Adverse local tissue reactions in metal-onpolyethylene total hip arthroplasty due to trunnion corrosion

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1 M. R. Whitehouse, M. Endo, S. Zachara, T. O. Nielsen, N. V. Greidanus, B. A. Masri, D. S. Garbuz, C. P. Duncan From Vancouver General Hospital, Vancouver, Canada M. R. Whitehouse, FRCS (Tr & Orth), PhD, MSc (Orth Eng), Consultant Senior Lecturer in Trauma and Orthopaedics, Musculoskeletal Research Unit University of Bristol, Bristol, BS 5NB, UK. M. Endo, MD, PhD, Assistant Professor of Orthopedic Surgery Kyushu University Hospital, - -, Maidashi, Higashi-ku, Fukuoka City, 8-858, Japan. S. Zachara, MD, BSc, Pathology Resident, Anatomical Pathology T. O. Nielsen, MD, PhD, FRCPC, Professor of Pathology and Laboratory Medicine, Anatomical Pathology Vancouver General Hospital, 855 W th Ave, Vancouver, V5Z M9, Canada. N. V. Greidanus, MD, MPH, Assistant Professor of Orthopaedics B. A. Masri, MD, FRCS(C), Professor & Head of Department of Orthopaedics D. S. Garbuz, MD, MHSc, Associate Professor of Orthopaedics C. P. Duncan, MD, MSc, Professor of Orthopaedics University of British Columbia, Third Floor, 9 West th Avenue, Vancouver, BC V5Z E, Canada. Correspondence should be sent to Mr M. R. Whitehouse; 5 The British Editorial Society of Bone & Joint Surgery doi:./-6x.97b8. 68 $. Bone Joint J 5;97-B:. Received 7 June ; Accepted after revision April 5 HIP Adverse local tissue reactions in metal-onpolyethylene total hip arthroplasty due to trunnion corrosion THE RISK OF MISDIAGNOSIS Adverse reaction to wear and corrosion debris is a cause for concern in total hip arthroplasty (THA). Modular junctions are a potential source of such wear products and are associated with secondary pseudotumour formation. We present a consecutive series of 7 patients treated at our unit for this complication following metal-on-highly cross-linked polyethylene (MoP) THA. We emphasise the risk of misdiagnosis as infection, and present the aggregate laboratory results and pathological findings in this series. The clinical presentation was pain, swelling or instability. Solid, cystic and mixed softtissue lesions were noted on imaging and confirmed intra-operatively. Corrosion at the head neck junction was noted in all cases. bacteria were isolated on multiple pre- and intra-operative samples yet the mean erythrocyte sedimentation rate was 9 (9 to ) and C-reactive protein (.6 to 6) and stromal polymorphonuclear cell counts were noted in nine cases. Adverse soft tissue reactions can occur in MoP THA owing to corrosion products released from the head neck junction. The diagnosis should be carefully considered when investigating pain after THA. This may avoid the misdiagnosis of periprosthetic infection with an unidentified organism and mitigate the unnecessary management of these cases with complete single- or two-stage exchange. Cite this article: Bone Joint J 5;97-B:. Debris generated from total hip arthroplasty (THA) is known to trigger adverse soft-tissue reactions. Recently, academic attention has focused on metal-on-metal (MoM) bearings. Patients with an adverse reaction to metal debris have a variable presentation of pain, softtissue pseudotumour, instability or asymptomatic lesions. The presentation may be confused with periprosthetic joint infection (PJI). -5 Debris generated from modular junctions has also been reported to cause adverse softtissue reactions 6-9 in both mixed-metal interfaces, and similar metal interfaces. 8 The mechanism may be fretting, crevice corrosion or a mixture of both. As the number of symptomatic reported cases remains small 6-8, it is difficult to interpret the available data and form clear diagnostic criteria. We performed a detailed review of 7 consecutive metal-on-highly cross-linked polyethylene (MoP) THAs with a histopathologically confirmed pseudotumour associated with corrosion of the trunnion at the head neck junction. The purpose of the review was to highlight the risk of misdiagnosis in this cohort and support efforts to refine the accurate diagnosis of PJI. We also present our clinical findings and the results of our investigations. Patients and Methods After ethical approval from our institutional review board we identified 7 consecutive patients with histopathologically confirmed pseudotumours in MoP THAs from our institutional arthroplasty database. In all, patients who had their index MoP THA performed at our centre required revision arthroplasty for symptomatic pseudotumours. Their index procedure was between and ; revision took place between three and ten years later. During this period, we performed a total of 8 MoP THAs, representing a re-operation rate for pseudotumours of.5%. A further two cases were revised at our centre following an index procedure performed elsewhere. Two more were revised following a revision THA performed in our unit and one following a revision performed elsewhere. A summary of patient demographic details is shown in Table I. The revision procedures for pseudotumour attributed to trunnion corrosion in MoP THA THE BONE & JOINT JOURNAL

2 ADVERSE LOCAL TISSUE REACTIONS IN METAL-ON-POLYETHYLENE TOTAL HIP ARTHROPLASTY DUE TO TRUNNION CORROSION 5 Table I. Summary of patient demographics Index surgery Primary Revision Median interval in months between index procedure and revision (IQR) Gender Mean age at revision (yrs) (SD; range) Mean BMI (kg/m ) SD; range) Mean egfr ml/min/.7 m (SD; range) Charlson comorbidity index 7 (IQR 8 to 6) 8 male 67 (., 5 to 87) 8 (.9; to 6) 78 (7.9; to ) : n = : n = 9 female : n = IQR, interquartile range; SD, standard deviation; BMI, body mass index; egfr, estimated glomerular filtration rate Table II. Patient details and index operation implants Case Gender Age at revision (yrs) Time to revision (mths) Femoral component Acetabular component Taper interface Taper Head size, neck length (mm) Male 6 68 Zimmer Anatomic Zimmer TM Modular Titanium/cobalt chrome 6, 7 Male 68 Zimmer ML Taper, Zimmer Trilogy Titanium/cobalt chrome / 6, Female 87 Zimmer ML Taper, Zimmer Trilogy Titanium/cobalt chrome / 6, Male 56 DePuy Prodigy, Zimmer Trilogy Cobalt chrome/cobalt / 6, chrome 5 Female 56 7 Zimmer ML Taper, Zimmer Trilogy Titanium/cobalt chrome /, 6 Female 7 8 Zimmer ML Taper, Zimmer Trilogy Titanium/cobalt chrome /, 7 Male 56 9 Zimmer ML Taper, Zimmer Trilogy Titanium/cobalt chrome / 6, extended offset 8 Female 65 Zimmer ML Taper, Zimmer Trilogy Titanium/cobalt chrome / 6, Male 68 6 Zimmer ML Taper, Zimmer Trilogy Titanium/cobalt chrome / 6, +.5 extended offset Male 66 Zimmer ML Taper, Zimmer Trilogy Titanium/cobalt chrome / 6, Female 7 88 Stryker Accolade, Stryker Trident Titanium/cobalt chrome /, Female 76 5 Zimmer ML Taper, Zimmer Trilogy Titanium/cobalt chrome / 6, extended offset Female 65 8 Zimmer ML Taper, Zimmer Trilogy Titanium/cobalt chrome /, +.5 Male 5 6 DePuy Prodigy, Zimmer TM Modular 5 Male 6 5 Zimmer ML Taper, 6 Female 69 Stryker Accolade, 7 Female 87 6 Zimmer ML Taper, Zimmer (Warsaw, Indiana); DePuy (Warsaw, Indiana); Stryker (Hamilton, Ontario, Canada) Cobalt chrome/cobalt chrome / 6, + 5 Zimmer Trilogy Titanium/cobalt chrome / 6,.5 Zimmer Trilogy Titanium/cobalt chrome / 8, + Zimmer Trilogy Titanium/cobalt chrome / 6, were performed between vember and December, this represented.% of our total revision THA burden of 59 cases during this time period. During the same period, sepsis accounted for revisions (%), aseptic loosening 7 (%), instability 9 (8%), periprosthetic fracture (8%), osteolysis (8%), bearing wear 7 (7%), pseudotumour from all causes 7 (5%), implant fracture (%), pain (%) and other reasons 9 (%). Implant details are shown in Table II. Pre-revision radiographs were calibrated from the known size of the prosthetic femoral head and assessed for implant orientation using defined landmarks and axes (Table III). Femoral offset was defined as the perpendicular distance from the femoral axis to the centre of rotation. Acetabular offset was defined as the perpendicular distance from the centre of rotation to a vertical line constructed perpendicular to the inter-teardrop line, originating from the most inferior point of the teardrop. The stem angle was defined as the varus/ valgus angle between the axis of the stem and the axis of the femur. Acetabular component inclination was the angle measured between the face of the implant and the interteardrop line. A free of charge web based program was used to analyse implant orientation. 5 The Imatri (Johannesburg, South Africa) anteversion tool uses a five-point detection system to define the rim of the acetabular component and a trigonomic calculation to determine its anteversion. 6 VOL. 97-B,. 8, AUGUST 5

3 6 M. R. WHITEHOUSE, M. ENDO, S. ZACHARA, T. O. NIELSEN, N. V. GREIDANUS, B. A. MASRI, D. S. GARBUZ, C. P. DUNCAN Table III. Orientation of prosthetic components assessed on pre-revision radiographs Acetabular anteversion ( ) Acetabular inclination ( ) Acetabular offset (mm) Femoral offset (mm) Stem angle * ( ) Mean SD 7 5. * Stem angle: negative values, varus; positive values, valgus SD, standard deviation Fig. Photograph showing the typical appearance of an incised solid pseudotumour in this series. Fig. Photograph of the ring of corrosion products (indicated by white arrow) at modular junction of head and neck. The head has been partially dislodged to reveal the underlying corrosion ring. In seven patients, the clinical presentation was with pain and a localised swelling or mass palpable on examination around the hip. Four patients presented with pain but no palpable mass and one with pain in association with a loose acetabular component. Five patients presented with unexpected recurrent instability associated with no mass palpable on examination or pain. The diagnosis of pseudotumour was made by the responsible clinician on the basis of pre-operative clinical findings, pre-operative investigations, intra-operative macroscopic appearance and, in all patients, the histopathological examination. Revision surgery. In all cases, the macroscopic bland, pale mass or granulomatous necrotic appearance of the periprosthetic tissue was typical of a pseudotumour (Fig. ). All head neck junctions were secure and well-fixed but after disassembly were noted to have a skin or ring of corrosion products on the trunnion and within the head (Fig. ). Well-fixed stems were retained (n = 6) as the trunnions were judged to be macroscopically intact. The trunnion was cleaned with the use of a sponge and/or an abrasive diathermy scratch pad. In of the 6 retained stems a titanium taper sleeve adapter and ceramic head was applied. Early in the series, two femoral heads were exchanged for cobalt chrome (CoCr) heads, as the preferred use of a ceramic head was not yet standard practice. In one patient, the articulation was revised to a dual mobility bearing (Stryker, Hamilton, Ontario, Canada) with a CoCr head. The acetabular shell was also revised in six patients. In the one patient with a possibly loose femoral stem, the implant was revised and a ceramic head applied. At revision, a minimum of three tissue samples were immediately sent from each patient to the laboratory for urgent processing of aerobic and anaerobic cultures and susceptibility testing. A disposable sterile scalpel was then used to divide the tissue into small pieces and a sterile inoculating loop used to streak the media. Specimens were plated to the following agars and liquid media (Thermo Fisher Scientific, Burlington, Ontario, Canada): 5% sheep blood in sheep blood agar base, MacConkey, Chocolate, Colistin-Nalidixic acid (CNA), brucella, and thioglycollate broth. All plates and broth media were incubated at 5 C in 5% carbon dioxide with the exception of the Brucella and CNA agars, which were incubated in an anaerobic jar using an AnaeroGen atmosphere generation system (Thermo Fisher) to achieve anaerobiasis. Plates and broth were examined daily and held for a total of five days before the report was finalised. Any growth on cultures was investigated for identification and susceptibility testing using standard microbiologic techniques. Pathology. Tissue samples from the associated pseudotumours were sent for standard haemotoxylin and eosin (H&E) processing and assessment by a subspecialised musculoskeletal pathologist. In patients adequate tissue was available for subanalysis and this was used for a detailed consensus review by two subspecialty pathologists (ME and TON). Owing to the limited number of viable THE BONE & JOINT JOURNAL

4 ADVERSE LOCAL TISSUE REACTIONS IN METAL-ON-POLYETHYLENE TOTAL HIP ARTHROPLASTY DUE TO TRUNNION CORROSION 7 Fig. Images of haemotoxylin and eosin staining showing the typical histological appearance of a necrotic granulomatous pseudotumour with necrotic hyalinised tissue (indicated by white arrow) surrounded by a rim of lymphohistiocytic infiltration (indicated by black arrow). cells present in the specimens, they were initially scanned at low power. Areas with viable cells were then subjected to detailed analysis at high power. Each specimen was scored for features previously described as characteristic of MoM implant-associated pseudotumours; neutrophils, macrophages, chronic inflammatory cells (lymphocytes, plasma cells and lymphoid follicles), eosinophils, multinucleated giant cells, necrosis, the pattern of necrotic debris surrounded by histiocytes, granulomatous inflamed tissue, metal particles, bone chips and aseptic lymphocytic vasculitis-associated lesions (ALVAL). 7,8 Polymorph numbers were confirmed by chloroacetate esterase (CAE) staining; these were scored by an independent pathologist (SZ) who was blinded to the H&E results. Metal ion trace element analysis was performed on serum samples by the London Laboratory Services Group (Ontario, Canada) using high resolution sector field inductively coupled plasma mass spectrometry. The reference range for cobalt (based on a non-occupationally exposed population) was. μ/l to. μg/l and for chromium was. μ/l to. μg/l. Statistical analysis. GraphPad Prism software (GraphPad Prism Inc., La Jolla, California) was used for data analysis. Data distribution was tested with a D Agostino and Pearson test. rmally distributed data was described with the mean and range, and comparison performed with parametric tests (two-sided paired t-test). n-normally distributed data were described with the median and interquartile range (IQR). Correlation of the polymorph counts for the H&E staining with the CAE staining assessed by Spearman s Rho, as these paired observations were ordinal and semiquantitative with a non-parametric distribution. A p-value <.5 was considered statistically significant. Results Clinical and laboratory findings. All patients were afebrile before revision. The pre-operative inflammatory markers were high; the mean erythrocyte sedimentation rate was 9 mm/hr (9 to ), with an upper limit for normal at our centre of. The mean C-reactive protein (CRP) was (.6 to 6), with the upper limit for normal being ten. The median white cell count was /L (IQR 6. to 8.8). Pre-operative aspiration and synovial biopsy was performed in patients but not in the five patients presenting with recurrent instability; in whom trunnion corrosion and pseudotumour were unexpected findings. In one hip Staphylococcus lugdunensis was detected on enrichment broth culture in one pre-operative synovial biopsy sample; the CRP was 8.8 and multiple intra-operative samples demonstrated no growth. This was therefore interpreted as a contaminant and not treated as an infection; subsequently no clinical signs of infection developed. Differential cell counts of aspirated joint fluid were available in seven patients. The median nucleated cell count was /L (IQR 7 to 7). The median proportion of neutrophils was 7% (IQR 6% to 8%). Multiple samples were taken intra-operatively for microscopy, culture and sensitivity in all patients (minimum n = ). The pathological examination of the excised masses demonstrated the typical appearance of necrotic granulomatous pseudotumours. 9 These are characterised by large areas of bland necrotic hyalinised tissue surrounded by a rim of lymphohistiocytic infiltration (Fig. ). Stromal eosinophils were noted in all samples, although they were often rare and required the examination of multiple sections. Neutrophils were observed more frequently, particularly in perivascular stroma; their presence was confirmed by CAE staining (Fig. ). Detailed data from the consensus review of cases is given in Table IV. Polymorph counts on H&E staining and ordinal quantification of CAE positive cells by an independent, blinded pathologist (SZ) correlated well (ρ =.7, two-tail p =.). All 7 patients were treated with a single-stage revision. Extensive soft-tissue damage was noted in ten cases. Postoperative infection was diagnosed in one case at four weeks post revision surgery and a radical debridement was performed. Staphylococcus lugdudensis was identified on five out of five debridement samples at debridment. This was considered to be a post-operative infection as the preoperative CRP was 6.6 and microbiology samples before revision were negative. Intra-operative samples from the revision did not show increased polymorphonuclear cell counts or organisms. Cobalt and chromium metal ion levels were available in patients. The mean cobalt value was 5.5 μg/l (.9 to.5) and the mean chromium value was. μg/l (.5 to.). Analysis of the paired data revealed that the mean cobalt level was significantly higher than the chromium level (two-sided paired t-test; p <.). VOL. 97-B,. 8, AUGUST 5

5 8 M. R. WHITEHOUSE, M. ENDO, S. ZACHARA, T. O. NIELSEN, N. V. GREIDANUS, B. A. MASRI, D. S. GARBUZ, C. P. DUNCAN Fig. b Fig. a Images of chloroacetate staining at a) magnification and b) magnification demonstrating polymorphs (indicated by black arrow). Table IV. Detailed data from the consensus review of patients. Scores are based on the modified Mirra classification (*)7 or histological scoring criteria for aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL) score ( ).8 Total neutrophils represents neutrophils in both perivascular and non-perivascular areas Necrotic debris Chronic surrounded GranulomaTissue Macroph Giant Plasma Bone Synovial Inflammatory organi- ALVAL by histiotous inflam- Metal Perivascular Lymphoid inflammatory Perivascular Total cells* particles* chips* lining cells* cells* Eosinophils* Necrosis* cytes infiltrate mation sation score neutrophils neutrophils* ages* Case lymphocytes follicle Low Moderate 8 9 Radiological findings. Implant orientation: The orientation of the prostheses, assessed on pre-revision plain radiographs, was considered to be within acceptable limits (Table III). There was no osteolysis in the primary cases. The one patient with a loose acetabular component exhibited circumferential radiolucency of the acetabular component. In patients in whom the index operation was a revision there were no progressive radiolucencies, osteolysis or component migration. Imaging: Ultrasound scans (USS) were performed preoperatively in seven patients, five of whom had complex hypoechoic masses detected, in one patient there were multiple fluid collections with no soft-tissue component and in one there was a small hypoechoic area. The largest of these masses was 5 cm cm 6 cm in maximum dimensions. Metal artefact reduction sequence MRI scans were performed in seven patients (five of whom also had an USS performed). Solid masses were noted in two patients, a fluid collection in one, mixed lesions in three and no mass with an area of high signal only in one patient. Complications: Five of the 7 patients suffered a significant complication requiring re-operation. The pseudotumour recurred in three patients; one in whom reimplantation of a new CoCr head had been performed at revision, one with a ceramic head on a titanium adapter sleeve and one where both the stem and acetabular component were revised and a ceramic head was used. Postoperative instability occurred in two patients, this was attributed to the extensive soft-tissue infiltration by the pseudotumour, and its resection. This is in keeping with our experience following revision for MoM bearing pseudotumours.6,, Discussion Patients with adverse soft-tissue reactions associated with THA may be asymptomatic. The patients in our series presented with a variety of symptoms in common with previously reported series of this pathology.6 Without being alert to the possibility of adverse tissue reactions in association with corrosion at the head neck taper junction, five THE BONE & JOINT JOURNAL

6 ADVERSE LOCAL TISSUE REACTIONS IN METAL-ON-POLYETHYLENE TOTAL HIP ARTHROPLASTY DUE TO TRUNNION CORROSION 9 of our patients may have been treated as recurrent instability and between three and ten as infection, potentially preventing adequate treatment. Inflammatory markers were commonly elevated in our series, raising the possibility of infection. According to the guidelines of the American Academy of Orthopedic Surgeons for the diagnosis of periprosthetic joint infection, only two patients had no criteria for infection; ten cases exhibited two or more of the minor criteria for the diagnosis of periprosthetic infection. The histology findings were compatible with the entity of necrotic granulomatous pseudotumour as previously described in association with MoM THA. 8,9, Although the histological findings associated with corrosion products from modular junctions in MoP THA are recognised, 9,5 they have not previously been reported according to the standardised criteria developed from our analysis of failed MoM THAs. From the patients with tissue available for histological review, nine exhibited neutrophilic infiltration. Three of these nine patients also exhibited raised inflammatory markers. In these, infection was ruled out by incompatible intra-operative and laboratory features, including negative cultures. For pathologists, it is important to recognise that stromal neutrophilic infiltrates can be a feature of pseudotumours in MoP THA secondary to corrosion, and does not necessarily imply bacterial infection. There is a risk of erroneous diagnosis in these cases if the diagnosis hinges on the polymorphonuclear count per high-power field, as popularised by Mirra et al 6 and Lonner et al. 7 The concept that corrosion may occur at the mixed alloy modular head-neck taper junction in hip arthroplasty was first introduced over years ago. 8 Mechanical disruption of the passivation layer and crevice corrosion were suggested as potential causes. 9 The effect may be time-dependent and is greater in mixed alloy couples.,,9- Once initiated, crevice corrosion may continue even in the absence of loading. Torsional moments acting on the trunnion may contribute to the generation of wear debris 5 and longer headneck extensions may exacerbate fretting. 6 Larger bearing sizes create a greater lever arm, which creates a characteristic pattern of wear. 7 Well-fixed stems were retained in this series so we were unable to formally analyse the trunnions. Adverse reaction to corrosion and wear debris has a detrimental effect on the stability of THA. er dislocation rates following revision for pseudotumours have been noted. 6,, Cooper et al 6 reported that two of their cases presented with recurrent dislocation in association with extensive necrosis and gross abductor deficiency, requiring the use of a constrained liner. A further case in their series went on to dislocate post-revision, requiring revision to a constrained liner. The elevation of cobalt levels in excess of chromium levels has previously been noted to occur in large diameter MoM THA. 8,9 This effect has been attributed to debris produced from the head neck taper junction rather than the bearing surface. We agree with the findings of one previous report on MoP THA that also found a differential elevation of metal ion levels. 6 Serum metal ion measurement should be considered in the investigation of unexplained pain following MoP THA, especially if there is clinical evidence of a mass or swelling, or if cross sectional imaging introduces the possibility of an adverse local reaction to metal. Our revision strategy has evolved during the series with our understanding of the pathology. In common with Cooper et al 6 our strategy is to retain well-fixed stems where the trunnion is not grossly damaged. Earlier in our series we re-implanted CoCr heads in three cases; a potential generator of corrosion products. We have since followed the practice of using a ceramic head coupled with a titanium adaptor, in the belief that the CoCr elements of the original head played a role in the trunnion corrosion. However, we have an incomplete understanding of the pathogenesis of ALVAL in this setting; pseudotumour recurrence has already been observed in two of the patients revised to a ceramic head, in one of which a new stem, and hence new trunnion, was also implanted. Adverse soft-tissue reactions and pain in association with the release of corrosion products from the head-neck interface of MoP THA remains a rare diagnosis; to our knowledge, only such cases have previously been reported in the literature. 6,7,, The evidence generated by this series is limited by the small number of cases, short follow-up period and lack of retrieval analysis. Our experience has striking similarities to that of the Rush University group 6 but there are differences. In the majority of our cases the corrosion occurred between dis-similar metals and following the use of large diameter heads (6 mm) which differed from other published case series. 6,7,, In conclusion, we have observed clinically significant soft-tissue reactions in patients with MoP THA secondary to the release of corrosion products from the head-neck taper junction. We feel there is a substantial risk of misdiagnosis in this population. We recommend investigation of patients with unexplained pain following MoP THA with this diagnosis in mind. Author Contributions: M. R. Whitehouse: Study design, Data collection, Data analysis, Performed surgeries, Drafting manuscript, Manuscript revisions, Approval of final manuscript. M. Endo: Data collection, Data analysis, Performed pathology analysis, Drafting manuscript, Manuscript revisions, Approval of final manuscript. S. Zachara: Data collection, Data analysis, Performed pathology analysis, Manuscript revisions, Approval of final manuscript. T. O. Nielsen: Study design, Data collection, Data analysis, Performed pathology analysis, Drafting manuscript, Manuscript revisions, Approval of final manuscript. N. V. Greidanus: Data collection, Data analysis, Performed surgeries, Drafting manuscript, Approval of final manuscript. B. A. Masri: Data collection, Data analysis, Performed surgeries, Drafting manuscript, Approval of final manuscript. D. S. Garbuz: Data collection, Data analysis, Performed surgeries, Drafting manuscript, Approval of final manuscript. C. P. Duncan: Study design, Data collection, Data analysis, Performed surgeries, Drafting manuscript, Manuscript revisions, Approval of final manuscript. We thank M. C. Parry MBChB, MD, FRCS (Tr & Orth), for his assistance with data collection, D. Savoy BA, for her assistance in the preparation of this manuscript and D. Roscoe MD, FRCPC, Clinical Professor, for her assistance with microbiological testing and descriptions. VOL. 97-B,. 8, AUGUST 5

7 M. R. WHITEHOUSE, M. ENDO, S. ZACHARA, T. O. NIELSEN, N. V. GREIDANUS, B. A. MASRI, D. S. GARBUZ, C. P. DUNCAN benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. This article was primary edited by E. Moulder and first proof edited by G. Scott. References. Haddad FS, Thakrar RR, Hart AJ, et al. Metal-on-metal bearings: the evidence so far. J Bone Joint Surg [Br] ;9-B: Browne JA, Bechtold CD, Berry DJ, Hanssen AD, Lewallen DG. Failed metalon-metal hip arthroplasties: a spectrum of clinical presentations and operative findings. Clin Orthop Relat Res ;68:.. Parvizi J, Gehrke T, Chen AF. Proceedings of the international consensus on periprosthetic joint infection. Bone Joint J ;95-B:5 5.. Workgroup Convened by the Musculoskeletal Infection Society. New definition for periprosthetic joint infection. J Arthroplasty ;6: Liddle AD, Satchithananda K, Henckel J, et al. 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Inflammatory pseudotumor complicating metal-on-highly cross-linked polyethylene total hip arthroplasty. J Arthroplasty ;7: 5. THE BONE & JOINT JOURNAL