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

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.

Objectives

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.

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.

Aim

The aim of our study was to evaluate culture-negative prosthetic joint infections in patients who were pre-operatively evaluated as aseptic failure.

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.

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.

Background

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.

Background

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.

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.

Introduction and Aims: Accumulating evidence suggests that bacterially derived endotoxins may contribute to aseptic loosening. This study determined whether lipopolysaccharide (LPS), the classical endotoxin from Gram-negative bacteria, can be detected in periprosthetic tissue from patients with aseptic loosening. We utilised an assay that detects all forms of LPS and is unaffected by beta-glucan-like molecules.

Method: Periprosthetic tissue from revision total hip arthroplasty and synovia from primary total joint arthroplasty were homogenised in PBS in endotoxin-free conditions. Non-specific amidases in the homogenates were inactivated at 100 degrees C. LPS was measured using the Endospecy assay (Associate of Cap Cod). Multiple dilutions of the homogenates were assayed to maximise sensitivity, while avoiding assay inhibition assessed by spike recovery determinations. Results were corrected for colour and spike recovery. Assay results were considered positive if the absorbances were higher than the lowest standard and the LPS level was significantly greater (p< 0.05) than the PBS control. Statistical analysis was by ANOVA with Bonferroni-Dunn (Control) post-hoc tests.

Results: Samples from 13 patients have been studied to date. Multiple assays of four of these samples showed no detectable LPS while nine of these samples resulted in both positive and negative assays. This inter-assay variability prevents measurement of the concentration of LPS in the samples. Nonetheless, many of the samples contain detectable amount of LPS. Thus, six out of eight samples from revision THA patients with aseptic loosening had positive assays, as did two of four primary TJA patients. LPS was also detected in a sample from a revision control. These results demonstrate that samples from THA patients with aseptic loosening and from primary TJA contain detectable amounts of LPS derived from Gram-negative bacteria.

Conclusion: This conclusion is consistent with numerous studies, showing that human serum contains LPS derived from minor infections, gut flora, or dental procedures. It is likely that many of these samples also contain molecules derived from Gram-positive bacteria that have very similar biological effects as LPS. However, detection of these Gram-positive molecules await further improvements in assay specificity and sensitivity.

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).

Hypothesis: That PMMA increases Osteoblast susceptibility to necrosis and apoptosis following inflammatory challenge.

Materials and Methods: Osteoblast cell cultures were grown on PMMA cement plates and assessed for apoptosis and necrosis by PI exclusion staining, morphological changes on light and electron microscopy and flow cytometry.

Results: PMMA induced osteonecrosis is highest at 1 hour (34.45) in comparison to control levels (4.55). There is no significant change in Apoptosis at 24 hours. Culture of the Osteoblasts on cement and delayed stimulation with TNF-α causes increased Apoptosis and Necrosis.

Conclusion: PMMA cement causes Osteoblast necrosis in the early stages of polymerisation, after 24 hours there is little increase in apoptosis/necrosis. However Osteoblasts that grow in contact with cement are more susceptible to apoptosis and necrosis following TNFα challenge. This may prove to be an important step in the pathogenesis of Aseptic loosening.

Background

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.

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 (J Bone Mineral Res2003; 18:1995–2001) we found that carriage of the −238A allele within the promoter region of the TNF gene was an independent risk factor for aseptic loosening. A subsequent reporter gene assay showed differential TNF gene responsiveness between the –238A and –238G alleles to polyethylene particule stimulation (Calcified Tissue Int 2003; 72: 251-273). In a cross-sectional study (J Orthop Res 2003; 214: 691–696) we found that subjects with aseptic loosening had lower bone mineral density (BMD) in the region of the femoral calcar and higher urinary excretion of cross-linked collagen breakdown products than their counterparts with fixed femoral implants. In a randomised controlled trial we found that a single dose infusion of a bisphosphonate (pamidronate) reduced femoral bone loss over 2 years after THA, but did not affect pelvic bone loss or implant migration (J Bone Miner Res2002; 17: 1328). Transient increases in bone turnover markers occurred after surgery and were highly predictive of later femoral BMD change. The main predictor of early implant migration was patient age, but not periprosthetic BMD change. In summary, genetic as well as environmental factors affect implant survival after THA. Aseptic loosening is associated with regional changes in bone mass and turnover as well as focal osteolytic lesions. Bisphosphonate therapy is well tolerated after THA and has a clear biological effect. However, the impact of preventing early bone loss on late aseptic loosening remains unclear and awaits long term study.

[Winner, Robert Jones Gold Medal and Association Prize, 2003]

Introduction: The biological processes underlying osteolysis in aseptic loosening are not completely understood, but are believed to include factors such as hydrostatic pressure and wear debris. Characterisation of the pseudosynovial membrane from failed implants has revealed numerous cell types with well characterised roles in osteoclastogenesis and bone resorption. More recent work has demonstrated the presence of immunomodulatory cells, including T cells. IL-17 is a T cell product that is believed to be capable of inducing bone resorption. The aims of our study were to characterise the effects of IL-17 on the expression of RANKL and OPG by synovial fibroblasts and to evaluate its role in supporting osteoclastogenesis in vitro.

Materials and Methods: Synovial fibroblasts (SFB) were isolated from tissue obtained at joint replacement surgery. SFB were expanded in culture and used in experiments between passage 4 and 5. Human SFB, and for comparison the human osteosarcoma cell line MG63, were treated with IL-17 (5 and 50ng/ml) for up to 48 hours. The expression and production of RANKL and OPG at 6, 24 and 48hours was assessed by RT-PCR, quantiative real-time PCR, Northern blot and Western blot analyses. To investigate osteoclastogenesis, peripheral blood mononuclear cells (PBMCs) were cultured with IL-17 (5 and 50ng/ml) either alone or with M-CSF (25 ng/ml). After 14–21 days, cultures were fixed and stained for tartrate-resistant acid phosphatase (TRAP) and multinucleated, TRAP positive cells counted. Experiments were repeated on ivory slices and resorption evaluated.

Results: RT-PCR and QT-PCR analysis demonstrated that RANKL mRNA levels in SFB (4 of 5 patients) are enhanced by IL-17 in a biphasic manner. RANKL expression was elevated at 6 hours, returned to near control values at 24 hours before demonstrating increased levels at 48 hours. The expression of RANKL in MG63 cells was enhanced by IL-17 (5ng/ml) at 6 and 24 hours, and by IL-17 (50ng/ml) at 48 hours. The expression of OPG by SFB was upregulated by IL-17 (5 and 50ng/ml) at 6, 24 and 48 hours. The elevated expression of OPG in MG63 cells by IL-17 was time dependent, and this elevated expression was confirmed by Western blot. In cultures of PBMCs, IL-17 alone increased the numbers of TRAP+ve multinucleate cells dose-dependently. Similar levels of TRAP+ve cells were observed in the cultures treated with RANKL and M-CSF, but numbers of multinucleated cells were further increased when M-CSF was supplemented with IL-17. Resorption of ivory wafers was also observed in cultures treated with IL-17.

Conclusions: These results suggest that IL-17 induced osteoclast formation could contribute to the bone loss associated with a wide range of pathological states involving osteolysis and aseptic loosening.

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.

Aseptic loosening is generally associated with the presence of wear particle-associated macrophages in the pseudomembrane commonly formed around failed prosthetic implants. The extent of the macrophage response evoked by the wear particles has been shown to correlate with the amount of periprosthetic osteolysis. Numerous studies have shown that wear particle-associated macrophages contribute to osteolysis by (i) releasing inflammatory cytokines and/or (ii) differentiating into bone resorbing osteoclasts. Although macrophages and macrophage polykaryons are the main inflammatory cells found in periprosthetic tissues, numerous fibroblasts are also present in the connective tissue pseudomembrane. The recently identified molecule, RANKL has been shown to play a central role in the osteoclast formation and bone resorption observed in aseptic loosening. We have shown that arthroplasty macrophages, which express RANK, the receptor for RANKL, are capable of osteoclast differentiation; this process is inhibited by osteoprotegerin (OPG), the soluble decoy receptor for RANKL. As fibroblasts are known to express RANKL, the aim of the present study was to determine whether fibroblasts isolated from periprosthetic tissues could induce the generation of bone resorbing osteoclasts that would contribute to the osteolysis commonly seen in the periprosthetic loosening.

Fibroblast-like cells were isolated from pseudomembrane from patients (n=5) undergoing hip revision due to aseptic loosening, by routine collagenase enzyme digestion. The isolated cells were seeded in flasks for 2–4 weeks before being passaged for a further 3–4 times. Generated fibroblast-like cells (10⁴) were then co-cultured with 5x10⁵ normal human peripheral blood monocytes (n=5) on glass coverslips and dentine slices in the presence of (i) no added factors, (ii) macrophage colony stimulating factor (M-CSF) and (iii) M-CSF plus OPG. All cultures were maintained for 1,17 and 21 days. The extent of osteoclast differentiation was then determined by the expression of specific osteoclast markers including tartrate-resistant acid phosphatase (TRAP) and vitronectin receptor (VNR) and evidence of lacunar resorption.

In the absence M-CSF, no osteoclast formation was noted in 24 hours, 17 or 21 days in fibroblast/monocyte cultures. However, in the presence of M-CSF alone, large numbers of TRAP⁺ and VNR⁺ multinucleated cells capable of lacunar resorption were noted in these co-cultures. The addition of OPG, which is known to inhibit RANKL-mediated osteoclast formation, significantly reduced the extent of osteoclast formation and lacunar resorption in these co-cultures.

These results indicate that one means whereby peri-prosthetic osteolysis may occur is by fibroblasts in the arthroplasty pseudomembrane inducing macrophage-osteoclast differentiation. Fibroblasts express RANKL and interact with arthroplasty macrophages, which express RANK and function as osteoclast precursors. These findings indicate that suppression of osteoclast formation by OPG may be a possible form of therapy for reducing prosthetic loosening.

The longevity of the fixation of implants in a formerly dysplastic hip is compromised by several risk factors:

Young age.

Preoperative planning is mandatory. Procedure, choice of method, and availability of appropriate equipment and endoprosthetic implants must be ensured. Computerised tomography with 3-D reconstruction is recommended for more complex anatomical situations.