The inflammatory cascade associated with prosthetic implant wear debris, in addition to diseases such as rheumatoid arthritis and periodontitis, it is shown to drastically influence bone turnover in the local environment. Ultimately, this leads to enhanced osteoclastic resorption and the suppression of bone formation by osteoblasts causing implant failure, joint failure, and tooth loosening in the respective conditions if untreated. Regulation of this pathogenic bone metabolism can enhance bone integrity and the treatment bone loss. The current study used novel compounds that target a group of enzymes involved with the epigenetic regulation of gene expression and protein function, histone deacetylases (HDAC), to reduce the catabolism and improve the anabolism of bone material in vitro. Human osteoclasts were differentiated from peripheral blood monocytes and cultured over a 17 day period. In separate experiments, human osteoblasts were differentiated from human mesenchymal stem cells isolated from bone chips collected during bone marrow donations, and cultured over 21 days. In these assays, cells were exposed to the key inflammatory cytokine involved with the cascade of the abovementioned conditions, tumour necrosis factor-α (TNFα), to represent an inflammatory environment in vitro. Cells were then treated with HDAC inhibitors (HDACi) that target the individual isoforms previously shown to be altered in pathological bone loss conditions, HDAC-1, −2, −5 and −7. Analysis of bone turnover through dentine resorptive measurements and bone mineral deposition analyses were used to quantify the activity of bone cells. Immunohistochemistry of tartrate resistant acid phosphatase (TRAP), WST-assay and automated cell counting was used to assess cell formation, viability and proliferation rates. Real-time quantitative PCR was conducted to identify alterations in the expression of anti- and pro-inflammatory chemokines and cytokines, osteoclastic and osteoblastic factors, in addition to multiplex assays for the quantification of cytokine/chemokine release in cell supernatant in response to HDACi treatments in the presence or absence of TNFα. TNFα stimulated robust production of pro-inflammatory cytokines and chemokines by PBMCs (IL-1β, TNFα, MCP1 and MIP-1α) both at the mRNA and protein level (p < 0 .05). HDACi that target the isoforms HDAC-1 and −2 in combination significantly suppressed the expression or production of these inflammatory factors with greater efficacy than targeting these HDAC isoforms individually. Suppression of HDAC-5 and −7 had no effect on the inflammatory cascade induced by TNFα in monocytes. During osteoclastic differentiation, TNFα stimulated the size and number of active cells, increasing the bone destruction observed on dentine slices (p < 0 .05). Targeting HDAC-1 and −2 significantly reduced bone resorption through modulation of the expression of RANKL signalling factors (NFATc1, TRAF6, CatK, TRAP, and CTR) and fusion factors (DC-STAMP and β3-integerin). Conversely, the anabolic activity of osteoblasts was preserved with HDACi targeting HDAC-5 and −7, significantly increasing their mineralising capacity in the presence of TNFαthrough enhanced RUNX2, OCN and Coll-1a expression. These results identify the therapeutic potential of HDACi through epigenetic regulation of cell activity, critical to the processes of inflammatory bone destruction

Aim. Pre-operative distinction between prosthetic joint infections (PJI) and non-infectious causes of joint failure is particularly challenging, especially in chronic situations. Guidelines propose different algorithms using numerous preoperative tests. We evaluated place of serology. Method. During a 9 month period, we included consecutive patients undergoing arthroplasty revision for a suspected chronic hip or knee infection. Serologies were sampled at the same day than the other blood tests. Results were compared with the final diagnosis, determined with peroperative bacteriological and histological results. Serology was performed using a multiplex antibody detection*. This multiplex antibody detection assay detects antibodies against Staphylococcus species, Propionibacterium acnes and Streptococcus agalactiae. Results. A total of 52 patients were enrolled. Median time from last arthroplasty was 30 months (extremes 8 months − 17 years). Median clinical signs duration was 6 months (extremes 1 – 40 months). Median CRP value was 6 mg/l (extremes 2 – 150) and sedimentation rate 12 mm (extremes 2 – 82). Diagnostic of PJI was finally retained for 17 patients and ruled out for 35. It was Staphylococcus aureus 3 times, coagulase negative staphylococci (CoNS) 5 times, P. acnes 4 times, candida sp. 2 times, Streptococcus agalactiae one time, Enterobacter cloacae one time and undetermined one time. Serology was concordant and accurate with the final diagnosis for 38 patients (27 sterile and 11 infected). For 7 of them, serology was the key parameter. In these cases, a CoNS or a P. acnes was isolated per-operatively on a single culture, out of 5 samples. Serology allowed confirming a contamination in 5 cases; and in 2 cases, even if not fulfilling the definition, it determined a PJI. In this study, serology had a global sensitivity of 65%, 77% specificity, 58% positive predictive value, and 82% negative predictive value. Serology reached 89% sensitivity with unchanged specificity in the subgroup of 11 patients with a CRP > 10 mg/l. Conclusions. We evaluated place of serology in the most complex cases of suspected chronic PJIs, with finally, only 33% cases with an infection. Modest results of serology can be explained because antigens included in the assay were not those expressed in sessile bacteria. And by persistence of a humoral response, witnesses of past infections, for patients who had past surgeries on the joint. However, simple and practical, when combined with all other parameters, serology could provide a valuable support in preoperative evaluation of chronic PJIs. * BJI InoplexTM

Aim. Clear differentiation between aseptic failure and prosthetic joint infection remains one of the goals of modern orthopaedic surgery. New diagnostic methods can provide more precise evaluation of the etiology of prosthetic joint failure. With the introduction of sonication an increasing number of culture-negative prosthetic joint infection were detected. The aim of our study was to evaluate culture-negative prosthetic joint infections in patients who were preoperatively evaluated as aseptic failure. Method. For the purpose of the study we included patients planed for revision surgery for presumed aseptic failure. Intraoperatively acquired samples of periprosthetic tissue and explanted prosthesis were microbiologically evaluated using standard microbiologic methods and sonication. If prosthetic joint infection was discovered, additional therapy was introduced. Results. Between October 2010 and till the end of 2014 151 cases were operated (38 revision knee arthroplasty, 113 revision hip arthroplasty). 40 (26,5%) cases had positive sonication and negative periprosthetic tissue samples (knee 7 cases, hips 33 cases), 13 (8,6%) cases had positive tissue samples but negative sonication (knee 7 cases, hips 6 cases), in 13 (8,6%) cases both tests were positive (knee none, hips 13 cases) and in 85 (56,3%) cases all microbiologic tests were negative (knee 24 cases, hips 61 cases). In both groups cases coagulase-negative staphylococci and P.acnes were most common, followed by mixed flora. Conclusions. With the increasing number of patients requiring revision arthroplasty, a clear differentiation between aseptic failure and prosthetic joint infection is crucial for the optimal treatment. Sonication of explanted material is more successful in the isolation of pathogens compared to periprosthetic tissue cultures. Sonication of explanted prosthetic material is helpful in the detection of culture-negative prosthetic joint infections

Background. Constitutional knee varus increases the risk of medial OA disease due to increase in the knee adduction moment and shifting of the mechanical axis medially. Hueter-Volkmann's law states that the amount of load experienced by the growth plate during development influences the bone morphology. For this reason, heightened sports activity during growth is associated with constitutional varus due to added knee adduction moment. In early OA, X-rays often show a flattened medial femoral condyle extension facet (EF). However, it is unknown whether this is a result of osteoarthritic wear, creep deformation over decades of use, or an outcome of Hueter-Volkmann's law during development. A larger and flattened medial EF can bear more weight, due to increased load distribution. However, a flattened EF may also extrude the meniscus, leading meniscus degeneration and joint failure. Therefore, this study aimed to investigate whether varus knees have flattened medial EFs of both femur and tibia in a cohort of patients with no signs yet of bony attrition. Methods. Segmentation and morphology analysis was conducted using Materialise software (version 8.0, Materialise Inc., Belgium). This study excluded knees with bony attrition of the EFs based on Ahlbäck criteria, intraoperative findings, and operation notes history. Standard reference frames were used for both the femur and tibia to ensure reliable and repeatable measurements. The hip-knee-angle (HKA) angle defined varus or valgus knee alignment. Femur: The femoral EFs and flexion facets (FFs) had best-fit spheres fitted with 6 repetitions. (Fig1). Tibia: The slopes of the antero-medial medial tibial plateau were approximated using lines. (fig2). Results. 72 knees met the inclusion and exclusion criteria. The average age was 59 ± 11 years. The youngest was 31 and the oldest 84 years. Thirty-three were male and 39 were female. There was good intra- and inter-observer reliability for EF sphere fitting. Femur: The results demonstrated that the medial femoral condyle EF is flattened in knees with constitutional varus, as measured by the Sphere Ratios between the medial and lateral EF (varus versus straight: p = 0.006), and in the scaled values for the medial EF sphere radius (varus versus straight: p = 0.005). There was a statistically significant, moderate and positive correlation between the medial femoral EF radius, and the medial femoral EF-FF AP offset. (fig3). Tibia: There was a statistically significant difference between the steepness of the slopes of the medial tibial plateau EF in varus and valgus knees, suggesting varus knees have a less concave (flatter) medial EF. (fig3). Conclusions. In comparison to straight knees, varus knees have flattened medial EFs in both femur and tibia. As this was the case in knees with no evidence of bony attrition, this could mean flattened medial EFs may be a result of medial physis inhibition during development, due to Hueter-Volkmann's law. Flattened medial EFs may increase load distribution in the medial compartment, but could also be a potential aetiology in primary knee OA due to over extrusion of the medial meniscus and edge loading

Clear differentiation between aseptic failure and prosthetic joint infection remains one of the goals of modern orthopaedic surgery. The development of new diagnostic methods enabled more precise evaluation of the etiology of prosthetic joint failure. With the introduction of sonication an increasing number of culture-negative prosthetic joint infection were detected. The aim of our study was to evaluate culture-negative prosthetic joint infections in patients who were preoperatively evaluated as aseptic failure. For the purpose of the study we included patients planed for revision surgery for aseptic failure. Intraoperatively acquired samples of periprosthetic tissue and explanted prosthesis were microbiologicaly evaluated using standard microbiologic methods and sonication. If prosthetic joint infection was discovered, additional therapy was introduced. Between October 2010 and April 2013 54 patients were operated (12 revision knee arthroplasty, 42 revision hip arthroplasty). 10 (18,6%) patients had positive sonication and negative periprosthetic tissue sample, 5 (9,2%) patients had positive tissue samples, but negative sonication, in 9 (16,7%) patients both tests were positive and in 30 (55,5%) patients all microbiologic tests were negative. The microbiologic isolates of sonicate fluid were in 12 cases coagulase-negative staphylococci, in 3 cases P.acnes in 3 cases mixed flora, in 1 case enterococcus and in 1 case SA. From periprosthetic tissue cultures 5 samples have yielded coagulase-negative staphylococci in 5 cases P.acnes in 2 cases mixed flora, in 1 case enterococcus and in 1 case SA were isolated. With the increasing number of patients requiring revision arthroplasty, a clear differentiation between aseptic failure and prosthetic joint infection is crucial for the optimal treatment. Sonication of explanted material is more successful in the isolation of pathogens compared to periprosthetic tissue cultures. Sonication of explanted prosthetic material is helpful in the detection of culture-negative prosthetic joint infections

Effectiveness and long term stability of hip resurfacing and total hip arthroplasty for osteoarthritis patients are still debated nowadays. Several clinical and biomechanical issues have to be considered, including pain relief, return to function, femoral neck fractures, impingement and prosthesis loosening. Normally, patients with hip arthroplasties are facing gait adaptation and at risk of fall. Sudden impact loading and twisting during sideway falls may lead to femoral fractures and joint failures. The purposes of this study are (i) to investigate the stress behavior of hip resurfacing and total hip arthroplasty, and (ii) to predict pattern of femoral fractures during sideway falls and twisting configurations. Computed tomography (CT) based images of a 54-year old male were used in developing a 3D femoral model. The femur model was designed to be inhomogeneous material as defined by Hounsfield Unit of the CT images. CAD data of hip arthroplasties were imported and aligned to represent RHA and THA femur modelas shown in Fig.1. Prosthesis stem is modeled as Ti-6Al-4V material while femoral ball as Alumina properties. Meanwhile, RHA implant is assigned as Co-Cr-Mo material. Four types of loading and boundary conditions were assigned to demonstrate different falling (FC) and twisting (TC) configurations (see Fig.2). Finite element analysis combined with a damage mechanics model was then performed to predict bone fractures in both arthroplasty models. Different loading magnitudes up to 4BW were applied to extrapolate the fracture patterns. Prediction of femoral fracture for RHA and THA femurs are discussed in corresponding to maximum principal stress and damage formation criterion. The load bearing strain was set to 3000micron, the physiological bone loading that leads to bone formation. The test strength was wet to 80% of the yield strength determined from the CT images. Different locations of fracture are predicted in each configuration due to different loading direction and boundary conditions as shown in Fig.3. For falling configurations, fractures were projected at trochanteric region for intact and RHA femur, while THA femurs experience fracture at inner proximal region of bone. Differs to twisting configurations, both arthroplasties were predicted to fracture at the distal end of femurs

Ultra-high molecular weight polyethylene (UHMWPE) has been the gold standard material of choice for the load-bearing articulating surface in knee joint prostheses. However, the application of joint replacements to younger (aged < 64 years) and more active people plus the general increase in life expectancy results in an urgent need for a longer lasting material with better in-use performance. There are three major material related causes that can lead to joint failure in UHMWPE knee joint replacements: free radical induced chemical degradation; mechanical degradation through wear and delamination; and UHMWPE micron and submicron wear debris induced osteolysis. As a potential solution to these problems, highly crosslinked UHMWPE stabilised with infused antioxidant vitamin E (α-Tocopherol), which is abbreviated as E-Poly, has been of great interest. In the current work, the wear performance and mechanical properties of Vanguard cruciate retaining (CR) E-Poly tibial inserts were assessed and compared with Vanguard CR Arcom tibial inserts. Also E-Poly plates were compared with direct compression moulded UHMWPE wear plates. Both a multi-directional pin-on-plate tester and a six-station Prosim (Manchester, UK) knee wear simulator were used to assess wear properties of E-Poly plates and E-Poly tibial inserts respectively. All E-Poly plates and tibial inserts were sterilised and vacuum packed in the same way as Vanguard implants before wear testing. The wear knee simulator test was conducted in accordance with ISO 14243-3:2004 with the exception that a more aggressive Tibial Rotation and Anterior/Posterior displacement profiles, based on the kinematics of the natural knee were incorporated. Under the same aggressive pre-clinical wear testing condition, compared with Vanguard Arcom CR tibial inserts, Vanguard E-Poly CR tibial inserts experienced an 85% reduction in the mean wear rate. The former had a mean wear rate of 6.51±1.75 mm. 3. per million cycles (MC) and the latter had a mean wear rate of 0.96±0.11 mm. 3. /MC over the 7 million cycle testing period. A similar reduction (80%±8.5) in the mean wear factor was also observed on E-Poly plates compared with a series of direct compression moulded GUR1050 UHMWPE plates processed under a range of manufacturing processing conditions. Wear testing was conducted with a configuration of flat-ended stainless steel indenters multi-directionally sliding against the UHMWPE plates. Mechanical properties on Vanguard Arcom UHMWPE and E-Polys were evaluated using the small punch test. All tests were carried out using an Instron 5565 Universal Testing System at a constant crosshead speed of 0.5mm/min. With regard to work-to-failure, no statistical difference was observed, with the former being 254.2±4.1 mJ and the latter 255.6±28.2 mJ. However, all E-Polys exhibited strain stiffening due to the stretch of crosslinks. This resulted in a ca 12% reduction in elongation to break observed for E-Polys compared with that of Arcom UHMWPE. The former had an elongation to break of 4.1±0.2 mm and the latter of 4.7±0.3 mm. In conclusion, we have found that Vitamin E Stabilised UHMWPE tibial inserts are promising for knee joint prostheses. However, further investigations are needed to address potential issues such as the particle size and size distribution of E-Poly wear debris and the associated reactivity

Background. Ankle arthroplasty is increasingly used to reduce pain and improve or maintain joint mobility in end-stage ankle arthritis. Both treatments show similar results with regard to functional outcome scores and sport related activities. However, the rates of complications and reoperations were higher after ankle replacement. Particularly for the first implant designs, with more promising results for newer designs. One of these newer designs is the Mobility Total Ankle System. Short term results in recent literature describe an improvement of functional outcomes; however complication rates vary widely, ranging from 9 to 37% and the 4-year survival rates ranging between 84 and 98 percent. Therefore, the aim of this study was to assess the clinical and radiographic short term results of the Mobility prosthesis. Methods. Between March 2008 and September 2013, 67 primary total ankle arthroplasties with the Mobility prosthesis were performed, in 64 patients, by one experienced foot and ankle surgeon. Complications, reoperations, failures and the survival rate were retrospectively examined. Patient reported outcomes were assessed with the use of the FFI score and visual analogue scale (VAS) for pain. Prosthesis alignment was measured on the first weightbearing radiographs of the ankle according to the procedure described by Rippstein et al.1 (Fig. 1). Results. The mean follow-up period was 40 months (range 12–78 months). There were two intraoperative and 13 postoperative complications, requiring seven reoperations. The reason for reoperation was painful impingement of the medial and/or lateral gutter (n=4), a deep infection (n=1), subsidence of the talus component (n=1) and a cyst located in the tibiofibular joint (n=1). Failure occurred in three of the 67 cases, with one early deep infection with a loose tibia component, one case of aseptic loosening and one case of chronic ankle pain without an assignable cause. A two-stage revision, ankle arthrodesis and amputation of the lower leg was performed, respectively. The mean cumulative survival after 61.4 months was 95% (CI 84–98) (Fig. 2). There was a significant decrease in the median FFI pain and disability score. The pain subscore decreased from 56.4 to 22.2 points and the disability score from 61.1 to 33.3 points. The mean VAS pain was 26.5 for the ankle region. The tibial components were placed in a mean of 1.5° varus relative to the mechanical axis of the tibia in the frontal plane. Malalignment (>5°) was observed in four cases with a mean of 6.0° varus. In the sagittal plane, a mean posterior slope of 1.6° relative to the mechanical axis of the tibia was measured, with one case of 7.5° of anterior slope. The talar component was centred too far posteriorly in five cases, which was considered as malalignment. Conclusion. Despite few intraoperative complications and satisfactory clinical and radiological outcome, the incidence of postoperative complications, reoperations and failure indicate the importance of further development and research in the field of ankle arthroplasty. To view tables/figures, please contact authors directly