Aims. Loosening of components after total knee arthroplasty (TKA) can be associated with the development of radiolucent lines (RLLs). The aim of this study was to assess the rate of formation of RLLs in the cemented original design of the ATTUNE TKA and their relationship to loosening. Methods. A systematic search was undertaken using the Cochrane methodology in three online databases: MEDLINE, Embase, and CINAHL. Studies were screened against predetermined criteria, and data were extracted. Available National Joint Registries in the Network of Orthopaedic Registries of Europe were also screened. A random effects model meta-analysis was undertaken. Results. Of 263 studies, 12 were included with a total of 3,861 TKAs. Meta-analysis of ten studies showed high rates of overall tibial or femoral RLLs for the cemented original design of the ATTUNE TKA. The overall rate was 21.4% (95% confidence interval (CI) 12.7% to 33.7%) for all types of design but was higher for certain subgroups: 27.4% (95% CI 13.4% to 47.9%) for the cruciate-retaining type, and 29.9% (95% CI 15.6% to 49.6%) for the fixed-bearing type. Meta-analysis of five studies comparing the ATTUNE TKA with other implants showed a significantly higher risk of overall tibial or femoral RLLs (odds ratio (OR) 2.841 (95% CI 1.219 to 6.623); p = 0.016) for the ATTUNE. The rates of loosening or revision for loosening were lower, at 1.2% and 0.9% respectively, but the rates varied from 0% to 16.3%. The registry data did not report specifically on the original ATTUNE TKA or on revision due to loosening, but ‘all-cause’ five-year revision rates for the cemented ATTUNE varied from 2.6% to 5.9%. Conclusion. The original cemented ATTUNE TKA has high rates of RLLs, but their clinical significance is uncertain given the overall low associated rates of loosening and revision. However, in view of the high rates of RLLs and the variation in the rates of loosening and revision between studies and registries, close surveillance of patients who have undergone TKA with the original ATTUNE system is recommended. Cite this article: Bone Joint J 2023;105-B(6):610–621

Abstract. Introduction. Choosing a hinged implant in the revision knee arthroplasty (rTKA) setting is challenging and limited data on implant performance exists. We present the survivorship and reason for failure in rTKA performed at our institution using the LINK hinge prosthesis, predominantly the cemented modular Endo-Model prosthesis. Methodology. 260 consecutive revision knee cases performed between 2012 and 2020 were reviewed retrospectively. Mean follow up was 27 months (range 0 to 107). Survivorship was analysed in Stata using a Log Rank test to compare performance in patients stratified according to age (≥80 years old (76 cases), 70–79 years (104 cases) and ≤70 years (80 cases). Results. 53 patients died and 48/207 (23%) cases in 40 patients underwent re-revision. Reasons for re-revision were aseptic loosening (21), infection (12), instability (4), extensor failure (1), stiffness (1), fracture (1) and other (8). Loosening was seen in the femur (8), tibia (5), and both the femur and tibia (8). Sub-group analysis of patients according to age showed a significantly higher failure rate in younger patients (6 failures (8%) in patients ≥80, 27 failures (26%) in 70–79 and 15 (19%) in ≤70 (p = 0.02). Failure in patients ≤70 was predominantly due to aseptic loosening (8/15). Conclusion. Here we report a significantly higher rate of LINK hinge prostheses failure in patients <70 undergoing rTKA. Consent should consider the risk of re-revision in this patient group

Introduction & Aims. In other medical fields, smart implantable devices are enabling decentralised monitoring of patients and early detection of disease. Despite research-focused smart orthopaedic implants dating back to the 1980s, such implants have not been adopted into regular clinical practice. The hardware footprint and commercial cost of components for sensing, powering, processing, and communicating are too large for mass-market use. However, a low-cost, minimal-modification solution that could detect loosening and infection would have considerable benefits for both patients and healthcare providers. This proof-of-concept study aimed to determine if loosening/infection data could be monitored with only two components inside an implant: a single-element sensor and simple communication element. Methods. The sensor and coil were embedded onto a representative cemented total knee replacement. The implant was then cemented onto synthetic bone using polymethylmethacrylate (PMMA). Wireless measurements for loosening and infection were then made across different thicknesses of porcine tissue to characterise the sensor's accuracy for a range of implantation depths. Loosening was simulated by taking measurements before and after compromising the implant-cement interface, with fluid influx simulated with phosphate-buffered saline solution. Elevated temperature was used as a proxy for infection, with the sensor calibrated wirelessly through 5 mm of porcine tissue across a temperature range of 26–40°C. Results. Measurements for loosening and infection could be acquired simultaneously with a duration of 4 s per measurement. For loosening, the debonded implant-cement interface was detectable up to 10 mm with 95% confidence. For temperature, the sensor was calibrated with a root mean square error of 0.19°C at 5 mm implantation depth and prediction intervals of ±0.38°C for new measurements with 95% confidence. Conclusions. This study has demonstrated that with only two onboard electrical components, it is possible to wirelessly measure cement debonding and elevated temperature on a smart implant. With further development, this minimal hardware/cost approach could enable mass-market smart arthroplasty implants

Introduction. Aseptic loosening of the acetabular cup in total hip replacement (THR) remains a major problem. Current diagnostic imaging techniques are ineffective at detecting early loosening, especially for the acetabular component. The aim of this preliminary study was to assess the viability of using a vibration analysis technique to accurately detect acetabular component loosening. Methods. A simplified acetabular model was constructed using a Sawbones foam block into which an acetabular cup was fitted. Different levels of loosening were simulated by the interposition of thin layer of silicon between the acetabular component and the Sawbones block. This included a simulation of a secure (stable) fixation and various combinations of cup zone loosening. A constant amplitude sinusoidal excitation with a sweep range of 100–1500 Hz was used. Output vibration from the model was measured using an accelerometer and an ultrasound probe. Loosening was determined from output signal features such as the number and relative strength of the observed harmonic frequencies. Results. Both measurement methods were capable of measuring the output vibration. Preliminary findings show different patterns in the output signal spectra were visible when comparing the stable cup with the 1mm of simulated spherical loosening at driving frequencies 1050 Hz, 1100 Hz and 1150 Hz (p < 0.05) using the accelerometer, whereas for ultrasound at frequencies 950 Hz and 1350 Hz (p < 0.05). Conclusions. Experimental testing showed that vibration analysis could be used as a potential detection method for acetabular cup component loosening using either an accelerometer or ultrasound probe to detect the vibration. However, the capacity of ultrasound to overcome the attenuating effect of the surrounding soft tissues and its high signal to noise ratio suggest it has the best potential for clinical use

The incidence of loosening of a cemented glenoid component in total shoulder arthroplasty, detected by means of radiolucent lines or positional shift of the component on true antero-posterior radiographs, has been reported to be between 0% to 44%. These numbers depend on the criteria used for loosening and on the length of follow-up. Radiolucent lines are however difficult to detect and to interpret, because of the mobility of the shoulder girdle and the obliquity of the glenoid, which hinder standardisation of radiographs. After review of radiolucencies around cemented glenoid components with a mean follow-up of 5. 3 years in 48 patients we found progressive changes to be present predominantly at the inferior pole of the component. This may hold a clue for the mechanism behind loosening of this implant. Since loosening is generally defined as a complete radiolucent line around the glenoid component and is difficult to assess as a result of the oblique orientation of the glenoid, an underestimation of the loosening rate using radiological data was suspected. Therefore a pilot study using Roentgen Stereophotogrammatric Analysis (RSA) was performed. In five patients an additional analysis of glenoid component loosening using digital Roentgen Stereophotogrammetric Analysis (RSA) was performed. The relative motion of the glenoid component with respect to the scapula was assessed and the length of this translation vector was used to represent migration. Loosening was defined as a migration of the component, exceeding the pessimistic estimate of the accuracy of RSA 0. 3 mm for this study. After three years of follow-up, three out of five glenoid components had loosened (1. 2 – 5. 5 mm migration). In only one patient with a gross loosened glenoid, the radiological signs were consistent with the RSA findings. It was concluded that when traditional radiographs are used for assessment of early loosening, the loosening rate is underestimated. We recommend that RSA be used for this

This systematic review of the literature summarises the clinical experience with ceramic-on-ceramic hip bearings over the past 40 years and discusses the concerns that exist in relation to the bearing combination. Loosening, fracture, liner chipping on insertion, liner canting and dissociation, edge-loading and squeaking have all been reported, and the relationship between these issues and implant design and surgical technique is investigated. New design concepts are introduced and analysed with respect to previous clinical experience

Introduction: High-flexion (HF) TKA designs were introduced in order to achieve greater flexion than with conventional TKA designs. Although early clinical results are promising, recent literature raises concerns about fixation and risk for early loosening of the femoral component during high demanding activities. This study’s aim was to measure the loosening force of the femoral component of several PS-TKA designs in a deep flexion configuration. Methods: The loosening force of the femoral component of ten contemporary PS-TKAs, including five HF and five conventional designs from the major orthopaedic companies were evaluated. To simulate a deep flexion configuration, each TKA was implanted in a femoral bone model and placed in a loading frame in 135° of flexion, with the tibia vertically. Loosening of the femoral component was induced by raising the tibial insert with constant displacement rate, maintaining the same flexion angle. The resisting force was recorded continuously. A stereo-photogrammetric system registered the relative motion between the femoral component and the bone model. The loosening force was determined when a gap of 2 mm was observed. The influence of pegs on the loosening force was also investigated. Results: Generally, conventional femoral designs required higher forces before loosening occurred compared to HF designs (p< 0.001). In the group of the HF designs there was a statistically significant difference between the designs (p=0.015) due to the shape of the internal box cut. For some designs, the presence of pegs induced a statistically significant change in loosening force. Discussion and Conclusion: Several design characteristics of the femoral component can alter its resistance to loosening. In this in vitro study, it was shown that the shape of the internal box cut and the presence of pegs, as well as the geometry of the pegs, are important factors for the loosening force. In the group of the HF components there was a statistically significant difference between the designs with an open and a closed box

The purpose of the present study was to identify risk factors for femoral loosening and neck fracture for Conserve+ metal-on-metal hybrid surface atrhroplasty. The first 500 hips (of over 700 implanted by the senior author) in 436 patients were reviewed. Mean age was 48.6 with 74% of males patients. 16 hips were converted to THR secondary to aseptic failure on the femoral side (11 femoral component loosenings and 5 femoral neck fractures). 14 hips showed radiolucencies around the short metaphyseal stem at last follow-up. A retrieval analysis was performed and analyzed specimens compared with the intra operative photos of the prepared femoral head and the post-op X-rays. The cause of neck fractures is multifactorial. Risk factors include: uncovered reamed bone, leaving the component proud, notching the neck, impingement, osteopenia and cysts, and trauma. Avoidance of technical deficiencies and proper patient selection can eliminate neck fractures. Loosening is also multifactorial. Risk factors for loosening included: cysts > 1 cm, small femoral head size, female gender, early cases (before improved acrylic fixation including femoral suctioning measures were instituted) and reduced stem shaft angle. Meticulous initial preparation of the femoral bone surfaces, drying with suctioning, and maximizing the fixation area are critical when the fixation area is small, especially with osteopenia and cystic degeneration. These techniques have dramatically diminished the incidence of loosening and radiolucencies. Cementing the femoral metaphyseal stem is a meaningful technical improvement towards the prevention of early femoral failure in patients with risk factors

The goal of the study was to describe the features of the aseptic loosening of the cup in CoC THR and to determine factors that affect the time to revision.

It is a retrospective study including all patients who had a revision of CoC THR for aseptic failure fixation of the cup, between 2007 and 2017. 55 patients (27 women, 28 men) (56 hips) were included in the study. Eight hips (13 %) had also a stem exchange. At the primary T HR, the mean age of the patients was 47.9 years (17–72), 28 press fit cups had screws, the mean diameter of the cup was 51.2 mm (46–62) and the mean inclination was 52° (37–67). Clinical and radiological data were retrospectively recorded by an observer different to the initial operators.

The mean age of the patients at the revision was 55.4 years (26–84). The mean time to revision was 90.1 months (14–240), and was significantly greater in patients aged less than 52 years, in cups without screws and with a 28mm head. The trend curve of the time to cup revision showed a bimodal distribution at three and ten years. 20 cups had migrated (33%). Bone loss was rated type 1 in 41 hips (73.0%), type 2 in 12 hips and type 3 in three hips). The mean diameter of the new cup was 52.3 mm (46–64). It was inferior to that of the initial cup in 26 hips (46.4%). 31 cups were impacted (55.5%) and 25 needed to be cemented (45.5%). No macroscopic wear was detected on the ceramic implant.

Aseptic loosening of the cup in CoC THA does not appear to increase over time, supporting the fact that the failure is unrelated to wear and is not due to a biological mechanism. The occurrence of two peaks of frequency over time may suggest that different mechanisms occur.

Purpose: Loosening remains a problem with semi-constrained total elbow prostheses. The trend in recent years has been to improve prosthesis design to achieve stability of the humeral implant. We report a small series of nine Coonrad-Morrey total elbow prostheses where three early loosenings were observed in the ulnar implant. We attempt to analyse the causes and present a review of the recent literature. Material and methods: Nine patients, mean age 60 years, age range 57–63 years, underwent total elbow arthroplasty with a Coonrad-Morrey prosthesis for rheumatoid disease (n=5), stiff degenerative joints after trauma (n=3, flexion-extension 20°), floating joint after trauma (n=1). The posterolateral approach described by Bryan and Morrey was used for eight elbows and the posterior approach for one. Clinical and radiological results were assessed with the performance index and the Mayo clinic score respectively. Results: Mean follow-up was 3.6 years (1.5–4.7). Outcome was very good or good for seven elbows (score > 75 and > 50), fair for one (< 50) and poor for one (< 25). Three elbows were pain free, two presented pain during movement against force. Flexion was greater than 120° in four elbows (all four rheumatoid polyarthritis). Radiologically, we observed three cases of ulnar implant loosening with two type IV lucent lines, and one type III line. There was one humeral implant with a lucent line which did not change over time (type I). The two cases of type IV lines were associated with radial and anterior translation migration of the prosthetic stem with effraction or lysis of the ulnar cortical. The three ulnar loosenings appeared between the second and third postoperative year on two post-trauma stiff degenerative elbows (flexion-extension < 20°) and one rheumatoid elbow. At last follow-up, there was one poor result requiring revision surgery, one fair result, and one very good result (totally asymptomatic type 4 lucent line). Discussion: The causes of these loosenings were studied: difficult cementing technique in a tight canal, mediocre primary stability of the ulnar implant opposing the excellent fit of the humeral implant with an encased graft under the anterior wing, excessive constraint. Our results are similar to those reported by Hilebrand who had 30% evolving ulnar lucent lines and suggest that we should reserve this prosthesis for unstable elbows

High-flexion total knee replacement (TKR) designs have been introduced to improve flexion after TKR. Although the early results of such designs were promising, recent literature has raised concerns about the incidence of early loosening of the femoral component. We compared the minimum force required to cause femoral component loosening for six high-flexion and six conventional TKR designs in a laboratory experiment. Each TKR design was implanted in a femoral bone model and placed in a loading frame in 135° of flexion. Loosening of the femoral component was induced by moving the tibial component at a constant rate of displacement while maintaining the same angle of flexion. A stereophotogrammetric system registered the relative movement between the femoral component and the underlying bone until loosening occurred. Compared with high-flexion designs, conventional TKR designs required a significantly higher force before loosening occurred (p < 0.001). High-flexion designs with closed box geometry required significantly higher loosening forces than high-flexion designs with open box geometry (p = 0.0478). The presence of pegs further contributed to the fixation strength of components. We conclude that high-flexion designs have a greater risk for femoral component loosening than conventional TKR designs. We believe this is attributable to the absence of femoral load sharing between the prosthetic component and the condylar bone during flexion

Prosthetic joint infection (PJI) is a complex disease that causes significant damage to the peri-implant tissue. Developing an animal model that is clinically relevant in depicting this disease process is an important step towards developing novel successful therapies. In this study, we have performed a thorough histologic analysis of peri-implant tissue harvested post Staphylococcus aureus (S. aureus) infection of a cemented 3D-printed titanium hip implant in rats.

Sprague-Dawley rats underwent left hip cemented 3D-printed titanium hemiarthroplasty via posterior approach under general anesthesia. Four surgeries were performed for the control group and another four for the infected group. The hip joint was inoculated with 5×10⁹ CFU/mL of S. aureus Xen36 prior to capsule closure. The animals were scarified 3 weeks after infection. The femur was harvested and underwent micro-CT and histologic analysis. Hematoxylin and eosin (H&E), as well as Masson's trichrome (MT) stains were performed. Immunohistochemistry (IHC) using rabbit antibody for S. aureus was also used to localize bacterial presence within femur and acetabulum tissue .

The histologic analysis revealed strong resemblance to tissue changes in the clinical setting of chronic PJI. IHC demonstrated the extent of bacterial spread within the peri-implant tissue away from the site of infection. The H&E and MT stains showed 5 main features in infected bone: 1) increased PMNs, 2) fibrovascular inflammation, 3) bone necrosis, and 4) increased osteoclasts 5) fibrosis of muscular tissue and cartilage. Micro CT data showed significantly more osteolysis present around the infected prosthesis compared to control (surgery with no infection).

This is the first clinically relevant PJI animal model with detailed histologic analysis that strongly resembles the clinical tissue pathology of chronic PJI. This model can provide a better understanding of how various PJI therapies can halt or reverse peri-implant tissue damage caused by infection.

Total joint replacement (TJR) was one of the most revolutionary breakthroughs in joint surgery. The majority studies had shown that most implants could last about 25 years, anyway, there is still variation in the longevity of implants. In US, for all the hip revisions from 2012 to 2017 in the United States, 12.0% of the patients were diagnosed as aseptic loosening. Variable studies have showed that any factor that could cause a systemic or partial bone loss, might be the risk of periprosthetic osteolysis and aseptic loosening.

Breast cancer is the most frequent malignancy in women, more than 2.1 million women were newly diagnosed with breast cancer, 626,679 women with breast cancer died in 2018. It's been reported that the mean incidence of THA was 0.29% for medicare population with breast cancer in USA, of which the incidence was 3.46% in Norwegian. However, the effects of breast cancer chemotherapy and hormonotherapy, such as aromatase inhibitors (AI), significantly increased the risk of osteoporosis, and had been proved to become a great threat to hip implants survival.

In this case, a 46-year-old female undertook chemotherapy and hormonotherapy of breast cancer 3 years after her primary THA, was diagnosed with aseptic loosening of the hip prosthesis. Her treatment was summarized and analyzed.

Breast cancer chemotherapy and hormonotherapy might be a threat to the stability of THA prosthesis. More attention should be paid when a THA paitent occurred with breast cancer. More studies about the effect of breast cancer treatments on skeleton are required.

Elderly patients with a high mortality risk for revision surgery are severely handicapped by a loosened hip prosthesis. Loosening is mainly caused by particle-induced osteolysis leading to the formation of a synovium-like interface tissue. As an alternative to revision surgery we have investigated the possibility of removing the tissue using a gene therapy approach and thereafter stabilizing the prosthesis with percutaneous cement injection. First we demonstrated that transduction of interface cells with a gene coding for E.coli nitroreductase (NTR) resulted in a 60-fold increase in sensitivity to the prodrug CB1954 that is converted to a toxic metabolite by NTR. Given these in-vitro data, we explored if intra-articular administration of this adenoviral vector encoding NTR followed by the prodrug was able to kill sufficient tissue in-vivo to allow refixation of the prosthesis by cement. We report the first three patients from a phase 1 study of 12 patients with a loosened hip who are experiencing debilitating pain and have significant comorbidity. On day 1 the vector is injected into the hip joint and on day 3 the prodrug is injected. On day 10 three holes are drilled in the femur and one in the acetabulum. Biopsies are taken from the periprosthetic space and low viscosity cement (Osteopal, Biomet Merck, Sjöbo, Sweden) is injected under fluoroscopic guidance. The first three patients have been included in the study and five more are planned for treatment before June 2005. The patients are females of 86, 72, and 79 years old. There were no adverse effects from vector injection (3x10 exp 9 particles). Six hours after prodrug injection the patients experienced nausea, (WHO grade 1) a commonly reported reaction to this prodrug. There was vomiting in two patients. Hip pain increased, but this was anticipated as this therapy will increase prosthesis loosening. 16 ml of cement was subsequently injected into the periprosthetic space in the first patient and 18 ml in the second. The patients were ambulated the day after surgery. The first two patients have a follow-up of twelve and six weeks. There was no pain in the hip. The maximum walking distance had increased from 5 to 30 meters in the first patient. The current study is the first to use in vivo intra-articular adenoviral mediated gene transfer in a clinical setting. Our preliminary results suggest that gene therapy and cement injection for hip prosthesis refixation is clinically feasible

It has been suggested that occult infection of joint prostheses contributes to a proportion of aseptic loosening. The aims of the study were to determine the incidence of occult infection in a sample of patients undergoing revision surgery for aseptic loosening and examine the role of ultrasound sonication in its detection. A prospective trial was conducted at Christchurch and Burwood Hospitals. At the time of revision surgery, intra-operative tissue and fluid samples were taken. The removed prosthesis was immersed in saline solution in a sterile plastic container, and then sonicated. The sonicate fluid underwent prolonged routine cultures (14 days) to increase the rate of detection of slow growing organisms. The cases were patients undergoing revision surgery for aseptic loosening or infection. The control group was comprised of patients having revision surgery for any other indication. These implants were subjected to the same protocol as the study group. A total of 122 patients were included in the study; 54 in the Aseptic Loosening [AL] group, 15 Infections and 53 controls. There were significantly more smokers in the AL group and less smokers in the control group (p=0.04 and p=0.04 respectively). The mean age for revision in the Infection and Periprosthetic fracture groups was less than those of other groups (p=0.007 and p=0.02) respectively. There were 18 cases with positive intra-operative cultures. Eight of those were in the aseptic group (i.e. 14.8% of the group). Conventional sampling techniques were positive in 17 of 18 cultures (94%). Sonication was only positive in 10 out of the 18 cultures (56%). Sonication was concordant with the conventional sampling techniques in half of the positive cultures in the AL group and overall. The only bacteria to be isolated from sonicate cultures were Staphylococcus Aureus and Coagulase Negative Staphylococci. Diabetes Mellitus was the only risk factor to have a significant association with having a positive culture result (p=0.03). There was also a significant association with having raised pre-operative Neutrophil differential count or inflammatory markers with having a positive culture (p=0.0001). However this association was not present when the AL group was examined separately. There was a significant rate of positive culture results in the aseptic loosening group of around 15%. Ultrasound sonication was less sensitive than current sampling techniques with no apparent added benefit. This paper does not support the hypothesis that occult infection is a significant driver of aseptic loosening

Abstract

Increasing femoral offset in total hip replacement (THR) has several benefits including improved hip abductor strength and enhanced range of motion. Biomechanical studies have suggested that this may negatively impact on stem stability. However, it is unclear whether this has a clinical impact. Using data from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR), the aim of this study was to determine the impact of stem offset and stem size for the three most common cementless THR prostheses revised for aseptic loosening.

The study period was September 1999 to December 2020. The study population included all primary procedures for osteoarthritis with a cementless THR using the Corail, Quadra-H and Polarstem. Procedures were divided into small and large stem sizes and by standard and high stem offset for each stem system. Hazard ratios (HR) from Cox proportional hazards models, adjusting for age and gender, were performed to compare revision for aseptic loosening for offset and stem size for each of the three femoral stems.

There were 55,194 Corail stems, 13,642 Quadra-H stem, and 13,736 Polarstem prostheses included in this study. For the Corail stem, offset had an impact only when small stems were used (sizes 8-11). Revision for aseptic loosening was increased for the high offset stem (HR=1.90;95% CI 1.53–2.37;p<0.001).

There was also a higher revision risk for aseptic loosening for high offset small size Quadra-H stems (sizes 0-3). Similar to the Corail stem, offset did not impact on the revision risk for larger stems (Corail sizes 12-20, Quadra-H sizes 4-7). The Polarstem did not show any difference in aseptic loosening revision risk when high and standard offset stems were compared, and this was irrespective of stem size.

High offset may be associated with increased revision for aseptic loosening, but this is both stem size and prosthesis specific.

In a recent phase 2 superiority clinical trial we demonstrated that a single dose of 60mg of the human monoclonal antibody denosumab inhibits osteolytic lesion activity in patients undergoing revision total hip arthroplasty (THA), demonstrating proof of biological efficacy for this clinical application. Here, we examined the effect that denosumab has on disease biology at the osteolysis tissue level.

Osteolytic tissue taken from the prosthesis-bone lesion interface at revision surgery in patients with osteolysis (n=10 participants that had received a single 60 mg dose of denosumab 8 weeks prior to revision surgery and n=10 that had received placebo) was examined for total genetic message activity and protein levels using whole genome sequencing and mass spectrometry, respectively.

The top five upregulated enriched pathways with denosumab treatment included inflammatory response, myeloid cell activation, myeloid leukocyte migration, neutrophil and granulocyte activation (p<6.26 × 10⁻²⁸). Cell morphogenesis was amongst the most downregulated pathways (p<3.42 ×10⁻²³). Finally, comparison of the trial mRNA and protein data versus mouse single cell RNA sequencing data of the same pathway blockade in mouse tibia showed the same direction of effect, suggesting that giving the drug causes then cells responsible for osteolysis to disperse into a more immature form (128 of 189 genes (z=4.87, P<0.0001) disease and functional pathways at the mRNA level and 10 of 11 (z=2.72, P=0.0065) at the protein level).

In this first-in-man study we identify multiple genes and pathways within periprosthetic osteolysis tissue that are affected by denosumab treatment. The dominant pathways involved upregulation of innate inflammatory signaling and downregulation of cell morphogenesis. We also found enrichment of similar disease and functional pathways at both the mRNA and protein levels versus mRNA pathway enrichment found in mouse osteomorphs. These data provide the first human data of the mechanistic effect of denosumab treatment on inflammatory osteolytic lesion activity after joint replacement that is necessary to support its clinical application.

∗Winner of The Bone & Joint Journal prize∗

Aims

The aim of this study was to determine if uncemented acetabular polyethylene (PE) liner geometry, and lip size, influenced the risk of revision for instability or loosening.

Aims

The aim of this study is to report the implant survival and factors associated with revision of total elbow arthroplasty (TEA) using data from the Dutch national registry.