Urolithin B inhibits the differentiation of M1 macrophages and relieves the inflammation around the implants under osteoporosis via down-regulating the phosphorylation of VEGFR2.

The inflammation causes the destroyed osseointegration at the implant-bone interface, significantly increasing the probability of implant loosening in osteoporotic patients. Currently, inhibiting the differentiation of M1 macrophages and the inflammatory response could be a solution to stabilize the microenvironment of implants. Interestingly, some natural products have anti-inflammatory and anti-polarization effects, which could be a promising candidate for stabilizing the implants' microenvironment in osteoporotic patients. This research aims to explore the inhibitory effect of Urolithin B(UB) on macrophage M1 polarization, which ameliorates inflammation, thus alleviating implant instability. We established an osteoporosis mouse model of implant loosening. The mouse tissues were taken out for morphological analysis, staining analysis, and bone metabolic index analysis. In in vitro experiments, RAW264.7 cells were polarized to M1 macrophages using lipopolysaccharide (LPS) and analyzed by immunofluorescence (IF) staining, Western blot (WB), and flow cytometry. The CSP100 plus chip experiments were used to explore the potential mechanisms behind the inhibiting effects of UB. Through observation of these experiments, UB can improve the osseointegration between the implants and femurs in osteoporotic mice and enhance the stability of implants. The UB can inhibit the differentiation of M1 macrophages and local inflammation via inhibiting the phosphorylation of VEGFR2, which can be further proved by the weakened inhibited effects of UB in macrophages with lentivirus-induced overexpression of VEGFR2. Overall, UB can specifically inhibit the activation of VEGFR2, alleviate local inflammation, and improve the stability of implants in osteoporotic mice.

Detection of Total Hip Replacement Loosening Based on Structure-Borne Sound: Influence of the Position of the Sensor on the Hip Stem.

Accurate detection of implant loosening is crucial for early intervention in total hip replacements, but current imaging methods lack sensitivity and specificity. Vibration methods, already successful in dentistry, represent a promising approach. In order to detect loosening of the total hip replacement, excitation and measurement should be performed intracorporeally to minimize the influence of soft tissue on damping of the signals. However, only implants with a single sensor intracorporeally integrated into the implant for detecting vibrations have been presented in the literature. Considering different mode shapes, the sensor's position on the implant is assumed to influence the signals. In the work at hand, the influence of the position of the sensor on the recording of the vibrations on the implant was investigated. For this purpose, a simplified test setup was created with a titanium rod implanted in a cylinder of artificial cancellous bone. Mechanical stimulation via an exciter attached to the rod was recorded by three accelerometers at varying positions along the titanium rod. Three states of peri-implant loosening within the bone stock were simulated by extracting the bone material around the titanium rod, and different markers were analyzed to distinguish between these states of loosening. In addition, a modal analysis was performed using the finite element method to analyze the mode shapes. Distinct differences in the signals recorded by the acceleration sensors within defects highlight the influence of sensor position on mode detection and natural frequencies. Thus, using multiple sensors could be advantageous in accurately detecting all modes and determining the implant loosening state more precisely.

Systemically administered zoledronic acid activates locally implanted synthetic hydroxyapatite particles enhancing peri-implant bone formation: A regenerative medicine approach to improve fracture fixation.

Fracture fixation in an ageing population is challenging and fixation failure increases mortality and societal costs. We report a novel fracture fixation treatment by applying a hydroxyapatite (HA) based biomaterial at the bone-implant interface and biologically activating the biomaterial by systemic administration of a bisphosphonate (zoledronic acid, ZA). We first used an animal model of implant integration and applied a calcium sulphate (CaS)/HA biomaterial around a metallic screw in the tibia of osteoporotic rats. Using systemic ZA administration at 2-weeks post-surgery, we demonstrated that the implant surrounded by HA particles showed significantly higher peri­implant bone formation compared to the unaugmented implants at 6-weeks. We then evaluated the optimal timing (day 1, 3, 7 and 14) of ZA administration to achieve a robust effect on peri­implant bone formation. Using fluorescent ZA, we demonstrated that the uptake of ZA in the CaS/HA material was the highest at 3- and 7-days post-implantation and the uptake kinetics had a profound effect on the eventual peri­implant bone formation. We furthered our concept in a feasibility study on trochanteric fracture patients randomized to either CaS/HA augmentation or no augmentation followed by systemic ZA treatment. Radiographically, the CaS/HA group showed signs of increased peri­implant bone formation compared with the controls. Finally, apart from HA, we demonstrated that the concept of biologically activating a ceramic material by ZA could also be applied to ß-tricalcium phosphate. This novel approach for fracture treatment that enhances immediate and long-term fracture fixation in osteoporotic bone could potentially reduce reoperations, morbidity and mortality. STATEMENT OF SIGNIFICANCE: • Fracture fixation in an ageing population is challenging. Biomaterial-based augmentation of fracture fixation devices has been attempted but lack of satisfactory biological response limits their widespread use. • We report the biological activation of locally implanted microparticulate hydroxyapatite (HA) particles placed around an implant by systemic administration of the bisphosphonate zoledronic acid (ZA). The biological activation of HA by ZA enhances peri­implant bone formation. •Timing of ZA administration after HA implantation is critical for optimal ZA uptake and consequently determines the extent of peri­implant bone formation. • We translate the developed concept from small animal models of implant integration to a proof-of-concept clinical study on osteoporotic trochanteric fracture patients. • ZA based biological activation can also be applied to other calcium phosphate biomaterials.

Infection Microenvironment-Responsive Coating on Titanium Surfaces for On-Demand Release of Therapeutic Gas and Antibiotic.

Aseptic loosening and bacterial infection pose significant challenges in the clinical application of titanium (Ti) orthopedic implants, which are primarily caused by insufficient osseointegration and bacterial contamination. To address these issues, a responsive coating on Ti surface is constructed, which achieves enhanced osseointegration and infection elimination by on-demand release of therapeutic gas hydrogen sulfide (H2S) and antibiotic. TiO2 nanotubes (TNT) are anodized on the Ti surface to enhance its bioactivity and serve as reservoirs for the antibiotic. An infection microenvironment-responsive macromolecular H2S donor layer is coated on top of TNT to inhibit premature leakage of antibiotic. This layer exhibits a sustained release of low-dosage H2S, which is capable of promoting the osteogenic differentiation and migration of cells. Moreover, the compactness of the macromolecular H2S donor layer could be broken by bacterial invasion, leading to rapid antibiotic release thus preventing infection. In vitro antibacterial experiments validates significant antibacterial activity of the coating against both Gram-negative (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus). Crucially, this coating effectively suppresses implant-associated infection with 98.7% antibacterial efficiency in a rat femoral bone defect model, mitigates inflammation at the defect site and promotes osseointegration of the Ti orthopedic implant.

Microsporidia (Encephalitozoon cuniculi) in Patients with Degenerative Hip and Knee Disease, Czech Republic.

Total joint arthroplasty is a commonly used surgical procedure in orthopedics. Revision surgeries are required in >10% of patients mainly because of prosthetic joint infection caused by bacteria or aseptic implant loosening caused by chronic inflammation. Encephalitozoon cuniculi is a microsporidium, an obligate intracellular parasite, capable of exploiting migrating proinflammatory immune cells for dissemination within the host. We used molecular detection methods to evaluate the incidence of E. cuniculi among patients who had total hip or knee arthroplasty revision. Out of 49 patients, E. cuniculi genotypes I, II, or III were confirmed in joint samples from 3 men and 2 women who had implant loosening. Understanding the risks associated with the presence of microsporidia in periprosthetic joint infections is essential for proper management of arthroplasty. Furthermore, E. cuniculi should be considered a potential contributing cause of joint inflammation and arthrosis.

Metallosis with spinal implant loosening after spinal instrumentation: A case report.

BACKGROUND: Spinal metallosis is a rare complication following spinal instrumentation whereby an inflammatory response to the metal implants results in the development of granulomatous tissue. CASE SUMMARY: We describe the case of a 78-year-old woman who had recurrence of back pain 5 years after lumbar spine posterior decompression and instrumented fusion. Lumbar spine radiographs showed hardware loosening and magnetic resonance imaging showed adjacent segment disease. Revision surgery revealed evidence of metallosis intraoperatively. CONCLUSION: Spinal metallosis can present several years after instrumentation. Radiography and computed tomography may demonstrate hardware loosening secondary to metallosis. Blood metal concentrations associated with spinal metallosis have yet to be established. Hence, metallosis is still an intraoperative and histopathological diagnosis. The presence of metallosis after spinal instrumentation likely indicates a more complex underlying problem: Pseudarthrosis, failure to address sagittal balance, infection, and cross-threading of set screws. Hence, identifying metallosis is important, but initiating treatment promptly for symptomatic implant loosening is of greater paramount.

Nail-stem construct method for periprosthetic humeral fractures with recalcitrant nonunion after total elbow arthroplasty: A surgical technique.

Objectives: The objective of this study was to describe the surgical technique using an innovative nail-stem construct in treatment of periprosthetic humeral fractures with recalcitrant nonunion after total elbow arthroplasty (TEA). Materials and Methods: Patients diagnosed with humeral recalcitrant nonunion in periprosthetic fractures and stem loosening after TEA were retrospectively recruited between 2018 and 2019. The demographic data and related clinical outcomes were recorded. We use a cutting length of the nail pushing into the humeral canal and then pull back distally to dock the tip of the humeral stem. The cement was packed into the humeral canal, and the periprosthetic bone defect was impacting with harvested allograft chip. Results: Patient age, gender, lesion site, number of previous surgeries, and the time period from the primary TEA to the nail-stem reconstruction were allocated. Moreover, the range of motion, degree of elbow stability, and level of pain were evaluated for each patient following this procedure. All the four patients achieved an optimal range of motion and secure stability with painless elbow at final follow-up. Conclusion: Our proposed nail-stem construct with double allogenous bone plate is a feasible alternative for revisional TEA in patients with implant loosening, periprosthetic humeral fractures, and recalcitrant nonunion.

Capacitive stimulation-sensing system for instrumented bone implants: Finite element model to predict the electric stimuli delivered to the interface.

BACKGROUND: Prevalence of orthopaedic replacements are increasing around the world. The main cause of revision remains associated to the interface loosening. In this work, a computational study using the Finite element method was developed to predict the electric field stimuli delivered to trabecular bone structures, as well as to predict the sensing ability to detect different bone-implant interface scenarios. METHODS: Three finite element models were developed: two simplified models, including a Gyroid TMP structure, and a realistic model based on microCT scan of a trabecular bone from sheep vertebra. Simulations were performed using a co-surface capacitive technology for stimulating and sensing bone-implant interfaces. Different fixation scenarios were considered, namely by establishing bone-stimulator gap sizes up to 1 mm (from fixation to massive loosening scenario). Electrodes were excited with sinusoidal and square electric signals up to 10V voltage and 64kHz frequency. RESULTS: Simplification of bone geometry resulted in significant electric stimuli differences compared to the realistic bone geometry. Realistic modelling allowed to observe that, in the fixation scenario, the electric field stimuli decreased 85% from the sensor interface to a parallel plane 2 mm apart from such interface. A significant influence of the bone-stimulator distance on the electric stimuli was found: the electric stimuli magnitudes varied in the range between 0.38 V/mm (fixation scenario) and 4.8 mV/mm (massive loosening scenario) for voltages up to 10V. Strong frequency-dependent behaviours were also observed in the electric stimuli: their magnitudes can reach 106-fold decreases when the excitation frequency is decreased from 32 kHz to 14 Hz CONCLUSION: This study points out the inability of our two simplified models to predict the electric stimulation provided to different bone-implant interface scenarios. Results highlight that co-surface stimulators can deliver osteogenic electric stimuli along trabecular bone structures, ensuring low electric power excitations. Moreover, realistic models strongly enhance the sensing predictability of the bone-implant fixation states. These new and significant evidences provide a strong support to integrate co-surface capacitive into bioelectronic implants for both therapeutic and sensing operations.

Influence of sportive activity on functional and radiographic outcomes following reverse total shoulder arthroplasty: a comparative study.

BACKGROUND: The purpose of the present study was to compare the functional and radiographic outcomes following reverse total shoulder arthroplasty (RTSA) in a senior athletic and non-athletic population. MATERIAL AND METHODS: In this retrospective cohort study, patients who underwent RTSA between 06/2013 and 04/2018 at a single institution were included. Minimum follow-up was 2 years. A standardized questionnaire was utilized for assessment of patients' pre- and postoperative physical fitness and sportive activity. Patients who resumed at least one sport were assigned to the athletic group, while patients who ceased participating in sports were assigned to the non-athletic group. Postoperative clinical outcome measures included the Constant score (CS), American Shoulder and Elbow Surgeons (ASES) score, Simple Shoulder Test (SST), and visual analog scale (VAS) for pain. Active shoulder range of motion (ROM) and abduction strength were assessed. Radiographic evaluation was based on a standardized core set of parameters for radiographic monitoring of patients following shoulder arthroplasty. RESULTS: Sixty-one of 71 patients (85.9%; mean age: 72.1 ± 6.6 years) were available for clinical and radiographic follow-up at a mean of 47.1 ± 18.1 months. Thirty-four patients (55.7%) were assigned to the athletic group and 27 patients (44.3%) to the non-athletic group. The athletic group demonstrated significantly better results for CS (P = 0.002), ASES score (P = 0.001), SST (P = 0.001), VAS (P = 0.022), active external rotation (P = 0.045) and abduction strength (P = 0.016) compared to the non-athletic group. The overall rate of return to sport was 78.0% at an average of 5.3 ± 3.6 months postoperatively. Incomplete radiolucent lines (RLL) around the humeral component were found significantly more frequently in the athletic group compared to the non-athletic group (P = 0.019), whereas the occurrence of complete RLLs around the implant components was similar (P = 0.382). Scapular notching was observed in 18 patients (52.9%) of the athletic group and 12 patients (44.9%) of the non-athletic group (P = 0.51). The overall rate for revision surgery was 8.2%, while postoperative complications were encountered in 3.3% of cases. CONCLUSION: At mid-term follow-up, the athletic population demonstrated significantly better clinical results following RTSA without a higher rate of implant loosening and scapular notching when compared to non-athletic patients. However, incomplete radiolucency around the humeral component was observed significantly more often in the athletic group. LEVEL OF EVIDENCE: III.

Artificial intelligence for image analysis in total hip and total knee arthroplasty : a scoping review.

AIMS: Total hip arthroplasty (THA) and total knee arthroplasty (TKA) are common orthopaedic procedures requiring postoperative radiographs to confirm implant positioning and identify complications. Artificial intelligence (AI)-based image analysis has the potential to automate this postoperative surveillance. The aim of this study was to prepare a scoping review to investigate how AI is being used in the analysis of radiographs following THA and TKA, and how accurate these tools are. METHODS: The Embase, MEDLINE, and PubMed libraries were systematically searched to identify relevant articles. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews and Arksey and O'Malley framework were followed. Study quality was assessed using a modified Methodological Index for Non-Randomized Studies tool. AI performance was reported using either the area under the curve (AUC) or accuracy. RESULTS: Of the 455 studies identified, only 12 were suitable for inclusion. Nine reported implant identification and three described predicting risk of implant failure. Of the 12, three studies compared AI performance with orthopaedic surgeons. AI-based implant identification achieved AUC 0.992 to 1, and most algorithms reported an accuracy > 90%, using 550 to 320,000 training radiographs. AI prediction of dislocation risk post-THA, determined after five-year follow-up, was satisfactory (AUC 76.67; 8,500 training radiographs). Diagnosis of hip implant loosening was good (accuracy 88.3%; 420 training radiographs) and measurement of postoperative acetabular angles was comparable to humans (mean absolute difference 1.35° to 1.39°). However, 11 of the 12 studies had several methodological limitations introducing a high risk of bias. None of the studies were externally validated. CONCLUSION: These studies show that AI is promising. While it already has the ability to analyze images with significant precision, there is currently insufficient high-level evidence to support its widespread clinical use. Further research to design robust studies that follow standard reporting guidelines should be encouraged to develop AI models that could be easily translated into real-world conditions. Cite this article: Bone Joint J 2022;104-B(8):929-937.

Additive Effect of Parathyroid Hormone and Zoledronate Acid on Prevention Particle Wears-Induced Implant Loosening by Promoting Periprosthetic Bone Architecture and Strength in an Ovariectomized Rat Model.

Implant-generated particle wears are considered as the major cause for the induction of implant loosening, which is more susceptible to patients with osteoporosis. Monotherapy with parathyroid hormone (PTH) or zoledronate acid (ZOL) has been proven efficient for preventing early-stage periprosthetic osteolysis, while the combination therapy with PTH and ZOL has exerted beneficial effects on the treatment of posterior lumbar vertebral fusion and disuse osteopenia. However, PTH and ZOL still have not been licensed for the treatment of implant loosening to date clinically. In this study, we have explored the effect of single or combined administration with PTH and ZOL on implant loosening in a rat model of osteoporosis. After 12 weeks of ovariectomized surgery, a femoral particle-induced periprosthetic osteolysis model was established. Vehicle, PTH (5 days per week), ZOL (100 mg/kg per week), or combination therapy was utilized for another 6 weeks before sacrifice, followed by micro-CT, histology, mechanical testing, and bone turnover examination. PTH monotherapy or combined PTH with ZOL exerted a protective effect on maintaining implant stability by elevating periprosthetic bone mass and inhibiting pseudomembrane formation. Moreover, an additive effect was observed when combining PTH with ZOL, resulting in better fixation strength, higher periprosthetic bone mass, and less pseudomembrane than PTH monotherapy. Taken together, our results suggested that a combination therapy of PTH and ZOL might be a promising approach for the intervention of early-stage implant loosening in patients with osteoporosis.

Posterior spinal stabilization: A biomechanical comparison of Laminar Hook Fusion to a Pedicle Screw System.

BACKGROUND: Several spine instrumentation techniques have been introduced to correct inter-segmental alignment, or provide long-term stability. Whilst pedicle screws are considered the intervention of reference, we hypothesize that the week hold of osteoporotic bone, might be a clinical indicator for an alternative surgical approach. METHODS: To put this to the test, a non-linear Finite Element model, of a ligamentous lumbosacral spine, was employed to examine a stabilization spanning over L3-L5. Two different immobilization techniques (a Pedicle Screw System and Laminar Hook Fusion) are compared as to their biomechanical response during 7.5 Nm flexion, lateral flexion and torsion, while considering a 280 N follower load. Fifteen analyses performed in total, simulating patients of healthy and osteoporotic Bone Mineral Density. FINDINGS: Range of Motion was significantly reduced after instrumentation for both implant systems. This trend was more pronounced in the Pedicle Screw models, which were stressed to a higher degree. To evaluate implant loosening risk, we introduce the consideration of strain energy patterns around the screw tract. The notably higher intensity of these, for the osteoporotic model, taken into consideration with the weaker strength of the tissue and inconsistencies in the stress allocation between implant and bone, affirmed an increased risk for loosening of the Pedicle Screws in osteoporotic patients. INTERPRETATION: The analysis provided refined insight as to the treatment of osteoporotic patients as well as to their postoperative care, as restriction of specific movements (e.g. through bracing), could significantly restrict the stress values in the bone-implant interface and thus, reduce implant failure.

Spinal Surgery Site Infection Leading to Implant Loosening Is Influenced by the Number of Prior Operations.

STUDY DESIGN: Retrospective Cohort Study. OBJECTIVES: Spinal surgery site infection and chronic implant infection are possible causes for ongoing pain, implant loosening, and failed back surgery syndrome. Evidence of chronic infection was found in 29.1% of revision cases but is also found in a considerable number of degenerative cases without prior surgery. Infection mechanisms and possible clinical correlations are unclear. METHODS: Retrospective analysis of standardized surgery site screening (swab, tissue samples, implant sonication) in 181 cases without clinical evidence of preoperative surgery site infection. RESULTS: Screening results of cases without prior spinal surgery (n = 49, 10.2% positive) were compared to cases with prior spine surgery without implant placement (e.g. micro discectomy) (n = 21, 23.8% positive), revision cases following singular spinal fusion (n = 73, 23.2% positive), and cases with multiple revisions (n = 38, 50.0% positive). Propionibacterium spp. detection rate increased to 80% in positive cases with multiple revisions. Implants in place during revision surgery had a significantly higher infection rate (32.4%) compared to no implant (14.2%, p = 0.007). Positive cases had a significantly higher pain level prior to surgery compared to negative cases (p = 0.019). Laboratory parameters had no predictive value. Logistic regression revealed that previous spinal surgeries (odds ratio [OR] 1.38 per operation, p < 0.001) and male sex (OR 1.15, p = 0.028) were independent predictive factors for infection. CONCLUSIONS: Previous spinal surgery is a risk factor for chronic surgery site infection, leading to chronic pain, implant loosening, and revision. The presence of Propionibacterium spp. was correlated with chronic implant loosening and was more likely with cumulative surgeries.

Variation of synovial fluid leucocyte cell count and polymorphonuclear percentage in patients with aseptic revision total knee arthroplasty.

AIMS: Current guidelines consider analyses of joint aspirates, including leucocyte cell count (LC) and polymorphonuclear percentage (PMN%) as a diagnostic mainstay of periprosthetic joint infection (PJI). It is unclear if these parameters are subject to a certain degree of variability over time. Therefore, the aim of this study was to evaluate the variation of LC and PMN% in patients with aseptic revision total knee arthroplasty (TKA). METHODS: We conducted a prospective, double-centre study of 40 patients with 40 knee joints. Patients underwent joint aspiration at two different time points with a maximum period of 120 days in between these interventions and without any events such as other joint aspirations or surgeries. The main indications for TKA revision surgery were aseptic implant loosening (n = 24) and joint instability (n = 11). RESULTS: Overall, 80 synovial fluid samples of 40 patients were analyzed. The average time period between the joint aspirations was 50 days (SD 32). There was a significantly higher percentage change in LC when compared to PMN% (44.1% (SD 28.6%) vs 27.3% (SD 23.7%); p = 0.003). When applying standard definition criteria, LC counts were found to skip back and forth between the two time points with exceeding the thresholds in up to 20% of cases, which was significantly more compared to PMN% for the European Bone and Joint Infection Society (EBJIS) criteria (p = 0.001), as well as for Musculoskeletal Infection Society (MSIS) (p = 0.029). CONCLUSION: LC and PMN% are subject to considerable variation. According to its higher interindividual variance, LC evaluation might contribute to false-positive or false-negative results in PJI assessment. Single LC testing prior to TKA revision surgery seems to be insufficient to exclude PJI. On the basis of the obtained results, PMN% analyses overrule LC measurements with regard to a conclusive diagnostic algorithm. Cite this article: Bone Jt Open 2021;2(8):566-572.

Therapeutic Potential of Vasoactive Intestinal Peptide and its Derivative Stearyl-Norleucine-VIP in Inflammation-Induced Osteolysis.

The common use of dental and orthopedic implants calls for special attention to the immune response leading to peri-prosthetic bone loss and implant failure. In addition to the well-established microbial etiology for oral implant failure, wear debris and in particular titanium (Ti) particles (TiP) in the implant vicinity are an important trigger of inflammation and activation of bone resorption around oral and orthopedic implants, presenting an unmet medical need. Here, we employed bacterial-derived lipopolysaccharides (LPS) to model infection and TiP to model aseptic inflammation and osteolysis. We assessed inflammation in vitro by measuring IL1ß, IL6 and TNFα mRNA expression in primary macrophages, osteoclastogenesis in RANKL-induced bone marrow derived pre-osteoclasts and osteolysis in vivo in a mouse calvarial model. We also assessed the trans-epithelial penetrability and safety of the tested compound in rats. Our results show that a lipophilic super-active derivative of vasoactive intestinal peptide (VIP), namely stearyl-norleucine-VIP (SNV) presented superior anti-inflammatory and anti-osteoclastogenic effects compared to VIP in vitro. In the bacterial infection model (LPS), SNV significantly reduced IL1ß expression, while VIP increased IL6 expression. In the aseptic models of osteolysis, SNV showed greater suppression of in vitro osteoclastogenesis than VIP, and significantly inhibited inflammation-induced osteolysis in vivo. We also observed that expression levels of the VIP receptor VPAC-2, but not that of VPAC-1, dramatically decreased during osteoclast differentiation. Importantly, SNV previously shown to have an increased stability compared to VIP, showed here significant trans-epithelial penetration and a clean toxicological profile, presenting a novel drug candidate that could be applied topically to counter both aseptic and infection-related bone destruction.

The effect of TNF-α on osteoblasts in metal wear-induced periprosthetic bone loss.

AIMS: This study aimed to examine the effects of tumour necrosis factor-alpha (TNF-α) on osteoblasts in metal wear-induced bone loss. METHODS: TNF-α immunoexpression was examined in periprosthetic tissues of patients with failed metal-on-metal hip arthroplasties and also in myeloid MM6 cells after treatment with cobalt ions. Viability and function of human osteoblast-like SaOs-2 cells treated with recombinant TNF-α were studied by immunofluorescence, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assay, western blotting, and enzyme-linked immunosorbent assay (ELISA). RESULTS: Macrophages, lymphocytes, and endothelial cells displayed strong TNF-α immunoexpression in periprosthetic tissues containing metal wear debris. Colocalization of TNF-α with the macrophage marker CD68 and the pan-T cell marker CD3 confirmed TNF-α expression in these cells. Cobalt-treated MM6 cells secreted more TNF-α than control cells, reflecting the role of metal wear products in activating the TNF-α pathway in the myeloid cells. While TNF-α did not alter the immunoexpression of the TNF-receptor 1 (TNF-R1) in SaOs-2 cells, it increased the release of the soluble TNF-receptor 1 (sTNF-R1). There was also evidence for TNF-α-induced apoptosis. TNF-α further elicited the expression of the endoplasmic reticulum stress markers inositol-requiring enzyme (IRE)-1α, binding-immunoglobulin protein (BiP), and endoplasmic oxidoreductin1 (Ero1)-Lα. In addition, TNF-α decreased pro-collagen I α 1 secretion without diminishing its synthesis. TNF-α also induced an inflammatory response in SaOs-2 cells, as evidenced by the release of reactive oxygen and nitrogen species and the proinflammatory cytokine vascular endothelial growth factor. CONCLUSION: The results suggest a novel osteoblastic mechanism, which could be mediated by TNF-α and may be involved in metal wear debris-induced periprosthetic bone loss. Cite this article: Bone Joint Res 2020;9(11):827-839.

Incremental inputs improve the automated detection of implant loosening using machine-learning algorithms.

AIMS: The aim of this study was to evaluate the ability of a machine-learning algorithm to diagnose prosthetic loosening from preoperative radiographs and to investigate the inputs that might improve its performance. METHODS: A group of 697 patients underwent a first-time revision of a total hip (THA) or total knee arthroplasty (TKA) at our institution between 2012 and 2018. Preoperative anteroposterior (AP) and lateral radiographs, and historical and comorbidity information were collected from their electronic records. Each patient was defined as having loose or fixed components based on the operation notes. We trained a series of convolutional neural network (CNN) models to predict a diagnosis of loosening at the time of surgery from the preoperative radiographs. We then added historical data about the patients to the best performing model to create a final model and tested it on an independent dataset. RESULTS: The convolutional neural network we built performed well when detecting loosening from radiographs alone. The first model built de novo with only the radiological image as input had an accuracy of 70%. The final model, which was built by fine-tuning a publicly available model named DenseNet, combining the AP and lateral radiographs, and incorporating information from the patient's history, had an accuracy, sensitivity, and specificity of 88.3%, 70.2%, and 95.6% on the independent test dataset. It performed better for cases of revision THA with an accuracy of 90.1%, than for cases of revision TKA with an accuracy of 85.8%. CONCLUSION: This study showed that machine learning can detect prosthetic loosening from radiographs. Its accuracy is enhanced when using highly trained public algorithms, and when adding clinical data to the algorithm. While this algorithm may not be sufficient in its present state of development as a standalone metric of loosening, it is currently a useful augment for clinical decision making. Cite this article: Bone Joint J 2020;102-B(6 Supple A):101-106.

Convincing long-term results independent from the postoperative leg alignment following cementless total knee arthroplasty.

BACKGROUND: Cementless primary total knee arthroplasty shows numerous advantages compared with cemented implants (e.g., shorter operation time, preservation of the bone stock). Up to now an increasing number of clinical long-term studies exist. Despite this fact, there is no evidence about the influence of the postoperative leg alignment on the results of cementless knee arthroplasty. There is no work on the clinical outcome of the specific implant, which was used in this study (VANGUARD®, ZimmerBiomet). The purpose of this study was to assess the clinical and radiological long-term results after cementless knee arthroplasty in relation to the postoperative mechanical leg alignment. METHODS: Clinical and radiological results were retrospectively assessed in 83 patients at 10.3 years (ranging from 9.6 to 11.8 years) after implantation. Hip-knee-ankle angle (HKA) was measured, and the patients were separated into a corrected (HKA between three degrees of varus and three degrees of valgus, n = 60) and a varus/valgus (HKA > 3° of varus and valgus, n = 23) group. RESULTS: Up to the time of the clinical follow-up, three out of 83 patients already underwent a revision surgery due to a deep infection (3.6%). Tegner-Lysholm Knee scale was 89.1 in the corrected group and 88.8 in the varus/valgus group (p = .94). The mean Knee Injury and Osteoarthritis Outcome score (KOOS) was 81.2 in the corrected group and 82.4 in the varus/valgus group (p = .63). CONCLUSIONS: Results of this study showed convincing clinical and radiological results after primary cementless knee arthroplasty. Under- or overcorrected postoperative mechanical leg alignments did not influence the long-term clinical results.

Is prophylaxis for heterotopic ossification with radiation therapy after THR associated with early loosening or carcinogenesis?

INTRODUCTION: Heterotopic ossification may develop after major hip surgeries, thus preventive strategies including radiation therapy and non steroid anti-inflammatory drugs are commonly employed. There are certain concerns regarding the effects of radiation therapy on implant loosening and carcinogenesis. Our study aims to evaluate whether radiation therapy results in implant loosening or radiation-induced tumours in the long term. PATIENTS AND METHODS: This was a prospective study including 97 high-risk patients for heterotopic ossification who underwent total hip arthroplasty. Patients were divided into 2 groups and received either a combination of radiation therapy and indomethacin (Group A), or indomethacin alone (Group B). Evaluated outcomes included implant loosening or development of radiation-induced tumours during the follow-up period. RESULTS: The follow-up period of the study was 10 years. Group A consisted of 50 patients, while Group B consisted of 47 patients. 3 patients died during the follow-up. There were 2 cases of implant loosening, 1 from each of the 2 groups at 9 and 10 years after surgery respectively; thus, no statistically significant difference regarding implant loosening was found (p < 0.05). During the follow-up period no cases of radiation-induced tumours were identified. CONCLUSION: Our results are consistent with those of other studies supporting the safety of radiation therapy as a preventive strategy for heterotopic ossification following major surgeries in high risk patients. Further studies with even longer follow-up may be required to definitely exclude the possibility of adverse outcomes linked with radiation therapy.

Cementation technique for elbow arthroplasty; an international survey.

BACKGROUND: Modern cementation techniques have markedly improved survivorship in lower limb arthroplasty, which have been heavily researched in the hip and knee but less so for upper limb procedures. Aseptic loosening is a leading cause of failure in total elbow arthroplasty (TEA) which could be related to the quality of cementation. The aim of this study was to investigate the cementation techniques used for TEA among practicing elbow surgeons. METHODS: An electronic questionnaire was emailed to members of the British elbow and shoulder society (BESS) and PubMed identified experts. Questions focused on the type of prosthesis, operative rates for elective and trauma cases, nature of cement used, canal preparation and cement insertion. Opinions regarding satisfaction with current techniques and mantle quality were also collected. RESULTS: A total of 26 surgeons completed the questionnaire. The Coonrad-Moorey was the most popular device amongst respondents. Most cemented both components, used antibiotic loaded cement, washed the canal with saline and inserted the cement retrograde. There was wide variation in cementation techniques used for the humerus and ulna, particularly regarding cement preparation, insertion, and use of a restrictor and pressurisation. CONCLUSION: Modern cementation techniques are not being utilised in TEA which could be contributing to implant loosening rates and longevity.