Aims. Hip resurfacing remains a potentially valuable surgical procedure for appropriately-selected patients with optimised implant choices. However, concern regarding high early failure rates continues to undermine confidence in use. A large contributor to failure is adverse local tissue reactions around metal-on-metal (MoM) bearing surfaces. Such phenomena have been well-explored around MoM total hip arthroplasties, but comparable data in equivalent hip resurfacing procedures is lacking. In order to define genetic predisposition, we performed a case-control study investigating the role of human leucocyte antigen (HLA) genotype in the development of pseudotumours around MoM hip resurfacings. Methods. A matched case-control study was performed using the prospectively-collected database at the host institution. In all, 16 MoM hip resurfacing 'cases' were identified as having symptomatic periprosthetic pseudotumours on preoperative metal artefact reduction sequence (MARS) MRI, and were subsequently histologically confirmed as high-grade aseptic lymphocyte-dominated vasculitis-associated lesions (ALVALs) at revision surgery. ‘Controls’ were matched by implant type in the absence of evidence of pseudotumour. Blood samples from all cases and controls were collected prospectively for high resolution genetic a nalysis targeting 11 separate HLA loci. Statistical significance was set at 0.10 a priori to determine the association between HLA genotype and pseudotumour formation, given the small sample size. Results. Using a previously-reported ALVAL classification, the majority of pseudotumour-positive caseswere found to have intermediate-grade group 2 (n = 10; 63%) or group 3 (n = 4; 25%) histological findings. Two further patients (13%) had high-grade group 4 lesions. HLA-DQB1*05:03:01 (p = 0.0676) and HLA-DRB1*14:54:01 (p = 0.0676) alleles were significantly associated with a higher risk of pseudotumour formation, while HLA-DQA1*03:01:01 (p = 0.0240), HLA-DRB1*04:04:01 (p = 0.0453), HLA-C*01:02:01 (p = 0.0453), and HLA-B*27:05:02 (p = 0.0855) were noted to confer risk reduction. Conclusion. These findings confirm the association between specific HLA genotypes and the risk of pseudotumour development around MoM hip resurfacings. Specifically, the two ‘at risk’ alleles (DQB1*05:03:01 and DRB1*14:54:01) may hold clinical value in preoperative screening and prospective surgical decision-making. Cite this article: Bone Jt Open 2023;4(3):182–187

The prevalence of pseudotumours in patients with large-head metal-on-metal (MOM) THA has been the subject of implant recalls and warnings from various regulatory agencies. To date, there is no consensus on whether ultrasound or MRI is superior for the detection and following the progression of pseudotumours. Ultrasound is relatively cheap but can be operator dependent. MARS MRI has the advantage of excellent visibility of the soft tissue. However, MRI comes at a marked increase cost and takes about twice as long to perform. At our institution, we prospectively compared ultrasound to MRI for pseudotumour detection in an asymptomatic cohort of patients with MOM THAs. We enrolled 40 patients with large-head MOM THAs in the study. The mean age was 54 years (range, 34–76 years). The mean time from surgery was 54 months (range, 40–81 months). There were 28 men and 12 women. All patients underwent ultrasound and MRI using slice encoding for metal artifact correction. The gold standard was defined as follows: if both ultrasound and MRI agreed, this was interpreted as concordant and the result was considered accurate. Ultrasound and MRI agreed in 37 of 40 patients (93%). The prevalence of pseudotumours was 31% (12 of 39) in our cohort. Twenty-three of 39 patients (59%) had completely normal tests and four (10%) had simple fluid collections. Ultrasound had a sensitivity of 100% and specificity of 96% while MRI had a sensitivity of 92% and specificity of 100%. Conclusions: A negative ultrasound rules out pseudotumour in asymptomatic patients as this test is 100% sensitive. Given its lower cost, we recommend ultrasound as the initial screening tool for pseudotumours. More recently, Kwon et al have compared ultrasound to MARS MRI for following the progression of pseudotumours. They found a strong agreement between the 2 modalities for assessing change in size and consistency of pseudotumours

The prevalence of pseudotumours in patients with large-head metal-on-metal (MOM) THA has been the subject of implant recalls and warnings from various regulatory agencies. To date, there is no consensus on whether ultrasound or MRI is superior for the detection of pseudotumours. Ultrasound is relatively cheap but can be operator dependent. MARS MRI has the advantage of excellent visibility of the soft tissue. However MRI comes at a marked increase cost and takes about twice as long to perform. At our institution we prospectively compared ultrasound to MRI for pseudotumour detection in an asymptomatic cohort of patients with MOM THAs. Methods. We enrolled 40 patients with large-head MOM THAs in the study. The mean age was 54 years (range, 34–76 years). The mean time from surgery was 54 months (range, 40–81 months). There were 28 men and 12 women. All patients underwent ultrasound and MRI using slice encoding for metal artifact correction. The gold standard was defined as follows: if both ultrasound and MRI agreed, this was interpreted as concordant and the result was considered accurate. Results. Ultrasound and MRI agreed in 37 of 40 patients (93%). The prevalence of pseudotumours was 31% (12 of 39) in our cohort. Twenty-three of 39 patients (59%) had completely normal tests and four (10%) had simple fluid collections. Ultrasound had a sensitivity of 100% and specificity of 96% while MRI had a sensitivity of 92% and specificity of 100%

Introduction. Solid or cystic pseudotumour is a potentially destructive complication of metal on metal (MoM) couples, usually needing revision surgery. However, complete clearance of the pseudotumour is unlikely at times. This prospective case-controlled study reports cases which had recurrence after revision surgery for pseudotumour related to metal on metal hip couples. Methods. A total of 37 hips (33 MoM hip resurfacing and four big head MoM total hip arthroplasty (THA)) were revised for pseudotumour during the last 10 years. The patient demographics, time to revision, cup orientation, operative and histological findings were recorded for this cohort. Patients were divided into two groups - group R (needing re-revision for disease progression) and group C (control - no evidence of disease progression). Oxford hip scores (OHS, 0–48, 48 best outcome) were used to assess clinical outcome. The diagnosis of disease progression was based on recurrence of clinical symptoms, cross-sectional imaging, operative and histological findings. Results. Nine of 37 (24%) patients identified with worsening symptoms, eight underwent further re-revision surgery while one is awaiting revision surgery (group R). All patients were females and the mean time to initial revision in group R was 34 months (SD 21.8) and 60.5 months in group C (SD 27.5, p< 0.01). The mean cup abduction angle and anteversion in group R were 480 (SD 9.3) and 5.10 (SD 5.0), and 500 (SD 8.7) and 14.50 (SD 8.5) respectively. Re-revision surgery confirmed disease progression in all cases. Oxford hip score was significantly worse in group R 19 (SD 8.0) as compared to group C 33 (SD14.2) (p=0.03). Discussion. This study demonstrates that solid pseudotumour can progress following initial revision. This is likely to be an ongoing reaction to retained metal debris despite adequate clearance. All patients revised for pseudotumour should be monitored using early ultrasound or MRI

Background. Pseudotumours have been associated with metal-on-metal (MoM) hip replacements. We define it as a solid mass which may have cystic components that is neither neoplastic nor infectious in aetiology. The cause of a pseudotumour is not fully understood but could be due to excessive wear, metal hypersensitivity or due to an as-yet unknown cause. Aim. We present the retrieval analysis of early failure MoM hips revised for pain, loosening or a symptomatic mass. Tissues and implants were examined for the possible causes of failure and pseudotumour formation. Corrosion as a potential new cause for pseudotumour formation will be presented. Methods. A group of 16 MoM hip replacements were collected for retrieval analysis. Six of which had a pseudotumour. An Artificial Hip Profiler (Redlux Ltd) was used to measure wear. Edge loading was determined using the 3D wear data. Tissues were histologically evaluated using a 10-point ALVAL scoring system, which strongly suggests hypersensitivity (1). Cases were assigned to one of three categories: high wear (rates >5m/yr), hypersensitivity or corrosion. Results. Of the 6 pseudotumours, 3 had edge loading, 2 had high ALVAL scores and one had corrosion at the head taper junction. The high wear group, (3 cases) all demonstrated edge loading. Histology revealed more metal wear particles and macrophages, with a low ALVAL score in these cases. Two cases were found to have hypersensitivity with a high ALVAL score, more lymphocytes with less visible wear debris and macrophages. The wear rates were also lower, <4m/yr. One total hip replacement had corrosion at the junction between the head and adaptor taper for the stem. The bearings had low wear and the tissue had extensive necrosis as well as products of corrosion enclosed in fibrin (2). There was no suggestion of hypersensitivity (low ALVAL score). Conclusion. Pseudotumours can be caused by high wear, but if this is ruled out, a hypersensitivity or corrosion product reaction should be considered

Introduction: Metal on metal hip resurfacing arthroplasty (MoMHRA) has become an alternative option to THR in the treatment of young adults with OA. A recognised MoMHRA complication is the development of an inflammatory pseudotumour (IP). IPs can be cystic (predominantly posterio-laterally located), solid (mostly anteriorly located) or mixed in nature. Diagnosis is made with the aid of US and/or MRI. To-date, no radiographic aid in the diagnosis of IP has been identified. Neck thinning is a recognised phenomenon following MoMHRA, occurring in up to 90% of resurfaced hips, which has not been associated with any adverse clinical events. Its pathogenesis is considered multi-factorial secondary to stress shielding, impingement, pressure effect on cancellous femoral neck, bone necrosis secondary to femoral preparation and altered vascularity/AVN. Our aim was to establish whether neck thinning is associated with the presence of a pseudotumour. Methods: Thirty-one hips (30 patients) with IP confirmed clinically, radiologically, intra-operatively and histologically were matched for sex, age, pre-operative diagnosis, component size and follow-up with an asymptomatic MoMHRA cohort without pseudotumour (Control n=60). Radiological and operative findings at the time of revision of all IP patients were reviewed regarding location of pseudotumour; 4 different locations were defined: anteriorly-extending, posteriorly-extending, anteriorly & posteriorly-extending and within joint only. For all patients, prosthesis-neck ratio (PNR) at follow-up was measured on plain AP pelvic radiographs as previously described and validated. Results: All IP patients (6M:24F) and all (12M:48F) but two controls had a posterior approach at the time of MoMHRA. Mean femoral component size was 46 mm for both groups. At an average follow up of 3.5 years (0.7–8.3), IP patients (mean 1.26, 1.10–1.79) had a significantly higher (p< 0.0001) PNR in comparison to their controls (mean 1.14, 1.03–1.35). Greater neck thinning had occurred in both IP-males (p< 0.001) and IP-females (p=0.002) in comparison to their controls. Location of IP and hence nature did not appear to have an effect on the degree of neck thinning. Discussion: This study shows that IP patients had significantly narrower femoral necks at follow-up. Processes, such as impingement and increased wear that are thought to contribute to the process of neck narrowing are also thought to be factors in IP development. Furthermore, the presence of an IP, could lead to altered vascularity via a mass effect and further contribute to neck narrowing. Interestingly, nature of IP did not have a significantly affect PNR. Although one cannot be certain whether neck narrowing is a consequence or a contributing factor for IP development, their association is significant. Surgeons should consider the possibility of pseudotumour in symptomatic MoMHRA patients with neck narrowing

Metal on metal hip resurfacing (MMHR) is a popular procedure for the treatment of osteoarthritis in young patients. Several centres have observed masses, arising from around these devices, we call these inflammatory pseudotumours. They are locally invasive and may cause massive soft tissue destruction. The aim of this study was to determine the incidence and risk factors for pseudotumours that are serious enough to require revision surgery. In out unit, 1,419 MMHRs were performed between June 1999 and November 2008. All revisions were identified, including all cases revised for pseudotumour. Pseudotumour diagnosis was made by histological examination of samples from revision. A Kaplan-Meier survival analysis was performed, Cox regression analysis was used to estimate the independent effects of different factors. The revision rate for pseudotumour increased with time and was 4% (95% CI: 2.2% to 5.8%) at eight years. Female gender was a strong risk factor: at eight years the revision rate for pseudotumours in men was 0.5% (95% CI 0% to 1.1%), in women over 40 it was 6% (95% CI 2.3% to 10.1%) and in women under 40 it was 25% (95% CI 7.3% to 42.9%) (p< 0.001). Other factors associated with an increase in revision rate were, small components (p=0.003) and dysplasia (p=0.019), whereas implant type was not (p=0.156). We recommend that resurfacings are undertaken with caution in women, especially those younger than 40 years of age, but they remain a good option in men. Further work is required to understand the patho-aetiology of pseudotumours so that this severe complication can be avoided

Introduction. Incidence of adverse soft tissue reaction following metal on metal hip has a reported incidence of up to 48%. The current imaging modality of choice is metal artefact reduction sequence (MARS) MRI. Consensus is that large, symptomatic pseudotumours should be treated surgically, changing the bearing surfaces to other materials. There is debate as to how asymptomatic pseudotumours should be monitored and managed. Patients/Materials & Methods. From our unit's database, 22 patients (7 female, 15 male) were identified with metal on metal hip replacements that had a ‘pseudotumour’ detected on MARS MRI but remained assymptomatic (mean 68 months post op). All underwent serial imaging and clinical follow up (mean interval 14.5 months). Results. At initial imaging 16 pseudotumours were Norwich classification C1 (mild), 5 were C2 (moderate) and 1 was C3 (severe). At follow up no pseudotumours had increased in size or increased in severity with regards to Norwich classification. Four initially classified as C1 had changed to ‘A’. Oxford Hip score did not change significantly in this interval. Discussion. Previously published studies have been either small or ‘snap shot’ and have not provided conclusive guidance as to how these patients should be managed. Our study shows that this patient group can be treated expectantly and avoid revision surgery. Conclusion. Pseudotumour Norwich grade, size and characteristics remain unchanged on MARS MRI at a period of over one year in our cohort. Our study suggests serial imaging is not necessary unless patients develop symptoms

Introduction: Metal on metal hip resurfacing arthroplasty(MoMHRA) is an alternative option to THR in the treatment of young adults with OA. A recognised MoMHRA complication is the development of an inflammatory pseudotumour(IP). Diagnosis is made with the aid of US and/or MRI. To-date, no radiographic indication of the presence of IP has been identified. Neck thinning is a recognised phenomenon in MoMHRA hips not associated with any adverse clinical events. Its pathogenesis is considered multi-factorial. Our aim was to establish whether excessive neck narrowing is associated with the presence of a pseudotumour. Methods: Twenty-seven hips (26 patients) with IP confirmed clinically, radiologically, intra-operatively and histologically were matched for sex, age, pre-operative diagnosis, component size and follow-up with an asymptomatic MoMHRA cohort (Control n=60). For all patients, prosthesis-neck-ratio(PNR) was measured on plain AP pelvic radiographs post-operatively and at follow-up as previously described and validated. Results: All IP patients (4M:23F) and all (12M:48F) but two controls had a posterior approach at the time of MoMHRA. Post-operatively, there was no difference in the PNR between the two groups (p=0.19). At an average follow up of 3.5 years (range:0.7–8.3), IP patients(mean 1.26, 1.10–1.79) had a significantly higher (p< 0.0001) PNR in comparison to their controls(mean 1.14, 1.03–1.35). Greater neck narrowing occurred in both genders. IP necks had narrowed by an average of 8% (range:3–23). The degree of neck narrowing was correlated with length of survival of implant (p=0.001). Discussion: This study shows a strong association between IP and neck narrowing. Processes such as impingement and increased wear are considered to be involved in the pathogenesis of both IP and neck narrowing. Furthermore, the presence of an IP, could lead to altered vascularity via a mass effect and further contribute to neck narrowing. Neck narrowing in symptomatic MOMHRA patients should alert surgeons of the possible presence of IP

Introduction

Modular neck (MN) components in total hip arthroplasty (THA) offer intraoperative flexibility, but adverse local tissue reactions (ALTR) due to tribocorrosion at modular junctions are a potential complication of such designs. Serum ion levels and metal artifact reduction sequence (MARS) MRI are used to assess ALTR following modular THA. This study investigates serum ion levels and MARS MRI findings in a series of hips with MN components and differing articulating surfaces.

Metal on metal total hip arthroplasty (MoM THA) provides the potential improvement in articular wear. However, several adverse events including pseudotumor had been reported. Magnetic resonance imaging (MRI) was considered to be the proposal tool for detection of pseudotumor after MoM THA. In this study, we performed the screening of pseudotumor after MoM THA using the MRI.

We studied 43 patients with M2a Magnum® (Biomet) and 34 patients with M2a Taper® (Biomet) of MoM THA from December 2009 to December 2011 with follow-up of 2.5 years (2.0–4.0 years) after surgery. MRI assessments were performed at a mean of 2.1 years postoperatively. Pseudotumor findings were graded using Anderson classification (Skeletal Radiol, 2011: 40; 303). Age, sex, height, weight, Harris Hip Score, EQ5D satisfaction score, UCLA activity score, and blood metal ion levels were evaluated.

The prevalence of pseudotumor was 27.2%; 56 normal (Type A), 13 mild (C1), 8 moderate (C2) and none were graded severe (C3). Weight and BMI in the mild group was significantly higher than those in normal. There was no significant difference in age, sex and height among these groups. With regard to Harris Hip score, pain and ROM score in moderate group was significantly lower than that in normal and mild group. EQ5D satisfaction score and UCLA activity score showed not significant differences among groups. 3.01±3.32 μg/L of blood cobalt ion levels in the moderate groups was significantly higher than 0.97±0.64 μg/L in normal group. Blood cobalt ion levels of 1 mild and 2 moderate were over the threshold of 7 μg/L. These patients were implanted with M2a Taper, not M2a Magnum. 14% of the prevalence in the patients with M2a Magnum was significantly lower than 41% in the patients with M2a Taper. No revision surgeries were required.

The patients with no pseudotumor did not show the increase of blood metal ion. Contrarily, several patients showed the increase of blood metal ion in case of detecting pseudotumor. MRI assessments were useful for screening of pseudotumor after MoM THA and blood metal ion should be investigated for patients with mild and moderate pseudotumor in MoM THA.

(Introduction)

Metal on Metal (MoM) THA bearing as the second generation Total Hip Arthroplasty, widely came into use in Japan since 2000s. And it was expected to be able to ensure long-term use, the range of motion in the joints after surgeries, and the resistance to the dislocation, because MoM THAhad been considered to be able to use the large diameter head for its lower wear. However, there are some reports that the metal wear debris from MoM bearing surface generates the elevated serum ion level in the blood and the incidence of pseudotumor may occur subsequent to the metal wear debris. We performed MoM THA for 291 joints in 234 patients in our hospital since May 2005. But now, we refrain to use this. In this time, we will describe two cases of pseudotumor after implantation of MoM THA.

We present here a case of pseudotumor formation likely due to metal wear debris generated at the head-neck taper (trunnion) of the femoral stem and head components in a metal-on-highly cross-linked polyethylene (MOP) total hip arthroplasty. Over the last few years, this recently described diagnosis, trunnionosis, is being recognized and reported more frequently. This patient presented with a rather large (12 cm diameter) pseudotumor with accompanying loss of abductors and a pelvic discontinuity making reconstruction more challenging. We believe the psuedotumor in this patient developed from trunnionosis. This is an interesting case of aseptic lymphocyte-dominated vasculitis-associated lesions (ALVAL) in a MOP total hip arthroplasty.

Hip simulator studies with ceramic-on-metal (COM) predicted less wear than metal-on-metal (MOM: Isaac. 2009). While clinical evidence is scant, two COM case reports described pseudotumors with adverse cup positioning (Deshmukh 2012, Koper 2014). It would appear that our Korean case report is the first to describe pseudotumor formation in well-positioned COM arthroplasty and including detailed failure analysis. A 50-year old female (active salesperson) had bilateral avascular necrosis of her femoral heads. A left metal-on-polyethylene (MPE) hip was performed at outside institution in 2003. At our 3-yrs evaluation, radiographs showed well-functioning MPE hip. Five years later she complained of gradual left-hip pain (2011). Radiographs and CT scan demonstrated wear, osteolysis and loosening of both components. The revision in 2011 was by COM (Fig. 1), using S-ROM stem/sleeve, 36mm ceramic head (Biolox-delta), a CoCr liner and 54mm shell (Pinnacle: Depuy Inc). Cup inclination and anteversion were considered appropriate at 45° and 20° respectively; femoral anteversion of 15° was also appropriate.

At 1-yr follow-up patient complained of mild discomfort in left COM hip (2012). Range of motion was painless and normal. Examination revealed a soft, non-tender swelling (2×3cm) in left inguinal region with no inflammation and radiographs were normal (Fig. 1a). One month later the patient complained of left hip pain, the previously noted swelling had increased in size, and she started to limp. Radiographs showed cup migration with increased inclination. CT scans showed a circumscribed lesion extending into iliopsoas region (Fig 2). Serum cobalt and chromium levels were high at 2.4 and 22.5µg/ L, respectively.

At revision the pseudotumor and surrounding inflamed synovium was excised. The cystic soft-tissue swelling (stained black) extended into the joint (Fig. 2a). The ceramic head showed a large “black stripe” across the dome (Fig 2b). The cup was loose while the femoral stem was well fixed. Operative cultures of soft tissues and joint fluid were negative for infection while histopathology was consistent for metallosis (Fig. 3). Aggressive debridement was carried out, acetabular defects were filled with bone graft. Revision incorporated 32mm ceramic head (Biolox-delta), highly cross-linked liner and 52mm trabecular-metal shell (Depuy). Functionally the patient has continued to improve. By 6 months, serum ion concentrations decreased to Co:1.3 and Cr:2.54µg/ L with most recent ion levels lower still (Co:0.66 and Cr:0.42µg/ L).

Ceramic head surfaces showed normal wear appearance. The large gray stripe identified on the highly polished dome contained Co and Cr metal-transfer from the CoCr liner (Fig. 2b). Thin gray stripes on equatorial head regions (x4 rougher than dome) represented contamination by Ti, Al and V, typical of adverse impingement against Ti6Al4V neck (Clarke 2013). There was a 100–150um defect on rim of CoCr liner as a result of impingement. Cup out-of-roundness was 476um compared to only 7um for ceramic head, thus cup wear dominated at 25–30mm³ volume. This case report was illustrative of the unpredictable and seldom diagnosed risk of habitual cup-to-neck impingement and the risk of relying on pristine simulator studies to predict outcomes in novel THA bearings.

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Metal-on-metal (MOM) hip arthroplasty, including resurfacing, has become the subject of recent research and debate. There is the perceived benefit of improved wear rates of bearing surfaces leading to superior durability and performance of these types of implant. An associated feature of MOM bearing surfaces is the generation of metal ions. These can have local and systemic cytotoxic effects. An immunoloigical response has been suggested, however, metal wear debris may cause direct damage to cellular DNA. Studies have shown that release of these ions is related to bearing diameter and component alignment. However, little is known about the relationship between metal ion levels and implant survivorship. The MHRA has published guidelines on the follow-up of patients with MOM implants including measurement of serum ion levels and cross sectional imaging.

Between February 2001 and November 2009, 135 patients (164 hips) had MOM resurfacing arthroplasty at our institution. We report a retrospective analysis of the data generated by review of these patients. Of the 135 patients, 91 were identified for clinical review. Each patient had serum metal ion levels measured, plain AP radiographs of the pelvis examined and, in the presence of raised metal ions, a Metal Artefact Reduction Sequence (MARS) MRI performed. 27 patients (35 hips) had raised metal ion levels (Cobalt and Chromium). Patients with raised metal ion levels had a mean acetabular cup inclination of 52.7 degrees compared with a mean inclination of 48.6 degrees in patients with normal ion levels (p<0.05). MARS MRI in the raised ion group revealed 9 patients with appearances suggestive of ALVAL. A number of these patients had hip revision surgery with the remainder awaiting potential revision.

These findings reflect current evidence suggesting a relationship between sub-optimal component position and raised metal ion levels and an increased rate of ALVAL.

Aims. Large-diameter metal-on-metal (MoM) total hip arthroplasty (THA) has demonstrated unexpected high failure rates and pseudotumour formation. The purpose of this prospective cohort study is to report ten-year results in order to establish revision rate, prevalence of pseudotumour formation, and relation with whole blood cobalt levels. Methods. All patients were recalled according to the guidelines of the Dutch Orthopaedic Association. They underwent clinical and radiographical assessments (radiograph and CT scan) of the hip prosthesis and whole blood cobalt ion measurements. Overall, 94 patients (95 hips) fulfilled our requirements for a minimum ten-year follow-up. Results. Mean follow-up was 10.9 years (10 to 12), with a cumulative survival rate of 82.4%. Reason for revision was predominantly pseudotumour formation (68%), apart from loosening, pain, infection, and osteolysis. The prevalence of pseudotumour formation around the prostheses was 41%, while our previous report of this cohort (with a mean follow-up of 3.6 years) revealed a 39% prevalence. The ten-year revision-free survival with pseudotumour was 66.7% and without pseudotumour 92.4% (p < 0.05). There was poor discriminatory ability for cobalt for pseudotumour formation. Conclusion. This prospective study reports a minimum ten-year follow-up of large-head MoM THA. Revision rates are high, with the main reason being the sequelae of pseudotumour formation, which were rarely observed after five years of implantation. Blood ion measurements show limited discriminatory capacity in diagnosing pseudotumour formation. Our results evidence that an early comprehensive follow-up strategy is essential for MoM THA to promptly identify and manage early complications and revise on time. After ten years follow-up, we do not recommend continuing routine CT scanning or whole cobalt blood measurements, but instead enrolling these patients in routine follow-up protocols for THA. Cite this article: Bone Jt Open 2022;3(1):61–67

Hip resurfacing may be a useful surgical procedure when patient selection is correct and only implants with superior performance are used. In order to establish a body of evidence in relation to hip resurfacing, pseudotumour formation and its genetic predisposition, we performed a case-control study investigating the role of HLA genotype in the development of pseudotumour around MoM hip resurfacings. All metal-on-metal (MoM) hip resurfacings performed in the history of the institution were assessed. A total of 392 hip resurfacings were performed by 12 surgeons between February 1st 2005 and October 31st 2007. In all cases, pseudotumour was confirmed in the preoperative setting on Metal Artefact Reduction Sequencing (MARS) MRI. Controls were matched by implant (ASR or BHR) and absence of pseudotumour was confirmed on MRI. Blood samples from all cases and controls underwent genetic analysis using Next Generation Sequencing (NGS) assessing for the following alleles of 11 HLA loci (A, B, C, DRB1, DRB3/4/5, DQA1, DQB1, DPB1, DPA1). Statistical significance was determined using a Fisher's exact test or Chi-Squared test given the small sample size to quantify the clinical association between HLA genotype and the need for revision surgery due to pseudotumour. Both groups were matched for implant type (55% ASR, 45% BHR in both the case and control groups). According to the ALVAL histological classification described by Kurmis et al., the majority of cases (63%, n=10) were found to have group 2 histological findings. Four cases (25%) had group 3 histological findings and 2 (12%) patients had group 4 findings. Of the 11 HLA loci analysed, 2 were significantly associated with a higher risk of pseudotumour formation (DQB1*05:03:01 and DRB1*14:54:01) and 4 were noted to be protective against pseudotumour formation (DQA1*03:01:01, DRB1*04:04:01, C*01:02:01, B*27:05:02). These findings further develop the knowledge base around specific HLA genotypes and their role in the development of pseudotumour formation in MoM hip resurfacing. Specifically, the two alleles at higher risk of pseudotumour formation (DQB1*05:03:01 and DRB1*14:54:01) in MoM hip resurfacing should be noted, particularly as patient-specific genotype-dependent surgical treatments continue to develop in the future

Introduction and Objective. Total joint replacement is indicated for osteoarthritis where conservative treatment has failed, and in the UK the number of patients requiring hip and knee replacements is set to increase with an ageing population. Survival of total hip replacements is around 85% at 20 years with the most common reason for revision being aseptic loosening of the implant secondary to osteolysis, which is caused by immune-mediated reactions to implant debris. These debris can also cause pseudotumour formation. As revision surgery is associated with higher morbidity, mortality, infection rates, venous thromboembolism, resource demand and poorer subsequent function it is important to understand the mechanisms underlying the pro-inflammatory process to improve implant survival. Toll-like receptor 4 (TLR4), an innate immune receptor, has been demonstrated to mediate deleterious immune responses by the Tyson-Capper research group, including inflammatory cytokine interleukin-8 (IL-8) secretion. Statin use in epidemiological studies has been associated with reduced overall risk of revision surgery after hip replacement. In-vitro studies have demonstrated the potential for statins to reduce orthopaedic debris-induced immune responses which can lead to osteolysis and pseudotumour formation. As literature from cardiological investigations demonstrate that statins can reduce the expression and responsiveness of TLR4, this could be an exciting mechanism to exploit to reduce the host immune response to orthopaedic wear debris, thereby improving implant survival by reducing immune mediated osteolysis. This ongoing study investigates simvastatin's effect on cobalt ion-mediated changes in gene and protein expression of interleukin-8 and soluble-ICAM-1 (sICAM-1) which is an angiogenic factor implicated in pseudotumour formation. Materials and Methods. TLR4-expressing human monocyte/macrophage THP-1 cells were pre-incubated with 50μM simvastatin for 2-hours or a vehicle control, before being exposed to exposed to 0.75mM cobalt chloride, in addition to a further 24-hour co-incubation with 50μM simvastatin or vehicle control. IL-8 protein and sICAM-1 secretion was measured by enzyme-linked immunosorbent assay (ELISA). Gene expression changes were quantified by TaqMan-based real time polymerase chain reaction. Results. Pre-treatment with simvastatin significantly reduced cobalt-mediated IL-8 protein secretion (n=3) and sICAM-1 protein secretion (n=2) in THP-1 cells (p-value<0.0001). Work will be undertaken to determine changes in gene expression, the role of TLR4 in these responses and the effect of simvastatin on additional inflammatory markers. Conclusions. Simvastatin significantly reduces cobalt-ion mediated IL-8 and sICAM-1 protein secretion in THP-1 cells. This in-vitro finding demonstrates the potential for simvastatin to reduce recruitment of leukocytes which mediate the deleterious inflammatory processes driving aseptic loosening and pseudotumour formation

The most common reason for revision surgery of total hip replacements is aseptic loosening of implants secondary to osteolysis, which is caused by immune-mediated reactions to implant debris. These debris can cause pseudotumour formation. As revision surgery is associated with higher mortality and infection, it is important to understand the pro-inflammatory process to improve implant survival. Toll-like receptor 4 (TLR4) has been shown to mediate immune responses to cobalt ions. Statin use in epidemiological studies has been associated with reduced risk of revision surgery. In-vitro studies have demonstrated the potential for statins to reduce orthopaedic debris-induced immune responses and there is evidence that statins can modulate TLR4 activity. This study investigates simvastatin's effect on orthopaedic biomaterial-mediated changes in protein expression of key inflammatory markers and soluble-ICAM-1 (sICAM-1), an angiogenic factor implicated in pseudotumour formation. Human macrophage THP-1 cells were pre-incubated with 50µM simvastatin for 2-hours or a vehicle control (VC), before being exposed to 0.75mM cobalt chloride, 50μm3 per cell zirconium oxide or LPS as a positive control, in addition to a further 24-hour co-incubation with 50µM simvastatin or VC. Interleukin −8 (IL-8), sICAM-1, chemokine ligand 2 (CCL2), CCL3 and CCL4 protein secretion was measured by enzyme-linked immunosorbent assay (ELISA). GraphPad Prism 10 was used for statistical analysis including a one-way ANOVA. Pre-treatment with simvastatin significantly reduced LPS and cobalt-mediated IL-8 secretion (n=3) and sICAM-1 protein secretion (n=2) in THP-1 cells. Pre-treatment with simvastatin significantly reduced LPS-mediated but not cobalt ion-mediated CCL2 (n=3) and CCL3 protein (n=3) secretion in THP-1 cells. Simvastatin significantly reduced zirconium oxide-mediated CCL4 secretion (n=3). Simvastatin significantly reduced cobalt-ion mediated IL-8 and sICAM-1 protein secretion in THP-1 cells. This in-vitro finding demonstrates the potential for simvastatin to reduce recruitment of leukocytes which mediate the deleterious inflammatory processes driving implant failure

Objectives. Pseudotumours (abnormal peri-prosthetic soft-tissue reactions) following metal-on-metal hip resurfacing arthroplasty (MoMHRA) have been associated with elevated metal ion levels, suggesting that excessive wear may occur due to edge-loading of these MoM implants. This study aimed to quantify in vivo edge-loading in MoMHRA patients with and without pseudotumours during functional activities. Methods. The duration and magnitude of edge-loading in vivo was quantified during functional activities by combining the dynamic hip joint segment contact force calculated from the three-dimensional (3D) motion analysis system with the 3D reconstruction of orientation of the acetabular component and each patient’s specific hip joint centre, based on CT scans. Results. Edge-loading in the hips with pseudotumours occurred with a four-fold increase in duration and magnitude of force compared with the hips without pseudotumours (p = 0.02). Conclusions. The study provides the first in vivo evidence to support that edge-loading is an important mechanism that leads to localised excessive wear (edge-wear), with subsequent elevation of metal ion levels in MoMHRA patients with pseudotumours