Aims

The surgical helmet system (SHS) was developed to reduce the risk of periprosthetic joint infection (PJI), but the evidence is contradictory, with some studies suggesting an increased risk of PJI due to potential leakage through the glove-gown interface (GGI) caused by its positive pressure. We assumed that SHS and glove exchange had an impact on the leakage via GGI.

Aims

This study investigates head-neck taper corrosion with varying head size in a novel hip simulator instrumented to measure corrosion related electrical activity under torsional loads.

Arthritis is a common and debilitating disease and is associated with an increased fall risk. The purpose of this study was to examine the effect of impacted joint and limb on fall risk as measured by the margin of stability (MOS). There were 110 participants, including healthy controls (HC; n=30), ankle arthritis (AA; n=30), knee arthritis (KA; n=20) and hip arthritis (HA; n=30) patients. All protocols were Institutional Review Board approved and all participants signed informed consent. Participants walked approximately 6 meters at a self-selected pace. MOS was calculated in the foot coordinate system in the anterior/posterior (AP) and medial/lateral (ML) directions at heel strike. A one-way ANOVA was used to examine group effects (HC, AA, KA, HA) on gait speed. A two-way repeated measures ANOVA was used to examine the effects of limb (Non-Surgical, Surgical) and group on AP and ML MOS. HC had the fastest gait speed (1.40±0.24 m/s; p<0.001) when compared to AA (0.85±0.24 m/s), KA (0.94±0.22 m/s) and HA (1.05±0.22 m/s). HA participants had a greater gait speed compared to AA (p=0.004). AP MOS was greater in the surgical limb compared to the non-surgical limb for AA (p<0.001) and HA (p<0.001). AP MOS was smaller in HC compared to AA, KA, and HA, regardless of limb (p<0.030). AP MOS was similar between AA, KA, and HA for the non-surgical limb (p>0.194) and the surgical limb (p>0.096). ML MOS was greater in the surgical compared to non-surgical limb (p=0.003). ML MOS was smaller in KA participants compared to all other groups (p<0.001). Our results demonstrate stability during gait varies between limbs in arthritis patients, with a more conservative pattern for the surgical limb and suggest KA may be at an increased risk of falls with a smaller ML MOS

Bone turnover and microdamage are impacted by skeletal metastases which can contribute to increased fracture risk. Treatments for metastatic disease may further impact bone quality. This study aimed to establish an understanding of microdamage accumulation and load to failure in healthy and osteolytic vertebrae following cancer treatment (stereotactic body radiotherapy (SBRT), zoledronic acid (ZA), or docetaxel (DTX)). Forty-two 6-week old athymic female rats (Hsd:RH-Foxn1rnu, Envigo) were studied; 22 were inoculated with HeLa cervical cancer cells through intracardiac injection (day 0). Animals were randomly assigned to four groups: untreated (healthy=5, osteolytic=6), SBRT on day 14 (healthy=6, osteolytic=6), ZA on day 7 (healthy=4, osteolytic=5), and DTX on day 14 (healthy=5, osteolytic=5). Animals were euthanized on day 21. L1-L3 motion segments were compression loaded to failure and force-displacement data recorded. T13 vertebrae were stained with BaSO. 4. and µCT imaged (90kVp, 44uA, 4.9µm) to visualize microdamage location and volume. Damage volume fraction (DV/BV) was calculated as the ratio of BaSO. 4. to bone volume. Differences in mean load-to-failure were compared using three-way ANOVA (disease status, treatment, cells injected). Differences in mean DV/BV between treatment groups were compared using one-way ANOVA. Treatment had a significant effect on load-to-failure (p=0.004) with ZA strengthening the healthy and osteolytic vertebrae. Reduced strength post SBRT seen in the metastatic (but not the healthy) group may be explained by greater tumor involvement secondary to higher cell injection concentrations. Untreated metastatic samples had higher DV/BV (16.25±2.54%) compared to all treatment groups (p<0.05) suggesting a benefit of treatment to bone quality. Focal and systemic cancer treatments were shown to effect load-to-failure and microdamage accumulation in healthy and osteolytic vertebrae. Developing a better understanding of how treatments effect bone quality and mechanical stability is critical for effective management of patients with spinal metastases

We aimed to examine outcomes between displaced femoral neck fracture (FNF) patients managed with total hip arthroplasty (THA) or hemi-arthroplasty (HA) via the anterolateral vs. posterior approach. We used data from the HEALTH trial (1,441 patients aged ≥50 with displaced FNFs randomized to THA vs. HA). We calculated each patient's propensity to undergo arthroplasty via the posterior approach, and matched them to 1 control (anterolateral approach) based on age (±5 years), and propensity score. We used Chi-Square/Fisher-Exact tests to compare dichotomous outcomes, and repeated measures ANOVA to examine differences in patient-reported outcomes (via the WOMAC subscores) from baseline to one-year postoperative. We used logistic regression to identify independent predictors of reoperation for instability in the posterior group. We identified 1,306 patients for this sub-analysis, 876 (67.1%) who received arthroplasty via an anterolateral approach, and 430 (32.9%) a posterior approach. The unadjusted rate of reoperation was significantly higher in the posterior group (10.7% vs. 7.1%). Following propensity score matching, we retained 790 patients (395 per group), with no between-group differences in patient, fracture, or implant characteristics. The matched cohort had a higher rate of comorbidities, and were less likely to be employed vs. the unmatched cohort. The rate of treatment for dislocation remained higher in the posterior group (6.1% vs. 2.0%) following matching. Repeated measures ANOVA revealed significantly better WOMAC pain, stiffness, function, and total scores in the posterior group. Between-group differences at 12-months were: pain - 0.59 (0.03–1.15); stiffness - 0.62 (0.35–0.87); function - 2.99 (0.12–5.86); total - 3.90 (0.24–7.56). We identified THA (vs. HA, odds ratio 2.05 [1.05–4.01]) as the only independent predictor of treatment for dislocation in the posterior group. Our analyses revealed that compromised patients with displaced FNFs who undergo arthroplasty via the posterior approach may report better symptoms at one-year vs. the anterolateral approach, despite a higher odds of reoperation for instability

Adult Spine Deformity (ASD) is a degenerative condition of the adult spine leading to altered spine curvatures and mechanical balance. Computational approaches, like Finite Element (FE) Models have been proposed to explore the etiology or the treatment of ASD, through biomechanical simulations. However, while the personalization of the models is a cornerstone, personalized FE models are cumbersome to generate. To cover this need, we share a virtual cohort of 16807 thoracolumbar spine FE models with different spine morphologies, presented in an online user-interface platform (SpineView). To generate these models, EOS images are used, and 3D surface spine models are reconstructed. Then, a Statistical Shape Model (SSM), is built, to further adapt a FE structured mesh template for both the bone and the soft tissues of the spine, through mesh morphing. Eventually, the SSM deformation fields allow the personalization of the mean structured FE model, leading to generate FE meshes of thoracolumbar spines with different morphologies. Models can be selectively viewed and downloaded through SpineView, according to personalized user requests of specific morphologies characterized by the geometrical parameters: Pelvic Incidence; Pelvic Tilt; Sacral Slope; Lumbar Lordosis; Global Tilt; Cobb Angle; and GAP score. Data quality is assessed using visual aids, correlation analyses, heatmaps, network graphs, Anova and t-tests, and kernel density plots to compare spinopelvic parameter distributions and identify similarities and differences. Mesh quality and ranges of motion have been assessed to evaluate the quality of the FE models. This functional repository is unique to generate virtual patient cohorts in ASD. Acknowledgements: European Commission (MSCA-TN-ETN-2020-Disc4All-955735, ERC-2021-CoG-O-Health-101044828)

Introduction. Fibula shortening with an intact anterior tibiofibular ligament (ATFL) and medial ligament instability causes lateral translation of the talus. Our hypothesis was that the interaction of the AITFL tubercle of the fibular with the tibial incisura would propagate lateral translation due to the size differential. Aim. To assess what degree of shortening of the fibular would cause the lateral translation of the talus. Methodology. Twelve cadaveric ankle specimens were dissected removing all soft tissue except for ligaments. They were fixed on a specially-designed platform within an augmented ankle cage allowing tibial fixation and free movement of the talus. The fibula was progressively shortened in 5mm increments until complete ankle dislocation. The medial clear space was measured with each increment of shortening. Results. The larger AITFL tubercle interaction with the smaller tibial incisura caused a significant increase in lateral translation of the talus. This occurred in most ankles between 5–10mm of fibular shortening. The medial clear space widened following 5mm of shortening in 5 specimens (mean=2.0725, SD=±2.5338). All 12 specimens experienced widening by 10mm fibula shortening (Mean=7.2133mm, SD=±2.2061). All specimens reached complete dislocation by 35mm fibula shortening. Results of ANOVA analysis found the data statistically significant (p<0.0001). Conclusion. This study shows that shortening of the fibula causes a significant lateral translation of the talus provided the ATFL remains intact. Furthermore, the interaction of the fibula notch with the ATFL tubercle of the tibia appears to cause a disproportionate widening of the medial clear space due to its differential in size. Knowledge of the extent of fibula shortening can guide further intervention when presented with a patient experiencing medial clear space widening following treatment of an ankle fracture

Hypermobility Spectrum Disorder (HSD or hEDS) is attributed to a collagen abnormality associated with excessive joint flexibility. Approximately 90% of females with hip dysplasia have hypermobility. Manifestations of hypermobility in various body systems are unique to every patient, affecting different tissues of the body with varying degrees of severity. Our purposes were to identify the manifestations of hypermobility across multiple body systems and to study the recognition of hypermobility in the medical literature of multiple specialties over multiple decades. A literature search of the major medical disciplines for key words associated with HSD was performed. These specialties included gastroenterology, gynecology, neurology, psychiatry, oral-maxillofacial surgery, cardiology, and orthopaedic surgery. A specialty-specific impact factor (IF) score was calculated as the percentage of research articles that referenced hypermobility as a comorbidity over all articles within that specialty. Statistical differences were identified using single factor ANOVA with significance determined at p<0.05. We reviewed many published, specialty-specific manifestations of hypermobility, and describe them. All six non-orthopaedic specialties demonstrated a continually increasing relative IF ratio throughout the study period with a peak impact average of 0.22 (p<0.05 compared with other time ranges). There was a 93.3% overall increase in IF scores from the 1992–1998 period to the most recent period examined (p<0.05). Hypermobility is increasingly recognized as a significant health issue in multiple disciplines. Since dysplasia is associated with approximately 40% of all primary total hip arthroplasty cases, understanding the multi-system manifestations, and broad impact of hypermobility on patients, is relevant for every hip surgeon. We are expanding our research into other medical disciplines, including urology, ophthalmology, dermatology, clinical psychology, and others

This study investigated concurrent talar dome injuries associated with tibial pilon fractures, mapping their distribution across the proximal talar dome articular surface. It compared the two main mechanisms of injury (MOI), falling from a height and motor vehicle accident (MVA), and whether the fractures were open or closed. From a previously compiled database of acute distal tibial pilon fractures (AO/OTA 43B/C) in adults of 105 cases, 53 cases were identified with a concurrent injury to the talar dome with a known mechanism of injury and in 44 it was known if the fracture was open or closed. Case specific 2D injury maps were created using a 1x1mm grid, which were overlayed in an Excel document to allow for comparative analyses. A two-way ANOVA was conducted that examined the effect of both MOI and if the fracture was open or closed on what percentage of the talar dome surface was injured. There was a statistically-significant difference between the average percentage of injured squares on the talar dome by both whether the fracture was open or closed (f(1)=5.27, p= .027) and the mechanism of injury (f(1)=8.08, p= .007), though the interaction between these was not significant (p= .156). Open injuries and injuries that occurred during an MVA were more likely to increase the surface area of the talar dome injuries. We have identified both MOI and if the fracture was either open or closed impacts the size of the injury present on the talar dome. Future research will investigate the aetiology of the differences noted, highlighting the clinical implications. Surgeons treating tibial pilon fractures caused by either a MVA or an open fracture, should be aware of an increased risk of large injuries to the surface of the talar dome

The study compared thigh-shank and shank-foot coordination during gait before and after total knee arthroplasty (TKA) with controls (CTRL). Twenty-seven patients (male=15/female=12; age=63.2±6.9 years) were evaluated one month prior to and twelve months after surgery, and compared to 27 controls (male=14/female=13; age=62.2±4.3). The participants were outfitted with a full-body marker set. Gait speed (normalized by leg length) was calculated. The time series of the thigh, shank, and foot orientation in relation to the laboratory coordinate system were extracted. The coordination between the thigh-shank and shank-foot in the sagittal plane were calculated using a vector coding technique. The coupling angles were categorized into four coordination patterns. The stance phase was divided into thirds: early, mid, and late stance. The frequency of each pattern and gait speed were compared using a one-way ANOVA with a post-hoc Bonferroni correction. Walking speed and shank-foot coordination showed no differences between the groups. The thigh-shank showed differences. The pre-TKA group showed a more in-phase pattern compared to the CTRL group during early-stance. During mid-stance, the pre- and post-TKA presented a more in-phase pattern compared to the CTRL group. Regarding shank-foot coordination, the groups presented an in-phase and shank pattern, with more shank phase during mid-stance and more in-phase during late-stance. The pre-TKA group showed greater differences than the post-TKA compared to the controls. The more in-phase pattern in the pre- and post-TKA groups could relate to a reduced capacity for the thigh that leads the movement. During mid-stance in normal gait, the knee is extending, where the thigh and shank movements are in opposite directions. The in-phase results in the TKA groups indicate knee stiffness during the stance phase, which may relate to a muscular deficit or a gait strategy to reduce joint stress

Introduction. Knee dislocations, vascular injuries and floating knee injuries can be initially managed by a external fixator. Fixator design constructs include the AO pattern and the Diamond pattern. However, these traditional constructs do not adhere to basic principles of external fixation. The Manchester pattern knee-spanning external fixator is a new construct pattern, which uses beam loading and multiplanar fixation. There is no data on any construct pattern. This study compares the stability of these designs. Materials & Methods. Hoffman III (Stryker, USA) external fixation constructs were applied to articulated models of the lower limb, spanning the knee with a diamond pattern and a Manchester pattern. The stiffness was loaded both statically and cyclically with a Bose 3510 Electroforce mechanical testing jig (TA Instruments). A ramp to load test was performed initially and cyclical loading for measurement of stiffness over the test period. The results were analysed with a paired t-test and ANOVA. Results. The mean stiffness with the diamond pattern fixator was significantly less stiff than the Manchester pattern fixator – by a factor of 3 (40N/mm vs 115N/mm). Displacement increased in all patterns over simulated loading equating to six weeks. The diamond pattern demonstrated a 50%% increase in displacement over time. The Manchester pattern demonstrated only 20% increase in displacement over time. These are all statistically significant (p<0.01). Conclusions. The aim of an external fixator in knee dislocations and vascular injuries is to provide stability, prevent displacement and protect repairs. Vascular injuries often require fixation for several weeks to protect a repair. The Manchester pattern, applying the principles of external fixation, provides a stiffer construct and also confers greater stability over the time a fixator may be required. We commend this more informed design for the management of knee dislocations and vascular injuries

Polymethylmethacrylate (PMMA) bone cement is strong in compression, however it tends to fail under torsion. Sufficient pressurisation and subsequent interdigitation between cement and bone are critical for the mechanical interlock of cemented orthopaedic implants, and an irregular surface on the acetabular cup is necessary for reasonable fixation at the cup-cement interface. There is limited literature investigating discrepancies in the failure mechanisms of cemented all-polyethylene acetabular cups with and without cement spacers, under torsional loading. In vitro experimental comparison of three groups of polyethylene acetabular prosthesis (PAP) cemented into prepared sawbone hemipelvises:. * PAP without PMMA spacers maintaining an equal cement mantle circumferentially. (Group 1 n=3). * PAP without PMMA spacers cemented deliberately ‘bottoming-out’ the implant within the acetabulum. (Group 2 n=3). * PAP with PMMA spacers. (Group 3 n=3). The constructs were tested to torstional failure on a custom designed setup, and statistical analysis done by a one-way ANOVA and Tukey-Welsh test. Group 3 demonstrated superior torsional resistance with a statistically significant torque of 145Nm (SD±12Nm) at failure, compared to group 2 (109Nm, SD±7Nm) and group 1 (99Nm, SD±8Nm). Group 3 experienced failure predominantly at the bone-cement interface, in contrast, Groups 1 and 2 exhibited failure predominantly at the cup-cement interface. There was no significant difference between Group 1 and 2. Qualitative analysis of the failure mode indicates the efficient redistribution of stress throughout the cement mantle, consistent with the greater uniformity of cement. PMMA spacers increase the resistance to torsional failure at the implant-cement interface. Acetabular components without spacers (Groups 1 and 2) failed at the implant-cement interface before the cement-bone interface, at a statistically significantly lower level of torque to failure. Although the PMMA spacers may reduce cement interdigitation at the cement-bone interface the torsional forces required to fail are likely supraphysiological

Introduction. Pes cavovarus is a foot deformity that can be idiopathic (I-PC) or acquired secondary to other pathology. Charcot-Marie-Tooth disease (CMT) is the most common adult cause for acquired pes cavovarus deformity (CMT-PC). The foot morphology of these distinct patient groups has not been previously investigated. The aim of this study was to assess if morphological differences exist between CMT-PC, I-PC and normal feet (controls) using weightbearing computed tomography (WBCT). Methods. A retrospective analysis of WBCT scans performed between May 2013 and June 2017 was undertaken. WBCT scans from 17 CMT-PC, 17 I-PC and 17 healthy normally-aligned control feet (age-, side-, sex- and body mass index-matched) identified from a prospectively collected database, were analysed. Eight 2-dimensional (2D) and three 3-dimensional (3D) measurements were undertaken for each foot and mean values in the three groups were compared using one-way ANOVA with the Bonferroni correction. Results. Significant differences were observed between CMT-PC or I-PC and controls (p< 0.05). Two-dimensional measurements were similar in CMT-PC and I-PC, except for forefoot arch angle (p= 0.04). 3D measurements (foot and ankle offset, calcaneal offset and hindfoot alignment angle) demonstrated that CMT-PC exhibited more severe hindfoot varus malalignment than I-PC (p= 0.03, 0.04 and 0.02 respectively). Discussion. CMT-related cavovarus and idiopathic cavovarus feet are morphologically different from healthy feet, and CMT feet exhibit increased forefoot supination and hindfoot malalignment compared to idiopathic forms. The use of novel three-dimensional analysis may help highlight subtle structural differences in patients with similar foot morphology but aetiologically different pathology

The novel, highly-sensitive and non-destructive method for the quantification of the osteogenic potential of bone marrow mesenchymal stem cells (BM-MSCs), by the evaluation of its hydroxyapatite (HA), in vitro is 99mTc-HDP-Labelling. 99mTc-HDP (tracer) binds rapidly to HA and this uptake can be visualized and quantified. This study was performed to evaluate if this method is suitable to perform a real-time assessment during an ongoing cell culture and if the radioactive tracer may influence the cells and their ability to differentiate. BM-MSCs (n=3) were cultivated in 35mm-dishes. Groups 1 and 3 received DMEM-LG based osteogenic media while Groups 2 und 4 were non-osteogenic controls. Groups 1 and 2 (multi-labelling) were incubated with 5 MBq 99mTc-HDP for 30min on day 7 (d7) and the bound activity was measured using an activimeter. Subsequently the cell-culture was continued and again labelled with 99mTc-HDP on day 14 and 21 (d14, d21). Groups 3 and 4 (single labelling), cultivation of the respective triplicates, ended on day 7, 14 and 21 (d7, d14, d21) followed by 99mTc-HDP-Labelling. Statistical analysis using one-factor ANOVA (p<0.05). Absolute tracer uptake increased steadily in both osteogenic groups: 1 (d7: 0.315; d14: 1.093; d21: 3.283 MBq) and 3 (d7: 0.208; d14: 0.822; d: 212.437 MBq) and was significantly higher than in the corresponding non-osteogenic control-group (Group 2 and 4) at all timepoints. (p<0.001). No significant negative effect of the radioactive tracer could be revealed in group 1 (multi radioactive labelling on d7, d14, d21) compared to Group 3 (singe labelling). The 99mTc-Uptake of groups 2 and 4 was not significantly different at any time. Our data show that the repeated exposition to 99mTc-HDP has no negative influence on the osteogenic differentiation potential of BM-MSCs. Therefore, the method is capable of determining the amount of HA during an ongoing cell culture

3D spheroid culture is a bridge between standard 2D cell culture and in vivo research which mimics the physiological microenvironment in scaffold-free conditions. Here, this 3D technique is being investigated as a potential method for engineering bone tissue in vitro. However, spheroid culture can exhibit limitations, such as necrotic core formation due to the restricted access of oxygen and nutrients. It is therefore important to determine if spheroids without a sizeable necrotic core can be produced. This study aims to understand necrotic core formation and cell viability in 3D bone cell spheroids using different seeding densities and media formulations. Differentiated rat osteoblasts (dRObs) were seeded in three different seeding densities (1×10. 4. , 5×10. 4. , 1×10 cells) in 96 well U-bottom cell-repellent plates and in three different media i.e., Growth medium (GM), Mineralisation medium 1 (MM1) and MM2. Spheroids were analysed from day 1 to 28 (N=3, n=2). Cell count and viability was assessed by trypan blue method. One way ANOVA and post-hoc Tukey test was performed to compare cell viability among different media and seeding densities. Histological spheroid sections were stained with hematoxylin and eosin (H&E) to identify any visible necrotic core. Cell number increased from day 1 to 28 in all three seeding densities with a notable decrease in cell viability. 1×10. 4. cells proliferated faster than 5×10. 4. and 1×10. 5. cells and had proportionately similar cell death. The necrotic core area was relatively equivalent between all cell seeding densities. The larger the spheroid size, the larger is the size of the necrotic core. This study has demonstrated that 3D spheroids can be formed from dRobs at a variety of seeding densities with no marked difference in necrotic core formation. Future studies will focus on utilising the bone cell spheroids for engineering scalable scaffold-free bone tissue constructs

To analyse bone stresses in humerus-megaprosthesis construct in response to axial loading under varying implant lengths in proximal humeral replacement following tumour excision. CT scans of 10 cadaveric humeri were processed in 3D Slicer to obtain three-dimensional (3D) models of the cortical and cancellous bone. Megaprostheses of varying body lengths (L) were modelled in FreeCAD to obtain the 3D geometry. Four FE models: group A consisting of intact bone; groups B (L=40mm), C (L=100mm) and D (L=120mm) comprising of humerus-megaprosthesis constructs were created. Isotropic linear elastic behaviour was assigned for all materials. A tensile load of 200N was applied to the elbow joint surface with the glenohumeral joint fixed with fully bonded contact interfaces. Static analysis was performed in Abaqus. The bone was divided at every 5% bone length beginning distally. Statistical analysis was performed on maximum von Mises stresses in cortical and cancellous bone across each slice using one-way ANOVA (0-45% bone length) and paired t-tests (45-70% bone length). To quantify extent of stress shielding, average percentage change in stress from intact bone was also computed. Maximum stress was seen to occur distally and anteriorly above the coronoid fossa. Results indicated statistically significant differences between intact state and shorter megaprostheses relative to longer megaprostheses and proximally between intact and implanted bones. Varying levels of stress shielding were recorded across multiple slices for all megaprosthesis lengths. The degree of stress shielding increased with implant lengthening being 2-4 times in C and D compared to B. Axial loading of the humerus can occur with direct loading on outstretched upper limbs or indirectly through the elbow. Resultant stress shielding effect predicted in longer megaprosthesis models may become clinically relevant in repetitive axial loading during activities of daily living. It is recommended to use shorter megaprosthesis to prevent failure

Nuclear factor erythroid 2–related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is key in maintaining redox homeostasis and the pathogenesis of osteoarthritis (OA) involves oxidative distress. We thus investigated whether Nrf2/ARE signaling may control expression of key chondrogenic differentiation and hyaline cartilage maintenance factor SOX9. In human C-28/I2 chondrocytes SOX9 expression was measured by RT–qPCR after shRNA-mediated knockdown of Nrf2 or its antagonist the Kelch-like erythroid cell-derived protein with cap “n” collar homology-associated protein 1 (Keap1). Putative ARE-binding sites in the proximal SOX9 promoter region were inactivated, cloned into pGL3, and co-transfected with phRL–TK for dual-luciferase assays to verify whether Nrf2 transcriptionally regulates SOX9. SOX9 promoter activity without and with Nrf2-inducer methysticin were analyzed. Sox9 expression in articular chondrocytes was correlated to cartilage thickness and degeneration in wild-type (WT) and Nrf2-knockout mice. Data were analyzed by one-way ANOVA, a Student's t-test, or Wilcoxon rank-sum test, according to the normal distribution. Statistical significance was set to p < 0.05. While Keap1-specific RNAi increased SOX9 expression, Nrf2-specific RNAi significantly decreased it. Putative ARE sites (ARE. 1. , ARE. 2. ) were identified in the SOX9 promoter region. ARE. 2. mutagenesis significantly reduced SOX9 promoter activity, while truncation of ARE. 1. did not. A functional ARE. 2. site was thus essential for methysticin-mediated induction of SOX9 promoter activity. Knee cartilage of young Nrf2-knockout mice further revealed significantly fewer Sox9-positive chondrocytes as compared to old Nrf2-knockout animals, which further showed thinner cartilage and more severe cartilage erosion. Our data suggest that SOX9 expression in articular cartilage is directly Nrf2-dependent and that pharmacological Nrf2 activation may hold potential to diminish age-dependent osteoarthritic changes in knee cartilage through improving protective SOX9 expression

Patients with bone and muscle weakness from disuse have higher risk of fracture and worse post-injury mortality rates. The goal of this current study was to better inform post-fracture rehabilitation strategies by investigating if physical remobilization following disuse by hindlimb unloading improves osteochondral callus formation compared to continued disuse by hindlimb suspension (HLS). We hypothesized that continued HLS would impair callus bone and cartilage formation and that physical rehabilitation after HLS would increase callus properties. All animal procedures were approved by the VCU IACUC. Skeletally mature, male and female C57BL/6J mice (18 weeks) underwent HLS for 3 weeks. Mice then had their right femur fractured by open surgical dissection (stabilized with 24-gauge pin). Mice were then either randomly assigned to continued HLS or allow normal physical weight-bearing remobilization (HLS + R). Mice allowed normal cage activity throughout the experiment served as controls (GC). All mice were sacrificed 14-days following fracture with 4-8 mice (male and female) per treatment. Data analyzed by respective ANOVA with Tukey post-hoc (*p< 0.05; # p < 0.10). Male and female mice showed conserved and significant decreases in hindlimb callus bone formation from continued HLS versus HLS + R. Combining treatment groups regardless of mouse sex, histological analyses using staining on these same calluses demonstrated that HLS resulted in trends toward decreased cartilage cross-sectional area and increased osteoclast density in woven bone versus physically rehabilitated mice. In support of our hypothesis, physical remobilization increases callus bone formation following fracture compared to continued disuse potentially due to increased endochondral ossification and decreased bone resorption. In all, partial weight-bearing exercise immediately following fracture may improve callus healing compared to delayed rehabilitation regimens that are frequently used

Introduction. Osteoarthritis in the foot and ankle affects approximately 30,000 patients annually in the UK. Evidence has shown that excess weight exacerbates foot pain, with significant increases in joint forces. However, despite the current trend for Clinical Commissioning Groups to ration surgery for obese patients, studies have not yet determined the effect of weight loss in obese patients with foot and ankle arthritis. Aim. Pilot study to investigate the effect of simulated weight loss on pain scores in obese patients with symptomatic foot and ankle arthritis. Methods. Following ethical approval, a prospective study of 17 obese patients (mean BMI 39.2, range 31.2 – 50.3) with foot and ankle arthritis was undertaken (BOFAS funded). Under physiotherapist supervision, patients walked for one minute on an anti-gravity treadmill, which allowed simulated weight reduction. Following baseline assessment, reduced BMI was simulated, starting at 20, rising in increments of 5, until each patient's usual BMI was reached. Pain was assessed using a Visual Analogue Scale (VAS). Repeated measures ANOVA was used to assess for significant changes in pain, comparing baseline with each simulated BMI category (significance set at p< 0.05). Results. Simulated weight loss caused a significant reduction in pain (p=0.005, power 0.91). Mean VAS pain scores improved by 24% (p=0.003) and 17% (p=0.040) for BMI categories 20 and 25, compared with baseline. Pain scores were not significantly different comparing BMI categories of 25 and 20. Conclusion. Simulated weight loss to normal BMI significantly decreased pain in obese patients with foot and ankle arthritis. The use of the anti-gravity treadmill to demonstrate the feeling of normal BMI has also provided motivation to several patients to lose weight. The current study could be used to power future studies to investigate the effects of weight loss in foot and ankle patients

The most common reason for revision surgery of total hip replacements is aseptic loosening of implants secondary to osteolysis, which is caused by immune-mediated reactions to implant debris. These debris can cause pseudotumour formation. As revision surgery is associated with higher mortality and infection, it is important to understand the pro-inflammatory process to improve implant survival. Toll-like receptor 4 (TLR4) has been shown to mediate immune responses to cobalt ions. Statin use in epidemiological studies has been associated with reduced risk of revision surgery. In-vitro studies have demonstrated the potential for statins to reduce orthopaedic debris-induced immune responses and there is evidence that statins can modulate TLR4 activity. This study investigates simvastatin's effect on orthopaedic biomaterial-mediated changes in protein expression of key inflammatory markers and soluble-ICAM-1 (sICAM-1), an angiogenic factor implicated in pseudotumour formation. Human macrophage THP-1 cells were pre-incubated with 50µM simvastatin for 2-hours or a vehicle control (VC), before being exposed to 0.75mM cobalt chloride, 50μm3 per cell zirconium oxide or LPS as a positive control, in addition to a further 24-hour co-incubation with 50µM simvastatin or VC. Interleukin −8 (IL-8), sICAM-1, chemokine ligand 2 (CCL2), CCL3 and CCL4 protein secretion was measured by enzyme-linked immunosorbent assay (ELISA). GraphPad Prism 10 was used for statistical analysis including a one-way ANOVA. Pre-treatment with simvastatin significantly reduced LPS and cobalt-mediated IL-8 secretion (n=3) and sICAM-1 protein secretion (n=2) in THP-1 cells. Pre-treatment with simvastatin significantly reduced LPS-mediated but not cobalt ion-mediated CCL2 (n=3) and CCL3 protein (n=3) secretion in THP-1 cells. Simvastatin significantly reduced zirconium oxide-mediated CCL4 secretion (n=3). Simvastatin significantly reduced cobalt-ion mediated IL-8 and sICAM-1 protein secretion in THP-1 cells. This in-vitro finding demonstrates the potential for simvastatin to reduce recruitment of leukocytes which mediate the deleterious inflammatory processes driving implant failure