness were quantified. The overall cartilage thickness was reduced by 0.27 mm between the OA and non-OA knees and the subchondral bone quality decreased accordingly (reduction of 33.52 % in BV/TV in the layer from 3 to 8 mm below the cartilage) for the femoral medial condyle. The largest differences were observed at the medial part of the femoral medial condyle both for cartilage and for bone parameters, corresponding to clinical observations. Subchondral bone microstructural parameters and cartilage thickness were quantified using in vivo available imaging and apparent differences between the OA and non-OA knees were detected. Those results may improve OA follow-up and diagnosis and could lead to a better understanding of OA. However, further in vivo studies are needed to validate these methods in clinical practice

There is currently no commercially available and clinically successful treatment for scapholunate interosseous ligament rupture, the latter leading to the development of hand-wrist osteoarthritis. We have created a novel biodegradable implant which fixed the dissociated scaphoid and lunate bones and encourages regeneration of the ruptured native ligament. To determine if scaphoid and lunate kinematics in cadaveric specimens were maintained during robotic manipulation, when comparing the native wrist with intact ligament and when the implant was installed. Ten cadaveric experiments were performed with identical conditions, except for implant geometry that was personalised to the anatomy of each cadaveric specimen. Each cadaveric arm was mounted upright in a six degrees of freedom robot using k-wires drilled through the radius, ulna, and metacarpals. Infrared markers were attached to scaphoid, lunate, radius, and 3rd metacarpal. Cadaveric specimens were robotically manipulated through flexion-extension and ulnar-radial deviation by ±40° and ±30°, respectively. The cadaveric scaphoid and lunate kinematics were examined with 1) intact native ligament, 2) severed ligament, 3) and installed implant. Digital wrist models were generated from computed tomography scans and included implant geometry, orientation, and location. Motion data were filtered and aligned relative to neutral wrist in the digital models of each specimen using anatomical landmarks. Implant insertion points in the scaphoid and lunate over time were then calculated using digital models, marker data, and inverse kinematics. Root mean squared distance was compared between severed and implant configurations, relative to intact. Preliminary data from five cadaveric specimens indicate that the implant reduced distance between scaphoid and lunate compared to severed configuration for all but three trials. Preliminary results indicate our novel implant reduced scapho-lunate gap caused by ligament transection. Future analysis will reveal if the implant can achieve wrist kinematics similar to the native intact wrist

Applications of weightbearing computed tomography (WBCT) imaging in the foot and ankle have emerged over the past decade. However, the potential diagnostic benefits are scattered across the literature, and a concise overview is currently lacking. Therefore, we aimed to systematically review all reported diagnostic applications per anatomical region in the foot and ankle. A systematic literature search was performed in the electronic databases PubMed, EMBASE, Cochrane Library, and Web of Science. Search terms consisted of “weightbearing/standing CT and ankle, hind-, mid- or forefoot”. English language studies analyzing the diagnostic applications of WBCT were included. Studies were excluded if they simulated weightbearing CT, described normal subjects, included cadaveric samples or samples were case reports. The modified Methodological Index for Non-Randomized Studies (MINORS) was applied for quality assessment. The added value was defined as the review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and registered in the Prospero database (CRD42019106980). A total of 48 studies (prospective N=8, retrospective N=36, cohort study N=1, diagnostic N=2, prognostic comparative study N=1) were found to be eligible for review. The following diagnostic applications were identified per anatomical area in the foot: ankle (osteoarthritis N=5, ligament injury N=6); hindfoot (deformity N=9); midfoot (Lisfranc injury N=2, flatfoot deformity N=13, osteoarthritis N=1); forefoot (hallux valgus N=12). The identified studies contained diagnostic applications that could not be used on plain radiographs. The mean MINORS equaled 10.1 on a total of 16 (range: 8 to 12). Diagnostic applications of weightbearing CT imaging are most frequently studied in hindfoot deformity, but other area's areas are on the rise. Post-processing of images was identified as the main added value compared to WBRX. However, the findings should be interpreted with caution as the average quality score was moderate. Therefore, future prospective studies are warranted to consolidate the role of WBCT in diagnostic and therapeutic algorithms

Stand-alone anterior lumbar interbody fusion (ALIF) provides the opportunity to avoid supplemental posterior fixation. This may reduce morbidity and complication rate, which is of special interest in patients with reduced bone mineral density (BMD). This study aims to assess immediate biomechanical stability and radiographic outcome of a stand-alone ALIF device with integrated screws in specimens of low BMD. Eight human cadaveric spines (L4-sacrum) were instrumented with SynFix-LR™ (DePuy Synthes) at L5/S1. Quantitative computed tomography was used to measure BMD of L5 in AMIRA. Threshold values proposed by the American Society of Radiology 80 and 120 mg CaHa/mL were used to differentiate between Osteoporosis, Osteopenia, and normal BMD. Segmental lordosis, anterior and posterior disc height were analysed on pre- and postoperative radiographs (Fig 1). Specimens were tested intact and following instrumentation using a flexibility protocol consisting of three loading cycles to ±7.5 Nm in flexion-extension, lateral bending, and axial rotation. The ranges of motion (ROM) of the index level were assessed using an optoelectronic system. BMD ranged 58–181mg CaHA/mL. Comparison of pre- and postoperative radiographs revealed significant increase of L5/S1 segmental lordosis (mean 14.6°, SD 5.1, p < 0.001) and anterior disc height (mean 5.8mm, SD 1.8, p < 0.001), but not posterior disc height. ROM of 6 specimens was reduced compared to the intact state. Two specimens showed destructive failure in extension. Mean decrease was most distinct in axial rotation up to 83% followed by flexion-extension. ALIF device with integrated screws at L5/S1 significantly increases segmental lordosis and anterior disc height without correlation to BMD. Primary stability in the immediate postoperative situation is mostly warranted in axial rotation. The risk of failure might be increased in extension for some patients with reduced lumbar BMD, therefore additional posterior stabilization could be considered. For any figures or tables, please contact the authors directly

Bone metastases radiographically appear as regions with high (i.e. blastic metastases) or low (i.e. lytic metastases) bone mineral density. The clinical assessment of metastatic features is based on computed tomography (CT) but it is still unclear if the actual size of the metastases can be accurately detected from the CT images and if the microstructure in regions surrounding the metastases is altered (Nägele et al., 2004, Calc Tiss Int). This study aims to evaluate (i) the capability of the CT in evaluating the metastases size and (ii) if metastases affect the bone microstructure around them. Ten spine segments consisted of a vertebra with lytic or mixed metastases and an adjacent control (radiologically healthy) were obtained through an ethically approved donation program. The specimens were scanned with a clinical CT (AquilionOne, Toshiba: slice thickness:1mm, in-plane resolution:0.45mm) to assess clinical metastatic features and a micro-CT (VivaCT80, Scanco, isotropic voxel size:0.039mm) to evaluate the detailed microstructure. The volume of the metastases was measured from both CT and micro-CT images (Palanca et al., 2021, Bone) and compared with a linear regression. The microstructural alteration around the metastases was evaluated in the volume of interest (VOI) defined in the micro-CT images as the volume of the vertebral body excluding the metastases. Three 3D microstructural parameters were calculated in the VOI (CTAn, Bruker SkyScan): Bone Volume Fraction (BV/TV), Trabecular Thickness (Tb.Th.), Trabecular Spacing (Tb.Sp.). Medians of each parameter were compared (Kruskal-Wallis, p=0.05). One specimen was excluded as it was not possible to define the size of the metastases in the CT scans. A strong correlation between the volume obtained from the CT and micro-CT images was found (R2=0.91, Slope=0.97, Intercept=2.55, RMSE=5.7%, MaxError=13.12%). The differences in BV/TV, Tb.Th. and Tb.Sp. among vertebrae with lytic and mixed metastases and control vertebrae were not statistically significant (p-value>0.6). Similar median values of BV/TV were found in vertebrae with lytic (13.2±2.4%) and mixed (12.8±9.8%) metastases, and in controls (13.0±10.1%). The median Tb.Th. was 176±18 ∓m, 179±43 ∓m and 167±91 ∓m in vertebrae with lytic and mixed metastases and control vertebrae, respectively. The median Tb. Sp. was 846±26 ∓m, 849±286 ∓m and 880±116 ∓m in vertebrae with lytic and mixed metastases and control vertebrae, respectively. In conclusion, the size of vertebral metastases can be accurately assess using CT images. The 3D microstructural parameters measured were comparable with those reported in the literature for healthy vertebrae (Nägele et al., 2004, Calc Tiss Int, Sone et al., 2004, Bone) and showed how the microstructure of the bone tissue surrounding the lesion is not altered by the metastases

Osteoarthritis (OA) is a degenerative disease that lacks regenerative treatment options. Current research focuses on mesenchymal stem cells (MSCs) and Platelet-Rich Plasma (PRP) as regenerative therapies, but extracellular vesicles (EVs) have shown to be more advantageous. This study compares the regenerative potential of human umbilical cord MSC-derived EVs (cEVs) and platelet-derived EVs (pEVs) in ex vivo and in vivo OA models. In the ex vivo study, OA conditions were induced in human cartilage explants, which were then treated either with pEVs or cEVs. Results showed a higher content of DNA and collagen in the pEVs group compared to control and cEVs groups, suggesting that pEVs could be a potential alternative to cEVs. In the in vivo study, an OA model was established in the knee joints of rats through MIA (monoiodoacetate) injection and then treated either with pEVs or cEVs. Results showed that pEVs-treated knee joints had better subchondral bone integrity and greater OA reversion, particularly in female rats, indicating that pEVs are a viable regeneration treatment for OA and outperform cEVs in terms of efficacy. Overall, the study demonstrates the potential of EVs as a regenerative treatment for OA, with pEVs showing promising results in both ex vivo and in vivo models. The use of pEVs in clinical practice could provide a faster path to translation due to the established use of platelet concentrates in therapeutics. However, further studies are needed to fully evaluate the potential of pEVs for OA treatment and to elucidate the mechanisms behind their regenerative effects. Acknowledgments: The authors thank Dr Fernando Hierro (UIB) for their technical contribution with TEM, Mª Trinidad García (UIB) for the access to radioactivity facilities, Aina Arbós (IUNICS) for her contribution in the histology staining, María Tortosa (IdISBa) for her assistance with the animal care and ADEMA School of Dentistry for the access to the cone beam computed tomography (CBCT). Funding: This research was funded by Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, co-funded by the ESF European Social Fund and the ERDF European Regional Development Fund (MS16/00124; CP16/00124), PROGRAMA JUNIOR del proyecto TALENT PLUS, construyendo SALUD, generando VALOR (JUNIOR01/18), financed by the sustainable tourism tax of the Balearic Islands; the Direcció General d'Investigació and Conselleria d'Investigació, Govern Balear (FPI/2046/2017); the Mecanisme de Recuperació i Resiliència, intended to execute research projects of «Noves polítiques públiques per a un mercat de treball dinàmic, resilient i inclusiu», collected in Pla de Recuperació, Transformació i Resiliència, financed by European Union-Next Generation EU and driven by SOIB and Conselleria de Fons Europeus, Universitat i Cultura i la Conselleria de Model Econòmic, Turisme i Treball (NG0421) and the grant SYN20/03 from IdISBa

Abstract. Objectives. This abstract provides an update on the Open Ankle Models being developed at the University of Bath. The goal of this project is to create three fully open-source finite element (FE) ankle models, including bones, ligaments, and cartilages, appropriate musculoskeletal loading and boundary conditions, and heterogeneous material property distribution for a standardised representation of ankle biomechanics and pre-clinical ankle joint analysis. Methods. A computed tomography (CT) scan data (pixel size of 0.815 mm, and slice thickness of 1 mm) was used to develop the 3D geometry of the bones (tibia, talus, calcaneus, fibula, and navicular). Each bone was given the properties of a heterogeneous elastic material based on the CT greyscale. The density values for each bone element were calculated using a linear empirical relation, ρ= 0.0405 + (0.000918) HU and then power law equations were utilised to get the Young's Modulus value for each bone element [1]. At the bone junction, a thickness of cartilage ranging from 0.5–1 mm, and was modelled as a linear material (E=10 MPa, ν=0.4 [2]). All ligament insertions and positions were represented by four parallel spring elements, and the ligament stiffness and material attributes were applied in accordance with the published literature [2]. The ankle model was subjected to static loading (balance standing position). Four noded tetrahedral elements were used for the discretization of bones and cartilages. All degrees of freedom were restricted at the proximal ends of the tibia and fibula. The ground reaction forces were applied at the underneath of the calcaneus bone. The interaction between the cartilages and bones was modelled using an augmented contact algorithm with a sliding elastic contact between each cartilage. A tied elastic contact was used between the cartilages and the bone. FEbio 2.1.0 (University of Utah, USA) was used to construct the open-source ankle model. Results. When the double-legged stance phase loading condition was taken into consideration, stress at the antero-medial tibial wall (ranged from 1 to 7 MPa) was found to be similar to the prior work [2], indicating bulk of the load transfer was through this region. The maximum principal strain was predicted at the different regions on bones around the ankle joint. The proximal surface of the talus, and tibial distal surface were shown to have the highest maximum principal strains followed by antero-medial walls of the tibia bone, at the proximal location. Conclusions. The present open 3D FE model of the ankle will assist researchers in better understanding ankle biomechanics, precisely predicting load transfer, and examining the ankle to address unmet clinical needs for this joint. The results of the current investigation are realistic in terms of load transfer and stress-strain distribution across the ankle joint and well comparable to those reported in the literature [2]. However, sensitivity and ankle instability simulations will be performed in future work to investigate the model's reliability and robustness. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Introduction and Objective. The geometry of the proximal tibia and distal femur is intimately linked with the biomechanics of the knee and it is to be considered in total knee arthroplasty (TKA) component positioning. The aim of the present study was to evaluate the proximal tibial torsion in relation to the flexion-extension axis of the knee in healthy and pathological cohort affected by knee osteoarthritis (OA). Materials and Methods. We retrospectively analyzed computed tomography scans of OA knee of 59 patients prior to TKA and non-arthritic knee of 39 patients as control. Posterior condylar angle (PCA), femoral tibial torsion (TEAs-PTC and TEAs-PTT), proximal tibial torsion (PTC-PTT and PCAx-PTC) and distance between tibial tuberosity and the trochlear groove (TT-TG) were measured. Results. No differences were found for gender, age, TG-TT and PCAn angles. Statistically significant differences were found for all the other angles considered. Significant relation was found between Tibial Torsion and TEA-PTT angles, between PCAx-PTC and TEA-PTC, between TEA-PTT and TEA-PTC and between PCAx-PTC and TEA-PTT. All measures, except TG-TT and PCAn angles, showed high validity (AUC > 75%) in detecting OA, with TEA-PTT displaying the highest validity with an AUC of 94.38%. Conclusions. This is the first study to find significant differences in terms of proximal tibia geometry and anatomy between non arthritic and OA knees. It is conceivable that such anatomy could be implicated in the development of OA. Based on our data, the TEAs is a valid reference for correct positioning of tibial component in TKA. Indeed, setting the tibial component parallel to TEAs makes the prosthetic knee more similar to the native non-arthritic knee

Abstract. Objectives. High tibial osteotomy for knee realignment is effective at relieving symptoms of knee osteoarthritis but the operation is surgically challenging. A new personalised treatment with simpler surgery using pre-operatively planned measurements from computed tomography (CT) imaging and 3D-printed implants and instrumentation has been designed and is undergoing clinical trial. The aim of this study was to evaluate the early clinical results of a preliminary pilot study evaluating the safety of this new personalised treatment. Methods. The single-centre prospective clinical trial is ongoing (IRCCS Istituto Ortopedico Rizzoli; IRB-0013355; ClinicalTrials.gov NCT04574570), with recruitment completed and all patients having received the novel custom surgical treatment. To preserve the completeness of the trial reporting, only surgical aspects were evaluated in the present study. Specifically, the length of the implanted osteosynthesis screws was considered, being determined pre-operatively eliminating intraoperative measurements, and examined post-operatively (n=7) using CT image processing (ScanIP, Synopsys) and surface distance mapping. The surgical time, patient discharge date and ease of wound closure were recorded for all patients (n=25). Results. Over the study period the average surgical time (skin incision to suture) reduced from 54 to 31 minutes (range: 17–62, n=25). It was noted that wound closure was easier than the conventional surgery due to the lower profile of the implant. Over seventy percent of patients were discharged day 2 post-op. The position, orientation and length of all screws matched the pre-operative configuration to within approximately 1mm. Conclusions. The early trial results are promising from a clinical perspective. It was evident that surgical time was saved because no intraoperative screw length measurements were required, and the use of custom instrumentation significantly reduced the surgical inventory. The reduced invasiveness and ease of surgery may contribute to faster patient recovery compared to conventional techniques. The full trial results will be reported later this year. Declaration of Interest. (a) fully declare any financial or other potential conflict of interest

Abstract. Introduction. Osteoarthritis (OA) is one of the lead causes of pain and disability in adults. Bone marrow lesions (BMLs) are one feature of subchondral bone involvement in OA. MRI images suggest changes in tissue content and properties in the affected regions however, it is not known if this alters the mechanical behavior of the bone, which could in turn affect OA progression. The aim of this study was to characterize the mechanical properties of BMLs, using a combined experimental and computational approach. Methods. Six human cadaveric patellae from donors aged 56–76 were used in this study; all exhibited BML regions under MRI. Bone plugs were taken from non-BML (n = 6) and BML (n = 7) regions within the patellae, with guidance from the MRI. The plugs were imaged at 82µm resolution using micro computed tomography (µCT) and tested under uniaxial compression. Finite element (FE) models were created for each plug from the µCT scans and morphological properties such as bone volume fraction (BV/TV) were also determined. The relationship between bone volume fraction and apparent modulus was investigated for both sample groups. Results. The BV/TV range was similar for the BML and non-BML groups (0.25–0.46 and 0.18–0.44) From the experimental tests, a moderate positive correlation was found between BV/TV and apparent modulus in the no BML group (r= 0.57) while no correlation was found in the BML group (r = −0.02). From the FE results, a different relationship between BV/TV and element elastic modulus was found for the BML and non-BML groups. Conclusions. The results of this study show that in regions of bone containing BMLs, bone volume fraction does not predict overall apparent modulus and has different relationship to local modulus, suggesting the BML associated tissue structural changes affect mechanical behavior. Funders: EPSRC

Abstract. Objectives. Current therapies for osteoporosis are limited to generalised antiresorptive or anabolic interventions, which do not target specific regions to improve skeletal health. Moreover, the adaptive changes of separate and combined pharmacological and biomechanical treatments in the ovariectomised (OVX) mouse tibia has not been studied yet. Therefore, this study combines micro- computed tomography (micro-CT) imaging and computational modelling to evaluate the efficacies of treatments in reducing bone loss. Methodology. In vivo micro-CT (10.4µm/voxel) images of the right tibiae of N=18 female OVX C57BL/6 mice were acquired at weeks 14, 16, 18, 20 and 22 of age for 3 groups: mechanical loading (ML), parathyroid hormone (PTH) or combined therapies (PTHML). All mice received either injection of PTH (100μg/kg/day, 5days/week) or vehicle from week 18. The right tibiae were mechanically loaded in vivo at week 19 and 21 with a 12N peak load, 40 cycles/day and 3 days/week. Bone adaptation was quantified through spatial changes in bone mineral density (BMD) and strain distribution was obtained from micro-CT-based finite element models. Results. Densitometric parameters improved for all treatment between week 18–20 (10–21%), with the strongest benefits due to loading in the proximal regions (16–35%). At week 22, PTHML treatment induced 23–76% higher bone apposition in the proximal tibia than either monotherapy. Compared to the OVX control, all treatments reduced periosteal resorption at weeks 18–20 and 20–22 (20–87%). However, resorption in weeks 20–22 were 29–55% higher than weeks 18–20, increasing the strain in the proximal tibia. Synergistic effects of PTH and ML were observed on the periosteal surface of proximal tibia, but additive effects were seen predominately on the distal and lateral tibia. Conclusions. ML had a more dominant effect in improving bone health. PTH enhances bone's osteogenic response to ML additively and synergistically in a site- and time-dependent manner

Worldwide, osteoporosis, causes more than 8.9 million fractures annually, resulting in an osteoporotic fracture every 3 seconds, where 1 in every 3 women and 1 in every 5 men aged over 50 will experience osteoporotic fractures at least once in their lifetime. Vertebral fractures, estimated at 1.4 million/year are among the most common fractures, posing enormous health and socioeconomic challenges to the individual and society at large. Considering that the great majority of individuals at high risk (up to 80%), who have already had at least one osteoporotic fracture, are neither identified nor treated, prediction of the risk factors for vertebral fractures can be of great value for prevention/early diagnosis. Recent studies show that finite element analysis of computed tomography (CT) scans provides noninvasive means to assess fracture risk and has the potential to be clinically implemented upon proper validation. The objective of this study was to develop a voxel-based finite element model using quantitative computed tomography (QCT) images in conjunction with in-vitro experiments to evaluate the strength of the vertebral bodies and predict the fracture risk criteria. A total of 10 vertebrae were dissected from juvenile sheep lumbar spines. The attached soft tissues and posterior elements and facet joints were completely removed, and the upper and lower vertebral bodies were polished using glass paper to provide smooth surfaces. The specimens were wrapped in phosphate buffer saline (PBS) soaked gauze, sealed in plastic bags, and stored in a refrigerator at −22°C. QCT scans of the specimens were captured using a bone density calibration phantom (QRM Co., Moehrendorf, Germany) with three 18 mm cylindrical inserts, providing 0, 100 and 200 mg HA/ccm, respectively. All the specimens, preserved hydrated in PBS solution, were mechanically tested at room temperature using a mechanical testing apparatus (Zwick/Roell, Ulm-Germany). The QCT images were then used to reconstruct the voxel-based FE model employing a custom-developed heterogeneous material mapping code. Five different equations for the correlation of the density and the elastic modulus were used to validate the efficiency of the FE model as compared to the in-vitro experiments. The results of the voxel-based FE models matched well with the in-vitro experiments, with an average error of 11.38 (±4.09)% based on the power law equation. A failure criterion was embedded in the FE models and the initiation of fracture was successfully predicted for all specimens. Further, typical kyphoplasty treatment was simulated in the 5 models to evaluate the application of the validated algorithm in the estimation of the failure patterns. Our novel voxel-based FE model can be used in future studies to predict the outcome of different types of therapeutic modalities/surgeries and estimate fracture risk including postoperative fractures

This study was designed to test the hypothesis that the sensory innervation of bone might play an important role in sensing and responding to low-intensity pulsed ultrasound and explain its effect in promoting fracture healing. In 112 rats a standardised mid-shaft tibial fracture was created, supported with an intramedullary needle and divided into four groups of 28. These either had a sciatic neurectomy or a patellar tendon resection as control, and received the ultrasound or not as a sham treatment. Fracture union, callus mineralisation and remodelling were assessed using plain radiography, peripheral quantitative computed tomography and histomorphology. Daily ultrasound treatment significantly increased the rate of union and the volumetric bone mineral density in the fracture callus in the neurally intact rats (p = 0.025), but this stimulating effect was absent in the rats with sciatic neurectomy. Histomorphology demonstrated faster maturation of the callus in the group treated with ultrasound when compared with the control group. The results supported the hypothesis that intact innervation plays an important role in allowing low-intensity pulsed ultrasound to promote fracture healing

The Hospital (Trust) guidelines generally recommend 40mg of Low molecular weight heparin (LMWH) twice daily (BD) for all patients over 100kg for those undergoing total hip (THR) and knee replacements (TKR) respectively. British National Formulary (BNF) recommends 40mg of LMWH once daily (OD) for all patients regardless of their overall weight or body mass index (BMI). We evaluated the outcome of prophylactic LMWH dosage for patients undergoing THR and TKR by monitoring surgery related venous-thromboembolic events up to a minimum of three months after surgery. A retrospective audit was carried out after obtaining institutional approval and all consecutive elective patients weighing over 100kg and undergoing THR and TKR were included. All patients were followed up for a minimum of 3 months after their operation to investigate the dose of prophylactic LMWH received, and whether they had developed any venous thromboembolic events (VTE) post operatively. This was done using a combination of electronic notes, drug charts and deep venous thrombosis (DVT) or computed tomography pulmonary angiogram (CTPA) reports on the hospital/trust database. A total of 53 patients underwent elective THR (18) and TKR (35) between the period of March 2017 and September 2017. Forty-four patients received 40 mg OD and 9 patients had 40 mg BD. None of the patients developed a confirmed DVT or pulmonary embolism in the 3 months following surgery regardless of the dose received. We demonstrate that there is no clinical benefit in having patients over 100kg on twice daily LMWH with the aim of preventing post-op thromboembolic complications. This conclusion is in line with the BNF recommendations for VTE prophylaxis

Abstract. Objectives. Prediction of bone adaptation in response to mechanical loading is useful in the clinical management of osteoporosis. However, few studies have investigated the effect of repeated mechanical loading in the mouse tibia. Therefore, this study uses a combined experimental and computational approach to evaluate the effect of mechanical loading on bone adaptation in a mouse model of osteoporosis. Methods. Six female C57BL/6 mice were ovariectomised (OVX) at week 14 and scanned using in vivo micro computed tomography (10.4µm/voxel) at week 14, 16, 18, 20 and 22. The right tibiae were mechanically loaded in vivo at week 19 and 21 with a 12N peak load, 40 cycles/day, 3 days/week. Linear isotropic homogeneous finite element (microFE) models were created from the tissue mineral density calibrated microCT images. Changes in bone adaptation, densitometric and spatial analyses were measured by comparing the longitudinal images after image registration. Results. Mechanical loading increased periosteal apposition between weeks 18–20, which reduced slightly between weeks 20–22. Periosteal resorption reduced between weeks 18–20. At weeks 20–22, it remained lower than before treatment, but was up to 70% higher than after the first week of loading. Average SED increased due to OVX before decreasing due to mechanical loading. The highest increase in SED was at the proximal tibia between weeks 14 to 16 (102%), whereas the highest reduction (40%) occurred after the second week of loading in the proximal tibia. Conclusions. The decrease/increase in bone apposition/resorption between weeks 20–22, despite the similar strain distributions between weeks 18–20 and 20–22, suggests that the first application of mechanical loading had a greater effect on reversing the adverse effects of the disease than the second. This imply that a systematic increase in peak load or loading rate may be required to achieve a similar bone adaptation rate with time. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Abstract. Objectives. This study aids the control of remodelling and strain response in bone; providing a quantified map of apparent modulus and strength in the proximal tibia in 3 anatomically relevant directions in terms of apparent density and factor groups. Methods. 7 fresh-frozen cadaveric specimens were quantified computed tomography (qCT) scanned, segmented and packed with 3 layers of 9mm side length cubic cores aligned to anatomical mechanical axes. Cores were removed with printed custom cutting and their densities found from qCT. Cores (n = 195) were quasi-statically compression tested. Modulus was estimated from a load cycle hysteresis loop, between 40% and 20% of yield stress. Sequential testing order in 3 orthogonal directions was randomised. Group differences were identified via an analysis of variance for the factors density, age, gender, testing order, subchondral depth, condyle and sub-meniscal location. Regression models were fit for significant factor sub-groups, predicting properties from density. Results. Axial modulus was 1.5 times greater than the two transverse directions (p<0.001), between which no difference was found. For all test directions, differences were quantified for density and modulus across all subchondral depths (p<0.001). 60% of transverse modulus variation was explained by density within subgroups for each subchondral depth. Medial axial modulus was 1.3 times greater than the lateral side (p = 0.011). Lateral axial modulus halved over a 25mm depth whilst remaining constant for the medial side. Density explained 75% of variation when grouped by subchondral depth and condyle. Yield strength was well predicted across all test directions, with density explaining 81% of axial strength variation and no differences over subchondral depth. Conclusions. The quantification of bone multiaxial modulus based on condyle and subchondral depth has been shown for the first time in a clinically viable protocol using conventional CT. Accounting for spatial variation improves upon literature property prediction models. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Novel biomaterials are being developed and studied, intended to be applied as bone graft substitute materials. Typically, these materials are being tested in in vitro setups, where among others their cytotoxicity and alkaline phosphatase activity (as a marker for osteoblastic differentiation) are being evaluated. However, it has been reported that in vitro tests correlate poorly with in vivo results and therefore many promising biomaterials may not reach the clinic as a bone graft substitute product. One of the reasons for the poor correlation, may be the minimal complexity of the in vitro tests, as compared to the in vivo environment. Ex vivo models, mimicking the natural tissue environment whilst maintaining control of culture parameters, may be a promising alternative to assess biomaterials for bone formation. Assess the possibility of an ex vivo culture platform to test biomaterials on their potential to stimulate new bone formation. Osteochondral plugs (cylinders n=10, Ø 10 mm, height 15 mm) were drilled from fresh porcine knees, from the slaughterhouse. A bone defect (Ø 6 mm) was created and which was filled with a biomaterial graft (S53P4 bioactive glass (n=3); collagen sponges loaded with BMP-2 (n=3, as positive control)) or kept empty (n=4). The explants were cultured in custom-made two-chamber bioreactors for six weeks (LifeTec Group BV). Cartilage and bone were physically separated, similar to the in vivo situation, by a sealing ring. The two tissues were cultured in separate compartments, allowing for specific culture medium for each tissue. Medium was changed every 2–3 days and weekly micro computed tomography (µCT) images were obtained to longitudinally monitor the formation of new bone. An MTT assay was performed on half of the samples after six weeks of culture. The other samples were fixed for histology, to determine which cells were present after six weeks. The MTT metabolic assay showed that a number of cells in the bone were viable after six weeks. The further away from the border, the fewer living cells were observed. The cells in the cartilage also survived. No significant bone formation was observed with µCT in either of groups, even though abundant bone formation was expected in the BMP-2 group. Explanations of the negative results of the positive group might be that too few viable cells remain after six weeks, or that the cells that are still present are not able to form bone. No significant bone formation was observed in the bone defects in osteochondral explants that were cultured with, or without, biomaterials for six weeks. However, the platform showed that it is capable to successfully culture osteochondral explants for six weeks. Histology needs to be performed to evaluate which cells were present at the end of the culture and this will be compared to the cells present directly after drilling the explants