Osteoarthritis (OA) of the equine distal interphalangeal joint (DIPJ) is a common cause of lameness. MicroRNAs (miRNAs) from biofluids such as plasma and synovial fluid make promising biomarker and therapeutic candidates.

The objectives of this study are (1) Identify differentially expressed (DE) miRNAs in mild and severe equine DIPJ OA synovial fluid samples and (2) Determine the effects of DE miRNAs on equine chondrocytes in monolayer culture.

Synovial fluid samples from five horses with mild and twelve horses with severe DIPJ OA were submitted for RNA-sequencing; OA diagnosis was made from MRI T2 mapping, macroscopic and histological evaluation. Transfection of equine chondrocytes (n=3) was performed using the Lipofectamine® RNAiMAX system with a negative control and a miR-92a mimic and inhibitor. qPCR was used to quantify target mRNA genes.

RNA-seq showed two miRNAs (miR-16 and miR-92a) were significantly DE (p<0.05). Ingenuity Pathway Analysis (IPA) identified important downstream targets of miR-92a involved in the pathogenesis of osteoarthritis and so this miRNA was used to transfect equine chondrocytes from three donor horses diagnosed with OA. Transfection was successfully demonstrated by a 1000-20000 fold increase in miR-92a expression in the equine chondrocytes. There was a significant (p<0.05) increase in COMP, COL3A1 and Sox9 in the miR-92a mimic treatment and there was no difference in ADAMTS-5 expression between the miR-92 mimic and inhibitor treatment.

RNA-seq demonstrated miR-92a was downregulated in severe OA synovial fluid samples which has not previously been reported in horses, however miR-92a is known to play a role in the pathogenesis of OA in other species. Over expression of miR-92a in equine chondrocytes led to significantly increased COMP and Sox9 expression, consistent with a chondrogenic phenotype which has been identified in human and murine chondrocytes.

Is Non-Weight-Bearing Necessary? (INWN) is a pragmatic multicentre randomised controlled trial comparing immediate protected weight-bearing (IWB) with non-weight-bearing cast immobilisation (NWB) following ankle fracture fixation (ORIF). This trial compares; functional outcomes, complication rates and performs an economic analysis to estimate cost-utility.

IWB within 24hrs was compared to NWB, following ORIF of all types of unstable ankle fractures. Skeletally immature patients and tibial plafond fractures were excluded. Functional outcomes were assessed by the Olerud-Molander Ankle Score (OMAS) and RAND-36 Item Short Form Survey (SF-36) taken at regular follow-up intervals up to one year. A cost-utility analysis via decision tree modelling was performed to derive an incremental cost effectiveness ratio (ICER). A standard gamble health state valuation model utilising SF-36 scores was used to calculate Quality Adjusted Life Years (QALYs) for each arm.

We recruited 160 patients (80 per arm), aged 15 to 94 years (M = 45.5), 54% female. Complication rates were similar in both groups. IWB demonstrated a consistently higher OMAS score, with significant values at 6 weeks (MD=10.4, p=0.005) and 3 months (MD 12.0, p=0.003). Standard gamble utility values demonstrated consistently higher values (a score of 1 equals perfect health) with IWB, significant at 3 months (Ẋ = 0.75 [IWB] / 0.69 [NWB], p=0.018). Cost-utility analysis demonstrated NWB is €798.02 more expensive and results in 0.04 fewer QALYs over 1 year. This results in an ICER of −€21,682.42/QALY. This negative ICER indicates cost savings of €21,682.42 for every QALY (25 patients = 1 QALY gain) gained implementing an IWB regime.

IWB demonstrates a superior functional outcome, greater cost savings and similar complication rates, compared to NWB following ankle fracture fixation.

Abstract

Abstract

Abstract

Introduction and Objective

Ankle fractures are common and affect young adults as well as the elderly. An unstable ankle fracture treatment typically involves surgical fixation, immobilisation, and modified weight-bearing for six weeks. Non-weight bearing (NWB) cast immobilisation periods were used to protect the soft tissue envelope and osteosynthesis. This can have implications on patient function and may reduce independence, mobility and return to work. Newer trends in earlier mobilisation compete with traditional NWB doctrine, and weak consensus exists as to the best postoperative strategy. The purpose of this trial is to investigate the safety and efficacy of immediate weight-bearing (IWB) and range of motion (ROM) exercise regimes following ORIF of unstable ankle fractures with a particular focus on functional outcomes and complication rates.

Abstract

Abstract

Osteoarthritis (OA) affects over 8.75 million people in the UK creating the need for early stage interventions. Osteochondral (OC) grafting has been used to repair full thickness lesions but the efficacy of this therapy is questionable.

As a first step in developing a testing framework able to predict the potential and suitability of OC grafts for repair, here, we present experimental data to be used in informing boundary conditions, input parameters and testing sequences for developing and verifying an FE model of the interaction of OC grafts and surrounding host tissue.

Ten OC cylindrical grafts (height: 10mm; diameter: n=5–6.5mm; n=5–8.5mm) were harvested from adult porcine femurs (60–70kg). Unconfined compression tests were conducted using an Instron3365 with a 500N load cell and a BioBath filled with PBS at 37ºC. The OC grafts (prior to separation of cartilage and bone) and cartilage underwent four 5% strain (of cartilage layer) steps with displacement rate of 0.005mm/sec, each followed by a 45-minute relaxation. Final strain was 20%. Bone underwent a single displacement of 20% strain of bone at same displacement rate.

Young's moduli ranged from 6.2–42.0MPa, 0.7–3.9MPa, 46.8–123.7MPa for OC graft, cartilage and bone, respectively. The coefficient of variance between OC Grafts, cartilage and bone was 70.6%, 71.8%, and 25.2%, respectively.

Dispersion between samples was high. This may be due to intrinsic tissue variability but also due to the testing protocol: for cartilage in particular, the load was at the low end of the load cell capacity and the sample aspect ratio was poor for compressive testing. This work provides insight in understanding the effect of individual patient's and/or individual grafts used during osteochondral grafting. The results compel the need to accurately model these tissues when developing specimen-specific FE models for OC grafting.

Osteochondral (OC) grafting is one available method currently used to repair full thickness cartilage lesions with good results clinically when grafting occurs in patients with specific positive prognostic factors. However, there is poor understanding of the effect of individual patient and surgical factors. With limited tissue availability, development of Finite Element (FE) models taking into account these variations is essential. The aim of this study was to evaluate the effect of altering the material properties of OC grafts and their host environment through computer simulation.

A generic FE model (ABAQUS CAE 2017) of a push-out test was developed as a press-fit bone cylinder (graft) sliding inside a bone ring (host tissue). Press-fit fixation was simulated using an interference fit. Overlap between host and graft (0.01mm–0.05mm) and coefficient of friction (0.3–0.7) were varied sequentially. Bone Young's moduli (YM) were varied individually between graft and host within the range of otherwise derived tissue moduli (46MPa, 82MPa, 123MPa).

Increasing both overlap and frictional coefficient increased peak dislodging force independently (overlap: 490% & frictional coefficient: 176% across range tested). Increasing bone modulus also increased dislodging force, with host bone modulus (107%, 128%, and 140% increase across range, when Graft YM = 123MPa, 82 MPa, and 46MPa, respectively) having a greater influence than graft modulus (28%, 19% and 10% increase across range, when Host YM = 123 MPa, 82MPa and 46MPa, respectively).

As anticipated increasing overlap and friction caused an increase in force necessary to dislodge the graft. Importantly, differentially changing the graft and host material properties changed the dislodging force indicating that difference between graft and host may be an important factor in the success or failure clinically of osteochondral grafting.

Formation of micro-cracks occurs in bone due to daily activities. Through a mechanism of self-repair, these micro-cracks are detected, and the damaged areas are restored, avoiding further propagation. The Scissors Model suggests that the osteocyte processes that cross the micro-cracks break as consequence of the cyclic displacements of the micro-crack faces, due to fatigue, and this triggers the remodelling processes. A fresh bovine tibia bone was cut in sections oriented 20° from the transversal direction. The cortical bone was sliced using a circular saw and shaped to the dimensions: 20 × 10 × 1 (mm) and the surfaces were polished. µCT images were obtained from all the samples (μCT 40, Scanco Medical, Brüttisellen, Switzerland). From the DICOM files, the geometries were reconstructed and meshed using tetrahedrons, in ICEM CFD. The Elasticity Modulus (E) was determined in Bonemat, by applying an empirical relationship Elasticity-Density from the literature. The parts were then imported into ANSYS APDL to simulate micro-crack propagation in bone. This model will be validated with further experimental work where the micro-crack will be initiated in the prepared samples and propagated due to fatigue loading, and the osteocyte processes will be visualized in the Scanning Electron Microscope (SEM). This investigation aims to study how cyclic loading in bones and failure of osteocyte processes can trigger target the mechanism of bone remodelling. The resulting model can later contribute for the investigation of treatments for bone diseases such as osteoporosis and the response of bone to the presence of orthopaedic implants.

There is a critical need for safe innovation in total joint replacements to address the demands of an ageing yet increasingly active population. The development of robust implant designs requires consideration of uncertainties including patient related factors such as bone morphology but also activity related loads and the variability in the surgical procedure itself. Here we present an integrated framework considering these sources of variability and its application to assess the performance of the femoral component of a total hip replacement (THR).

The framework offers four key features. To consider variability in bone properties, an automated workflow for establishing statistical shape and intensity models (SSIM) was developed. Here, the inherent relationship between shape and bone density is captured and new meshes of the target bone structures are generated with specific morphology and density distributions. The second key feature is a virtual implantation capability including implant positioning, and bone resection. Implant positioning is performed using automatically identified bone features and flexibly defined rules reflecting surgical variability. Bone resection is performed according to manufacturer guidelines. Virtual implantation then occurs through Boolean operations to remove bone elements contained within the implant's volume. The third feature is the automatic application of loads at muscle attachment points or on the joint contact surfaces defined on the SSIM. The magnitude and orientation of the forces are derived from models of similar morphology for a range of activities from a database of musculoskeletal (MS) loads. The connection to this MS loading model allows the intricate link between morphology and muscle forces to be captured. Importantly, this model of the internal forces provides access to the spectrum of loading conditions across a patient population rather than just typical or average values. The final feature is an environment that allows finite element simulations to be run to assess the mechanics of the bone-implant construct and extract results for e.g. bone strains, interface mechanics and implant stresses. Results are automatically processed and mapped in an anatomically consistent manner and can be further exploited to establish surrogate models for efficient subsequent design optimization. To demonstrate the capability of the framework, it has been applied to the femoral component of a THR.

An SSIM was created from 102 segmented femurs capturing the heterogeneous bone density distributions. Cementless femoral stems were positioned such that for the optimal implantation the proximal shaft axis of the femurs coincided with the distal stem axis and the position of the native femoral head centre was restored. Here, the resection did not affect the greater trochanter and the implantations were clinically acceptable for 10000 virtual implantations performed to simulate variability in patient morphology and surgical variation. The MS database was established from musculoskeletal analyses run for a cohort of 17 THR subjects obtaining over 100,000 individual samples of 3D muscle and joint forces. An initial analysis of the mechanical performance in 7 bone-implant constructs showed levels of bone strains and implant stresses in general agreement with the literature.

Summary Statement

A population based finite element study that accounts for subject-specific morphology, density and load variations, suggests that osteoporosis does not markedly lower the mechanical compliance of the proximal femur to routine loads.

Aims

Osteoporosis and abnormal bone metabolism may prove to be significant factors influencing the outcome of arthroplasty surgery, predisposing to complications of aseptic loosening and peri-prosthetic fracture. We aimed to investigate baseline bone mineral density (BMD) and bone turnover in patients about to undergo arthroplasty of the hip and knee.

The aim of this study was to perform a comprehensive evaluation of the changes in function from pre- to post-surgery in total and unilateral knee arthroplasty (UKA/TKA) patients. Twenty healthy (age 62.4 ±5.9, 11 male), 14 UKA (age 60.9 ±10.1, 8 male) and 17 TKA (age 67.2 ±8.1, 9 male) patients were studied. KA patients were assessed four weeks pre- and six months post-operation. Measures of perceived pain and function were collected using Oxford Knee Score (OKS) questionnaire. Tests of objective function included joint range of motion (RoM), ultrasound imaging, and 3-D motion analysis/inverse modelling from gait and sit-stand. An optimal set of variables was used to classify KA function using the Cardiff DST method. Pre-KA and healthy individuals were accurately classified (96%). Post-operation questionnaire measures of function improved for both UKA and TKA groups. However, observed measures of RoM, muscle atrophy and gait had only limited gains. This resulted in 57% of UKA and only 27% of TKA patients being classified as healthy post-operation. The results of this study show that 6 months post-surgery UKA patients had higher function than TKA. Using statistical approaches to combine functional assessments has provided an accurate platform to classify function and estimate changes from pre- to post-surgery. The clinical application of this tool requires further investigation and comparison to commonly used clinical techniques.

Purpose and background

Effective reassurance is an essential element of treatment for conditions that do not require further investigations, referrals and on-going monitoring. However, research defining what reassurance should consist of and how to deliver it is scarce. The aim of this review was to identify consultation-related processes that improved patients' outcomes, in order to build an evidence-based model of effective reassurance in primary care.

Background

Doubt has been cast over the accuracy of dermatome charts. This study investigated a large group of patients with known lumbar nerve root compression (NRC), and identified whether their radicular pain corresponded with the predicted distribution on a dermatome chart.

Early diagnosis of delayed- and non-union tibial fractures is difficult, but treatment options are available if timely data are available. Direct correlation between implant forces and healing status is difficult during stance phase loading due to soft tissue forces. This ongoing study seeks to find a minimal set of strain gauge sites needed to determine healing at any of several fracture sites, using isometric loading suitable for routine clinical usage. A series of instrumented tibial nails are being used to help determine whether an alternative technology can replace or augment existing routine methods for assessment of fracture healing.

In a prior study, a single strain gauge positioned close to the fracture site had produced mixed results. In the current study, a TRIGEN META NAIL, 10mm OD x 380mm long, was instrumented with 8 gauged sites spiraled down the nail at 34mm axial and 120deg angular separation (Gen1), and loaded in a Sawbone model in offset axial compression, 3 point bending and torque.

In order to gain early clinical results, and in a design informed by the Gen1 data, a set of instrumented nails have been made for an ovine wireless telemetry study (Gen3a), shortly to commence, in which the tibial nail has been over-gauged enabling multiple d.o.f. measurements to be made during gait, torque, axial compression and 3 point bending; the latter protocols offering more controlled patient postures. This study is to be followed by a similar human study (Gen3) involving five subjects (12 gauges per nail). Meanwhile, a parallel biomechanical study involving six nails with 20 gauges each is also planned.

In the Gen1 study, the strains diminished with distance from the fracture site and with out-of-plane sites during bending. During torque, however, the response was much more uniform for all strain sites. Significant increases in strains due to both loading regimes were seen in the fractured case vs. an intact bone.

Preliminary conclusions are that strains measured due to applied torque may offer a more sensitive and fracture site-independent means of assessing healing than induced bending. We now aim to confirm these observations in animal and human studies.

Tribology and wear of articular cartilage is associated with the mechanical properties, which are governed by the extracellular matrix (ECM). The ECM adapts to resist the loads and motions applied to the tissue. Most investigations take cartilage samples from quadrupeds, where the loading and motions are different to human. However, very few studies have investigated the differences between human and animal femoral head geometry and the mechanical properties of cartilage.

This study assessed the differences between human, porcine, ovine and bovine cartilage from the femoral head; in terms of anatomical geometry, thickness, equilibrium elastic modulus and permeability.

Diameter of porcine (3-6 months old), bovine (18-24 months old), ovine (4 years old) and human femoral heads were measured (n=6). Plugs taken out of the superior region of each femoral head and creep indentation was performed. The human femoral heads were obtained from surgery due to femoral neck fracture. Cartilage thickness was measured by monitoring the resistive force change as a needle traversed the cartilage and bone at a constant feed rate using a mechanical testing machine. The percentage deformation over time was determined by dividing deformation by thickness. A biphasic finite element model was used to obtain the intrinsic material properties of each plug. Data is presented as the mean ± 95% confidence limits. One-way ANOVA was used to test for significant differences (p < or = 0.05).

Significant differences in average femoral head diameter were observed between all animals, where bovine showed the largest femoral head. Human cartilage was found to be significantly thicker than cartilage from all quadrupedal hips. Human cartilage had a significantly larger equilibrium elastic modulus compared to porcine and bovine cartilage. Porcine articular cartilage was measured to be the most permeable which was significantly larger than all the other species. No significant difference in permeability was observed between human and the other two animals: bovine and ovine (Table 1).

The current study has shown that articular cartilage mechanical properties, thickness and geometry of the femoral heads differ significantly between different species. Therefore, it is necessary to consider these variations when choosing animal tissue to represent human.

Post-operative regimes involving the use of intra-articular local anaesthetic infiltration may allow early mobilisation in patients undergoing total knee arthroplasty. Few studies have evaluated such regimes outside specialist arthroplasty units. We aimed to determine whether an enhanced recovery programme including the use of local anaesthetic administration could be adapted for use in a district general setting.

Following introduction of this regime to our unit, 100 consecutive patients undergoing primary total knee arthroplasty were reviewed. 56 patients underwent a standard analgesic regime involving a general or spinal anaesthetic and oral analgesics post operatively (group1). 48 patients underwent the newly introduced regime, which included pre-operative counselling, peri-articular local anaesthetic infiltration at operation and intra-articular local anaesthetic top-up administration post-operatively for 24 hours (group 2). Length of stay, post-operative analgesic requirements, and range of knee motion post-operatively were compared.

Median length of stay was less for patients in group 2 compared with those in group 1 (4 days compared to 5 days, p<0.05). Patients in group 2 required lower total doses of opiate analgesia post-operatively. 90% of patients in group 2 were ambulant on the first post operative day, compared with less than 25% of patients in group 1. Mean knee flexion on discharge was greater in patients in group 2 compared with those in group 1 (85 degrees compared with 75 degrees). No infective complications from intra-articular catheter placement were observed. However, technical difficulties were encountered during the introduction period, including loss of catheter placement, leakage of local anaesthetic and adaptation of nursing time for top-up anaesthetic administration.

A rehabilitation regime involving local anaesthetic infiltration for total knee arthroplasty can successfully be adapted for use in a district general setting. Our results suggest if initial technical difficulties are overcome, this regime can provide effective postoperative analgesia, early mobilisation and reduced hospital stay.