An innovative Kirschner (K-) wire point was developed and compared in fresh pig femora in terms of drilling efficiency and temperature elevation with the trochar and diamond points currently used in clinical practice. The tips of thermal couples were machined to the defined geometry and the temperature measured during drilling. Using the same drill speed (rev/min) and feed rate, the new K-wire point produced the lowest thrust force and torque as measured by a Kistler dynamometer. Drill point temperatures were highest with the trochar geometry (129 ± 6°C), followed by the diamond (98 ± 7°C). The lowest temperatures were recorded with the Medin K-wire (66 ± 2°C). On repeated drilling it could be used for up to 30 holes before reaching the less satisfactory drill performance of the diamond tip. The new K-wire provides a better alternative as it requires less effort for insertion, generates less heat and may be re-used

The periclavicular space is a conduit for the brachial plexus and subclavian-axillary vascular system. Changes in its shape/form generated by alteration in the anatomy of its bounding structures, e.g. clavicle malunion, cause distortion of the containing structures, particularly during arm motion, leading to syndromes of thoracic outlet stenosis etc., or alterations of scapular posture with potential reduction in shoulder function. Aim of this study was developing an in vitro methodology for systematic and repeatable measurements of the clinically poorly characterized periclavicular space during arm motion using CT-imaging and computer-aided 3D-methodologies. A radiolucent frame, mountable to the CT-table, was constructed to fix an upper torso in an upright position with the shoulder joint lying in the isocentre. The centrally osteotomized humerus is fixed to a semi-circular bracket mounted centrally at the end of the frame. All arm movements (ante-/retroversion, abduction/elevation, in-/external rotation) can be set and scanned in a defined and reproducible manner. Clavicle fractures healed in malposition can be simulated by osteotomy and fixation using a titanium/carbon external fixator. During image processing the first rib served as fixed reference in space. Clavicle, scapula and humerus were registered, segmented, and triangulated. The different positions were displayed as superimposed surface meshes and measurements performed automatically. Initial results of an intact shoulder girdle demonstrated that different arm positions including ante-/retroversion and abduction/elevation resulted solely in a transverse movement of the clavicle along/parallel to the first rib maintaining the periclavicular space. A radiolucent frame enabling systematic and reproducible CT scanning of upper torsos in various arm movements was developed and utilized to characterize the effect on the 3D volume of the periclavicular space. Initial results demonstrated exclusively transverse movement of the clavicle along/parallel to the first rib maintaining the periclavicular space during arm positions within a physiological range of motion

Osteosynthesis of high-energy metaphyseal proximal tibia fractures is still challenging, especially in patients with severe soft tissue injuries and/or short stature. Although the use of external fixators is the traditional treatment of choice for open comminuted fractures, patients' acceptance is low due to the high profile and therefore the physical burden of the devices. Recently, clinical case reports have shown that supercutaneous locked plating used as definite external fixation could be an efficient alternative. Therefore, the aim of this study was to evaluate the effect of implant configuration on stability and interfragmentary motions of unstable proximal tibia fractures fixed by means of externalized locked plating. Based on a right tibia CT scan of a 48 years-old male donor, a finite element model of an unstable proximal tibia fracture was developed to compare the stability of one internal and two different externalized plate fixations. A 2-cm osteotomy gap, located 5 cm distally to the articular surface and replicating an AO/OTA 41-C2.2 fracture, was virtually fixed with a medial stainless steel LISS-DF plate. Three implant configurations (IC) with different plate elevations were modelled and virtually tested biomechanically: IC-1 with 2-mm elevation (internal locked plate fixation), IC-2 with 22-mm elevation (externalized locked plate fixation with thin soft tissue simulation) and IC-3 with 32-mm elevation (externalized locked plate fixation with thick soft tissue simulation). Axial loads of 25 kg (partial weightbearing) and 80 kg (full weightbearing) were applied to the proximal tibia end and distributed at a ratio of 80%/20% on the medial/lateral condyles. A hinge joint was simulated at the distal end of the tibia. Parameters of interest were construct stiffness, as well as interfragmentary motion and longitudinal strain at the most lateral aspect of the fracture. Construct stiffness was 655 N/mm (IC-1), 197 N/mm (IC-2) and 128 N/mm (IC-3). Interfragmentary motions under partial weightbearing were 0.31 mm (IC-1), 1.09 mm (IC-2) and 1.74 mm (IC-3), whereas under full weightbearing they were 0.97 mm (IC-1), 3.50 mm (IC-2) and 5.56 mm (IC-3). The corresponding longitudinal strains at the fracture site under partial weightbearing were 1.55% (IC-1), 5.45% (IC-2) and 8.70% (IC-3). From virtual biomechanics point of view, externalized locked plating of unstable proximal tibia fractures with simulated thin and thick soft tissue environment seems to ensure favorable conditions for callus formation with longitudinal strains at the fracture site not exceeding 10%, thus providing appropriate relative stability for secondary bone healing under partial weightbearing during the early postoperative phase

Osteoarthritis, the most common degenerative joint disease, significantly impairs life quality and labor capability of patients. Synovial inflammation, initiated by HMGB1 (High mobility group box 1)-induced activation of macrophage, precedes other pathological changes. As an upstream regulator of NF-κB (nuclear factor-kappa B) and MAPK (mitogen-activated protein kinase) signaling pathway, TAK1 (TGF-β activated kinase 1) participates in macrophage activation, while its function in osteoarthritis remains unveiled. This study aims to investigate the role of TAK1 in the pathogenesis of osteoarthritis via both in vitro and in vivo approaches. We performed immunohistochemical staining for TAK1 in synovial tissue, both in osteoarthritis patients and healthy control. Besides, immunofluorescence staining for F4/80 as macrophage marker and TAK1 were conducted as well. TAK1 expression was examined in RAW264.7 macrophages stimulated by HMGB1 via qPCR (Quantitative polymerase chain reaction) and Western blotting, and the effect of TAK1 inhibitor (5z-7 oxozeaenol) on TNF-α production was evaluated by immunofluorescence staining. Further, we explored the influence of intra-articular shRNA (short hairpin RNA) targeting TAK1 on collagenase-induced osteoarthritis in mice. Immunohistochemical staining confirmed significant elevation of TAK1 in osteoarthritic synovium, and immunofluorescence staining suggested macrophages as predominant residence of TAK1. In HMGB1-stimulated RAW264.7 macrophages, TAK1 expression was up-regulated both in mRNA and protein level. Besides, TAK1 inhibitor significantly impairs the production of TNF-α by macrophages upon HMGB1 stimulation. Moreover, intra-articular injection of lentivirus loaded with shRNA targeting TAK1 (sh-TAK1) reduced peri-articular osteophyte formation in collagenase-induced osteoarthritis in mice. TAK1 exerts a potent role in the pathogenesis of osteoarthritis by mediating the activation of macrophages

Prompt mobilisation after the Fracture neck of femur surgery is one of the important key performance index (‘KPI caterpillar charts’ 2021) affecting the overall functional outcome and mortality. Better control of peri-operative blood pressure and minimal alteration of renal profile as a result of surgery and anaesthesia may have an implication on early post-operative mobilisation. Aim was to evaluate perioperative blood pressure measurements (duration of fall of systolic BP below the critical level of 90mmHg) and effect on the post-operative renal profile with the newer short acting spinal anaesthetic agent (prilocaine and chlorprocaine) used alongside the commonly used regional nerve block. 20 patients were randomly selected who were given the newer short acting spinal anaesthetic agent along with a regional nerve block between May 2019 and February 2020. Anaesthetic charts were reviewed from all patients for data collection. The assessment criteria for perioperative hypotension: Duration of systolic blood pressure less than 90 mm of Hg and change of pre and post operative renal functions. Only one patient had a significant drop in systolic BP less than 90mmHg (25 minutes). 3 other patients had a momentary fall of systolic BP of less than 5 minutes. None of the above patients had mortality and had negligible change in pre and post op renal function. Only one patient in this cohort had elevation of post-operative creatinine levels but did not have any mortality. Only 1 patient died on day 3 post operatively who had multiple comorbidities and was under evaluation for GI cancer. Even in this patient the peri-operative blood pressure was well maintained (never below 90mmHg systolic) and post-operative renal function was also shown to have improved (309 pre-operatively to 150 post-operatively) in this patient. The use of short-acting spinal anaesthesia has shown to be associated with a better control of blood pressure and end organ perfusion, less adverse effects on renal function leading to early mobilisation and a more favourable patient outcome with reduced mortality, earlier mobilisation, shorter hospital stay and earlier discharge in this elderly patient cohort

Introduction and Objective. The Cartilage Oligomeric Matrix Protein (COMP) is a glycoprotein that is elevated in patients with osteoarthritis. The elevation increases linearly with the radiological grade of osteoarthritis. The objective of this study was to study the levels of COMP in knee osteoarthritis in the Indian population and to correlate (establish ranges) with the specific radiological grade of osteoarthritis (Kellgreen and Lawrence grading). Since the radiological classification is subjective, the COMP levels would serve as a more objective way of classifying osteoarthritic joints. Materials and Methods. We analysed the COMP levels by the Enzyme Linked Immunosorbent Assay (ELISA) method in 100 patients presenting to the outpatient clinic of our hospital, after obtaining due approvals. The radiographs of these patients were classified according to the Kellgreen-Lawrence grading by a senior orthopaedic surgeon. Results. We found a linear correlation with the COMP levels and the radiological classification as established in the previous studies. We were also able to establish a range of COMP levels for each classification stage. Conclusions. This study would provide means to classify osteoarthritis without the need for radiographs thus minimising radiation to the patient. It would also help us to predict the radiological findings thus serving as a guide for further treatment planning

Introduction and Objective. Current cartilage repair strategies lack adequate tissue integration capacity and often present mechanical failure at the graft-to-host tissue junction. The design of multilayered osteochondral tissue engineering (TE) constructs is an attractive approach to overcome these problems. However, calcium ion-release from resorbable bone-replacement materials was suggested to compromise chondrogenic differentiation of adjacent cartilage tissue and it is unclear whether articular chondrocytes (AC) or mesenchymal stroma cells (MSC) are more sensitive to such conditions. Aim of the study was to compare how elevated calcium levels affect cartilage matrix production during re-differentiation of AC versus chondrogenic differentiation of MSC. The results of this study will help to identify the ideal cell source for growth of neocartilage adjacent to a calcified bone replacement material for design of multilayered osteochondral TE approaches. Materials and Methods. Expanded human AC and MSC (6–12 donors per group) were seeded in collagen type I/III scaffolds and cultured under standard chondrogenic conditions at control (1.8mM) or elevated (8.0mM) CaCl2 for 35 days. Proteoglycan and collagen production were assessed via radiolabel-incorporation, ELISA, qPCR and Western blotting. Differences between groups or cell types were calculated using the non-parametric Wilcoxon or Mann-Whitney U test, respectively, with p < 0.05 considered significant. Results. Elevated calcium significantly reduced GAG synthesis (63% of control, p=0.04) and chondrogenic marker expression of AC, lowering the GAG/DNA content (47% of control, p=0.004) and collagen type II deposition (24% of control, p=0.05) of neocartilage compared to control conditions. Opposite, at elevated calcium levels MSC-derived chondrocytes significantly increased GAG synthesis (130% of control, p=0.02) and collagen type II content (160% of control, p=0.03) of cartilage compared to control tissue. Chondrogenic and hypertrophic marker expression was insensitive to calcium levels in MSC-derived chondrocytes. As a result, maturation under elevated calcium allowed for a significantly higher GAG/DNA content in MSC-derived samples compared to AC constructs, although under control conditions both groups developed similarly. Conclusions. AC and MSC showed an opposite reaction to elevation of calcium levels regarding cartilage matrix production and we propose MSC as a preferred cell source to grow chondrocytes in vicinity to calcified bone replacement materials. Since MSC remained prone to hypertrophy under elevated calcium, trizonal cartilage TE constructs, where an AC-layer is separated from the bone replacement phase by an intermediate layer of MSC appear as an ideal design for multilayered osteochondral TE with respect to calcium sensitivity of cells and protection of the upper cartilage layer from hypertrophy

Introduction and Objective. Several in vitro studies have shed light on the osteogenic and chondrogenic potential of graphene and its derivatives. Now it is possible to combine the different biomaterial properties of graphene and 3D printing scaffolds produced by tissue engineering for cartilage repair. Owing to the limited repair capacity of articular cartilage and bone, it is essential to develop tissue-engineered scaffolds for patients suffering from joint disease and trauma. However, chondral lesions cannot be considered independently of the underlying bone tissue. Both the microcirculation and the mechanical support provided with bone tissue must be repaired. One of the distinctive features that distinguish graphene from other nanomaterials is that it can have an inductive effect on both bone and cartilage tissue. In this study, the effect of different concentrations of graphene on the in vivo performance of single-layer poly-ε-caprolactone based-scaffolds is examined. Our hypothesis is that graphene nanoplatelet- containing, robocast PCL scaffolds can be an effective treatment option for large osteochondral defect treatment. For this purpose, different proportions of graphene- containing (1%,3%,5%,10 wt%) PCL scaffolds were studied in a 5mm diameter osteochondral defect model created in the rabbit knee. Materials and Methods. In the study graphene-containing (1, 3, 5, 10 wt%), porous and oriented poly-ε-caprolactone-based scaffolds were prepared by robocasting method to use in the regeneration of large osteochondral defects. Methods: The scaffolds were implanted into the full-thickness osteochondral defect in a rabbit model to evaluate the regeneration of defect in vivo. For this purpose, twenty female New Zealand white rabbits were used and they were euthanized at 4 and 8 weeks of implantation. The reparative osteochondral tissues were harvested from rabbit distal femurs and then processed for gross appearance assessment, radiographic imaging, histopathological and immunohistochemical examinations. Results. Results revealed that, graphene- containing graft materials caused significant amelioration at the defect areas. Graphene-containing graft materials improved the fibrous, chondroid and osseous tissue regeneration compared to the control group. The expressions of bone morphogenetic protein-2 (BMP-2), collagen-1 (col-1), vascular endothelial growth factor (VEGF) and alkaline phosphatase (ALP) expressions were more prominent in graphene- containing PCL implanted groups. Results also revealed that the ameliorative effect of graphene increased by the elevation in concentration. The most prominent healing was observed in 10 wt% graphene-containing PCL based composite scaffold implanted group. Conclusions. This study demonstrated that graphene- containing, robocast PCL scaffolds has efficacy in the treatment of large osteochondral defect. Subchondral new bone formation and chondrogenesis were observed based on immunohistochemical examinations. 3D printed PCL platforms have great potential for the investigation of the osteochondral regeneration mechanism. The efficacy of graphene-containing PCL scaffolds on osteogenesis, vascularization, and mineralization was shown at different graphene concentrations at 4th and 8th weeks. Immunohistochemical studies showed statistical significance in the 5wt% and 10 wt% graphene-containing groups compared to the 1wt% and 3 wt% graphene-containing groups at the end of the eighth week

Introduction. Being challenging, multifragmentary proximal tibial fractures in patients with severe soft tissue injuries and/or short stature can be treated using externalized locked plating. A recent finite element study, investigating the fixation stability of plated unstable tibial fractures with 2-mm, 22-mm and 32-mm plate elevation under partial and full weight-bearing, reported that from a virtual biomechanical point of view, externalized plating seems to provide appropriate relative stability for secondary bone healing under partial weight-bearing during the early postoperative phase. The aim of the current study was to evaluate the clinical outcomes of using a LISS plate as a definitive external fixator for the treatment of multifragmentary proximal tibial fractures. Methods. Following appropriate indirect reduction, externalized locked plating was performed and followed up in 12 patients with multifragmentary proximal tibial fractures with simple intraarticular involvement and injured soft tissue envelope. Results. Among all patients, the average follow up period was 22 months (range14–48 months), revealing uneventful healing in all of them. Time to fracture union was 21.8 weeks on average (range 16–28weeks). The mean HSS knee score was 87 (range 72–98) at 4 weeks postoperatively and 97 (range 88–100) at the final follow up. The average AOFAS score was 92 (range 84–100) at 4 weeks postoperatively and 98 (range 94–100) at the final follow up. Conclusions. Externalized locked plating seems to be a successful surgical alternative treatment in selected cases with unstable proximal tibial fractures and severe soft tissue injury, following appropriate indirect fracture reduction

Introduction. Osteoarthritis (OA) of the knee, a prevalently degenerative joint disorder provoked by articular cartilage loss, accounts for the leading cause of total knee arthroplasty. Autophagy is an indispensable intracellular event that maintains chondrocyte survival and metabolism. MicroRNAs are non-coding small RNAs participating in tissue morphogenesis, remodeling, and homeostasis. This study was undertaken to investigate the effect of microRNA-128 (miR-128) knockdown on the development of OA knees. Materials/Methods. Knee joints in rats were subjected to anterior cruciate ligament transection (ACLT) for inducing OA. Articular cartilage, synovium, and subchondral bone microarchitecture were assessed by OARSI scoring system, histomorphometry, and μCT imaging. Chondrocyte autophagy in terms of the expression of autophagic markers Atg4, Atg12, microtubule-associated protein 1 light chain 3 (LC3), and autophagosome formation was verified. Expression of microRNA, mRNA and signaling transduction were quantified with in situ hybridization, RT- quantitative PCR, and immunoblotting. Results. Chondrocytes in the affected knees showed weak expression of autophagic markers Atg4, Atg12, and LC3-II abundances in conjunction with significant increases in OARSI scores and a 2.5-fold elevation in miR-128 expression. The gain of miR-128 signaling in intact joints through intra-articular injection of miR-128 precursor resulted in 1.8–2.1-fold elevations in serum cartilage breakdown products CTX-II and COMP concentrations. miR-128 overexpression caused the joints to show evident chondrocyte apoptosis as evidenced by TUNEL staining concomitant with severe cartilage damage. Of note, antisense oligonucleotide knockdown of miR-128 (miR-128-AS) enabled the affected knee joints to show minor responses to the ACLT escalation of autophagy dysfunction in chondrocytes, cartilage breakdown histopathology, and OARSI scores. Administration with miR-128-AS also attenuated the ACLT-induced synovial membrane thickening, hyper-angiogenesis, and hypercellularity, which subsequently alleviated osteophyte accumulation, subchondral plate destruction, and trabecular microstructure loss. Conclusion. miR-128 signaling impairs chondrocyte autophagy, which ramps up chondrocyte apoptosis and OA knee development. This study highlights an emerging miR-128 knockdown strategy that sustains cartilage microarchitecture integrity and thereby delays OA knee pathogenesis

Thermostability is a key property in determining the suitability of local delivery of antibiotics in the treatment of orthopaedic infections. Herein, we aimed to assess the thermal stability and antibacterial activity of ciprofloxacin, ceftriaxone, gentamycine and vancomycine in high temperature conditions. Using a standardized E-test method, minimally inhibited concentration of each antibiotic substance against Staphylococcus aureus cultures were determined. The solutions of antimicrobial drugs ciprofloxacin 2 mg/ml, ceftriaxone 200 mg/ml, gentamycine 40 mg/ml and vancomycine 200 mg/ml were diluted twofold in deionised water. Acquired solutions were divided into three aliquots. The first aliquot was held at 40°C for 30 min in a waterbath, the second and the third aliquots were exposed to 80 and 100°C for 30 min in hot-air sterilizer, respectively. The treated solutions were tested for residual activity against S. aureus using a standardized disk diffusion method. Mediums with untreated antibiotic solutions and S. aureus were used as control. Plates were incubated at 37°C, at which time zones of inhibition (ZoI) were measured to the nearest whole millimeter for 14 days. The investigation indicated that the temperature elevation impacted considerably on antimicrobial activity and antibiotic stability overall. The in vitro temperature-response curves showed that ZoI diameter decreases logarithmically with elevated temperatures. Gentamicin was the only drug that was found to be affected to some extent. Results from the study provides a valuable dataset for orthopaedic surgeons considering local application of antibiotics and methods of antibiotic impregnation

Orthopedic implants containing biodegradable magnesium have been used for fracture repair with considerable efficacy; however, the underlying mechanisms by which these implants improve fracture healing remain elusive. Here we show the formation of abundant new bone at peripheral cortical sites after intramedullary implantation of a pin containing ultrapure magnesium into the intact distal femur in rats. This response was accompanied by substantial increases of neuronal calcitonin gene-related polypeptide-a (CGRP) in both the peripheral cortex of the femur and the ipsilateral dorsal root ganglia (DRG). Surgical removal of the periosteum, capsaicin denervation of sensory nerves or knockdown in vivo of the CGRP-receptor-encoding genes Calcrl or Ramp1 substantially reversed the magnesium-induced osteogenesis that we observed in this model. Overexpression of these genes, however, enhanced magnesium-induced osteogenesis. We further found that an elevation of extracellular magnesium induces magnesium transporter 1 (MAGT1)-dependent and transient receptor potential cation channel, subfamily M, member 7 (TRPM7)-dependent magnesium entry, as well as an increase in intracellular adenosine triphosphate (ATP) and the accumulation of terminal synaptic vesicles in isolated rat DRG neurons. In isolated rat periosteum-derived stem cells, CGRP induces CALCRL- and RAMP1-dependent activation of cAMP-responsive element binding protein 1 (CREB1) and SP7 (also known as osterix), and thus enhances osteogenic differentiation of these stem cells. Furthermore, we have developed an innovative, magnesium-containing intramedullary nail that facilitates femur fracture repair in rats with ovariectomy-induced osteoporosis. Taken together, these findings reveal a previously undefined role of magnesium in promoting CGRP-mediated osteogenic differentiation, which suggests the therapeutic potential of this ion in orthopedics

Summary Statement. In this study, massive rotator cuff tears were treated using an absorbable collagen-based patch or a non-absorbable synthetic patch. Results demonstrated the efficacy of the use of the synthetic prolene patch especially for elderly patients. Introduction. The treatment of massive rotator cuff tears presents a challenging problem in shoulder surgery. Traditional repair techniques are associated with high rupture rates due to excessive tension on the repair and the presence of degenerated tendon tissue. These factors have led to attempts to reconstruct the rotator cuff with grafts, using synthetic materials or biologic tissues. The purpose of this study was to compare the efficacy of the use of pericardium patch with the use of prolene patch in the repair of extensive rotator cuff tears. Materials & Methods. A retrospective series of 180 patients, 115 men and 65 women with a mean age of 66.8 years treated for a massive rotator cuff tear from 1997 to 2008 is reported. The inclusion criteria were: patients symptomatic with pain, deficit of elevation, not responsive to the physiotherapy, tear size (massive: 2 or more tendons), minimum follow-up of 2 years since surgery, active and motivated patients. Patients were divided into three groups according to the type of treatment received: group 1 was treated with Pericardium patch, group 2 with Prolene patch, group 3 with simple suture. All groups were homogeneous. Plain radiographs, ultrasound and MRI were performed preoperatively and at 3 years. Patients were clinically evaluated using the UCLA score before surgery and at 2 months and 3 years after surgery (mean follow-up 2, 6 years). Pain was assessed by use of VAS scale, strength by the use of dynamometer. The surgical procedure (mini-open technique) was similar in all groups. Statistical analysis was conducted by one-way ANOVA between groups of treatment with Dunnett's C post-hoc correction for multiple comparisons. P-values of 0.05 or less were considered as statistically significant. Results. After 2 months the mean VAS was 6.85±1.11, 6.45±1.01, 4.9±0.9 while the mean UCLA was 11.28±1.43, 13.35±14.21, 20.85±12.77, respectively for Control, Collagen and Prolene group. After 36 months the mean VAS was 3.7±1.01, 4.05±0.98, 3.23±1.07, while the mean UCLA was 14.73±1.96, 14.86±2.08, 24.6±3.3 respectively for Control, Collagen and Prolene group. In addition, after 36 months elevation on the scapular plane was 140.75°±10.48, 141.58°±11.87, 174.75°±8.1 and abduction strength was 8.57kg±0.63, 8.82kg±0.7, 13.61kg±0.84, respectively for Control, Collagen and Prolene group. Retear rate after 12 months was 40% (24/60) for Control group, 48.33% (29/60) for Collagen group, 15% (9/60) for Prolene group. Conclusion. The use of Prolene patch as an augmentation graft in the treatment of massive rotator cuff tears is safe and, in most patients, can give a significant pain relief and improvement of range of motion and strength with few complications

Introduction. Excessive bone mass and microarchitecture loss exacerbate the risk of osteoporotic fracture, a skeletal disorder attributable to disability in the elder. Excessive marrow adipose development at the expense of osteoblastic bone acquisition is a prominent feature of aging-induced osteoporotic skeletons. MicroRNA-29a (miR-29a) modulates osteogenic and adipogenic commitment of mesenchymal progenitor cells. The purposes of this study were to test if miR-29a overexpression changed bone mass or microstructure in aged skeletal tissues. Materials/Methods. Transgenic mice that overexpressed miR-29a in osteoblasts driven by osteocalcin promoter (miR-29aTg) were generated. Littermates without carrying construct of interest were used as wild-type mice (WT). 3- and 12-month-old mice were designated into young and aged groups respectively. Bone mineral density (BMD), cortical, trabecular microarchitecture and morphometric profiles were quantified with ultrahigh resolution μCT system. Primary bone-marrow mesenchymal stem cells (BMMSCs) were incubated in osteogenic and adipogenic conditions. Expressions of osteogenic and adipogenic marker were quantified with RT-PCR. Results. Skeletons in the aged WT group showed 65% decrease in BMD in association with 72% reduction in miR-29a expression and 2.3-fold elevation in marrow fat volume as compared with those in young WT group. The young miR-29aTg mice showed 35–48% increases in serum osteocalcin and bone alkaline phosphatase levels concomitant with 22–35% increases in BMD, trabecular BV/TV, Tb.Th, Tb.N, and cortical morphology than those of young WT mice. Intriguing analyses are that miR-29aTg mice exhibited mild responses to the aging provocation of BMD loss, trabecular, cortical microstructure deterioration, and fatty marrow histopathology. In vitro, primary BMMSCs in miR-29aTg mice showed significant increases in osteogenic gene expression and mineralized matrices as probed with von Kossa staining, whereas adipogenic gene expression and adipocyte formation were evidently reduced as evidenced by fluorescence Nile Red. Conclusion. miR-29a overexpression in osteoblasts facilitates skeletal tissue anabolism. High osteogenic lineage commitment of bone-marrow mesenchymal progenitor cells contributes to high bone mass and microstructure phenotypes promoted by miR-29a signaling. Analyses shed a new light on the miR-29a signaling protection against the aging escalation of osteoporosis pathogenesis

The biomechanics of the patellofemoral joint can become disturbed during total knee replacement by alterations induced by the position and shape of the different prosthetic components. The role of the patella and femoral trochlea has been well studied. We have examined the effect of anterior or posterior positioning of the tibial component on the mechanisms of patellofemoral contact in total knee replacement. The hypothesis was that placing the tibial component more posteriorly would reduce patellofemoral contact stress while providing a more efficient lever arm during extension of the knee. We studied five different positions of the tibial component using a six degrees of freedom dynamic knee simulator system based on the Oxford rig, while simulating an active knee squat under physiological loading conditions. The patellofemoral contact force decreased at a mean of 2.2% for every millimetre of posterior translation of the tibial component. Anterior positions of the tibial component were associated with elevation of the patellofemoral joint pressure, which was particularly marked in flexion > 90°. From our results we believe that more posterior positioning of the tibial component in total knee replacement would be beneficial to the patellofemoral joint

We studied 51 patients with osteo-articular tuberculosis who were divided into two groups. Group I comprised 31 newly-diagnosed patients who were given first-line antituberculous treatment consisting of isoniazid, rifampicin, ethambutol and pyrazinamide. Group II (non-responders) consisted of 20 patients with a history of clinical non-responsiveness to supervised uninterrupted antituberculous treatment for a minimum of three months or a recurrence of a previous lesion which on clinical observation had healed. No patient in either group was HIV-positive. Group II were treated with an immunomodulation regime of intradermal BCG, oral levamisole and intramuscular diphtheria and tetanus vaccines as an adjunct for eight weeks in addition to antituberculous treatment. We gave antituberculous treatment for a total of 12 to 18 months in both groups and they were followed up for a mean of 30.2 months (24 to 49). A series of 20 healthy blood donors served as a control group. Twenty-nine (93.6%) of the 31 patients in group I and 14 of the 20 (70%) in group II had a clinicoradiological healing response to treatment by five months. The CD4 cell count in both groups was depressed at the time of enrolment, with a greater degree of depression in the group-II patients (686 cells/mm. 3. (. sd. 261) and 545 cells/mm. 3. (. sd. 137), respectively; p < 0.05). After treatment for three months both groups showed significant elevation of the CD4 cell count, reaching a level comparable with the control group. However, the mean CD4 cell count of group II (945 cells/mm. 3. (. sd. 343)) still remained lower than that of group I (1071 cells/mm. 3. (. sd. 290)), but the difference was not significant. Our study has shown encouraging results after immunomodulation and antituberculous treatment in non-responsive patients. The pattern of change in the CD4 cell count in response to treatment may be a reliable clinical indicator

Summary Statement. Osteonecrosis of the femoral head (ONFH) is a multifactorial skeletal disorder. S100A9 represseses angiogenesis and vessel integrity in ONFH. It also may function as a marker of diagnosis in ONFH. Introduction. Osteonecrosis of the femoral head (ONFH) is a multifactorial skeletal disorder characterised by ischemic deterioration, bone marrow edema and eventually femoral head collapse and joint destruction. Several surgical, pharmaceutical and non-invasive biophysical modalities have been employed to alleviate this joint disorder. Our proteomic analysis showed that ONFH patients displayed increased expression of S100A9 protein when compared with healthy volunteers. This study is designed to evaluate the pathogenesis of S100A9 on the patients of ONFH. Patients & Methods. We collected 56 patients with ONFH including stage I, II, III and IV and 14 health volunteers. 20 ml of peripheral venous blood is drawn from each subject or prior to general anesthesia for hip arthroplasty. We compared the ELISA of S100A9, Osteocalcin, TRAP-5b, sVCAM-1. Immunohistochemistry of S100A9, vWF and VEGF are compared using femoral head harvested from late stages of ONFH and femoral neck fracture when received hip arthroplasty. In vitro angiogenic assay was performed by tube formation assay. Results. There were significant elevation of S100A9 in the serum of ONFH patients then in healthy volunteers. sVCAM-1 and TRAP-5b were increased and Osteocalcin was decreased in ONFH patient when comapred with healthy volunteers. The expression of S100A9 protein in ONFH tissue was significantly higher than femoral neck fracture tissue. In tube formation assay, we found S100A9 and the serum of ONFH patient supressed angiogenesis in vascular endothelial cell culture. Discussion/Conclusion. The expression of S100A9 significantly increased in the serum and femoral head tissue of patients with ONFH. S100A9 also supressed angiogenesis expression. The results indicated that S100A9 represseses angiogenesis and vessel integrity in ONFH. It also may function as a marker of diagnosis in ONFH

Distal femur resection for correction of flexion contractures in total knee arthroplasty (TKA) can lead to joint line elevation, abnormal knee kinematics and patellofemoral problems. The aim of this retrospective study was to establish the contribution of soft tissue releases and bony cuts in the change in maximum knee extension in TKA. Data were available for 211 TKAs performed by a single surgeon using a medial approach. Intra-operatively pre- and post-implant extension angles and the size of bone resection were collected using a commercial navigation system. The thickness of polyethylene insert and the extent of soft tissue release performed (no release, moderate and extensive release) were collected from the patient record. A linear model was used to predict change in maximum extension from pre- to post-implant. The analysis showed that bone cuts (p<0.001), soft tissue release (p=0.001) and insert thickness (p=0.010) were all significant terms in the model (r. 2. adj. =0.170). This model predicted that carrying out a TKA with 19 mm bone cuts, 10 mm insert and no soft tissue release would give 4.2° increase in extension. It predicted that a moderate release would give a further 2.8° increase in extension with an extensive release giving 3.9°. For each mm increase in bone cuts the model predicted an 0.8° increase in extension and for each mm increase in insert size a decrease extension by 1.1°. The modelling results show that in general to increase maximum extension by the same as an extensive soft tissue release that bone cuts would have to be increased by 4–5 mm. However this model only accounted for 17% of the variation in change in extension pre- to post-implant so may not be accurate at predicting outcomes for specific patients

Summary Statement. We present a simple and useful geometrical equation system to carry out the pre-operative planning and intra-operative assessments for total knee arthroplasty. These methods are extremely helpful in severely deformed lower limbs. Introduction. Total knee arthroplasty is a highly successful surgery for most of the patients with knee osteoarthritis. With commercial instruments and jigs, most surgeons can correct the deformity and provided satisfactory results. However, in cases with severe extra-articular deformity, the instruments may mislead surgeons in making judgment of the true mechanical axis. We developed a geometrical equation system for pre-operative planning and intra-operative measurement to perform correct bony cuts and achieve good post-operative axis. Patients & Methods. From 2008 to 2012, twenty-four patients with severe extra-articular deformities of low limbs underwent total knee arthroplasties for osteoarthritis. The deformities included malunion of femoral or tibial shafts with angulation, non-union of femoral supracondylar fractures, failed high tibia osteotomies, severe bowing of femurs, and other post-traumatic sequelae. The intra-medullary or extra-medullary guide devices were not possible to provide correct axis in these cases. For pre-operative planning, we analyzed the deformities on triple-film scanography and standing anterior-posterior and lateral X-ray films. The angles needed to be corrected in coronal and sagittal planes were measured. A geometrical equation system was applied to calculate the thickness of the proximal tibia cut and distal femoral cut. If the flexion contracture was presented, the degree of necessary elevation of joint line was also calculated. Intra-operatively, the degree of rotation of anterior and posterior femoral cuts was assessed after proximal tibial and distal femoral cuts. The sizes of prosthesis were judged according to the balance between flexion and extension gaps. A 3-in-1 jig was used for chamfering of the femur. After fine-tuning of bony cuts and balancing of soft tissue, the prostheses were cemented. The conventional intra-medullary and extra-medullary guiding devices were not used during the whole procedure. Results. All of the patients achieved satisfactory results in the aspect of pain relief and functional outcomes. All patients had good post-operative axis in coronal plane (varus or valgus deformity < 3 degrees). Twenty-two patients (92%) achieved good sagittal alignments (deformity < 3 degrees). The results were compatible with those in the patient population without those severe deformities. There was no major complication among these patients. Discussion/Conclusion. In this series, we present a simple and useful geometrical equation system to carry out the pre-operative planning and intra-operative assessments for total knee arthroplasty. These methods are extremely helpful in severely deformed lower limbs. Optimal post-operative alignments were achieved in this series and no major complication was found

Background. Intervertebral disc cells exist in a challenging physiological environment. Disc degeneration occurs early in life implying that disc cells may no longer be able to maintain a functional tissue. We hypothesise that disc cells have a stress response different from most other cells because of the disc environment. We have compared the stress response of freshly isolated and cultured bovine nucleus pulposus (NP) cells with bovine dermal fibroblasts, representative of cells from a vascularised tissue. Methods. Freshly isolated and passaged bovine NP cells and dermal fibroblasts were cultured for 3 days then subjected to either thermal stress at 45°C for 1h followed by recovery times of 6, 24 and 48h or nutrient stress involving culture without serum for 6, 24 and 48 h. At each time point, cell number and viability were assessed and heat shock protein 70 (Hsp70) measured in cell lysates by an enzyme-linked immunosorbent assay. Results. In response to thermal stress, both freshly isolated and passaged dermal fibroblasts and also passaged NP cells showed a rapid elevation of Hsp70. In contrast, freshly isolated NP cells exhibited an attenuated Hsp70 response. With nutrient stress, Hsp70 increased with time in all dermal fibroblasts and passaged NP cells after 24 h, but freshly isolated NP cells responded differently again, producing less Hsp70 than controls. Conclusion. Freshly isolated bovine NP cells have a reduced response to applied stresses. This pilot study suggests that NP disc cells may have adapted to their physiologically challenging in vivo environment by attenuating their response to environmental stress. No conflicts of interest. Sources of Funding: The Wolfson Charitable Trust and Genodisc (EC's 7. th. Framework Programme (FP7, 2007–2013) under grant agreement no. HEALTH-F2-2008-201626). This abstract has not been previously published in whole or substantial part nor has it been presented previously at a national meeting