Aims.
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).
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.
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.
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.
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.
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.
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.
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:
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.
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 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.
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
Up to 20% of patients can remain dissatisfied following TKR. A proportion of TKRs will need early revision with aseptic loosening the most common. The ATTUNE TKR was introduced in 2011 as successor to its predicate design The PFC Sigma (DePuy Synthes, Warsaw, In). However, following reports of early failures of the tibial component there have been ongoing concerns of increased loosening rates with the ATTUNE TKR. In 2017 a redesigned tibial baseplate (S+) was introduced, which included cement pockets and an increased surface roughness to improve cement bonding. Given the concerns of early tibial loosening with the ATTUNE knee system, this study aimed to compare revision rates and those specific to aseptic loosening of the ATTUNE implant in comparison to an established predicate as well as other implant designs used in a high-volume arthroplasty centre. The Attune TKR was introduced to our unit in December 2011. Prior to this we routinely used a predicate design with an excellent long-term track record (PFC Sigma) which remains in use. In addition, other designs were available and used as per surgeon preference. Using a prospectively maintained database, we identified 10,202 patients who underwent primary cemented TKR at our institution between 01/04/2003–31/03/2022 with a minimum of 1 year follow-up (Mean 8.4years, range 1–20years): 1) 2406 with ATTUNE TKR (of which 557 were S+) 2) 4652 with PFC TKR 3) 3154 with other cemented designs. All implants were cemented using high viscosity cement. The primary outcome measures were all-cause revision, revision for aseptic loosening, and revision for tibial loosening. Kaplan-Meier survival analysis and Cox regression models were used to compare the primary outcomes between groups. Matched cohorts were selected from the ATTUNE subsets (original and S+) and PFC groups using the nearest neighbor method for radiographic analysis. Radiographs were assessed to compare the presence of radiolucent lines in the Attune S+, standard Attune, and PFC implants.Abstract
Objective
Methods
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∗
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. A total of 202,511 primary total hip arthroplasties (THAs) with uncemented acetabular components were identified from the National Joint Registry (NJR) dataset between 2003 and 2017. The effect of liner geometry on the risk of revision for instability or loosening was investigated using competing risk regression analyses adjusting for age, sex, American Society of Anesthesiologists grade, indication, side, institution type, surgeon grade, surgical approach, head size, and polyethylene crosslinking. Stratified analyses by surgical approach were performed, including pairwise comparisons of liner geometries.Aims
Methods
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. All TEAs recorded in the Dutch national registry between 2014 and 2020 were included. The Kaplan-Meier method was used for survival analysis, and a logistic regression model was used to assess the factors associated with revision.Aims
Methods
The current evidence comparing the two most common approaches for reverse total shoulder arthroplasty (rTSA), the deltopectoral and anterosuperior approach, is limited. This study aims to compare the rate of loosening, instability, and implant survival between the two approaches for rTSA using data from the Dutch National Arthroplasty Registry with a minimum follow-up of five years. All patients in the registry who underwent a primary rTSA between January 2014 and December 2016 using an anterosuperior or deltopectoral approach were included, with a minimum follow-up of five years. Cox and logistic regression models were used to assess the association between the approach and the implant survival, instability, and glenoid loosening, independent of confounders.Aims
Methods
The objective of this study was to compare the two-year migration and clinical outcomes of a new cementless hydroxyapatite (HA)-coated titanium acetabular shell with its previous version, which shared the same geometrical design but a different manufacturing process for applying the titanium surface. Overall, 87 patients undergoing total hip arthroplasty (THA) were randomized to either a Trident II HA or Trident HA shell, each cementless with clusterholes and HA-coating. All components were used in combination with a cemented Exeter V40 femoral stem. Implant migration was measured using radiostereometric analysis (RSA), with radiographs taken within two days of surgery (baseline), and at three, 12, and 24 months postoperatively. Proximal acetabular component migration was the primary outcome measure. Clinical scores and patient-reported outcome measures (PROMs) were collected at each follow-up.Aims
Methods
The patients with a total hip arthroplasty is growing in world manly in Europe and USA, and this solution present a high success at 10years in several orthopaedic registers. The application of total press-fit hip fixation presents the most used solution, but presents some failures associated to the acetabular component fixation, associated to the load transfer and bone loss at long term. The aim of this work is to investigate the influence of different acetabular bone loss in the strain distribution in iliac bone. To evaluate implant fixation, an experimental study was performed using acetabular press-fit component simulating different acetabular bone loss and measuring the strain distribution. The experimental samples developed was based in an iliac bone model of Sawbones supplier and a acetabular component Titanium (Stryker) in a condition press-fit fixation and was implanted according surgical procedure with 45º inclination angle and 20º in the anteversion angle. Were developed five models with same initial bone, one with intact condition simulating the cartilage between bones and four with different bone loss around the acetabular component. These four models representing the evolution of bone support of acetabular components presented in the literature. The evolution of bone loss was imposed with a CAD CAM process in same iliac bone model. The models were instrumented with 5 rosettes in critical region at the cortical bone to measure the strain evolution along the process.Introduction and Objective
Materials and Methods
For patients who took joint replacement, one of the complications, aseptic joint loosening, could cause a high risk of revision surgery. Studies have shown that MSCs have the ability of homing and differentiating, and also have highly effective immune regulation and anti-inflammatory effects. However, few studies had focused on the stem cells in preventing the occurrence and development of aseptic loosening. In this research, we aimed to clarify whether human umbilical cord mesenchymal stem cells could inhibited the aseptic joint loosening caused by wear particles. A Cranial osteolysis mice model was established on mice to examine the effect of hUC-MSCs on the Titanium particles injection area through micro-CT. The amount of stem cells injected was 2 × 10 5 cells. One week later, the mouse Cranial were obtained for micro-CT scan, and then stained with HE analysis immunohistochemical analysis of TNF-α, CD68, CCL3 and Il-1β. All mice were free of fever and other adverse reactions, and there was no death occurred. Titanium particles caused the osteolysis at the mice cranial, while local injection of hUC-MSCs did inhibit the cranial osteolysis, with a lower BV/TV and a higher porosity. Immunohistochemical results suggested that the expression of TNF-α, CD68, CCL3 and Il-1β in the cranial in Titanium particles mice increased significantly, but was significantly reduced in mice injected with hUC-MSCs. The inhibited CD68 expression indicated that the number of macrophage was lower, which might be a result of the inhibition of CCL3. According to the studies above, HUC-MSCs treatment of mouse cranial osteolysis model can significantly reduce osteolysis, inhibit macrophage recruitment, alleviate inflammatory response, without causing adverse reactions. It may become a promising treatment of aseptic joint loosening.
Previous work has demonstrated increased implant failure in patients with DDH compared to osteoarthritis with historic methods and implants. This study examines outcomes of modern total hip arthroplasty (THA) techniques using uncemented fixation and cross-linked PE (XLPE) bearings for DDH. A consecutive series of 879 patients with DDH who underwent primary THA with uncemented components and a XLPE bearing at a single institution between 1999 and 2016 were identified. Mean age at index arthroplasty was 51 years, with 78% females. Mean follow-up was 8 years. 5- and 10-year survivorships free of revision were 98.4% and 98%, respectively. 5- and 10-year survivorships free of reoperation for any reason were 97% and 96%, respectively. Survivorship free of acetabular revision for aseptic loosening was 99.8% at 5 and 10 years, while survivorships free of femoral revision for aseptic loosening were 99.7% at 5 years and 99.5% at 10 years. Survivorship free of reoperation for PE damage (2 liner fractures, 2 rim damage from impingement) was 99.3% at 10 years. There were no revisions for bearing surface wear or osteolysis. 13% of patients experienced complications (4% dislocation, 3.3% wound complication rate). Ten-year survivorship free of reoperation for instability was 99.2%. 8 patients developed infection requiring operation (<1%). 100 patients had a prior pelvic osteotomy (11%), which did not increase rate of complications (p=0.22) or reoperations (p=0.51). Fixation with modern uncemented implants has dramatically reduced implant loosening in patients with DDH, and the use of XLPE bearings has markedly reduced revision for PE wear/osteolysis in this young patient population, leading to dramatically improved mid/long-term survivorship compared to historic series.
Mortality following revision hip surgery for periprosthetic fracture (PPF) has been reported to be as high as 60% at 5 years. The aim of this study was to determine the mortality rate for PPF revisions, compared to revision for aseptic loosening or infection at our tertiary referral centre. Revision arthroplasty procedures performed for PPF, aseptic loosening or infection between January 2014 and December 2015 at our institution were identified using a prospectively collected PPF referral database and locally collected NJR data. Comparisons were made between the 3 groups for baseline demographics, admission to higher-level care, length of stay, complications, and Kaplan-Meier failure (mortality) at 1 & 5 years post-operative (with log-rank test for equality). There were 37 PPF, 71 infected and 221 aseptic revisions. PPF had a higher proportion of females (65% vs. 39% in infection and 53% in aseptic; p = 0.031) and grade 3 and 4 ASA patients (p = 0.006). Median time to surgery from injury for PPF was 8 days (95% CI, 6–16). Single-stage procedures were performed in 84% of PPF, 42% of infection and 99% of aseptic revisions (p < 0.001). 19% of PPF revisions required HDU admission, 1% in the aseptic group and none in the infection group (p<0.001). Median length of stay was significantly different (PPF 10; infection 14; aseptic 8 days (p < 0.001). The Kaplan-Meier estimate of 1-year mortality were: PPF = 0%; infection = 2.8% (0.7–11.1%); aseptic = 0.9% (0.2–3.5%). 5-year mortality estimates were: PPF = 17.1% (8–34%), infection = 8.7% (4–18.3%), aseptic = 12% (8.4–17%). Log-rank test of equality was not significant, p=0.833. Despite the PPF group having an average delay to surgery of 8 days, higher ASA grades and more admissions to HDU there was no significant difference in mortality rates between the groups at 1 and 5 years postoperatively. Using a coherent MDT approach with dedicated healthcare professionals this service demonstrates a low post operative mortality rate which merits further investment and development.
This study evaluates the association between consultant and hospital volume and the risk of re-revision and 90-day mortality following first-time revision of primary hip replacement for aseptic loosening. We conducted a cohort study of first-time, single-stage revision hip replacements (RHR) performed for aseptic loosening and recorded in the National Joint Registry (NJR) data for England, Wales, Northern Ireland, and the Isle of Man between 2003 and 2019. Patient identifiers were used to link records to national mortality data, and to NJR data to identify subsequent re-revision procedures. Multivariable Cox proportional hazard models with restricted cubic splines were used to define associations between volume and outcome. Among 12,676 RHR there were 513 re-revisions within two years, and 95 deaths within 90 days of surgery. The risk of re-revision was highest for a consultant's first RHR (Hazard Ratio (HR) 1·58 (95%CI 1·16 to 2·15)) and remained significantly elevated for their first 26 cases (HR 1·26 (95%CI 1·00 to 1·58)). Annual consultant volumes of five/year were associated with an almost 30% greater risk of re-revision (HR 1·28 (95%CI 1·00 to 1·64)) and 80% greater risk of 90-day mortality (HR 1·81 (95%CI 1·02 to 3·21)) compared to volumes of 20/year. RHR performed at hospitals which had cumulatively undertaken fewer than 168 RHR were at up to 70% greater risk of re-revision (HR 1·70 (95% CI 1·12 to 2·60)), and those having undertaken fewer than 309 RHR were at up to three times greater risk of 90-day mortality (HR 3·06 (95% CI 1·19 to 7·86)). This study found a significantly higher risk of re-revision and early postoperative mortality following first-time single-stage RHR for aseptic loosening when performed by lower-volume consultants and at lower-volume institutions, supporting the move towards the centralisation of such cases towards higher-volume units and surgeons.
Purpose:
Recent total knee arthroplasty (TKA) designs have featured more anatomic morphologies and shorter tibial keels. However, several reports have raised concerns regarding the impact of these modifications on implant longevity. This study's purpose is to report the early performance of a modern, cemented TKA design. All patients who received a primary, cemented TKA from 2012 to 2017 with a minimum two-year follow-up were included. This implant features an asymmetric tibial baseplate and a shortened keel. Patient demographics, Knee Society Scores (KSS), and component alignment were recorded, and Kaplan-Meier survivorship analyses were performed.Introduction
Methods
The aim of this study is the comparative assessment of long term clinical (subjective and objective), functional and quality of life outcome data between primary and revision THA. 122 patients (130 hips) who underwent cementless revision THA of both components (TMT cup, Wagner SL stem, Zimmer Biomet) for aseptic loosening only (Group A) were compared to a matched group of 100 patients (100 hips) who underwent cementless primary THA for osteoarthritis (Synergy stem, R3 cup, Smith & Nephew) (Group B). Outcomes were evaluated with survival analysis curves, Harris hip score (HHS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Oxford hip score (OHS), Short form-12 health survey (SF-12) and EQ-5D-5L scales. Mobility was assessed with walking speed, timed up and go test (TUG), Parker mobility, Lower extremity function score (LEFS) and UCLA scores. At a mean follow up of 14.4 years (10 to 20) a cumulative success rate of 96% (95% CI 96 to 99%) in Group A and 98% (95% CI 97 to 99%) in Group B with operation for any reason as an end point was recorded. Statistically significant differences between groups were developed for WOMAC (Mann-Whitney U test, p= 0.014), OHS (Mann-Whitney U test, p= 0.020) and physical component of SF-12 scores (Mann-Whitney U test, p= 0.029) only. In Group A, in multiple regression analysis, patients’ cognition (p=0.001), BMI (p=0.007) and pain (p=0.022) were found to be independent factors influencing functional recovery (WOMAC). Similarly, pain (p=0.03) was found to influence quality of life (EQ-5D-5). In the long term, revision THA shows satisfactory but inferior clinical, functional, and quality of life outcomes when compared to primary THA. Residual pain, BMI and cognitive impairment independently affect functional outcomes.
Tibial component loosening is a frequent cause of failure in primary total knee arthroplasty (TKA). Management options include isolated tibial component revision or full component revision. A full component revision is frequently selected by surgeons who are unfamiliar with the existing implant or have a “let's just start over attitude.” This option adds morbidity versus isolated tibial exchange. While isolated tibial exchange has lower morbidity, it is technically more challenging with regard to exposure and maintaining prosthetic stability. This study was designed to compare these two reconstructive options. Patients revised for isolated aseptic tibial loosening were identified from 2012–2017. Patients with revision implants, or those revised for infection, instability, osteolysis, or femoral component loosening were excluded. 161 patients met these criteria, 85 patients had an isolated tibial revision and 76 had revision of both components despite having only a loose tibial component. Patient demographics as well as clinical and radiographic outcomes were recorded for each cohort.Introduction
Methods
Investigate the incorporation of an antibiotic in bone cement using liposomes (a drug delivery system) with the potential to promote osseointegration at the bone cement interface whilst maintaining antibiotic elution, anti-microbiological efficacy and cement mechanical properties. Prosthetic joint infection and aseptic loosening are associated with significant morbidity. Antibiotic loaded bone cement is commonly used and successfully reduces infection rates; however, there is increasing resistance to the commonly used gentamicin. Previous studies have shown gentamicin incorporated into bone cement using liposomes can maintain the cement's mechanical properties and improve antibiotic elution. The phospholipid phosphatidyl-l-serine has been postulated to encourage surface osteoblast attachment and in a liposome could improve osseointegration, thereby reducing aseptic loosening. Preliminary clinical isolate testing showed excellent antimicrobial action with amoxicillin therefore the study aims were to test amoxicillin incorporated into bone cement using liposomes containing phosphatidyl-l-serine in terms of antibiotic elution, microbiological profile and mechanical properties. Amoxicillin was encapsulated within 100nm liposomes containing phosphatidyl-L-serine and added to PMMA bone cement (Palacos R (Heraeus Medical, Newbury, UK)). Mechanical testing was performed according to Acrylic Cement standards (ISO BS 5833:2002). Elution testing was carried out along with microbiological testing utilising clinical isolates.Objectives
Methods
Mechanical loosening of total hip replacement (THR) is primarily diagnosed using radiographs, which are diagnostically challenging and require review by experienced radiologists and orthopaedic surgeons. Automated tools that assist less-experienced clinicians and mitigate human error can reduce the risk of missed or delayed diagnosis. Thus the purposes of this study were to: 1) develop an automated tool to detect mechanical loosening of THR by training a deep convolutional neural network (CNN) using THR x-rays, and 2) visualize the CNN training process to interpret how it functions. A retrospective study was conducted using previously collected imaging data at a single institution with IRB approval. Twenty-three patients with cementless primary THR who underwent revision surgery due to mechanical loosening (either with a loose stem and/or a loose acetabular component) had their hip x-rays evaluated immediately prior to their revision surgery (32 “loose” x-rays). A comparison group was comprised of 23 patients who underwent primary cementless THR surgery with x-rays immediately after their primary surgery (31 “not loose” x-rays). Fig. 1 shows examples of “not loose” and “loose” THR x-ray. DenseNet201-CNN was utilized by swapping the top layer with a binary classifier using 90:10 split-validation [1]. Pre-trained CNN on ImageNet [2] and not pre-trained CNN (initial zero weights) were implemented to compare the results. Saliency maps were implemented to indicate the importance of each pixel of a given x-ray on the CNN's performance [3].INTRODUCTION
METHODS
Joint replacement is one of the most common orthopaedic procedures, with over 2 million surgeries performed each year across the globe. Loss of implant fixation, or aseptic loosening, is the leading cause of revision following primary joint replacement, accounting for ∼25% of all revision cases [1]. However, diagnosis of aseptic loosening and its underlying causes remain challenging due to the low sensitivity and specificity of plain radiographs. To address this, we propose a novel approach inspired by [2] involving the use of a self-sensing bone cement (by imparting strain-dependent electrical conductivity or piezoresistivity) combined with electrical impedance tomography (EIT). Piezoresistivity is imparted to cement via incorporation of micro/nanoscale conductive fillers. Therefore mechanical effects such as loosening and cracks will manifest as a conductivity change of the cement. This work explores if EIT is able to detect strains and cracks within the bone cement volume. Experiments were designed to determine whether EIT combined with piezoresistive cement can be used to detect strains and cracks (Fig. 1). The setup consists of a tank filled with water, 16 electrodes, sample, a loading machine (MTS), and an EIT system. To develop the piezoresistive bone cement, microscale carbon fibers were used with varying CF/PMMA volumetric ratios (VR) from VR = 0.25% to 3.0%. Three conical samples were made to model a loading condition similar to knee implants (Fig. 1). The samples were compressed while the conductivity map of the tank was measured with the EIT system.INTRODUCTION
METHODS
Surgical treatment of fragility sacrum fractures with percutaneous sacroiliac (SI) screw fixation is associated with high failure rates in terms of screw loosening, cut-through and turn-out. The latter is a common cause for complications, being detected in up to 20% of the patients. The aim of this study was to develop a new screw-in-screw concept and prototype implant for fragility sacrum fracture fixation and test it biomechanically versus transsacral and SI screw fixations. Twenty-seven artificial pelves with discontinued symphysis and a vertical osteotomy in zone 1 after Denis were assigned to three groups (n = 9) for implantation of their right sites with either an SI screw, the new screw-in-screw implant, or a transsacral screw. All specimens were biomechanically tested to failure in upright position with the right ilium constrained. Validated setup and test protocol were used for complex axial and torsional loading, applied through the S1 vertebral body. Interfragmentary movements were captured via optical motion tracking. Screw motions in the bone were evaluated by means of triggered anteroposterior X-rays. Interfragmentary movements and implant motions in terms of pull-out, cut-through, tilt, and turn-out were significantly higher for SI screw fixation compared to both transsacral screw and screw-in-screw fixations. In addition, transsacral screw and screw-in-screw fixations revealed similar construct stability. Moreover, screw-in-screw fixation successfully prevented turn-out of the implant, that remained at 0° rotation around the nominal screw axis unexceptionally during testing. From biomechanical perspective, fragility sacrum fracture fixation with the new screw-in-screw implant prototype provides higher stability than with the use of one SI screw, being able to successfully prevent turn-out. Moreover, it combines the higher stability of transsacral screw fixation with the less risky operational procedure of SI screw fixation and can be considered as their alternative treatment option.
Implant loosening is a common cause of a poor outcome and pain after total knee arthroplasty (TKA). Despite the increase in use of expensive techniques like arthrography, the detection of prosthetic loosening is often unclear pre-operatively, leading to diagnostic uncertainty and extensive workup. The objective of this study was to evaluate the ability of a machine learning (ML) algorithm to diagnose prosthetic loosening from pre-operative radiographs, and to observe what model inputs improve the performance of the model. 754 patients underwent a first-time revision of a total joint at our institution from 2012–2018. Pre-operative X-Rays (XR) were collected for each patient. AP and lateral X-Rays, in addition to demographic and comorbidity information, were collected for each patient. Each patient was determined to have either loose or fixed prosthetics based on a manual abstraction of the written findings in their operative report, which is considered the gold standard of diagnosing prosthetic loosening. We trained a series of deep convolution neural network (CNN) models to predict if a prosthesis was found to be loose in the operating room from the pre-operative XR. Each XR was pre-processed to segment the bone, implant, and bone-implant interface. A series of CNN models were built using existing, proven CNN architectures and weights optimized to our dataset. We then integrated our best performing model with historical patient data to create a final model and determine the incremental accuracy provided by additional layers of clinical information fed into the model. The models were evaluated by its accuracy, sensitivity and specificity.Background
Methods
Considerable evidence exists that aseptic loosening is initiated by wear particles that recruit macrophages and stimulate their production of pro-inflammatory cytokines. The cytokines primarily act indirectly by inducing production of RANKL, which stimulates osteoclast differentiation, osteolysis, and inflammatory bone loss. There is also considerable evidence that activation of macrophage Toll-like Receptors (TLRs) contributes to this cascade of events. It is however controversial whether bacterially-derived immunostimulatory molecules known as Pathogen-Associated Molecular Patterns (PAMPs) can contribute to aseptic loosening by stimulating their cognate TLRs on macrophages. Priming and subsequent activation of the NLRP3 inflammasome is essential for macrophage production of mature, active IL-1β in response to wear particles. We recently confirmed that wear particles can activate pre primed NLRP3 inflammasomes in the absence of PAMPs. Thus, activation of the NLRP3 inflammasome is the only macrophage-based event in the aseptic loosening cascade that we have found to date is independent of PAMPs. In contrast, priming of the NLRP3 inflammasome by wear particles requires PAMPs as well as their cognate TLRs. These results add to the growing body of evidence that bacterially-derived PAMPs can contribute to aseptic loosening.
A search of the literature indicates several constrained total knee arthroplasty (TKA) systems are at risk for articular surface lockdown bolts backing out. The backing out of a lockdown bolt may lead to an unstable and/or painful knee and may necessitate revision. Upon backing out, the bolt may damage implant components and surrounding tissues. To date, studies in the literature have not simulated or replicated loosening of bolts in TKA. Therefore, the objectives of this study were to 1) develop a set of physiological loading parameters that challenge bolted articular surfaces; 2) evaluate whether significant bolt torque is lost during application of this loading to a CCK device with a bolt as a secondary locking mechanism. Physical test parameters to loosen lockdown bolts were developed based on loading experienced during activities of daily living. Sinusoidal waveforms and timing were used to simulate worst case walking gait conditions. Compared to data from everyday activities in instrumented TKR patients, anterior posterior loads and internal/external torques exceeding the absolute maximums observed were selected. To transfer more shear and torsion to the joint interface, compressive load lower than typically reported for walking gait was used. Frequency was representative of walking gait motion. The offset in torsional waveform enables a ratcheting motion to drive a loose bolt out of the joint: during external femoral rotation of a left knee, reduced compressive load and posterior directed femoral loading on a CCK spine creates a potential articular surface lift-off. The lift-off may grab the underside of the front bolt shoulder while external (CCW) rotation loosens the bolt. These loading conditions exist during toe-off of walking gait. Two CCK devices were evaluated to capture potential difference in performance: a medium articular surface combination and a smaller articular surface combination. Testing was performed on a load frame capable of rotation and vertical / horizontal translation.Introduction
Materials and Methods
The aim of our study was to evaluate culture-negative prosthetic joint infections in patients who were pre-operatively evaluated as aseptic failure. 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 microbiologicaly evaluated using standard microbiologic methods and sonication. If prosthetic joint infection was discovered, additional therapy was introduced.Aim
Method
The modern modular implants allow surgeons to combine different combinations of components within the same brand of which some may have completely different design. During 1999–2012 the same cemented femur component was used together with a cemented stemmed tibia baseplate and also against a cemented pegged tibia baseplate. We decided to compare the revision rate of total knee arthroplasties (TKAs) using these two tibia baseplates. This is a register study. During 1999–2012, 32,429 cemented, CR TKA's of a specific brand were reported to the Swedish Knee Arthroplasty Register (SKAR). The part numbers for the femur, tibia and insert (in modular implants) were available in 99.2% of cases. The most common combination used the cemented CR femur against a cemented stemmed baseplate in 50.3% of cases while the same CR femur was used against a cemented pegged baseplate in 8.3% of cases, mainly at two hospitals. In order to make the material more comparable, only patients having osteoarthritis (OA) were included and only TKAs using two types of regular constraint inserts and in which the patella had been left un-resurfaced. Chi-Square test was used to investigate gender distribution in the groups and t-test for the mean age at surgery. Kaplan Meier analysis and the log-rank test were used to evaluate the risk of revision until the end of 2016. A p-value <0.05 was considered statistically significant.Background
Methods
Mechanisms underlying implant failure remain incompletely described, though the presence of macrophage-mediated inflammatory reactions is well documented. Hypoxia has a critical role in many diseases and is known to be interdependent with inflammation. Metals used for joint replacements have also been reported to provoke hypoxia-like conditions. In view of this, we aim to investigate hypoxia-associated factors in aseptic loosening and osteoarthritis with a focus on macrophages. Western blotting, calorimetric assay, haematoxylin-eosin staining, immunohistochemistry, double-immunofluorescence and transmission electron microscopy were performed on capsular tissue obtained from patients undergoing primary implantation of a total hip replacement for osteoarthritis and from patients undergoing revision surgery for aseptic loosening to investigate the presence of hypoxia-associated factors.Background
Methods
Non-large head Metal-on-metal (MoM) hip replacements were seen as a solution to concerns about implant wear in younger patients. Mid-term loosening of once well-fixed hydroxyapatite (HA) coated femoral stems was recently observed in select MoM patients upon revision surgery. Accordingly, an implant retrieval study was undertaken to examine the incidence of aseptic loosening of in HA-coated femoral stems with MoM, ceramic on ceramic (CoC) and metal on polyethylene (MoP) bearing couples. A single-centre implant retrieval lab reviewed 44 hydroxyapatite (HA)-coated titanium wedge taper stems of the same design retrieved over a period of 9 years. Ten were MoM articulations, 23 MoP and 11 CoC. Head sizes ranged from 28 to 40 with only four 40mm heads, all of which were MoM. Reason for revision, duration of implantation, femoral head size, patient age and body mass index was recorded for each retrieval. Goldberg corrosion scores were determined for the taper surfaces of each retrieval, with ‘0’ indicating no corrosion and ‘3’ indicating severe corrosion. Logistic regression analysis, Wilcoxan Rank Sum and Fischer's exact test were used for statistical analysis. Aseptic loosening was the listed reason for revision in 18 of 44 cases. MoM bearing was associated with increased probability of aseptic loosening (Odds ratio 7.1 (95%CI 1.1–47.0) p=0.042). Severity of corrosion was also associated with aseptic loosening (Odds ratio 2.75 (95%CI 1.1–6.6) p=0.02). Head size and patient age had no correlation. Median time to revision of implants for aseptic loosening was 4.5 years (range: 4.2–7.0 years) for MoM versus 1.4 years (range: 0.3–3.0) for other bearing couples (p=0.004). Aseptic loosening was categorised as early (<=2 years) or mid-term (>2 years). No MoM hips were revised for aseptic loosening in the first 2 years while 8 of the 11 mid-term revisions had MoM articulations (p=0.004). Taper corrosion was more severe in mid-term aseptic loosing cases (p=0.049). MoM HA-coated hip replacements appear to be associated with increased mid-term aseptic loosening compared to other bearing couples. Patients with MoM HA-coated hip replacements should be monitored regularly beyond the initial 1 to 2 years following surgery. Future analyses will examine the presence and progression of femoral radiolucency prior to revision surgery to determine an approximate timeline of stem loosening in this patient cohort. This research highlights the importance of implant retrieval programs to assess post-revision implant characteristics for early identification of possible device issues.
We describe a technique for the diagnosis of loosening of the femoral component of the Oxford Unicompartmental Knee Replacement using accurately aligned lateral radiographs in extension and flexion. If gaps are present between the component and cement on one radiograph and not on the other, the component is loose.
Cemented acetabular components commonly have a long posterior wall (LPW). Alternative components have a hooded or offset reorientating geometry, theoretically to reduce the risk of THR instability. We aimed to determine if cemented acetabular component geometry influences the risk of revision surgery for instability or loosening. The National Joint Registry for England, Wales and Northern Ireland (NJR) dataset was analysed for primary THAs performed between 2003 – 2017. A cohort of 224,874 cemented acetabular components were identified. The effect of acetabular component geometry on the risk of revision for instability or for loosening was investigated using binomial regression adjusting for age, gender, ASA grade, diagnosis, side, institution type, operating surgeon grade, surgical approach, polyethylene crosslinking and head size. A competing risk survival analysis was performed with the competing risks being revision for other indications or death. Among the cohort of subjects included, the distribution of acetabular component geometries was: LPW – 81.2%, hooded – 18.7% and offset reorientating – 0.1%. There were 3,313 (1.47%) revision THAs performed, of which 815 (0.36%) were for instability and 838 (0.37%) were for loosening. Compared to the LPW group, the adjusted subhazard ratio of revision for instability in the hooded group was 2.29 (p<0.001) and 4.12 (p=0.047) in the offset reorientating group. Likewise, the subhazard ratio of revision for loosening was 2.43 (p<0.001) in the hooded group and 11.47 (p<0.001) in the offset reorientating group. A time-varying subhazard ratio of revision for instability (hooded vs LPW) was found, being greatest within the first 6 months. This Registry based study confirms a significantly higher risk of revision THA for instability and for loosening when a cemented hooded or offset reorientating acetabular component is used, compared to an LPW component. Further research is required to clarify if certain patients benefit from the use of hooded or offset reorientating components, but we recommend caution when using such components in routine clinical practice.
Hard-on-hard bearings showed advantages of reduction of wear rates, osteolysis and aseptic loosening in total hip arthroplasty (THA). A new combination of ceramic-on-metal (COM) was developed to compensate the disadvantages of MOM and COC. COM showed good short-term results in vitro and in vivo studies. There was no report of stripe wear and metal ion level elevation. Our study was designed to evaluate the wear pattern of this bearing in early loosening THA. During January 2009 to December 2010, 121 primary THAs were performed at our institution by single-surgeon, using the same acetabular component and same uncemented femoral stem with a 32-mm modular head. All patients received the information of the bearing couples and made their own decision to choose one of the following bearings: COM, MOP and MOM. The functional outcomes (Harris Hip Score), Serum Co and Cr levels and survival rates were compared between groups at 5 years. The retrievals were tested by optical microscopy and Raman spectroscopy to evaluate the wear pattern in the cases those need revision.Background
Methods
Inflammation and chemokines play a pivotal role in aseptic loosening (AL) and prosthetic joint infection (PJI) of total joint arthroplasty (TJA). Recently, the Duffy antigen receptor for chemokines (DARC) on erythrocytes was identified as a potent chemokine receptor able to bind and carry without deactivating a wide range of CXC and CC chemokines from circulation to tissues. The role of DARC and its functional polymorphism (SNP) influencing the number of the DARC molecules on the erythrocytes in AL/PJI has not been studied yet. We genotyped functional polymorphism in the DARC gene (rs12075) using MassArray technology (Agena Bioscience) in 354 patients with TJA (hip and knee arthroplasties). Patients were further subdivided into those with a complication (AL, n = 110; PJI, n = 126) and a control group without complications for at least 10 years (n = 118). Statistics was performed by Plink 1.07 and relative entropy.Background
Methods
The protective effect of lipped polyethylene uncemented acetabular liners against revision THA for instability has been reported. However, the effect of lip size has not been explored, nor has the effect on revision THA for loosening. We aimed to determine if uncemented acetabular liner geometry, and lip size, influences the risk of revision THA for instability or loosening. 202511 primary THAs with uncemented polyethylene acetabular components were identified from the NJR dataset (2003 – 2017). The effect of acetabular liner geometry and lip size on the risk of revision THA for instability or loosening was investigated using binomial regression and competing risks survival analyses (competing risks were revision for other causes or death) adjusting for age, gender, ASA grade, diagnosis, side, institution type, surgeon grade, surgical approach, head size and polyethylene crosslinking. The distribution of acetabular liners was: neutral – 39.4%, offset neutral – 0.9%, 10-degree – 34.5%, 15-degree – 21.6%, 20-degree – 0.8%, offset reorientating – 2.82%. There were 690 (0.34%) revision THAs for instability and 604 (0.3%) for loosening. Significant subhazard risk ratios were found in revision THA for instability with 10-degree (0.63), 15-degree (0.48) and offset reorientating (1.6) liners, compared to neutral liners. There was no association found between liner geometry and risk of revision THA for loosening. This Registry based study confirms a significantly lower risk of revision THA for instability when a lipped liner is used, compared to neutral liners, and a higher risk with the use of offset reorientating liners. Furthermore, 15degree liners seem to have a lower risk than 10degree liners. We did not find an association between acetabular liner geometry and revision THA for loosening. 10- and 15-degree lipped polyethylene liners seem to offer a lower revision risk over neutral liners, at least at medium term followup. Further studies are required to confirm if this benefit continues into the long-term.
The process of osteolysis is well studied both in vivo and in vitro. Although multiple pathways have been implicated in osteolytic change and animal models have been developed there are few human tissue studies. There are no extensive human tissue studies comparing osteoarthritic hips to well fixed and loose prostheses. We have investigated 96 genes previously implicated in the osteolytic pathway. Genes were included based on previous implication in osteolysis in basic science studies. Candidates included cytokines, growth factors, apoptotic factors, matrix proteinases, interleukins, apoptotic proteins and macrophage activators.Background
Methods
Computer Tomography (CT) imaging has been limited to beam hardening artefacts until now. Literature has failed to describe sensitivity and specifity for loosening of endoprothesis in CTs, as metal artefacts have always influenced the diagnostic value of CTs. In recent years a new technology has been developed, the Dual Energy CT. Dual Energy CT scanners simultaneously scan with two tubes at different energy levels, most commonly 100kVp and 140kVp. Furthermore pictures gained from Dual Energy CTs are post-processed with monoenergetic reconstruction, which increases picture quality while further reducing metal artefacts. This promising technology has increased the diagnostic value preventing more radiation for the patients, for example in detection of kidney stones or to map lung perfusion. In the musculoskeletal imaging it has not been established yet and further clinical investigations are necessary. Thus the aim of this study is to describe sensitivity and sensibility for endoprothesis loosening of this novel technology. 53 prospective patients (31 total hip- and 22 total knee-arthoplasties) who were planned for revision surgery underwent preoperative Dual Energy CT examination. All scans were performed with a second-generation, dual-energy multi-detector CT scanner. And all pictures were post-processed with monoenergetic reconstruction. Radiologists were blinded for patient´s history. Senior consultants, who are specialized in arthroplasty of the hip and the knee, performed surgery. Intraoperative information was used as gold standard.Introduction
Material and Methods
Aseptic loosening is a major cause of failure of total hip arthroplasty. The adverse tissue response to prosthetic wear particles, with activation of cytokine and prostanoid production, contributes to bone loss around the implants. We have investigated the possibility that inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2) are expressed in macrophages in the pseudomembrane at the bone-implant interface, thereby contributing to the periprosthetic bone resorption. We also assessed whether peroxynitrite, a nitric oxide (NO)-derived oxidant associated with cellular injury, is generated in the membrane. Enzymatic activity of iNOS was measured using the arginine-citrulline assay technique and prostaglandin E2 (PGE2), as an indicator of COX-2 activity, was measured using an enzyme immunoassay. Cellular immunoreactivity for iNOS, nitrotyrosine (a marker of peroxynitrite-induced cellular injury) and COX-2 was assessed by quantitative peroxidase immunocytochemistry while immunofluorescence methods were used for subsequent co-localisation studies with CD68+ macrophages. The presence of calcium-independent iNOS activity and PGE2 production was confirmed in the homogenized interface membrane. Immunocytochemistry showed that periprosthetic CD68+ wear-debris-laden macrophages were the most prominent cell type immunoreactive for iNOS, nitrotyrosine and COX-2. Other periprosthetic inflammatory and resident cell types were also found to immunolocalise nitrotyrosine thereby suggesting peroxynitrite-induced protein nitrosylation and cellular damage not only in NO-producing CD68+ macrophages, but also in their neighbouring cells. These data indicate that both iNOS and COX-2 are expressed by CD68+ macrophages in the interface membrane and peroxynitrite-induced cellular damage is evident in such tissue. If high-output NO and peroxynitrite generation were to cause macrophage cell death, this would result in the release of phagocytosed wear debris into the extracellular matrix. A detrimental cycle of events would then be established with further phagocytosis by newly-recruited inflammatory cells and subsequent NO, peroxynitrite and prostanoid synthesis. Since both NO and have been implicated in the induction and PGE2 maintenance of chronic inflammation with resulting loss of bone, and peroxynitrite in the pathogenesis of disease states, they may be central to the pathogenesis of aseptic loosening.