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
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.
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
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.
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
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.
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.
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.
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
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
Aseptic loosening is the single most important long-term complication of total joint arthroplasty. Wear debris induced inflammation stimulates osteoclastic resorption of bone. Cellular mechanisms involved in osteoblast viability in PWD induced inflammation is poorly understood. Wear induced inflammation increases osteoblast necrosis and susceptibility to death by apoptosis. PMMA cement has a detrimental effect on osteoblast resistance to apoptosis, and that this is via an receptor mediated pathway. Osteoblast cell cultures (Human and MG63) were grown with and without PMMA cement and assessed for apoptosis and necrosis. TNF-α or Fas antibody simulated inflammation. Viability and apoptosis with PI exclusion, flow cytometry and western blotting assessed response. Cement induced osteoblast necrosis up to 1 hour. This effect was negated after 24 hours. Culture of osteob1asts on cement had no direct effect on spontaneous apoptosis but susceptibility to inflammation was increased. Polymerised cement has no direct effect on osteoblast cell death. Effects are mediated by inhibiting expression of anti-apoptotic protein (Bcl-2), and increasing susceptibility to inflammatory. Osteoblast resistance to death may represent a novel and important factor in aseptic loosening. The role of gene therapy is explored.
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.
Aseptic loosening has become the single most important long-term complication of total joint replacements. The pathophysiology of this loosening is multifactorial in origin ranging from mechanical wear, poor surgical technique, thermal damage and the inflammatory response to particulate wear debris. Cytokines are released in response to macrophage activation by particulate wear debris (PWD), the resultant inflammatory cascade stimulates osteoclastic resorption of bone. The failure of remodelling and repair mechanisms may be as a result of Osteonecrosis from cement (PMMA).
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
Aseptic loosening arises when periprosthetic bone loss results in mechanical failure at the host-implant interface, and is the main factor limiting implant survival after total hip arthroplasty (THA). The aims of this study were to determine whether genetic variation is a risk factor for loosening, explore the metabolic mechanisms of periprosthetic bone loss, and determine whether bisphosphonates may prevent bone loss and enhance implant mechanical stability after THA. In a genetic association study (
The role of matrix metalloproteinases (MMPs) in the aseptic loosening of hip prostheses is well established. Gelatinase MMPs have been identified in the interface membranes and the pseudosynovial tissues in the hips. Little data are available on gelatinase MMPs and their major regulators, including specific tissue inhibitors of matrix metalloproteinases (TIMPs) in the loosening of shoulder prostheses. The objectives of this study were to determine whether A) gelatinase MMPs and their regulators (MMP14, TIMP-1,-2) are produced by periprosthetic tissues in cases of aseptic loosening of shoulder prostheses, and, B) to identify which cell types, in both interface and synovial tissues, localize the enzymes. Interface tissues and synovial tissues were obtained during revision surgery for loose shoulder implants. In 9 patients (6-Total Shoulder Replacement, 3-Hemiarthro-plasty (Bipolar), 9 samples of interface tissues and 8 samples of synovial tissues were obtained. Of the interface tissues 2 were from the interface of the bipolar and the unresurfaced glenoid. Formalin-fixed paraffin embedded sections were stained using primary antibodies for MMP2 (Neomarkers), MMP9 (Oncogene Ltd), TIMP1, TIMP2 &
MMP14 (Chemicon Ltd). Antigen retrieval required pressure cooker treatment for MMP2 and MMP9 and trypsin for TIMP1. Visualisation used a standard DAB chromagen technique (Envision, Dako Ltd.). Appropriate control sections ensured reproducibility of the staining. The antibodies selected bind to both active and inactive forms of the MMPs. Both HDPE and metal debris were seen in both the synovial and interface tissues. Transformation of macrophages to giant cells was associated with PE debris, and was not observed with metal debris alone. The presence of gelatinase MMPs in both interface and synovial tissues in aseptic loosening of shoulder prostheses was demonstrated. Differences between the MMP content of macrophages and giant cells between the tissues was detected, positivity was associated with the presence of metallic and/or HDPE debris. Activation of endothelial MMP2 by both MMP14 and low levels of TIMP2 would support the development of a vascular network.