Abstract. Objectives. Neonatal motor development transitions from initially spontaneous to later increasingly complex voluntary movements. A delay in transitioning may indicate cerebral palsy (CP). The general movement optimality score (GMOS) evaluates infant movement variety and is used to diagnose CP, but depends on specialized physiotherapists, is time-consuming, and is subject to inter-observer differences. We hypothesised that an objective means of quantifying movements in young infants using motion tracking data may provide a more consistent early diagnosis of CP and reduce the burden on healthcare systems. This study assessed lower limb kinematic and muscle force variances during neonatal infant kicking movements, and determined that movement variances were associated with GMOS scores, and therefore CP. Methods. Electromagnetic motion tracking data (Polhemus) was collected from neonatal infants performing kicking movements (min 50° knee extension-flexion, <2 seconds) in the supine position over 7 minutes. Tracking data from lower limb anatomical landmarks (midfoot inferior, lateral malleolus, lateral knee epicondyle, ASIS, sacrum) were applied to subject-scaled musculoskeletal models (Gait2354_simbody, OpenSim). Inverse kinematics and static optimisation were applied to estimate lower limb kinematics (knee flexion, hip flexion, hip adduction) and muscle forces (quadriceps femoris, biceps femoris) for isolated kicks. Functional principal component analysis (fPCA) was carried out to reduce kicking kinematic and muscle force waveforms to PC scores capturing ‘modes’ of variance. GMOS scores (lower scores = reduced variety of movement) were collected in parallel with motion capture by a trained operator and specialised physiotherapist. Pearson's correlations were performed to assess if the standard deviation (SD) of kinematic and muscle force waveform PC scores, representing the intra-subject variance of movement or muscle activation, were associated with the GMOS scores. Results. The study compared GMOS scores, kinematics, and muscle force variances from a total of 26 infants with a mean corrected gestational age of 39.7 (±3.34) weeks and GMOS scores between 21 and 40. There was a significant association between the SD of the PC scores for knee flexion and the GMOS scores (PC1: R = 0.59, p = 0.002; PC2: R = 0.49, p = 0.011; PC3: R = 0.56, p = 0.003). The three PCs captured variances of the overall flexion magnitude (66% variance explained), early-to-late kick knee extension (20%), and continual to biphasic kicking (6%). For hip flexion, only the SD of PC1 correlated with GMOS scores (PC1: R = 0.52, p = 0.0068), which captured the variance of the overall flexion magnitude (81%). For the biceps femoris, the SD of PC1 and PC3 associated with GMOS scores (PC1: R = 0.50, p = 0.002; PC3: R = 0.45, p = 0.03), which captured the variance of the overall bicep force magnitude (79%) and early-to-late kick bicep activation (8%). Conclusions. Infants with reduced motor development as scored in the GMOS displayed reduced variances of knee and hip flexion and biceps femoris activation across kicking cycles. These findings suggest that combining objectively measured movement variances with existing classification methods could facilitate the development of more consistent and accurate diagnostic tools for early detection of CP. 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

The anatomy of the femur shows a high inter-patient variability, making it challenging to design standard prosthetic devices that perfectly adapt to the geometry of each individual. Over the past decade, Statistical Shape Models (SSMs) have been largely used as a tool to represent an average shape of many three-dimensional objects, as well as their variation in shape. However, no studies of the morphology of the residual femoral canal in patients who have undergone an amputation have been performed. The aim of this study was therefore to evaluate the main modes of variation in the shape of the canal, therefore simulating and analysing different levels of osteotomy. To assess the variability of the femoral canal, 72 CT-scans of the lower limb were selected. A segmentation was performed to isolate the region of interest (ROI), ranging from the lesser tip of the trochanter to the 75% of the length of the femur. The canals were then sized to scale, aligned, and 16 osteotomy levels were simulated, starting from a section corresponding to 25% of the ROI and up to the distal section. For each level, the main modes of variations of the femoral canal were identified through Principal Component Analysis (PCA), thus generating the mean geometry and the extreme shapes (±2 stdev) of the principal modes of variation. The shape of the canals obtained from these geometries was reconstructed every 10 mm, best- fitted with an ellipse and the following parameters were evaluated: i) ellipticity, by looking at the difference between axismax and axismin; ii) curvature of the canal, calculating the arc of circumference passing through the shapes’ centroids; iii) conicity, by looking at the maximum/minimum diameter; iv) mean diameter. To understand the association between the main modes and the shape variance, these parameters were compared, for each level of osteotomy, between the two extreme geometries of the main modes of variation. Results from PCA pointed out that the first three PCs explained more than the 87% of the total variance, for each level of simulated osteotomy. By analysing the extreme geometries for a distal osteotomy (e.g. 80% of the length of the canal), the first PC was associated to a combination of ROC (var%=41%), conicity (var%=28%) and ellipticity (var%=7%). PC2 was still associated with the ROC (var%=16%), while PC3 turned out to be associated with the diameter (var%=38%). Through the SSM presented in this study, a quantitatively evaluation of the deformation of the intramedullary canal has been made possible. By analysing the extreme geometries obtained from the first three modes of variance, it is clear that the first three PCs accounted for the variations in terms of curvature, conicity, ellipticity and diameter of the femoral canal with a different weight, depending on the level of osteotomy. Through this work, it was also possible to parametrize these variations according to the level of excision. The results given for the segment corresponding to the 80% of the length of the canal showed that, at that specified level, the ROC, conicity and ellipticity were the anatomical parameters with the highest range of variability, followed by the variation in terms of diameter. Therefore, the analysis carried out can provide information about the relevance of these parameters depending on the level of osteotomy suffered by the amputee. In this way, optimal strategies for the design and/or customization of osteo-integrated stems can be offered depending on the patient's residual limb

Abstract. OBJECTIVES. Dual mobility (DM) total hip replacements (THRs) were introduced to reduce the risk of hip dislocation in at-risk patients. DM THRs have shown good overall survivorship and low rates of dislocation, however, the mechanisms which describe how these bearings function in-vivo are not fully understood. This is partly due to a lack of suitable characterisation methodologies which are appropriate for the novel geometry and function of DM polyethylene liners, whereby both surfaces are subject to articulation. This study aimed to develop a novel semi-quantitative geometric characterisation methodology to assess the wear/deformation of DM liners. METHODS. Three-dimensional coordinate data of the internal and external surfaces of 14 in-vitro tested DM liners was collected using a Legex 322 coordinate measuring machine. Data was input into a custom Matlab script, whereby the unworn reference geometry was determined using a sphere fitting algorithm. The analysis method determined the geometric variance of each point from the reference surface and produced surface deviation heatmaps to visualise areas of wear/deformation. Repeatability of the method was also assessed. RESULTS. Semi-quantitative analysis of the surface deviation heatmaps revealed circumferential damage patterns similar to those reported in the literature. Additionally, the location of the damaged regions corresponded between the internal and external surfaces. Comparing five repeat measurements of the same liner, the maximum geometric variance of each surface varied by 1 µm (standard deviation) suggesting a high repeatability of the method. CONCLUSIONS. This study presents an effective and highly repeatable characterisation methodology to semi-quantitatively assess the wear/deformation of in-vitro tested DM liners. This method is suitable for the analysis of retrieved DM liners whereby no pre-service information is available, which may provide information about the complex in-vivo kinematics and mechanical failure mechanisms of these bearings

Abstract. Objectives. Principal Component Analysis (PCA) is a useful method for analysing human motion data. The objective of this study was to use PCA to quantify the biggest variance in knee kinematics waveforms between a Non-Pathological (NP) group and individuals awaiting High Tibial Osteotomy (HTO) surgery. Methods. Thirty knees (29 participants) who were scheduled for HTO surgery were included in this study. Twenty-eight NP volunteers were recruited into the study. Human motion analysis was performed during level gait using a modified Cleveland marker set. Subjects walked at their self-selected speed for a minimum of 6 successful trials. Knee kinematics were calculated within Visual3D (C-Motion). The first three Principal Components (PCs) of each input variable were selected. Single-component reconstruction was performed alongside representative extremes of each PC to aid interpretation of the biomechanical feature reconstructed by each component. Results. Pre-operatively patient demographics included (age: 50.70 (8.71) years; height: 1.75 (.11) m; body mass: 90.57 (20.17) kg; mTFA: 7.75 (3.72) degrees varus; gait speed: 1.06 (0.23) m/s). The HTO cohort was significantly older and had a higher mass than the NP control participants. For knee kinematics the first three PCs explained 88%, 95% and 89% of the sagittal, frontal, and transverse planes, respectively. The main variances can be explained by sagittal plane magnitude differences, peak swing is associated with toe-off, a reduced knee flexion angle is associated with a longer time spent in stance, pre-HTO remain adducted during stance and pre-HTO patients remain more externally rotated during stance and latter part of swing. Conclusions. This study has introduced PCA in trying to better understand the biomechanical differences between a control group and a cohort with medial knee osteoarthritis varus deformity awaiting HTO. Further analysis will be undertaken using PCA comparing pre- and post-surgery which will be of importance in clinical decision making

This study compared the pullout forces of the initial implantation and the “cement-in-cement” revision technique for short and standard-length (125 mm vs. 150 mm) Exeter. ®. V40 femoral stems used in total hip arthroplasty (THA). The idea that the pullout force for a double taper slip stem is relative to the force applied to the femur and that “cement-in-cement” revision provides the same reproduction of force. A total sample size of 15 femoral stems were tested (Short, n = 6 and Standard, n = 9). 3D printed fixtures for repeatable sample preparation were used to minimize variance during testing. To promote stem subsidence and to simulate an in vivo environment, the samples were placed in an incubator at 37°C at 100% humidity and experienced a constant compressive loading of 1335 N for 14 days. The samples underwent a displacement-controlled pullout test. After the initial pullout test, “cement-in-cement” revision will be performed and tested similar to the initial implantation to observe the efficacy of the revision technique. To compare the pullout forces between the two groups, a Kruskal-Wallis test using a significance level of 0.05 was conducted. The mean maximum pullout force for the short and standard-length femoral stems were 3939 ± 1178 N and 5078 ± 1168 N, respectively. The Kruskal-Wallis test determined no statistically significant difference between the two groups for the initial implantation (p = 0.13). The “cement-in-cement” revision pullout force will be conducted in future testing. This study demonstrated the potential use of short stem designs for THA as it provides similar levels of fixation as the standard-length femoral stem. The potential benefits for using a short stem design would be providing similar load transfer to the proximal femur, preserving proximal metaphyseal femoral bone in primary replacement, and reducing the invasiveness during revision

Gait measurements can vary due to various intrinsic and extrinsic factors, and this variability becomes more pronounced using inertial sensors in a free-living environment. Therefore, identifying and quantifying the sources of variability is essential to ensure measurement reliability and maintain data quality. This study aimed to determine the variability of daily accelerations recorded by an inertial sensor in a group of healthy individuals. Ten participants, four males and six females, with a mean age of 50 years (range: 29–61) and BMI of 26.9 kg/m. 2. (range: 21.4–36.8), were included. A single accelerometer continuously recorded lower limb accelerations over two weeks. We extracted and analyzed the accelerations of three consecutive strides within walking bouts if the time difference between the bouts was more than two hours. Multivariate mixed-effects modeling was performed on both the discretized acceleration waveforms at 101 points (0–100) and the harmonics of the signals in the frequency domain to determine the variance components for different subjects, days, bouts, and steps as the random effect variables. Intraclass correlation coefficients (ICCs) were calculated for between-day, between-bout, and between-step comparisons. The results showed that the ICCs for the between-day, between-bout, and between-step comparisons were 0.73, 0.82, 0.99 for the vertical axis; 0.64, 0.75, 0.99 for the anteroposterior axis; and 0.55, 0.96, 0.97 for the mediolateral axis. For the signal harmonics, the respective ICCs were 0.98, 0.98, 0.99 for the vertical axis; 0.54, 0.93, 0.98 for the anteroposterior axis; and 0.69, 0.78, 0.95 for the mediolateral axis. Overall, this study demonstrated that accelerations recorded continuously for multiple days in a free-living environment exhibit high variability, mainly between days, and some variability arising from differences between walking bouts during different times within days. However, reliable and repeatable gait measurements can be obtained by identifying and quantifying the sources of variability

Tibial shaft fractures require surgical stabilization preferably by intramedullary nailing. However, patients often report functional limitations even years after the injury. This study investigates the influence of the surgical approach (transpatellar vs. parapatellar) on gait performance and patient reported outcome six months after surgery. Twenty-two patients with tibial shaft fractures treated by intramedullary nailing through a transpatellar approach (TP: n=15, age 41±15, BMI 24±3) or a parapatellar approach (PP: n=7, age 34±15, BMI 23±2) and healthy, matched controls (n=22, age 39±13, BMI 24±2) were assessed by instrumented motion analysis six months after intramedullary nailing. Short musculoskeletal function assessment questionnaire (SMFA) as well as kinematic and kinetic gait data were collected during level walking. Comparisons among approach methods and control group were performed by analysis of variance and Mann-Whitney test. Six months after surgery, knee kinetics in both groups differed significantly compared to controls (p <.04). The approach method affected gait speed (TP: p = .002; PP: p = .08) and knee kinematics in the early stance phase (TP: p = .011; PP: p = .082), with the parapatellar approach showing a more favorable outcome. However, the difference between patient groups was not significant for any of the assessed gait parameters (p > .2). Also, no differences could be found in the bother index (BI) or function index (FI) of SMFA between surgical approach methods (BI: TP: Mdn = 7.2, PP: Mdn = 9.4; FI: TP: Mdn = 10.3, PP: Mdn = 9.2, p > .7). Our study demonstrates, that six months after surgery for tibial shaft fractures functional limitations remain. These limitations appear not to be different for either a trans- or a parapatellar approach for the insertion of the intramedullary nail. The findings of this study are limited by the relatively short follow up time period and small number of patients. Future studies should investigate the source of the functional limitation after intramedullary nailing of tibial shaft fractures

Biomedical imaging is essential in the diagnosis of musculoskeletal pathologies and postoperative evaluations. In this context, Cone-Beam technology-based Computed Tomography (CBCT) can make important contributions in orthopaedics. CBCT relies on divergent cone X-rays on the whole field of view and a rotating source-detector element to generate three-dimensional (3D) volumes. For the lower limb, they can allow acquisitions under real loading conditions, taking the name Weight-Bearing CBCT (WB-CBCT). Assessments at the foot, ankle, knee, and at the upper limb, can benefit from it in situations where loading is critical to understanding the interactions between anatomical structures. The present study reports 4 recent applications using WB-CBCT in an orthopaedic centre. Patient scans by WB-CBCT were collected for examinations of the lower limb in monopodal standing position. An initial volumetric reconstruction is obtained, and the DICOM file is segmented to obtain 3D bone models. A reference frame is then established on each bone model by virtual landmark palpation or principal component analysis. Based on the variance of the model point cloud, this analysis automatically calculates longitudinal, vertical and mid-lateral axes. Using the defined references, absolute or relative orientations of the bones can be calculated in 3D. In 19 diabetic patients, 3D reconstructed bone models of the foot under load were combined with plantar pressure measurement. Significant correlations were found between bone orientations, heights above the ground, and pressure values, revealing anatomic areas potentially prone to ulceration. In 4 patients enrolled for total ankle arthroplasty, preoperative 3D reconstructions were used for prosthetic design customization, allowing prosthesis-bone mismatch to be minimized. 20 knees with femoral ligament reconstruction were acquired with WB-CBCT and standard CT (in unloading). Bone reconstructions were used to assess congruency angle and patellar tilt and TT-TG. The values obtained show differences between loading and unloading, questioning what has been observed so far. Twenty flat feet were scanned before and after Grice surgery. WB-CBCT allowed characterization of the deformity and bone realignment after surgery, demonstrating the complexity and multi-planarity of the pathology. These applications show how a more complete and realistic 3D geometric characterization of the of lower limb bones is now possible in loading using WB-CBCT. This allows for more accurate diagnoses, surgical planning, and postoperative evaluations, even by automatisms. Other applications are in progress

Osteoarthritis (OA) is a common cause of chronic pain. Subchondral bone is highly innervated, and bone structural changes directly correlate with pain in OA. Mechanisms underlying skeletal–neural interactions are under-investigated. Bone derived axon guidance molecules are known to regulate bone remodelling. Such signals in the nervous system regulate neural plasticity, branching and neural inflammation. Perturbation of these signals during OA disease progression may disrupt sensory afferents activity, affecting tissue integrity, nociception, and proprioception. Osteocyte mechanical loading and IL-6 stimulation alters axon guidance signalling influencing innervation, proprioception, and nociception. Human Y201 MSC cells, embedded in 3D type I collagen gels (0.05 × 106 cell/gel) in 48 well plastic or silicone (load) plates, were differentiated to osteocytes for 7 days before stimulation with IL-6 (5ng/ml) with soluble IL-6 receptor (sIL-6r (40ng/ml) or unstimulated (n=5/group), or mechanically loaded (5000 μstrain, 10Hz, 3000 cycles) or not loaded (n=5/group). RNA extracted 1hr and 24hrs post load was quantified by RNAseq whole transcriptome analysis (NovaSeq S1 flow cell 2 × 100bp PE reads and differentially expressed neurotransmitters identified (>2-fold change in DEseq2 analysis on normalised count data with FDR p<0.05). After 24 hours, extracted IL-6 stimulated RNA was quantified by RT-qPCR for neurotrophic factors using 2–∆∆Ct method (efficiency=94-106%) normalised to reference gene GAPDH (stability = 1.12 REfinder). Normally distributed data with homogenous variances was analysed by two-tailed t test. All detected axonal guidance genes were regulated by mechanical load. Axonal guidance genes were both down-regulated (Netrin1 0.16-fold, p=0.001; Sema3A 0.4-fold, p<0.001; SEMA3C (0.4-fold, p<0.001), and up-regulated (SLIT2 2.3-fold, p<0.001; CXCL12 5-fold, p<0.001; SEMA3B 13-fold, p<0.001; SEMA4F 2-fold, p<0.001) by mechanical load. IL6 and IL6sR stimulation upregulated SEMA3A (7-fold, p=0.01), its receptor Plexin1 (3-fold, p=0.03). Neutrophins analysed in IL6 stimulated RNA did not show regulation. Here we show osteocytes regulate multiple factors which may influence innervation, nociception, and proprioception upon inflammatory or mechanical insult. Future studies will establish how these factors may combine and affect nerve activity during OA disease progression

Abstract. Objectives. Ultrasound speckle tracking is a safe and non-invasive diagnostic tool to measure soft tissue deformation and strain. In orthopaedics, it could have broad application to measure how injury or surgery affects muscle, tendon or ligament biomechanics. However, its application requires custom tuning of the speckle-tracking algorithm then validation against gold-standard reference data. Implementing an experiment to acquire these data takes months and is expensive, and therefore prohibits use for new applications. Here, we present an alternative optimisation approach that automatically finds suitable machine and algorithmic settings without requiring gold-standard reference data. Methods. The optimisation routine consisted of two steps. First, convergence of the displacement field was tested to exclude the settings that would not track the underlying tissue motion (e.g. frame rates that were too low). Second, repeatability was maximised through a surrogate optimisation scheme. All settings that could influence the strain calculation were included, ranging from acquisition settings to post-processing smoothing and filtering settings, totalling >1,000,000 combinations of settings. The optimisation criterion minimised the normalised standard deviation between strain maps of repeat measures. The optimisation approach was validated for the medial collateral ligament (MCL) with quasi-static testing on porcine joints (n=3), and dynamic testing on a cadaveric human knee (n=1, female, aged 49). Porcine joints were fully dissected except for the MCL and loaded in a material-testing machine (0 to 3% strain at 0.2 Hz), which was captured using both ultrasound (>14 repeats per specimen) and optical digital image correlation (DIC). For the human cadaveric knee (undissected), 3 repeat ultrasound acquisitions were taken at 18 different anterior/posterior positions over the MCL while the knee was extended/flexed between 0° and 90° in a knee extension rig. Simultaneous optical tracking recorded the position of the ultrasound transducer, knee kinematics and the MCL attachments (which were digitised under direct visualisation post testing). Half of the data collected was used for optimisation of the speckle tracking algorithms for the porcine and human MCLs separately, with the remaining unseen data used as a validation test set. Results. For the porcine MCLs, ultrasound strains closely matched DIC strains (R. 2. > 0.98, RMSE < 0.59%) (Figure 1A). For the human MCL (Figure 1B), ultrasound strains matched the strains estimated from the optically tracked displacements of the MCL attachments. Furthermore, strains developed during flexion were highly correlated with AP position (R = 0.94) with strains decreasing the further posterior the transducer was on the ligament. This is in line with previously reported length change values for the posterior, intermediate and anterior bundles of the MCL. Conclusions. Ultrasound speckle tracking algorithms can be adapted for new applications without ground-truth data by using an optimisation approach that verifies displacement field convergence then minimises variance between repeat measurements. This optimisation routine was insensitive to anatomical variation and loading conditions, working for both porcine and human MCLs, and for quasi-static and dynamic loading. This will facilitate research into changes in musculoskeletal tissue motion due to abnormalities or pathologies. Declaration of Interest. (a) fully declare any financial or other potential conflict of interest

Abstract. Objective. This study assesses the prevalence of major and minor discordance between hip and spine T scores using Radiofrequency Echographic Multi-spectrometry (REMS). REMS is a novel technology that uses ultrasound and radiofrequency analysis to measure bone density and bone fragility at the hip and lumbar spine. The objective was to compare the results with the existing literature on Dual-Energy X-ray Absorptiometry (DEXA) the current “gold standard” for bone densitometry. REMS and DEXA have been shown to have similar diagnostic accuracy, however, REMS has less human input when carrying out the scan, therefore the rates of discordance might be expected to be lower than for DEXA. Discordance poses a risk of misclassification of patients’ bone health status, causing diagnostic ambiguity and potentially sub-optimal management decisions. Reduction of discordance rates therefore has the potential to significantly improve treatment and patient outcomes. Methods. Results from 1,855 patients who underwent REMS investigations between 2018 and 2022 were available. Minor discordance is defined as a difference of one World Health Organisation (WHO) diagnostic classification (Normal / Osteopenia or Osteopenia / Osteoporosis). Major discordance is defined as a difference of two WHO diagnostic classifications (Normal / Osteoporosis). The results were compared with reported DEXA discordance rates. Results. 1,732 individuals had both hip and spine T scores available for analysis. There were 267 cases of discordance. No instances of major discordance were observed. The minor discordance rate was 15.4%. 6.5% of the REMS scans with minor discordance showed > 1.0 standard deviation (SD) difference between the T scores of the hip and spine. 19.4% had differences of between 0.6 SD and 1.0 SD while 73.9% had ≤ 0.5 SD or less. In 24.5% of the cases of REMS discordance the hip T scores were greater than the spine and in 75.5% of cases the spine T score was greater than the hip. Conclusions. The current analysis is the largest of its kind. It demonstrates that REMS has an overall lower rate of discordance than reported DEXA rates. Major discordance rates with DEXA range from 2–17%, but REMS avoids many of the positioning problems and post-processing errors inherent in DEXA scanning, which might account for the absence of major discordance. Rates of minor discordance in DEXA scans range between 38–51%. The REMS minor discordance rate being much lower than these rates suggests that it has the potential to enhance diagnostic accuracy considerably. Most REMS discordance results showed ≤ 0.5 SD variance between the T scores of the two sites, indicating close correlation in the bone densitometry analysis. Most studies of DEXA discordant results confirm that spinal T scores are more often higher than at the hip. The REMS results concur with this observation. Considering the comparable accuracy rates that have been shown between REMS and DEXA, with its much lower discordance rate, REMS can potentially improve current medical practice and enhance patient care. 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. OBJECTIVE. Changes in subchondral bone are one of few disease characteristics to correlate with pain in OA. 1. Profound neuroplasticity and nociceptor sprouting is displayed within osteoarthritic (OA) subchondral bone and is associated with pain and pathology. 2. The cause of these neural changes remains unestablished. Correct innervation patterns are indispensable for bone growth, homeostasis, and repair. Axon guidance signalling factor, Sema3A is essential for the correct innervation patterning of bony tissues. 3. , expressed in osteocytes. 4. and known to be downregulated in bone OA mechanical loading. 5. Bioinformatic analysis has also shown Sema3a as a differentially expressed pathway by bone in human OA patients. 6. HYPOTHESIS: Pathological mechanical load and inflammation of bone causes dysregulation of Sema3A signalling leading to perturbed sensory nerve plasticity and pain. METHODS. Human KOLF2-C1 iPSC derived nociceptors were generated by TALEN-mediated insertion of transcription factors NGN2+Brn3A and modified chambers differentiation protocol to produce nociceptor-like cells. Nociceptor phenotype was confirmed by immunocytochemistry. Human Y201-MSC cells were embedded in 3D type-I collagen gels (0.05 × 106 cell/gel), in 48-well plates and silicone plates, were differentiated to osteocytes for 7 days before stimulation with IL-6 (5ng/ml) and soluble IL-6 receptor (sIL-6r (40ng/ml), IL6/sIL6r and mechanical load mimetic Yoda1 (5μM) or unstimulated (n=5/group) (48-well plates) or were mechanically loaded in silicone plates (5000μstrain, 10Hz, 3000 cycles) or not loaded (n=5/group). Conditioned media transfer was performed from osteocyte to nociceptor cultures assessed by continuous 24-hour phase contrast confocal microscopy. 24-hours after stimulation RNA was quantified by RT-qPCR (IL6) or RNAseq whole transcriptome analysis/DEseq2 analysis (Load). Protein release was quantified by ELISA. Normally distributed data with homogenous variances was analysed by two-tailed t test. RESULTS. IPSC-derived nociceptor-like cells display elongated (>5mm) dendritic projections and nociceptive molecular markers such as TUJ1, PrPH and Neun and TrkA. Sema3A signalling ligands were expressed in 100% of osteocyte cultures. Mechanical loading regulated the Sema3 pathway; Sema3A (0.4-fold, p<0.001), Sema3B (13-fold, p<0.001), Sema3C (0.4-fold, p<0.001). Under inflammatory stimulation by IL6/IL6sR, SEMA3A (7-fold, p=0.01) and receptor Plexin1 (3-fold, p=0.03) show significant regulation. Sema3A protein release showed a significant downregulation of Sema3A release by IL6/sIL6r+Yoda1 (2-fold, p=0.02). Continuous 24-hour phase contrast confocal microscopy measuring the number of extending/retreating dendritic projections revealed that sensory nerve cultures exposed to media from osteocytes stimulated with IL-6/sIL-6R+Yoda1 displayed significantly more invading dendritic projections (p=0.0175, 12-fold±SEM 3.5) across 3 random fields of view within a single stimulated neural culture and significantly fewer retracting dendritic projections (p=0.0075, 2-fold±SEM 0.33) compared to controls. CONCLUSIONS. Here we show osteocytic regulation of Sema3A under pathological mechanical loading and the ability of media pathologically loaded osteocyte cultures to induce the branching and invasion of cultured nociceptor-like cells as displayed in OA subchondral bone. 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. The objective of this proof of concept study was to explore whether some total hip arthroplasty (THA) patients with well-functioning implants achieve normal sagittal plane hip kinematics during walking gait. Methods. Sagittal plane hip kinematics were recorded in eleven people with well-functioning THA (71 ± 8 years, Oxford Hip Score = 46 ± 3) and ten healthy controls (61 ± 5 years) using a three-dimensional motion capture system as they walked over-ground at a self-selected velocity. THA patients were classified as high- or low-functioning (HF and LF, respectively) depending on whether the mean absolute difference between their sagittal plane hip kinematics was within one standard deviation of the control group (5.4°) or not. Hedge's g effect size was used to compare the magnitude of the difference from the control group for the HF and LF THA groups. Results. Five THA patients were identified as HF and 6 as LF. The mean absolute difference in sagittal plane hip kinematics between the THA groups and the control group was on average 6.2° larger for the LF THA patients compared to the HF, with this difference associated with a large effect size (g = 1.84). Conclusions. The findings of this study challenge the findings of previous work which suggests THA patients do not achieve normal sagittal plane hip kinematics. Five patients were classified as HR and achieved motion patterns that were on average within the variance of the asymptomatic control group, suggesting normative sagittal plane hip kinematics. Understanding why some THA patients achieve motion patterns more comparable to healthy controls than others would help to develop means of maximising functional recovery, and potentially enhance both patient quality of life and implant survivorship through more normal loading of the implant

Introduction and Objective. Digital infra-red thermography may have the capability of identifying local inflammations. Nevertheless, the role of thermography in diagnosing pin site infection has not been explored yet and the reliability and validity of this method for pin site surveillance is in question. The purpose of this study was to explore the capability and intra-rater reliability of thermography in detecting pin site infection. Materials and Methods. This explorative proof of concept study follows GRRAS -guidelines for reporting reliability and agreement studies. After clinical assessment of pin sites by one examiner using Modified Gordon Pin Infection Classification (Grade 0 – 6), thermographic images of the pin sites were captured with a FLIR C3 camera and analyzed by the FLIR tools software package. The maximum skin temperature around the pin site and the maximum temperature for the whole thermographic picture was measured. Intra-rater agreement was established and test-retests were performed with different camera angles. Results. Thirteen (4 females) patients (age 9–72 years) were included. Indications for frames: 4 fracture, 2 deformity correction, 1 lengthening, 6 bone transport. Days from surgery to thermography ranged from 27 to 385 days. Overall, 231 pin sites were included. Eleven pin sites were diagnosed with early signs of infection: five grade 1, five grade 2, one grade 3. Mean pin site temperature was 33.9 °C (29.0–35.4). With 34 °C as cut-off value for infection, sensitivity was 73%, specificity 67%, positive predictive value 10% and negative predictive value 98%. Intra-rater reliability for thermography was ICC 0.85 (0.77–0.92). The temperature measured was influenced by the camera postioning in relation to pin site with a variance of 0.2. Conclusions. Measurements of pin sites using the handheld FLIR C3 infrared camera was a reliable method and the temperature was related to infection grading. This study demonstrates that digital thermography with a handheld camera might be used for monitoring the pin sites after operations to detect early infection, however, future larger prospective studies are necessary

Introduction and Objective. Slipped Capital Femoral Epiphysis (SCFE) is one of the most common hip disorders in children and is characterized by a proximal femoral deformity, resulting in early osteoarthritis. Several studies have suggested that SCFE patients after in situ fixation show an altered gait pattern. Early identification of gait alterations might lead to earlier intervention programs to prevent osteoarthritis. The aim of this study is to analyse gait alterations in SCFE patients after in situ fixation compared to typically developed children, using the Computer Assisted Rehabilitation Environment (CAREN) system. Materials and Methods. This is a cross-sectional, multi-center case-control study in the Netherlands. Eight SCFE patients and eight age- and sex-matched typically developed were included from two hospitals. Primary outcomes were kinematic parameters (absolute joint angles), studied with gait analysis using statistical parametric mapping (SPM). Secondary outcomes were spatiotemporal parameters, the Notzli alpha angle, muscle activation patterns (EMG), and clinical questionnaires (VAS, Borg CR10, SF-36, and HOOS), analyzed using non-parametric statistical methods. Results. Patients (mean BMI=28±9 kg/m. 2. ) showed altered gait patterns, with significantly increased external hip rotation and decreased downward pelvic obliquity during the pre-swing phase of the gait cycle compared to typically developed (mean BMI=22±3 kg/m. 2. ). Walking speed, cadence, % stance time, and step length were reduced in SCFE patients. Coefficient of variances of cadence, stance time, and step length were increased. Patients had a mean alpha angle of 64, SD=7.9. Clinical questionnaires showed that general health (SF-36) was 80±25, energy/fatigue (SF-36) was 67±15, pain (VAS) was 0±1.5, and total HOOS score was 85±18. Conclusions. SCFE patients after in situ fixation appear to have developed a compensation mechanism, showing slight alterations in gait parameters, good general health, little functional limitations of the hip, and no self-reported pain. Cam deformities, altered joint loading, and this compensation mechanism might influence long-term early osteoarthritis. BMI reduction should be implemented in care plans, as obesity might also play a role in unfavorable long-term outcomes

Introduction and Objective. Gait variability is the amplitude of the fluctuations in the time series with respect to the mean of kinematic (e.g., joint angles) or kinetic (e.g., joint moments) measurements. Although gait variability increases with normal ageing or pathological mechanisms, such as knee osteoarthritis (OA). The purpose was to determine if a patient who underwent a total knee arthroplasty (TKA) can reduce gait variability. Materials and Methods. Twenty-five patients awaiting TKA were randomly assigned to receive either medial pivot (MP, m=7/f=6, age=62.4±6.2 years) or posterior stabilized (PS, m=7/f=5, age=63.7±8.9 years) implants, and were compared to 13 controls (CTRL, m=7/f=6, age=63.9±4.3 years). All patients completed a gait analysis within one month prior and 12 months following surgery, CTRLs completed the protocol once. A waveform F-Test Method (WFM) was used to compare the variance in knee biomechanics variables at each interval of the gait cycle. Results. Preoperatively, the PS group had greater sagittal knee angle variability compared to the MP (32–58% gait cycle) and CTRL (21–53% gait cycle) groups. Postoperatively, no difference in sagittal knee angle variability existed between any of the groups. Preoperatively, sagittal knee moment variability was greater in the MP (2–39% gait cycle) and PS (5–19% and 42–57% gait cycle) groups compared to the CTRL. Postoperatively, sagittal knee moment was lower in the MP (49–55% gait cycle) and greater in the PS (23–36% gait cycle) compared to the CTRL. Knee power variability was greater preoperatively in the MP (52–61% gait cycle) and PS (52–62% gait cycle) compared to the CTRL. Postoperatively, knee power variability was lower in the MP (17–22% and 45–50% gait cycle) and PS (6–23%, 34–41% and 45–49% gait cycle) compared to the CTRL group. Conclusions. Preoperatively, knee OA patients have greater variability in knee moments than CTRLs during the transition from double-limb support to single-limb support on the affected limb. This indicates knee instability as patients are adopting a gait strategy that refers to knee muscle contraction avoidance. The MP group showed greater knee stability postoperatively as they had lower knee moment and power variability compared to the CTRL. The significance of having less variability than CTRLs is not well understood at this time. Future research on muscle activity is needed to determine if neuromuscular adaptations are causing these reductions in variability after TKA

Objectives. The aim of the current study was to assess whether calcaneal broadband ultrasound attenuation (BUA) can predict whole body and regional dual-energy x-ray absorptiometry (DXA)-derived bone mass in healthy, Australian children and adolescents at different stages of maturity. Methods. A total of 389 boys and girls across a wide age range (four to 18 years) volunteered to participate. The estimated age of peak height velocity (APHV) was used to classify children into pre-, peri-, and post-APHV groups. BUA was measured at the non-dominant heel with quantitative ultrasonometry (QUS) (Lunar Achilles Insight, GE), while bone mineral density (BMD) and bone mineral content (BMC) were examined at the femoral neck, lumbar spine and whole body (DXA, XR-800, Norland). Associations between BUA and DXA-derived measures were examined with Pearson correlations and linear regression. Participants were additionally ranked in quartiles for QUS and DXA measures in order to determine agreement in rankings. Results. For the whole sample, BUA predicted 29% of the study population variance in whole body BMC and BMD, 23% to 24% of the study population variance in lumbar spine BMC and BMD, and 21% to 24% of the variance in femoral neck BMC and BMD (p < 0.001). BUA predictions were strongest for the most mature participants (pre-APHV R. 2. = 0.03 to 0.19; peri-APHV R. 2. = 0.05 to 0.17; post-APHV R. 2. = 0.18 to 0.28) and marginally stronger for girls (R. 2. = 0.25-0.32, p < 0.001) than for boys (R. 2. = 0.21-0.27, p < 0.001). Agreement in quartile rankings between QUS and DXA measures of bone mass was generally poor (27.3% to 38.2%). Conclusion. Calcaneal BUA has a weak to moderate relationship with DXA measurements of bone mass in children, and has a tendency to misclassify children on the basis of quartile rankings. Cite this article: B. K. Weeks, R. Hirsch, R. C. Nogueira, B. R. Beck. Is calcaneal broadband ultrasound attenuation a valid index of dual-energy x-ray absorptiometry-derived bone mass in children? Bone Joint Res 2016;5:538–543. DOI: 10.1302/2046-3758.511.BJR-2016-0116.R1

Introduction and Objective. Malunion after trauma can lead to coronal plane malalignment in the lower limb. The mechanical hypothesis suggests that this alters the load distribution in the knee joint and that that this increased load may predispose to compartmental arthritis. This is generally accepted in the orthopaedic community and serves as the basis guiding deformity correction after malunion as well as congenital or insidious onset malalignment. Much of the literature surrounding the contribution of lower limb alignment to arthritis comes from cohort studies of incident osteoarthritis. There has been a causation dilemma perpetuated in a number of studies - suggesting malalignment does not contribute to, but is instead a consequence of, compartmental arthritis. In this investigation the relationship between compartmental (medial or lateral) arthritis and coronal plane malalignment (varus or valgus) in patients with post traumatic unilateral limb deformity was examined. This represents a specific niche cohort of patients in which worsened compartmental knee arthritis after extra-articular injury must rationally be attributed to malalignment. Materials and Methods. The picture archiving system was searched to identify all 1160 long leg x ray films available at a major metropolitan trauma center over a 12-year period. Images were screened for inclusion and exclusion criteria, namely patients >10 years after traumatic long bone fracture without contralateral injury or arthroplasty to give 39 cases. Alignment was measured according to established surgical standards on long leg films by 3 independent reviewers, and arthritis scores Osteoarthritis Research Society International (OARSI) and Kellegren-Lawrence (KL) were recorded independently for each compartment of both knees. Malalignment was defined conservatively as mechanical axis deviation outside of 0–20 mm medial from centre of the knee, to give 27 patients. Comparison of mean compartmental arthritis score was performed for patients with varus and valgus malalignment, using Analysis of Variance and linear regression. Results. In knees with varus malalignment there was a greater mean arthritis score in the medial compartment compared to the contralateral knee, with OARSI scores 5.69 vs 3.86 (0.32, 3.35 95% CI; p<0.05) and KL 2.92 vs 1.92 (0.38, 1.62; p<0.005). There was a similar trend in valgus knees for the lateral compartment OARSI 2.98 vs 1.84 (CI −0.16, 2.42; p=0.1) and KL 1.76 vs 1.31 (CI −0.12, 1.01; p=0.17), but the evidence was not conclusive. OARSI arthritis score was significantly associated with absolute MAD (0.7/10mm MAD, p<0.0005) and Time (0.6/decade, p=0.01) in a linear regression model. Conclusions. Malalignment in the coronal plane is correlated with worsened arthritis scores in the medial compartment for varus deformity and may similarly result in worsened lateral compartment arthritis in valgus knees. These findings support the mechanical hypothesis that arthritis may be related to altered stress distribution at the knee, larger studies may provide further conclusive evidence

Introduction and Objective. Curative resection of proximal humerus tumours is now possible in this era of limb salvage with endoprosthetic replacement considered as the preferred reconstructive option. However, it has also been linked with mechanical and non-mechanical failures such as stem fracture and aseptic loosening. One of the challenges is to ensure that implants will endure the mechanical strain under physiological loading conditions, especially crucial in long surviving patients. The objective is to investigate the effect of varying prosthesis length on the bone and implant stresses in a reconstructed humerus-prosthesis assembly after tumour resection using finite element (FE) modelling. Methods. Computed tomography (CT) scans of 10 humeri were processed in Mimics 17 to create three-dimensional (3D) cortical and cancellous solid bone models. Endoprostheses of different lengths manufactured by Stryker were modelled using Solidworks 2020. The FE models were divided into four groups namely group A consisting of the intact humerus and groups B, C and D composed of humerus-prosthesis assemblies with a body length of 40, 100 and 120 mm respectively and were meshed using linear 4-noded tetrahedral elements in 3matic 13. The models were then imported into Abaqus CAE 6.14. Isotropic linear elastic behaviour with an elastic modulus of 13400, 2000 and 208 000 MPa were assigned to the cortical bone, cancellous bone and prosthesis respectively and a Poisson's ratio of 0.3 was assumed for each material. To represent the lifting of heavy objects and twisting motion, a tensile load of 200 N for axial loading and a 5 Nm torsional load for torsional loading was applied separately to the elbow joint surface with the glenohumeral joint fixed and with all contact interfaces defined as fully bonded. A comparative analysis against literature was performed to validate the intact model. Statistical analysis of the peak von Mises stress values collected from predicted stress contour plots was performed using a one-way repeated measure of analysis of variance (with a Bonferroni post hoc test) using SPSS Statistics 26. The average change in stress of the resected models from the intact state were then determined. Results. The validation of the intact humerus displayed a good agreement with literature values. The peak bone stress occurred distally above the coronoid and olecranon fossa closer to the load application region in the intact and resected bone models with a significant amount of loading borne by the cortical bone, while the peak implant stress occurred at the bone-prosthesis contact interface under both loading conditions. Based on the results obtained, a statistically significant difference (p =.013) in implant stress was only seen to occur between groups B and C under tension. Results illustrate initiation of stress shielding with the bone bearing lesser stress with increasing resection length which may eventually lead to implant failure by causing bone resorption according to Wolff's law. The peak implant stress under torsion was 3–5 times the stress under tension. The best biomechanical behaviour was exhibited in Group D, having the least average change in stress from the intact model, 5% and 3.8% under tension and torsion respectively. It can be deduced that the shorter the prosthesis length, the more pronounced the effect on cortical bone remodelling. With the maximum bone and implant stresses obtained being less than their yield strength, it can be concluded that the bone-implant construct is safe from failure. Conclusions. The developed FE models verified the influence of varying the prosthesis length on the bone and implant stresses and predicted signs of stress shielding in longer endoprostheses. By allowing for 2 cm shortening in the upper extremity and post-surgical scarring, it is beneficial to err towards a shorter endoprosthesis

Abstract. Objectives. Unicompartmental (UKA) and bicompartmental (BCA) knee arthroplasty are associated with improved functional outcomes compared to Total Knee Arthroplasty (TKA) in suitable patients, although the reason is poorly understood. The aim of this study was to measure how the different arthroplasties affect knee extensor function. Methods. Extensor function was measured for sixteen cadaveric knees and then re-tested following the different arthroplasties. Eight knees underwent medial UKA then BCA, then posterior-cruciate retaining TKA, and eight underwent the lateral equivalents then TKA. Extensor efficiency was calculated for ranges of knee flexion associated with common activities of daily living. Data were analyzed with repeated measures analysis of variance (α=0.05). Results. Compared to native, no differences were detected in either extensor moment or efficiency following UKA. Conversion to BCA resulted in a small drop in extensor moment between 70-90° flexion (p<0.05), but when examined in the context of daily activity ranges of flexion, extensor efficiency was largely unaffected. Following TKA, large decreases in extensor moment were measured at low knee flexion angles (p<0.05), resulting in 8–43% reduction in extensor efficiency for daily activity ranges. Conclusion. This cadaveric study found that TKA is associated with inferior extensor function compared to UKA and BCA. This may, in part, help explain the reported differences in function and satisfaction differences between partial and total knee arthroplasty. Declaration of Interest. (a) fully declare any financial or other potential conflict of interest