Obesity is correlated with the development of osteoporotic diseases. Gut microbiota-derived metabolite trimethylamine-n-oxide (TMAO) accelerates obesity-mediated tissue deterioration. This study was aimed to investigate what role TMAO may play in osteoporosis development during obesity.

Mice were fed with high-fat diet (HFD; 60 kcal% fat) or chow diet (CD; 10 kcal% fat) or 0.2% TMAO in drinking water for 6 months. Body adiposis and bone microstructure were investigated using μCT imaging. Gut microbiome and serum metabolome were characterized using 16S rRNA sequencing and liquid chromatography-tandem mass spectrometry. Osteogenic differentiation of bone-marrow mesenchymal cells was quantified using RT-PCR and von Kossa staining. Cellular senescence was evaluated by key senescence markers p16, p21, p53, and senescence association β-galactosidase staining.

HFD-fed mice developed hyperglycemia, body adiposis and osteoporosis signs, including low bone mineral density, sparse trabecular microarchitecture, and decreased biomechanical strength. HFD consumption induced gut microbiota dysbiosis, which revealed a high Firmicutes/Bacteroidetes ratio and decreased α-diversity and abundances of beneficial microorganisms Akkermansiaceae, Lactobacillaceae, and Bifidobacteriaceae. Serum metabolome uncovered increased serum L-carnitine and TMAO levels in HFD-fed mice. Of note, transplantation of fecal microbiota from CD-fed mice compromised HFD consumption-induced TMAO overproduction and attenuated loss in bone mass, trabecular microstructure, and bone formation rate. TMAO treatment inhibited trabecular and cortical bone mass and biomechanical characteristics; and repressed osteogenic differentiation capacity of bone-marrow mesenchymal cells. Mechanistically, TMAO accelerated mitochondrial dysfunction and senescence program, interrupted mineralized matrix production in osteoblasts.

Gut microbial metabolite TMAO induced osteoblast dysfunction, accelerating the development of obesity-induced skeletal deterioration. This study, for the first time, conveys a productive insight into the catabolic role of gut microflora metabolite TMAO in regulating osteoblast activity and bone tissue integrity during obesity.

Chondrocytic activity is downregulated by compromised autophagy and mitochondrial dysfunction to accelerate the development of osteoarthritis (OA). Irisin is a cleaved form of fibronectin type III domain containing 5 (FNDC5) and known to regulate bone turnover and muscle homeostasis. However, little is known about the role of irisin in chondrocytes and the development of OA. This talk will shed light on FNDC5 expression by human articular chondrocytes and compare normal and osteoarthritic cells with respect to autophagosome marker LC3-II and oxidative DNA damage marker 8-hydroxydeoxyguanosine (8-OHdG). In chondrocytes in vitro, irisin improves IL-1β-mediated growth inhibition, loss of specific cartilage markers and glycosaminoglycan production. Irisin further suppressed Sirt3 and UCP- 1 to improve mitochondrial membrane potential, ATP production, and catalase. This attenuated IL-1β-mediated production of reactive oxygen species, mitochondrial fusion, mitophagy, and autophagosome formation. In a surgical murine model of destabilization of the medial meniscus (DMM) intra-articular administration of irisin alleviates symptoms like cartilage erosion and synovitis. Furthermore, gait profiles of the treated limbs improved. In chondrocytes, irisin treatment upregulates autophagy, 8-OHdG and apoptosis in cartilage of DMM limbs. Loss of FNDC5 in chondrocytes correlates with human knee OA and irisin repressed inflammation-mediated oxidative stress and deficient extracellular matrix synthesis through retaining mitochondrial biogenesis and autophagy. The talk sheds new light on the chondroprotective actions of this myokine and highlights the remedial effects of irisin during progression of OA.

Osteoarthritis (OA) is the leading cause of pain and disability worldwide and is characterized by the degenerative changes of articular cartilage. Joint loading is required for cartilage maintenance; however, hyper-physiologic loading is a risk factor for OA. Mechanosensitive ion channels Piezo1 and Piezo2 synergistically transduce hyper-physiologic compression of chondrocytes, leading to chondrocyte death and onset of OA. This injury response is inhibited by Piezo channel loss of function, however the mechanistic role of Piezo channels in vivo is unknown. We examined the hypothesis that deletion of Piezo in chondrocytes will protect mice from joint damage and pain-related behaviors following a surgical destabilization of the medial meniscus (DMM), investigating a key mechanistic and mechanobiological role of these channels in the pathogenesis of OA.

Aggrecan-Cre Piezo1 and Piezo1/2 knockout mice ((Agc)1-CRE^ERT2;Piezo1^fl/flPiezo2^fl/fl) were generated and given a 5-day Tamoxifen regimen at 12-weeks of age (n=6–12/group/sex). Cre-negative mice served as controls. At 16-weeks, mice received DMM surgery on the left knee. 12-weeks following DMM prior to sacrifice, activity and hyperalgesia were measured using spontaneous running wheels and a small animal algometer. Structural changes in bone, cartilage, and synovium were characterized using microCT, histology, and Modified Mankin Score criteria.

Knockout of Piezo1/2 channels was chondroprotective in both sexes following DMM surgery as demonstrated by reduced Modified Mankin Score compared to control animals. Piezo1 KO was chondroprotective in only female mice, indicating a sexually dimorphic response. Piezo1 and Piezo1/2 KO was protective against pain in male mice, while females displayed no differences compared to controls. No changes were observed in bone morphology.

Chondrocyte-specific Piezo1/2 knockout protects the knee joint from structural damage, hyperalgesia and functional deficits in a surgical model of PTOA in male and female mice, illustrating the importance of Piezo channels in response to injury in vivo. Future work aims to interrogate potential sexually dimorphic responses to cartilage damage and investigating Piezo2 KO mice.

Aims

Osteoporosis is characterized by decreased trabecular bone volume, and microarchitectural deterioration in the medullary cavity. Interleukin-19 (IL-19), a member of the IL-10 family, is an anti-inflammatory cytokine produced primarily by macrophages. The aim of our study was to investigate the effect of IL-19 on osteoporosis.

In this work, we propose a new quantitative way of evaluating acute compartment syndrome (ACS) by dynamic mechanical assessment of soft tissue changes. First, we have developed an animal model of ACS to replicate the physiological changes during the condition. Secondly, we have developed a mechanical assessment tool for quantitative pre-clinical assessment of ACS. Our hand-held indentation device provides an accurate method for investigations into the local dynamic mechanical properties of soft tissue and for in-situ non-invasive assessment and monitoring of ACS.

Our compartment syndrome model was developed on the cranial tibial and the peroneus tertius muscles of a pig's leg (postmortem). The compartment syndrome pressure values were obtained by injecting blood from the bone through the muscle.

To enable ACS assessment by a hand-held indentation device we combined three main components: a load cell, a linear actuator and a 3-axis accelerometer. Dynamic tests were performed at a frequency of 0.5 Hz and by applying an amplitude of 0.5 mm.

Another method used to observe the differences in the mechanical properties inside the leg was a 3D Digital Image Correlation (3D-DIC). Videos were taken from two different positions of the pig's leg at different pressure values: 0 mmHg, 15 mmHg and 40 mmHg. Two strains along the x axis (Exx) and y axis (Eyy) were measured.

Between the two pressure cases (15 mmHg and 40 mmHg) a clear deformation of the model is visible. In fact, the bigger the pressure, the more visible the increase in strain is.

In our animal model, local muscle pressures reached values higher than 40 mmHg, which correlate with observed human physiology in ACS. In our presentation we will share our dynamic indentation results on this model to demonstrate the sensitivity of our measurement techniques.

Compartment syndrome is recognised as needing improved clinical management tools. Our approach provides both a model that reflects physiological behaviour of ACS, and a method for in-situ non-invasive assessment and monitoring.

Jellyfish collagens exhibit auspicious perspectives for tissue engineering applications primarily due to their outstanding compatibility with a wide range of cell types, low immunogenicity and biodegradability. Furthermore, derived from a non-mammalian source, jellyfish collagens reduce the risk of disease transmission, minimising therefore the ethical and safety concerns. The current study aims to investigate the potential of 3-dimensional jellyfish collagen sponges (3D-JCS) in promoting bone tissue regeneration.

Both qualitative and quantitative analyses were performed in order to assess adhesion and proliferation of MC3T3 cells on 3D-JCL, as well as cell migration and bone-like ECM production. Histological and fluorescent dyes were used to stain mineral deposits (i.e. Alizarin Red S (ARS), Von Kossa, Tetracycline hydrochloride) while images were acquired using optical and confocal microscopy.

Qualitative data indicated successful adhesion and proliferation of MC3T3 cells on the 3D-JCS as well as cell migration along with ECM production both on the inner and outer surface of the scaffolds. Moreover, quantitative analyses indicated a four-fold increase of ARS uptake between 2- and 3-dimensional cultures (N=3) as well as an eighteen-fold increase of ARS uptake for the 3D-JCS (N=3) when cultured in osteogenic conditions compared to control. This suggests the augmented osteogenic potential of MC3T3 cells when cultured on 3D-JCS. Nevertheless, the cell-mediated mineral deposition appeared to alter the mechanical properties of the jellyfish collagen sponges that were previously reported to exhibit low mechanical properties (compressive modulus: 1-2 kPa before culture).

The biocompatibility, high porosity and pore interconnectivity of jellyfish collagen sponges promoted adhesion and proliferation of MC3T3 cells as well as cell migration and bone-like ECM production. Their unique features recommend the jellyfish collagen sponges as superior biomaterial scaffolds for bone tissue regeneration. Further studies are required to quantify the change in mechanical properties of the cell-seeded scaffolds and confirm their suitability for bone tissue regeneration. We predict that the 3D-JCS will be useful for future studies in both bone and bone-tendon interface regeneration.

Acknowledgments

This research has been supported by a Medical Research Scotland Studentship award (ref: -50177-2019) in collaboration with Jellagen Ltd.

Senescent chondrocyte and subchondral osteoclast overburden aggravate inflammatory cytokine and pro-catabolic proteinase overproduction, accelerating extracellular matrix degradation and pain during osteoarthritis (OA). Fibronectin type III domain containing 5 (FNDC5) is found to promote tissue homeostasis and alleviate inflammation. This study aimed to characterize what role Fndc5 may play in chondrocyte aging and OA development.

Serum and macroscopically healthy and osteoarthritic cartilage were biopsied from patients with knee OA who received total knee replacement. Murine chondrocytes were transfected with Fndc5 RNAi or cDNA. Mice overexpressing Fndc5 (Fndc5Tg) were operated to have destabilized medial meniscus mediated (DMM) joint injury as an experimental OA model. Cellular senescence was characterized using RT-PCR analysis of p16INK4A, p21CIP1, and p53 expression together with ß-galactosidase activity staining. Articular cartilage damage and synovitis were graded using OARSI scores. Osteophyte formation and mechanical allodynia were quantified using microCT imaging and von Frey filament, respectively. Osteoclast formation was examined using tartrate-resistant acid phosphatase staining.

Senescent chondrocyte and subchondral osteoclast overburden together with decreased serum FNDC5 levels were present in human osteoarthritic cartilage. Fndc5 knockdown upregulated senescence program together with increased IL-6, MMP9 and Adamts5 expression, whereas Alcian blue-stained glycosaminoglycan production were inhibited. Forced Fndc5 expression repressed senescence, apoptosis and IL-6 expression, reversing proliferation and extracellular matrix production in inflamed chondrocytes. Fndc5Tg mice showed few OA signs, including articular cartilage erosion, synovitis, osteophyte formation, subchondral plate sclerosis and mechanical allodynia together with decreased IL-6 production and few senescent chondrocytes and subchondral osteoclast formation during DMM-induced joint injury. Mechanistically, Fndc5 reversed histone H3K27me3-mediated IL-6 transcription repression to reduce reactive oxygen species production.

Fndc5 loss correlated with OA development. It was indispensable in chondrocyte growth and anabolism. This study sheds light onto the anti-ageing and anti-inflammatory actions of Fndc5 to chondrocytes; and highlights the chondroprotective function of Fndc5 to compromise OA.

The Femoral Neck System (FNS) was introduced as an alternative device for the fixation of neck of femur fractures (NOFFs). The purported advantages include superior angular and rotatory stability compared to multiple cancellous screws, via a minimally invasive instrumentation that is simpler than conventional fixed angle devices. There were limited clinical studies regarding the utility of this device. We aimed to study the outcomes of NOFFs fixed with the FNS.

This was a single-institution, retrospective review of all undisplaced elderly (≥60 years old) undisplaced young, and displaced young NOFFs fixed with the FNS. Demographics, surgical parameters, radiographic parameters, and clinical outcomes including complications were reviewed.

Thirty-six subjects with a median age of 75 [44,89] years old, had NOFF fixation using the FNS. Thirty-one (86.1%) had undisplaced fractures. There were 6 (16.7%), 26 (72.2%), and 4 (11.1%) subjects with Pauwels types 1, 2, and 3 respectively. Thirty-two (88.9%) had posterior tilt of <20º. The mean duration of surgery was 71±18 minutes. Excluding 4 patients whom required revision surgery, 2 patients whom demised, and 10 patients whom defaulted reviews, the mean follow-up duration was 55±13 weeks. Four complications were recorded, namely implant cut out at the femoral head at week 8, breaking of the locking screw at the run-off region at week 22, avascular necrosis at week 25, and a refracture following near fall, causing the fracture to fail in varus at week 7 postoperation.

While reasonably fast to instrument, failures still occur and it is likely multifactorial. However, the rate of reoperation is lower than what has been reported for NOFFs fixed with the a fixed-angle device or 3 cancellous screws. In conclusion, the FNS is a reasonably safe instrument to use. Surgeons’ discretion is still needed in patient selection, keeping in mind the need for satisfactory radiological parameters.

Aims

This study aimed to explore the role of small colony variants (SCVs) of Staphylococcus aureus in intraosseous invasion and colonization in patients with periprosthetic joint infection (PJI).

Aims

Alcoholism is a well-known detrimental factor in fracture healing. However, the underlying mechanism of alcohol-inhibited fracture healing remains poorly understood.

Aims

We aimed to evaluate the utility of ⁶⁸Ga-citrate positron emission tomography (PET)/CT in the differentiation of periprosthetic joint infection (PJI) and aseptic loosening (AL), and compare it with ^99mTc-methylene bisphosphonates (^99mTc-MDP) bone scan.

Introduction and Objective

Senescent bone cell overburden accelerates osteoporosis. Epigenetic alteration, including microRNA signalling and DND methylation, is one of prominent features of cellular senescence. This study aimed to investigate what role microRNA-29a signalling may play in the development of senile osteoporosis.

Aims

Circular RNAs (circRNAs) are a novel type of non-coding RNA that plays major roles in the development of diverse diseases including osteonecrosis of the femoral head (ONFH). Here, we explored the impact of hsa_circ_0066523 derived from forkhead box P1 (FOXP1) (also called circFOXP1) on bone mesenchymal stem cells (BMSCs), which is important for ONFH development.

Chronic glucocorticoid use causes osteogenesis loss, accelerating the progression of osteoporosis. Histone methylation is shown to epigenetically increase repressive transcription, altering lineage programming of mesenchymal stem cells (MSC). This study is undertaken to characterize the action of histone demethylase UTX to osteogenic lineage specification of bone-marrow MSC and bone integrity upon glucocorticoid treatment.

Bone-marrow MSC were incubated in osteogenic medium containing supraphysiological dexamethasone. Osteogenic gene expression and mineralized nodule formation were probed using RT-PCR and von Kossa staining. The enrichment of trimethylated lysine 27 at histone 3 (H3K27me3) in Dkk1 promoter was quantified using chromatin immunoprecipitation-PCR. Bone mass and trabecular morphometry in methylprednisolone-treated skeletons were quantified using microCT analysis.

Supraphysiological dexamethasone decreased osteogenic genes Runx2 and osteocalcin expression and mineralized matrix production along with reduced UTX expression in MSC. Forced UTX expression attenuated the glucocorticoid-mediated loss of osteogenic differentiation, whereas UTX knockdown provoked osteogenesis loss and cytoplasmic oil overproduction. UTX demethylated H3K27 and reduced the glucocorticoid-mediated the H3K27 enrichment in Dkk1 promoter, reversing beta-catenin signal, but downregulating Dkk1 production by MSC. In vivo, treatment with UTX inhibitor GSK-J4 significantly suppressed bone mineral density, trabecular volume, and thickness along with porous trabecular, fatty marrow and disturbed beta-catenin/Dkk1 histopathology comparable with glucocorticoid-induced osteoporosis condition.

This study offers a productive insight into how UTX protects MSC from methylated histone-mediated osteogenesis repression in the development of glucocorticoid-induced osteoporosis.

Aims

The aim of this study was to explore why some calcar screws are malpositioned when a proximal humeral fracture is treated by internal fixation with a locking plate, and to identify risk factors for this phenomenon. Some suggestions can be made of ways to avoid this error.

Aims

To determine whether half-threaded screw holes in a new titanium locking plate design can substantially decrease the notch effects of the threads and increase the plate fatigue life.

Aims

Patients with metabolic syndrome (MetS) are known to be at increased risk of postoperative complications, but it is unclear whether MetS is also associated with complications after total hip arthroplasty (THA) or total knee arthroplasty (TKA). Here, we perform a systematic review and meta-analysis linking MetS to postoperative complications in THA and TKA.

Background and aims

The Keele STarT Back approach is effective for stratifying patients with low back pain in primary care, but a similar approach has not been tested with a broader range of patients with musculoskeletal (MSK) pain. We report a feasibility and pilot trial examining the feasibility of a future main trial of a primary care based, risk-stratification (STarT MSK) approach for patients with back, neck, knee, shoulder or multi-site pain.

Fatty marrow and bone loss are prominent pathologic features of osteoporosis. DNA hypermethylation shifts mesenchymal stem cells towards adipocytes impairing bone formation. Brown adipocytes produce growth factors advantageous to osteogenesis, whereas white adipocytes secrete pro-inflammatory cytokines deleterious to bone homeostasis. We assess DNA methylation inhibitor action to brown and white adipocyte formation in marrow fat of osteoporotic skeletons. Osteoporotic skeletons in mice were induced by glucocorticoid, ovariectomy or ageing. Marrow adipose volume and bone structure were quantified using OsO4 contrast-μCT imaging. Brown and white adipocytes were probed using immunostaining, RT-PCR and primary bone-marrow mesenchymal stem cell cultures. Abundant marrow fat and spare trabecular bone existed in osteoporotic skeletons. Osteoporosis increased expressions of general adipogenic markers PPARγ2 and FABP4 and white adipocyte markers TCF21 and HOXc9, whereas expressions of brown adipocyte markers PGC-1α and UCP-1 and osteogenic markers Runx2 and osteocalcin were significantly decreased. Number of UCP-1 immunostaining-positive brown adipocytes also reduced in osteoporotic bone. In vitro, DNA methylation inhibitor 5'-aza-deoxycystidine significantly increased brown adipocyte formation and osteogenic differentiation and mitigated dexamethasone-induced white adipocyte formation in mesenchymal stem cells. 5'-aza-deoxycystidine control of brown adipogenesis and white fat formation appeared to be regulated by increasing Wnt3a/β-catenin and reducing Dkk1. Disintegrated brown adipocyte and white fat cell differentiation contribute to osteoporosis pathogenesis. Maintaining DNA hypomethylation promotes Wnt signalling and brown adipocyte differentiation facilitating osteogenic differentiation. This study shed a new light to the contribution of brown adipocytic cells to bone metabolism during osteoporosis.

When joints sustain injury, the release of inflammation cytokines can cleavage matrix proteins and result in cartilage degradation and the subsequent osteoarthritis. RNA therapeutics emerging recently is a very promising approach to efficiently and specifically inhibit disease gene expression. However, the major challenge is how to deliver therapeutic RNA into joint and cartilage. Janus base nanotubes are self-assembled from synthetic Janus bases inspired from DNA base pairs. Based on the charge interaction, we are able to “sandwich” small RNAs among Janus base nanotubes to form tiny, nano-rod shaped delivery vehicles. Such vehicles can be engineered into different sizes and shapes. We have found that short and slim morphologies can greatly increase their penetration to extracellular matrix and delivery into “difficult-to-reach” tissues, such as cartilage and brain. Moreover, by delivering therapeutic siRNA, we have demonstrated its high-efficacy in inhibiting expression of an inflammatory regulator, Interleukin-1 receptor (IL-1R) in articular cartilage. Moreover, the inhibition effect is long-lasting so that joint inflammation and cartilage degradation caused by meniscus injury are greatly inhibited in a mouse model. Therefore, the Janus base nanotubes present a great potential in engineering into nano-structures for RNA delivery. Such approach may become an effective therapeutic against joint inflammation and arthritis.

We present the first systematic review conducted by the UK Defence Medical Services in conjunction with the Cochrane Collaboration. Irrigation fluids are used to remove contamination during the surgical treatment of traumatic wounds in order to prevent infection. This review aims to determine whether there is evidence that one wound irrigation fluid is superior to another at reducing infection. A pre-published methodology was used and two reviewers independently assessed the search results. The search produced 917 studies, of which three met the inclusion criteria. All were studies in open fractures, incorporating a total of 2,903 patients. Each RCT involved a distinct comparison, precluding meta-analysis: i) sterile saline vs. distilled/boiled water; ii) antibiotic solution vs. soap solution; iii) saline vs. soap solution. The odds ratios of infection following irrigation with various fluids was as follows: i) saline vs. distilled or boiled water 0.25 (95%CI 0.08–0.73); ii) antibiotic solution vs. soap 1.42 (95%CI 0.82–2.46); iii) saline vs. soap solution 1.00 (95%CI 0.80–1.26). These results suggest that neither soap nor antibiotic solution is superior to saline and that saline is inferior to distilled or boiled water.

For the management of displaced patellar fractures, surgical fixation using cannulated screws along with anterior tension band wiring is getting popular. Clinical and biomechanical studies have reported that using cannulated screws and a wire instead of the modified tension band with Kirschner wires improves the stability of fractured patellae. However, the biomechanical effect of screw proximity on the fixed construction remains unclear. The aim of this study was to evaluate the mechanical behaviors of the fractured patella fixed with two cannulated screws and tension band at different depths of the patella using finite element method.

A patella model with simple transverse fracture [AO 34-C1] was developed; the surgical fixation consisted of two 4.0-mm parallel partial-threaded cannulated screws with a figure-of-eight anterior tension band wiring using a 1.25-mm stainless steel cable. Two different locations, including the screws 5-mm and 10-mm away from the leading edge of the patella, were used. A tension force of 850 N was applied on the patellar apexes at two loading angles (45° and 0° [parallel] to the long axis) to simulate different loading conditions while knee ambulation. The proximal side (base) of the patella was fixed, and the inferior articular surface was defined as a compression-only support in ANSYS to simulate the support from distal femur condyles. Compression-only support enables the articular surfaces of the present patella to only bear compression and no tension forces.

Under different loading conditions, the fixed fractured patella yielded higher stability during 0° loading of tension force than during 45° loading. When the screws were parallel placed at the depth of 5 mm away from the patellar surface, the deformation of patellar fragment and maximum gap opening at the fracture site were smaller than those obtained by screws placed at the depth of 10 mm away from the patellar surface. Compared to the superficial screw placement, the deeper placement (10 mm) increased the maximum gap opening at the fracture site by 1.56 times under 45° loading, and 1.58 times under 0° loading. The load on the tension band wire of the 10-mm screw placement was 3.12 times (from 230 to 717 N) higher than that of the 5-mm placement. Under the wire, the contact pressure on the patellar surface was higher with the 10-mm screw placement than the 5-mm screw placement. The peak bone contact pressures with the 10-mm placement were 7.7 times (99.5 to 764 MPa) higher.

This is the first numerical study to examine the biomechanical effects of different screw locations on the fixation of a fractured patella using screws and tension band. Based on a higher stability and lower cable tension obtained by the superficial screws placement, the authors recommended the superficial screw placement (5 mm below the leading edge of the patella) rather than the deep screws while fixing the transverse patellar fracture with cannulated screws and cable.

Background and objectives

Low back pain (LBP) is a major health challenge globally. Research has identified common trajectories of pain over time. We aimed to investigate whether trajectories described in one primary care cohort can be confirmed in another, and to determine the prognostic value of factors collected 5 years prior to the identification of the trajectory.

Joint assessment through manual physical examination is a fundamental skill that must be acquired by orthopaedic surgeons. These joint assessments allow surgeons to identify soft tissue injuries (e.g. ligament tears) which are critical in identifying appropriate treatment options.

The difficulty in communicating the feeling of different joint conditions and the limited opportunities for practice can make these skills challenging to learn, resulting in reduced treatment effectiveness and increased costs. This research seeks to improve the training of joint assessment with the creation of a haptic joint simulator that can train surgeons with increased effectiveness.

A first of its kind haptic simulator is presented, which incorporates: a newly defined kinetic knee simulation, a haptic device for user interaction, and a haptic control algorithm. The knee model has been specifically created for this application and allows six degree-of-freedom manipulation of the tibia while considering the effects of ten knee ligament bundles. The model has been mathematically formulated to allow for the high update rates necessary for smooth and stable haptic simulation.

Two quantitative assessments were made of the model to confirm its clinical validity. The first was against the widely used OpenSim biomechanical simulation software. Simulations of the model's performance for both anterior-posterior draw tests and varus-valgus rotation tests showed less than 0.7%RMSE for force and 5.5%RMSE for moments. Crucially, the proposed model could generate updated forces in less than 1ms, compared to 188ms for OpenSim. The second validation of the model was against a cadaveric knee that was tested using a validated robotic testing platform. This comparison showed that the model could generate similar force- motion pathways to the cadaveric knee after the model's parameters were scaled to match.

Having demonstrated that it is possible to create a computational knee model that has good conformance to gold-standard knee simulations and cadaveric recordings, while updating at less than 1ms, this research has overcome a major hurdle. The next stage of this research will be to incorporate the knee model into a full haptic simulator and perform skill acquisition trials. Given the effectiveness of past haptic training systems in aiding clinical skills acquisition, this research offers a promising way to improve surgeon training, and therefore also patient diagnosis and treatment.

Background

Long-term glucocorticoid treatment increases incidence of osteoporotic or osteonecrotic disorders. Excessive bone loss and marrow fat accumulation are prominent features of glucocorticoid-induced osteoporosis. MicroRNA-29 (miR-29) family members reportedly modulate lineage commitment of stem cells. This study was undertaken to define the biological roles of miR-29a in skeletal and fat metabolism in the pathogenesis of glucocorticoid-induced osteoporosis.

Background

Epigenetic regulation of gene transcription affects metabolism of chondrocytes and synovial fibroblasts and is associated with the prevalence of osteoarthritis (OA) of knees. Histone lysine demethylase (KDMs) reportedly modulates tissue homeostasis and deterioration. This study investigated whether KMD6a inhibitor treatment affected the joint injuries in the progression of OA.

Introduction

Total knee arthroplasty [TKA] is a common procedure to relieve painful disability from advanced knee arthritis. However, related blood loss, ranging from 800 to 1200 ml, increase risk and disruption of recovery in anemic patients following TKA. Various methods for blood conservation had been proposed and examined. In the literature, the intra-articular administration of a solution mixing bupivacaine and epinephrine was commonly used after knee surgeries. Therefore, we conducted a retrospective, case controlled review of our primary TKAs to determine the hemostatic efficacy of this regimen following TKAs.

Cannulated screw is commonly used in the fixation of proximal femoral neck fractures. In the literature, several configurations had been proposed for best mechanical support with clinical experiences or biomechanical tests. Although screws in triangle configuration contribute certain fixation stability, but sometimes the surgeons made their own choices have to conduct another fixation pattern for some factors such as fracture type, economic issues, and so on. Therefore the aim of this study is to analyze the mechanical responses of a fractured femur fixed with screws in different configurations, screw materials and screw diameters with finite element method, trying to find the most stable construct.

A solid femur model was built from the CT images of a standard saw bone. Three fracture types of the femoral neck were created according to Pauwel's classification (30?, 50?, 70?) by CAD software. The models of implanted screws were built according to a commercial cannulated screw (Stryker Osteosynthesis, Schoenkirchen/Kiel, Germany) with diameter 6.5mm and 4.5mm by CAD software, too. Three fixation configurations were analyzed in this study, including triangle with superior single screw with titanium diameter 6.5mm, triangle with inferior single screw with diameter 6.5mm and diamond with four stainless screw diameter 4.5mm (fig.1). Totally there were nine models constructed in this study, and all of them were then imported into ANSYS WORKBENCH v14 (Swanson Analysis, Houston, PA, USA) to mesh and further analysis. 700N vertical downward force was applied on the femur head and the distal end of femur shaft was totally fixed.

The triangle fixation with superior single screw resulted in a best stability, but the fracture fixed with screws in a diamond configuration has least fracture gap. The difference of the maximum displacement of the femur head with Pauwel's classification 70?between triangle fixation with superior single screw and diamond configuration is only 0.03mm (1.72–1.69 mm). In most unstable femoral neck fracture [Pauwel's classification 70], the maximum gap distance is 0.59mm under the diamond configuration, while it is 0.63mm as the fracture fixed with a triangle configuration.

Therefore, this study suggests that four 4.5mm stainless screws in a diamond configuration is an alternative for proximal femur fracture once 6.5mm titanium screws are not available.

Summary

This is the first ever study to report the successful elimination of malignant cells from salvaged blood obtained during metastatic spine tumour surgery using a leucocyte depletion filter.

Summary

Our meta-analysis showed that pooled mean blood loss during spinal tumour surgeries was 2180 ml. Standardised methods of calculating and reporting intra-operative blood loss are needed as it would be beneficial in the pre-operative planning of blood replenishment during surgery.

Summary

There is emerging evidence of successful application of IOCS and leucocyte depletion filter in removing tumour cells from blood salvaged during various oncological surgeries. Research on the use of IOCS-LDF in MSTS is urgently needed.

Summary

Neurological deficits resulting from spinal cord compression occur infrequently. When presented with neurological compromise, the most common management was radiotherapy, with surgery only being offered to patients who developed neurological deficit or pathological fracture resulting in unresolved severe pain post radiotherapy.

1.

Introduction

Metal-on-metal (MOM) hip joints have regained a favor in arthroplasty since they own excellent wear resistance. In this study, wear tests by using a hip joint simulator were conducted with MOM bearings of specified 40 mm femoral heads. The influence of clearance on the wear behavior was investigated. Furthermore, an optimized radial clearance was estimated by lubricant film thickness and contact pressure analysis.

Anterior only procedure for stable thoraco-lumbar burst fractures is controversial.

Prospective collection of clinical and radiological data in stable burst fractures with neurological deficit undergoing anterior only decompression and stabilisation with 2-year follow-up.

14 consecutive patients (8 females, 6 males) with two-column thoracolumbar burst fracture and neurological deficit underwent anterior corpectomy/hemi-corpectomy and instrumentation, from February 2007 to February 2009.

Radiological data included classification of fracture (AO classification), kyphus angle and degree of canal compromise. Post-operative CT scans done to assess radiological improvement.

Clinical data included neurological deficit at presentation, improvement or changes in neurology, length of surgery, estimated blood loss, post-operative complications and length of stay.

Commonest mechanism was fall from height. 10 patients had incomplete burst fractures amenable to hemi-corpectomy. 8 of our patients were ASIA D, 4 were ASIA C or lower. They all improved by at least one grade. 2 patients had identical ASIA grade pre and post operatively. Pre-operative spinal canal compromise averaged 52.6% and vertebral body height loss averaged 48.9%. The mean kyphotic angles improved from 19.6° to 7.9 °. There were two cases with minor injury to the diaphragm, one developing a pneumothorax. Mean length of surgery and hospital stay were 4hours and 21minutes and 11.8 days respectively.

The fractures in which the top part is burst and causing canal compromise, could be dealt with by top hemi-corpectomy requiring smaller approach. One stage anterior – only stabilization can yield successful clinical results.

Magnetic Resonance Imaging (MRI) is the cornerstone investigation for cervical disc disease (CDD). However, MRI changes suggestive of CDD are found in people above forty, even in asymptomatic healthy individuals [1].

Mere presence of MRI changes of CDD does not exclude the presence of concomitant extra-foraminal pathology.

No study design.

We present here a series of three cases where use of ‘high resolution ultrasound’ has allowed accurate diagnosis of concomitant extra-foraminal pathology in patients with MRI-proven CDD. The three cases were acute neuropraxia of aberrant C5 nerve root, anterior interossous nerve compression due to pseudo-aneurysm of brachial artery and ‘acute brachial neuritis’ respectively.

No outcome measure.

Use of diagnostic high resolution ultrasound revealed accurate diagnosis of concomitant extra-foraminal pathology in all three cases. The cases with acute neuropraxia and acute brachial neuritis recovered with conservative treatment. Pseudo-aneurysm was treated successfully with surgery.

High resolution ultrasound of the brachial plexus and peripheral nerves may be useful in following scenarios to identify an extra-foraminal pathology: (1) when symptoms and signs are out of proportion to the MRI findings of CDD; (2) when there is obvious discordance between MRI and nerve conduction findings; (3) where an entrapment neuropathy is suspected but the site of nerve lesion cannot be located.