The objectives of the study were to investigate demographic, injury and surgery/treatment-associated factors that could influence clinical outcome, following Autologous Chondrocyte Implantation (ACI) in a large, “real-world”, 20 year longitudinally collected clinical data set. Multilevel modelling was conducted using R and 363 ACI procedures were suitable for model inclusion. All longitudinal post-operative Lysholm scores collected after ACI treatment and before a second procedure (such as knee arthroplasty but excluding minor procedures such as arthroscopy) were included. Any patients requiring a bone graft at the time of ACI were excluded. Potential predictors of ACI outcome explored were age at the time of ACI, gender, smoker status, pre-operative Lysholm score, time from surgery, defect location, number of defects, patch type, previous operations, undergoing parallel procedure(s) at the time of ACI, cell count prior to implantation and cell passage number. The best fit model demonstrated that for every yearly increase in age at the time of surgery, Lysholm scores decreased by 0.2 at 1-year post-surgery. Additionally, for every point increase in pre-operative Lysholm score, post-operative Lysholm score at 1 year increased by 0.5. The number of cells implanted also impacted on Lysholm score at 1-year post-op with every point increase in log cell number resulting in a 5.3 lower score. In addition, those patients with a defect on the lateral femoral condyle (LFC), had on average Lysholm scores that were 6.3 points higher one year after surgery compared to medial femoral condyle (MFC) defects. Defect grade and location was shown to affect long term Lysholm scores, those with grade 3 and patella defects having on average higher scores compared to patients with grade 4 or trochlea defects. Some of the predictors identified agree with previous reports, particularly that increased age, poorer pre-operative function and worse defect grades predicted poorer outcomes. Other findings were more novel, such as that a lower cell number implanted and that LFC defects were predicted to have higher Lysholm scores at 1 year and that patella lesions are associated with improved long-term outcomes cf. trochlea lesions

An adult acquired flatfoot deformity (AAFD) is a complex 3D deformity. Surgical correction consists of a medial calcaneal osteotomy (MCO) but shows limitations due to the current 2D assessment. Therefore, the aim is to determine the influence of an MCO on the longitudinal foot arch assessed by 2D and 3D weightbearing CT (WBCT). Seventeen patients with a mean age of 44,5 years (range 18–66 yrs) were retrospectively included. MCO was indicated in a stage II AAFD (N=15) and a post-traumatic valgus deformity (N=2). Pre- and post-operative imaging was obtained from a WBCT. The height of the longitudinal foot arch was measured as the distance from the navicular tuberositas to the floor (Navicular Height, NH) on 2D CT images (NH. 2D. ) and computed on 3D CT data (NH. 3D. ). Additionally, 3D assessment could compute the degree of exorotation (α) of the navicular bone towards the vertical axis. The mean pre-operative NH. 2D. and NH. 3D. were respectively 29.57mm ± 7.59 and 28.34mm ± 6.51. These showed to be statistically different from the mean post-operative NH. 2D. and NH. 3D. , respectively 31.62mm ± 6.69 and 31.67mm ± 6.47 (p < 0,001). A statistical difference was also found when comparing the mean degree of exorotation in pre- and post-operative, respectively: α. pre. =14.08° ± 4,92 and the α. post. =19,88° ± 3.50 (p < 0,001). This study demonstrates a significant correction of the longitudinal foot arch after a MCO. The novelty is attributed to the accurate degree of rotation assessment using WBCT. This information could be assistive to optimise a pre-operative planning

The large bone defects with high risk of delayed bone union and pseudoarthrosis remain significant clinical challenge. Aim of the present study was the investigation of the critical size fracture healing process in transgenic mice using a novel beta-TCP scaffold. The luciferase transgenic mice strains (BALB/C-Tg(NF-kappaB-RE-luc)-Xen) and FVB/N-Tg(Vegfr2-luc)-Xen were used. Critical size fracture on femur was performed and stabilized using external fixation (RISystem). The fracture was bridged with a synthetic scaffold with and without Strontium. In consequence, the expression levels of NF-kappaB and VEGFR2 could be monitored in a longitudinal fashion using the Xenogen imaging system for two months. Animals were euthanized, serial section of femur were prepared, and the fracture sites were histologically examined. Sr reduced inflammation in the early phase of healing (15th days), but it was increased in the late healing stage. The level of VEGFR2 activity increases in the Sr doped beta-TCP group at the 15th day, the luciferase activity starts to decrease in this group and show significantly less activity compared to other groups in the second half. In the group without scaffold a connective tissue formation were observed. In both, beta-TCP and beta-TCP+Sr, the connection of newly formed tissue within integrated canals in scaffold was visible. Tissue formation in beta-TCP+Sr group was significantly higher than in the beta-TCP group, whereas the percentage of osseous tissue in relation to the newly formed tissue was in beta-TCP scaffold much more than in beta-TCP+ Sr groups. This study presents the first data regarding VEGFR2 and NF-kappB and angiogenesis activity profiles during fracture healing. The collected longitudinal data reduces the number of experimental animals in the study. Addition of strontium in scaffolds influenced the inflammation in different stage of the healing. This effect might influence the healing process and may prove to be advantageous for osteoporosis fracture healing

Introduction and Objective. Individuals with type 2 diabetes (T2D) have a 3-fold increased risk of bone fracture compared to non-diabetics, with the majority of fractures occurring in the hip, vertebrae and wrists. However, unlike osteoporosis, in T2D, increased bone fragility is generally not accompanied by a reduction in bone mineral density (BMD). This implies that T2D is explained by poorer bone quality, whereby the intrinsic properties of the bone tissue itself are impaired, rather than bone mass. Yet, the mechanics remain unclear. The objective of this study is to (1) assess the fracture mechanics of bone at the structural and tissue level; and (2) investigate for changes in the composition of bone tissue along with measuring total fluorescent advanced glycation end products (fAGEs) from the skin, as T2D progresses with age in Zucker diabetic fatty (ZDF (fa/fa)) and lean Zucker (ZL (fa/+)) rats. Materials and Methods. Right ulnae and skin sections were harvested from ZDF (fa/fa) (T2D) and ZL (fa/+) (Control) rats at 12 and 46 weeks (wks) of age (n = 8, per strain and age) and frozen. Right ulnae were thawed for 12 hrs before micro-CT (μCT) scanning to assess the microstructure and measure BMD. After scanning, ulnae were loaded until failure via three-point bending. Fourier transform-infrared microspectroscopy (FTIR) was used to measure various bone mineral- and collagen-related parameters such as, mineral-to-matrix ratio and nonenzymatic cross-link ratio. Finally, fAGEs were measured from skin sections using fluorescence spectrometry and an absorbance assay, reported in units of ng quinine/ mg collagen. Results. At 12 and 46 wks bone size was significantly smaller in length (p < 0.01), cortical area (p < 0.001) and cross-sectional moment of inertia (p < 0.001) in T2D rats compared to age-matched controls. A slight reduction in BMD was observed in T2D rats compared to controls at both ages, however, this was not significant. Structural properties of T2D bone were significantly altered at 12 and 46 wks, with bending rigidity increasing approximately 2.5-fold and 1.5-fold in control and T2D rats with age, respectively (p < 0.0001). Similarly, yield and ultimate moment significantly reduced in T2D rats with age in comparison to controls (p < 0.0001). Energy absorbed to failure was significantly reduced in T2D rats at 46 weeks of age compared to controls (p < 0.01). The amount of energy absorbed to failure increased approximately 1.4-fold from 12 to 46 wks in control rats, however, in T2D rats a reduction was seen with age, although not significant. At 12 wks, there was no significant deficits in tissue material properties, whereas, at 46 wks a significant reduction in yield stress, yield strain and ultimate stress was observed for T2D rats in comparison to controls (p < 0.05). Conclusions. These findings show that longitudinal growth is impaired as early as 12 wks of age and by 46 wks bone size is significantly reduced in T2D rats compared to controls. The reduction in T2D structural properties is likely attributed to the bone geometry deficits. At 12 wks of age, the tissue material properties are not altered in T2D bone versus controls. However, at 46 wks, bone strength is reduced in T2D, leading to the conclusion that tissue properties are altered as the disease progresses

Introduction. Skeletal abnormalities caused by disproportioned bone overgrowth (LBO), are a common trait in Marfan syndrome (MFS), a connective tissue disease caused by mutations in the extracellular matrix (ECM) protein and TGFβ regulator fibrillin-1 (Fbn1). The cause of LBO in MFS is unknown and therapies are not available. Fibrillin-1 hypomorphic mouse model (Fbn1mgR/mgR) faithfully replicates MFS skeletal manifestations including elongated bones however, its early demise due aortic rupture limit the magnitude of LBO investigation. Materials and Methods. To circumvent Fbn1mgR/mgR lethality and investigate the contribution of specific skeletal tissues to LBO, Fbn1 gene expression was targeted in developing limbs by crossing Fbn1Lox/Lox mice with Prx1-Cre, in or bone with Osx-Cre, in cartilage and perichondrium with Col2-Cre, in skeletal muscles with Mef2c-Cre, and ligaments and tendons with Scx-Cre. Bones length of Fbn1 conditional mice KO was measured and relevant histological, cellular and biomechanical parameters were assessed. Results. Fbn1Prx1−/+ and Fbn1Prx1−/− mice had longer limbs bones compared to WT mice and amount of fibrillin-1 in the limb matrix was inversely proportional to bone length. Interestingly, Fbn1 gene targeting in ligaments/tendons resulted in LBO, altered tissues' mechanics and TGFβ-induced switch of tendon stem cells to chondrocytes. Gene targeting in other limb's anatomical locations did not result in LBO thus ruling out the participation of surrounding tissues to this bone phenotype. Discussion. Fbn1 gene inactivation in ligament/tendon is associated with increased local TGFβ, altered biomechanical properties and LBO. As previously reported, ligaments/tendons respond to changes in mechanical load by increasing the levels and/or the activity of TGF-β while bones undergo morphological adaptation in response to muscle loads transmitted by tendons. We hypothesize that dysregulation of local TGFβ signaling and altered biomechanical properties of fibrillin-1 deficient ligaments/tendons affect endochondral ossification by improper load transmission to bone. By showing ligament/tendon-dependent regulation of postnatal longitudinal bone growth this study provides a paradigm-shift in tendon biology and it shades a new light on LBO pathophysiology in MFS, thus providing the bases for new pharmacological interventions for this and related skeletal conditions

This investigation of elite male collegiate basketball players aims to determine 1) the change in 3D dynamic functional variables across a single season and 2) correlate cross-season changes in functional variables with changes in clinical and quantitative ultrasound measures. Eleven male college basketball players (mean age 19, range 18–21 years) from a single team underwent baseline patellar tendon shear wave (SW) elastography and dynamic function at the start of the season (Visit1) and at a late-season time point (Visit2). Players reported their VISA-P scores every two weeks across their 24-week season. Each athlete performed a box-ground-box jump five times while 3D lower extremity kinematic and kinetic variables were collected. Functional measures included for landing (LAND) and take-off (TOFF) phases: knee valgus angle, valgus torque, and peak limb force. Knee valgus angular impulse and ground contact time were also measured. Paired t-tests and Pearson correlation coefficients (r) compared Visit1 and Visit2 variables and assessed the strength of linear dependency, respectively. The mean change in VISA-P score was 15.18 (+/-8.55). No functional variables were different across the season. Clinical, quantitative ultrasound and functional variables were moderately correlated with take-off valgus moment, landing force, take-off force and contact time. Other correlations were low (< 0.4). Our analyses have shown moderate correlations between important clinical, quantitative imaging and function measurements. These correlations reflect the changes that occur between relevant time points and which relate internal structure and external function.

Patellar tendinosis (PT) is common and can result in prolonged disability, especially in jumping athletes. Recently developed ultra-short-echo (UTE) MRI sequences allow for quantitative evaluation of tendon biostructure with T2* relaxometry. This study evaluated the relationships between changes over time (COT) in quantitative T2*-metrics, qualitative PT grades, and patient reported symptoms within 10 male basketball players from a single collegiate basketball team. All subjects completed weekly VISA-P symptomology questionnaires over the basketball season. Bilateral 3-Tesla MRIs (GE Healthcare) were obtained at pre- and post-season study visits. High-resolution, PD-weighted, FSE sequences were used to qualitatively grade PT. Quantitative T2*-metrics were evaluated using high-resolution, 3D, multi-echo, UTE-MRI sequences. Bilinear exponential fits of SI to corresponding echo time were used to calculate T2*-metrics. All qualitative and quantitative evaluations were region specific (proximal, middle, distal). Linear mixed effects models assessed associations of side and region with T2*-metrics. Spearman correlations evaluated relationships between outcome measures. Within and between study visits, significant side-to-side differences in T2*-metrics were found and were significantly impacted by leg dominance (p<0.05). Pre-season T2*-metrics correlated with COT in T2*-metrics, COT in T2*-metrics correlated with COT in qualitative PT grades, and post-season T2*-metrics correlated with max changes in VISA-P scores (ρ≥0.64). Quantitative T2*-metrics can detect PT and may be capable of predicting the onset of pathology. T2*-metrics could benefit the clinical management of PT: it is sensitive to changes in pathologic severity over time, and therefore can serve as a quantitative metric to guide treatment and evaluate intervention efficacy.

Introduction. Current treatments of rotational deformities of long bones in children are osteotomies and fixations. In recent years, the use of guided growth for correction of rotational deformities has been reported in several pre-clinical and clinical studies. Various techniques have been used, and different adverse effects, like growth retardation and articular deformities, have been reported. We tested a novel plate concept intended for correction of rotational deformities of long bones by guided growth, with sliding screw holes to allow for longitudinal growth, in a porcine model. Method. Twelve, 12-week-old female porcines were included in the study. Surgery was performed on the left femur. The right femur was used as control. Plates were placed distally to induce external rotation, as longitudinal growth occurred. CT-scans of the femurs were processed to 3-D models and used for measuring rotation. Result. The plates rotated as intended in all 12 porcines. One porcine was excluded due to congenital deformity of the proximal part of the femurs. Two porcines had cut-out of the proximal screw on the lateral side, observed at the end of the intervention. These two porcines were included in the results. We observed a Δrotation of 5.7° ± 2° in external direction (CI: 3.7°– 7.7°). ΔFemur length was -0.4 cm [-0.7 cm – 0 cm] equal to 1.5% shortening of the operated femur. No significant difference was observed in coronal or sagittal plane. Conclusion. Significant external rotation was achieved with minimal effect on longitudinal growth. While the use of guided growth for correction of rotational deformities is already being used clinically, it is still to be considered an experimental procedure with sparse evidence. This study shows promising results for the feasibility of the method in a large animal model and is an important first step in validating the technique and detecting possible adverse effects, before future clinical studies

Abstract. INTRODUCTION. In the NHS the structure of a “regular healthcare team” is no longer the case. The NHS is facing a workforce crisis where cross-covering of ward-based health professionals is at an all-time high, this includes nurses, doctors, therapists, pharmacists and clerks. Comprehensive post-operative care documentation is essential to maintain patient safety, reduce information clarification requests, delays in rehabilitation, treatment, and investigations. The value of complete surgical registry data is emerging, and in the UK this has recently become mandated, but the completeness of post-operative care documentation is not held to the same importance, and at present there is no published standard. This project summarises a 4-stage approach, including 6 audit cycles, >400 reviewed operation notes, over a 5 year period. OBJECTIVE. To deliver a sustainable change in post operative care documentation practices through quality improvement frameworks. METHODS. Stage 1: Characterise the problem and increase engagement through: SMART aims, process mapping, hybrid action-effect and driver diagram and stakeholder analysis. Multi disciplinary stakeholders were involved in achieving a consensus of evidence-based auditable criteria. Stage 2: Baseline audit to assess current practice. Stage 3: Intervention planning by stakeholders. Stage 4: Longitudinal monitoring through run charts and iterative refinement. RESULTS. Stage 1: Process mapping identified numerous downstream effects of the absence of critical information from operation notes, and the action-effect diagram highlighted the multiple unnecessary mitigating actions performed by ward staff. An MDT consensus was achieved on 15 essential criteria for complete documentation, including important negative fields. Interest-influence matrix identified stakeholder groups with high influence but low interest who needed engagement to deliver change. Stage 2: Baseline audit demonstrated unexpectedly poor documentation: >75% compliance in 4 criteria, and <50% compliance in 10 criteria, which elevated the interest of key stakeholders. Stage 3: A post-operative care template based on the 15 criteria was embedded within the existing IT software. It allowed use of existing operative templates, with a non-overwriting suffix requiring only two mouse clicks. Stage 4: Re-audit at 3 and 12 months showed improved and sustained compliance. At 24 months compliance had declined. Questionnaire of template usage identified problems of criteria response options, and lack of awareness of template by newly appointed staff. Template update improved compliance over the next 6 months (>75% compliance in 11 criteria). Finally, a further reaudit conducted 12 months after the template update (5 years post baseline audit) showed a sustained improvement in compliance (>75% compliance in 13 criteria). CONCLUSIONS. Simple innovation through quality improvement frameworks has changed documentation practices by 1) achieving a consensus from stakeholders, 2) a “shock and awe” moment to highlight existing poor documentation and increase engagement 3) implementing change which fit easily into existing systems, 4) respecting autonomy rather than enforcing change and 5) longitudinal monitoring using run charts and an iterative process to ensure the template remains fit for purpose. This model has now successfully been translated to other subspecialities within the orthopaedic department. 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 concept of guided growth was proposed by Andry in 1741. In the last decades the concept has been widely used as implants has been introduced that can modulate the growth of the bone and pediatric longitudinal and angular deformities is widely treated by this technique. However, there is there is a huge variation in techniques and implants used and high-quality clinical trials is still lacking. Recently implants correcting rotational bony deformities have been proposed and clinical case series have been published. The current status of guided growth will be presented in this narrative review and preliminary experiences with rotational guided growth will be shared. Is guided growth to be considered a safe treatment at this time point?

We sought to determine the relationship between patient preoperative psychological factors and postoperative THA outcomes. We performed an electronic search up to December 2021 using the following terms: “(mental OR psychological OR psychiatric) AND (function OR trait OR state OR predictor OR health) AND (outcome OR success OR recovery OR response) AND total joint arthroplasty)”. Peer-reviewed, English language studies regarding THA outcomes were analyzed for preoperative patient mental health metrics and objective postoperative results regarding pain, functionality and surgical complications. We extracted study data, assessed the risk of bias of included studies, grouped them by outcome measure and performed a GRADE assessment. Seventeen of 702 studies fulfilled inclusion criteria and were included in the review. Overall, compared to cohorts with a normal psychological status, patients with higher objective measures of preoperative depression and anxiety reported increased postoperative pain, decreased functionality and greater complications following THA. Additionally, participants with lower self-efficacy or somatization were found to have worse functional outcomes. Following surgery, both early and late pain scores remained higher in patients with preoperative depression and anxiety. Preoperative depression and anxiety may negatively impact patient reported postoperative pain, physical function and complications following THA. A meta-analysis was not performed because of the heterogeneity of studies, specifically the use of differing pain scales and measures of physical and psychological function as well as varied follow-up times. Future research could test interventions to treat pre-operative depression or anxiety and explore longitudinal outcomes in THA patients. Surgeons should consider the preoperative psychological status when counseling patients regarding expected surgical outcomes and attempt to treat a patient's depression or anxiety prior to undergoing total hip arthroplasty

Unicompartmental knee arthroplasty (UKA) and high tibial osteotomy (HTO) are well-established operative interventions in the treatment of knee osteoarthritis (KOA). However, which of these interventions is more beneficial, to patients with KOA, is not known and remains a topic of much debate. Aims: (i) To determine whether UKA or HTO is more beneficial in the treatment of isolated medial compartment KOA, via an assessment of patient-reported outcome measures (PROMs). (ii) To investigate the relationship between PROMs and radiographic parameters of knee joint orientation/alignment. This longitudinal observational study assessed a total of 42 patients that had undergone UKA (n=23) or HTO (n=19) to treat isolated medial compartment KOA. The PROMs assessed, pre-operatively and 1-year post-operatively, consisted of the: self-administered comorbidity questionnaire; short form-12; oxford knee score; knee injury and osteoarthritis outcome score; and the EQ-5D-5L. The radiographic parameters of knee joint alignment/orientation assessed, pre-operatively and 8-weeks post-operatively, included the: hip-knee-ankle angle; mechanical axis deviation; and the angle of the Mikulicz line. Statistical analysis demonstrated an overall significant (p<0.001), pre-operative to post-operative, improvement in the PROM scores of both groups. There were no significant differences in the post-operative PROM scores of the UKA and HTO group. Correlation analyses revealed that pre-operatively, a more distolaterally angled Mikulicz line was associated with worse knee function (p<0.05) and overall health (p<0.05); a relationship that, until now, has not been investigated nor commented upon within the literature. UKAs and HTOs are both efficacious operations that provide a comparable degree of clinical benefit to patients with isolated medial compartment KOA. To further the scientific/medical community's understanding of the factors that impact upon health-outcomes in KOA, future research should seek to investigate the mechanism underlying the relationship, between Mikulicz line and PROMs, observed within the current study

There is an evolving body of evidence that demonstrates the role of epigenetic mechanisms, such as DNA-methylation in the pathogenesis of OA. This systematic review aims to summarize the current evidence of DNA methylation and its influence on the pathogenesis of OA. A pre-defined protocol in alignment with the PRISMA guidelines was employed to systematically review eight bibliographic databases, to identify associations between DNA-methylation of articular chondrocytes and osteoarthritis. A search of Medline (Ovid), Embase, Web-of-Science, Scopus, PubMed, Cinahl (EBSCOhost), Cochrane Central and Google Scholar was performed between 1st January 2015 to 31st January 2021. Data extraction was performed by two independent reviewers. During the observation period, we identified 15 gene specific studies and 24 genome wide methylation analyses. The gene specific studies mostly focused on the expression of pro-inflammatory markers, such as IL8 and MMP13 which are overexpressed in OA chondrocytes. DNA hypomethylation in the promoter region resulted in overexpression, whereas hypermethylation was seen in non-OA chondrocytes. Others reported on the association between OA risk genes and the DNA methylation pattern close to RUNX2, which is an important OA signal. The genome wide methylation studies reported mostly on differentially methylated regions comparing OA chondrocytes and non-OA chondrocytes. Clustering of the regions identified genes that are involved in skeletal morphogenesis and development. Differentially methylated regions were seen in hip OA and knee OA chondrocytes, and even within different regions of an OA affected knee joint, differentially methylated regions were identified depending on the disease stage. This systematic review demonstrates the growing evidence of epigenetic mechanisms, such as DNA methylation, in the pathogenesis of OA. In recent years, there has been a focus on the interplay between OA risk genes and DNA methylation changes which revealed a reactivation of genes responsible for endochondral ossification during development. These are important findings and may help to identify eventual future therapeutic targets. However, the current body of literature is mostly showing the differences in DNA methylation of OA chondrocytes and non-OA chondrocytes, but a true longitudinal analysis demonstrating the DNA methylation changes actually happening is still not available

Knee osteoarthritis (KOA) diagnosis is based on symptoms, assessed through questionnaires such as the WOMAC. However, the inconsistency of pain recording and the discrepancy between joint phenotype and symptoms highlight the need for objective biomarkers in KOA diagnosis. To this end, we study relationships among clinical and molecular data in a cohort of women (n=51) with Kellgren-Lawrence grade 2–3 KOA through Support Vector Machine (SVM) and a regulation network model (RNM). Clinical descriptors (i.e., pain catastrophism (CA); depression (DE); functionality (FU); joint pain (JP); rigidity (RI); sensitization (SE); synovitis (SY)) are used to classify patients. A Youden's test is performed for each classifier to determine optimal binarization thresholds for the descriptors. Thresholds are tested against patient stratification according to baseline WOMAC data from the Osteoarthritis Initiative, and the mean accuracy is 0.97. For our cohort, the data used as SVM inputs are KOA descriptors, synovial fluid (SL) proteomic measurements (n=25), and transcription factors (TF) activation obtained from RNM [2] stimulated with the SL measurements. The relative weights after classification reflect input importance. The performance of each classifier is evaluated through AUC-ROC analysis. The best classifier with clinical data is CA (AUC = 0.9), highly influenced by FU and SE, suggesting that kinesophobia is involved in pain perception. With SL input, leptin strongly influences every classifier, suggesting the importance of low-grade inflammation. When TF are used, the mean AUC is limited to 0.608, which can be related to the pleomorphic behaviour of osteoarthritic chondrocytes. Nevertheless, FU has an AUC of 0.7 with strong importance of FOXO downregulation. Though larger and longitudinal cohorts are needed, this unique combination of SVM and RNM shall help to map objectively KOA descriptors. Acknowledgements: Catalan & Spanish governments 2020FI_b00680; STRATO-PID2021126469ob-C21-2, European Commission (MSCA-TN-ETN-2020-Disc4All-955735, ERC-2021-CoG-O-Health-101044828). ICREA Academia

X-Linked Hypophosphataemia (XLH) is a rare, progressive, hereditary phosphate-wasting disorder characterised by excessive activity of fibroblast growth factor 23. The International XLH Registry was established to provide information on the natural history of XLH and impact of treatment on patient outcomes. The cross-sectional orthopaedic data presented are from the first interim analysis. The XLH Registry (NCT03193476) was initiated in August 2017, aims to recruit 1,200 children and adults with XLH, and will run for 10 years. At the time of analysis (Last Patient In: 30/11/2020; Database Lock: 29/03/2021) 579 subjects diagnosed with XLH were enrolled from 81 hospital sites in 16 countries (360 (62.2%) children, 217 (37.5%) adults, and 2 subjects of unknown age). Of subjects with retrospective clinical data available, skeletal deficits were the most frequently self-reported clinical problems for children (223/239, 93.3%) and adults (79/110, 71.8%). Retrospective fracture data were available for 183 subjects (72 children, 111 adults); 50 had a fracture (9 children, 41 adults). In children, fractures tended to occur in tibia/fibula and/or wrist; only adults reported large bone fractures. Joint conditions were noted for 46 subjects (6 children, 40 adults). For adults reporting osteoarthritis, knees (60%), hips (42.5%), and shoulders (22.5%) were the most frequently affected joints. Retrospective orthopaedic surgery data were collected for 151 subjects (52 children, 99 adults). Osteotomy was the most frequent surgery reported (n=108); joint replacements were recorded for adults only. This is the largest set of orthopaedic data from XLH subjects collected to date. Longitudinal information collected during the 10-year Registry duration will generate real-world evidence which will help to inform clinical practice. Authors acknowledge the contribution of all International XLH Registry Steering Committee members

The aim of this research was to determine biomechanical markers which differentiate medial knee osteoarthritis (OA) patients who do and do not show structural progression over a 2-year period. A cohort of 36 subjects was selected from a longitudinal study (Meireles et al 2017) using Kellgren-Lawrence (KL) scores at baseline and 2-year follow-up. The cohort consisted of 10 healthy controls (HC) (KL=0 at both time points), 15 medial knee OA non-progressors (NPKOA) (KL≥1 at baseline and no change over 2 years), and 11 medial knee OA progressors (PKOA) (KL≥1 at baseline and increase of ≥1 over 2 years). 3D integrated motion capture data from three walking trials were processed through a musculoskeletal modelling framework (Smith et al 2016) to estimate knee joint loading parameters (i.e., magnitude of mean contact pressure, and centre of pressure (COP)). Parameters at first and second peak were extracted and compared between groups using Kruskal-Wallis and Mann-Whitney tests. Higher magnitudes were observed in PKOA vs NPKOA, and PKOA vs HC groups at both time points. Additionally, a posterior (1st and 2nd peak), and lateral (2nd peak) shift in medial compartment COP was shown between PKOA and NPKOA, and PKOA and HC subjects. Interestingly, in the studied parameters, no differences were observed between NPKOA and HC groups. Significantly higher magnitude, and a more posterior and lateral COP was observed between PKOA and NPKOA patients. These differences, combined with an absence of difference between NPKOA and HC suggest structural OA progression is driven by a combination of altered loading magnitude and location. These results may serve as guidelines for targeted gait retraining rehabilitation to slow or stop knee OA progression whereby shifting COP anterior and medial and reducing magnitude by ~22% may shift patients from a PKOA to a NPKOA trajectory

Treatment of both simple and complex patella fractures is a challenging clinical problem. The aim of this study was to investigate the biomechanical performance of recently developed lateral rim variable angle locking plates versus tension band wiring used for fixation of simple and complex patella fractures. Twelve pairs of human anatomical knees were used to simulate either two-part transverse simple AO/OTA 34C1 or five-part complex AO/OTA 34C3 patella fractures by means of osteotomies, with each fracture model created in six pairs. The complex fracture pattern was characterized by a medial and a lateral proximal fragment, together with an inferomedial, an inferolateral, and an inferior fragment mimicking comminution around the distal patellar pole. The specimens with simple fractures were pairwise assigned for fixation with either tension band wiring through two parallel cannulated screws, or a lateral rim variable angle locking plate. The knees with complex fractures were pairwise treated with either tension band wiring through two parallel cannulated screws plus circumferential cerclage wiring, or a lateral rim variable angle locking plate. Each specimen was tested over 5000 cycles by pulling on the quadriceps tendon, simulating active knee extension and passive knee flexion within the range of 90° flexion to full knee extension. Interfragmentary movements were captured via motion tracking. For both fracture types, the longitudinal and shear articular displacements measured between the proximal and distal fragments at the central patella aspect between 1000 and 5000 cycles, together with the relative rotations of these fragments around the mediolateral axis were all significantly smaller following the lateral rim variable angle locked plating compared with tension band wiring, p<0.01. Lateral rim locked plating of both simple and complex patella fractures provides superior construct stability versus tension band wiring under dynamic loading

Introduction. Understanding knee joint biomechanics is crucial, but studying Anterior cruciate ligament (ACL) biomechanics in human adolescents is challenging due to limited availability cadaveric specimens. This study aims to validate the adolescent porcine stifle joint as a model for ACL studies by examining the ACL's behavior under axial and torsion loads and assessing its deformation rate, stiffness, and load-to-failure. Methods. Human knee load during high-intensity sports can reach 5-6 times body weight. Based on these benchmarks, the study applied a force equivalent to 5-times body weight of juvenile porcine samples (90 pounds), estimating a force of 520N. Experiments involved 30 fresh porcine stifle joints (Yorkshire breed, Avg 90 lbs, 2-4 months old) stored at -22°C, then thawed and prepared. Joints were divided into three groups: control (load-to-failure test), axially loaded, and 30-degree torsion loaded. Using a servo-hydraulic material testing machine, the tibia's longitudinal axis was aligned with the load sensor, and specimens underwent unidirectional tensile loading at 1 mm/sec until rupture. Data on load and displacement were captured at 100 Hz. Results. One-way ANOVA showed statistically significant differences in maximum failure force among loading conditions (p = 0.0039). Post hoc analysis indicated significant differences between the control and 500N (non-twisted) groups (p = 0.014) and between the control and 500N (twisted) groups (p = 0.003). However, no significant difference was found between 500N (non-twisted) and 500N (twisted) groups (p = 0.2645). Two samples broke from the distal femur growth plates, indicating potential growth plate vulnerability in adolescent porcines. Conclusions. The study validates the adolescent porcine stifle joint as a suitable model for ACL biomechanical research, demonstrating that torsional loads are as damaging to the ACL's integrity as equivalent axial loads. It also highlights the potential vulnerability of growth plates in younger populations, reflected in the porcine model

This study aimed to quantify self-reported outcomes and walking gait biomechanics in patients following primary and revision THA. The specific goals of this study were to investigate: (i) if primary and revision THA patients have comparable preoperative outcomes; and (2) if revision THA patients have worse postoperative outcomes than primary THA patients. Forty-three patients undergoing primary THA for osteoarthritis and 23 patients undergoing revision THA were recruited and followed longitudinally for their first 12 postoperative months. Reasons for revision were loosening (73%), dislocation (9%), and infection (18%). Patients completed the Hip dysfunction and Osteoarthritis Outcome Score (HOOS), and underwent gait analysis preoperatively, and at 3 and 12 months postoperatively. A 10 camera motion analysis system (V5 Vantage, Vicon, UK) recorded marker trajectories (100 Hz) during walking at self- selected speeds. A generic lower-body musculoskeletal model (Gait2392) was scaled using principal component analysis [1] and the inverse kinematics tool in Opensim 3.3 was used to compute joint angles for the lower limbs in the sagittal plane. Independent samples t-test were used to compare patient reported outcomes between the primary and revision groups at each timepoint. Statistical parametric mapping was used to compare gait patterns between the two groups at each timepoint. Preoperatively, patients undergoing primary THA reported significantly worse pain (p<0.001), symptoms (p<0.001), function (p<0.001), and quality of life (p=0.004). No differences were observed at 3 and 12 months postoperatively between patients who had received a primary or revision THA. The only observed difference in gait pattern was that patients with a revision THA had reduced hip extension at 3 months, but no differences were observed preoperatively and 12 months. Despite the suggestions in the literature that revision THA is bound to have worse outcomes compared to primary THA, we found no differences in in patient-reported outcomes and gait patterns at 12 months postoperatively. This suggests that it may be possible, in some circumstances, for patients following revision THA to achieve similar outcomes to their peers undergoing primary THA

To evaluate the therapeutic effect of Pulsed Electromagnetic Field (PEMF) in the treatment of meniscal tears in the avascular region. Seventy-two twelve-week-old male Sprague-Dawley rats with full-thickness longitudinal medial meniscal tears in the avascular region were divided into 3 groups: control group (G. con. ), treated with classic signal PEMF (G. classic. ), and high slew rate signal PEMF(G. HSR. ). The HSR signal has the same pulse and burst frequencies as the classic signal, but with a higher slew rate. Macroscopic observation and histological analysis of the meniscus and articular cartilage were performed to evaluate the meniscal healing and progressions of osteoarthritis. The synovium was harvested for histological and immunofluorescent analysis to assess the intra-articular inflammation. The meniscal healing, articular cartilage degeneration, and synovitis were quantitatively evaluated according to their respective scoring system. Dramatic degenerative changes of the meniscus and articular cartilage were noticed during gross observation and histological evaluation in the control group at 8 weeks. However, the menisci in the two treatment groups were restored to normal morphology with a smooth surface and shiny white color. Particularly, the HSR signal remarkably enhanced the fibrochondrogenesis and accelerated the remodeling process of the regenerated tissue. The meniscal healing scores of PEMF treatment groups were significantly higher than those in the control group at 8 weeks. Specifically, the HSR signal showed a significantly higher meniscal repair score than the classic signal at week 8 (P < .01). The degeneration score (G. con. versus G. classic. : P < .0001; Gcon versus G. HSR. : P < .0001) and synovitis score (G. con. versus Gclassic: P < .0001; G. con. versus G. HSR. : P = .0002) of the control groups were significantly higher than those in the two treatment groups. PEMF promoted the healing of meniscal tears in the avascular region and restored the injured meniscus to its structural integrity in a rat model. Compared to the classic signal, the HSR signal showed the increased capability to promote fibrocartilaginous tissue formation and modulate the inflammatory environment and therefore protected the knee joint from post-traumatic osteoarthritis development