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The Bone & Joint Journal
Vol. 96-B, Issue 9 | Pages 1172 - 1177
1 Sep 2014
Lawrence H Deehan D Holland J Kirby J Tyson-Capper A

Abnormal wear of cobalt-containing metal-on-metal joints is associated with inflammatory pseudotumours. Cobalt ions activate human toll-like receptor 4 (TLR4), which normally responds to bacterial lipopolysaccharide (LPS) in sepsis. Activation of TLR4 by LPS increases the expression of chemokines IL-8 and CXCL10, which recruit leukocytes and activated T-cells, respectively. This study was designed to determine whether cobalt induces a similar inflammatory response to LPS by promoting the expression of IL-8 and CXCL10. A human monocytic cell line, derived from acute monocytic leukaemia, was treated with cobalt ions and expression of IL-8 and CXCL10 measured at mRNA and protein levels. Cobalt-treated macrophages showed a 60-fold increase in IL-8 mRNA, and an eightfold increase in production of the mature chemokine (both p < 0.001); expression of the CXCL10 gene and protein was also significantly increased by cobalt (both p < 0.001). Experiments were also performed in the presence of CLI-095, a TLR4-specific antagonist which abrogated the cobalt-mediated increase in IL-8 and CXCL10 expression.

These findings suggest that cobalt ions induce inflammation similar to that observed during sepsis by the simultaneous activation of two TLR4-mediated signalling pathways. These pathways result in increased production of IL-8 and CXCL10, and may be implicated in pseudotumour formation following metal-on-metal replacement.

Cite this article: Bone Joint J 2014; 96-B:1172–7.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 2 | Pages 173 - 178
1 Feb 2012
Malizos KN Papasoulis E Dailiana ZH Papatheodorou LK Varitimidis SE

The introduction of a trabecular tantalum rod has been proposed for the management of early-stage osteonecrosis of the femoral head but serves as a single-point of support of the necrotic lesion. We describe a technique using two or three 4.2 mm (or later 4.7 mm) tantalum pegs for the prevention of collapse of the necrotic lesion. We prospectively studied 21 patients (26 hips) with non-traumatic osteonecrosis of the femoral head treated in this manner. Of these, 21 patients (24 hips) were available for radiological and clinical evaluation at a mean follow-up of 46 months (18 to 67). Radiological assessment showed that only eight hips deteriorated according to the Association Research Circulation Osseous classification, and four hips according to the Classification of the Japanese Investigation Committee of Health and Welfare. Functional improvement was obtained with an improvement in the mean Harris hip score from 65.2 (33.67 to 95) to 88.1 (51.72 to 100), the mean Merle D’Aubigné-Postel score from 13 (6 to 18) to 16 (11 to 18), a mean visual analogue score for pain from 5.2 (0 to 9.5) to 2.6 (0 to 7), and the mean Short-Form 36 score from 80.4 (56.8 to 107.1) to 92.4 (67.5 to 115.7). Of these 24 hips followed for a minimum of 18 months, three were considered as failures at the final follow-up, having required total hip replacement. One of the hips without full follow-up was also considered to be a failure. In more than two-thirds of the surviving hips a satisfactory clinical outcome was achieved with promising radiological findings. The estimated mean implant survival was 60 months (95% confidence interval 53.7 to 66.3).


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 8 | Pages 1126 - 1134
1 Aug 2012
Granchi D Cenni E Giunti A Baldini N

We report a systematic review and meta-analysis of the peer-reviewed literature focusing on metal sensitivity testing in patients undergoing total joint replacement (TJR). Our purpose was to assess the risk of developing metal hypersensitivity post-operatively and its relationship with outcome and to investigate the advantages of performing hypersensitivity testing. We undertook a comprehensive search of the citations quoted in PubMed and EMBASE: 22 articles (comprising 3634 patients) met the inclusion criteria. The frequency of positive tests increased after TJR, especially in patients with implant failure or a metal-on-metal coupling. The probability of developing a metal allergy was higher post-operatively (odds ratio (OR) 1.52 (95% confidence interval (CI) 1.06 to 2.31)), and the risk was further increased when failed implants were compared with stable TJRs (OR 2.76 (95% CI 1.14 to 6.70)). Hypersensitivity testing was not able to discriminate between stable and failed TJRs, as its predictive value was not statistically proven. However, it is generally thought that hypersensitivity testing should be performed in patients with a history of metal allergy and in failed TJRs, especially with metal-on-metal implants and when the cause of the loosening is doubtful


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 2 | Pages 169 - 173
1 Feb 2007
Daniel J Ziaee H Pradhan C Pynsent PB McMinn DJW

This is a longitudinal study of the daily urinary output and the concentrations in whole blood of cobalt and chromium in patients with metal-on-metal resurfacings over a period of four years. Twelve-hour urine collections and whole blood specimens were collected before and periodically after a Birmingham hip resurfacing in 26 patients. All ion analyses were carried out using a high-resolution inductively-coupled plasma mass spectrometer. Clinical and radiological assessment, hip function scoring and activity level assessment revealed excellent hip function. There was a significant early increase in urinary metal output, reaching a peak at six months for cobalt and one year for chromium post-operatively. There was thereafter a steady decrease in the median urinary output of cobalt over the following three years, although the differences are not statistically significant. The mean whole blood levels of cobalt and chromium also showed a significant increase between the pre-operative and one-year post-operative periods. The blood levels then decreased to a lower level at four years, compared with the one-year levels. This late reduction was statistically significant for chromium but not for cobalt. The effects of systemic metal ion exposure in patients with metal-on-metal resurfacing arthroplasties continue to be a matter of concern. The levels in this study provide a baseline against which the in vivo wear performance of newer bearings can be compared


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 8 | Pages 1072 - 1078
1 Aug 2010
Grammatopoulos G Pandit H Glyn-Jones S McLardy-Smith P Gundle R Whitwell D Gill HS Murray DW

Pseudotumours are a rare complication of hip resurfacing. They are thought to be a response to metal debris which may be caused by edge loading due to poor orientation of the acetabular component. Our aim was to determine the optimal acetabular orientation to minimise the risk of pseudotumour formation. We matched 31 hip resurfacings revised for pseudotumour formation with 58 controls who had a satisfactory outcome from this procedure. The radiographic inclination and anteversion angles of the acetabular component were measured on anteroposterior radiographs of the pelvis using Einzel-Bild-Roentgen-Analyse software. The mean inclination angle (47°, 10° to 81°) and anteversion angle (14°, 4° to 34°) of the pseudotumour cases were the same (p = 0.8, p = 0.2) as the controls, 46° (29° to 60°) and 16° (4° to 30°) respectively, but the variation was greater. Assuming an accuracy of implantation of ± 10° about a target position, the optimal radiographic position was found to be approximately 45° of inclination and 20° of anteversion. The incidence of pseudotumours inside the zone was four times lower (p = 0.007) than outside the zone. In order to minimise the risk of pseudotumour formation we recommend that surgeons implant the acetabular component at an inclination of 45° (± 10) and anteversion of 20° (± 10) on post-operative radiographs. Because of differences between the radiographic and the operative angles, this may be best achieved by aiming for an inclination of 40° and an anteversion of 25°


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 7 | Pages 1006 - 1012
1 Jul 2010
Davids JR Hydorn C Dillingham C Hardin JW Pugh LI

We have reviewed our experience of the removal of deep extremity orthopaedic implants in children to establish the nature, rate and risk of complications associated with this procedure. A retrospective review was performed of 801 children who had 1223 implants inserted and subsequently removed over a period of 17 years. Bivariate analysis of possible predictors including clinical factors, complications associated with implant insertion and indications for removal and the complications encountered at removal was performed. A logistical regression model was then constructed using those predictors which were significantly associated with surgical complications from the bivariate analyses. Odds ratios estimated in the logistical regression models were converted to risk ratios.

The overall rate of complications after removal of the implant was 12.5% (100 complications in 801 patients), with 48 (6.0%) major and 52 (6.5%) minor. Children with a complication after insertion of the initial implant or with a non-elective indication for removal, a neuromuscular disease associated with a seizure disorder or a neuromuscular disease in those unable to walk, had a significantly greater chance of having a major complication after removal of the implant. Children with all four of these predictors were 14.6 times more likely to have a major complication.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 4 | Pages 469 - 476
1 Apr 2010
Shimmin AJ Walter WL Esposito C

The survivorship of contemporary resurfacing arthroplasty of the hip using metal-on-metal bearings is better than that of first generation designs, but short-term failures still occur. The most common reasons for failure are fracture of the femoral neck, loosening of the component, osteonecrosis of the femoral head, reaction to metal debris and malpositioning of the component. In 2008 the Australian National Joint Registry reported an inverse relationship between the size of the head component and the risk of revision in resurfacing hip arthroplasty. Hips with a femoral component size of ≤ 44 mm have a fivefold increased risk of revision than those with femoral components of ≥ 55 mm irrespective of gender. We have reviewed the literature to explore this observation and to identify possible reasons including the design of the implant, loading of the femoral neck, the orientation of the component, the production of wear debris and the effects of metal ions, penetration of cement and vascularity of the femoral head. Our conclusion is that although multifactorial, the most important contributors to failure in resurfacing arthroplasty of the hip are likely to be the design and geometry of the component and the orientation of the acetabular component


Bone & Joint 360
Vol. 2, Issue 2 | Pages 23 - 25
1 Apr 2013

The April 2013 Spine Roundup360 looks at: smuggling spinal implants; local bone graft and PLIF; predicting disability with slipped discs; mortality and spinal surgery; spondyloarthropathy; brachytherapy; and fibrin mesh and BMP.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 5 | Pages 603 - 608
1 May 2012
Vasukutty NL Middleton RG Matthews EC Young PS Uzoigwe CE Minhas THA

We present our experience with a double-mobility acetabular component in 155 consecutive revision total hip replacements in 149 patients undertaken between 2005 and 2009, with particular emphasis on the incidence of further dislocation. The mean age of the patients was 77 years (42 to 89) with 59 males and 90 females. In all, five patients died and seven were lost to follow-up. Indications for revision were aseptic loosening in 113 hips, recurrent instability in 29, peri-prosthetic fracture in 11 and sepsis in two. The mean follow-up was 42 months (18 to 68). Three hips (2%) in three patients dislocated within six weeks of surgery; one of these dislocated again after one year. All three were managed successfully with closed reduction. Two of the three dislocations occurred in patients who had undergone revision for recurrent dislocation. All three were found at revision to have abductor deficiency. There were no dislocations in those revised for either aseptic loosening or sepsis.

These results demonstrate a good mid-term outcome for this component. In the 29 patients revised for instability, only two had a further dislocation, both of which were managed by closed reduction.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 10 | Pages 1439 - 1444
1 Oct 2005
Davies AP Sood A Lewis AC Newson R Learmonth ID Case CP

Previous research has shown an increase in chromosomal aberrations in patients with worn implants. The type of aberration depended on the type of metal alloy in the prosthesis. We have investigated the metal-specific difference in the level of DNA damage (DNA stand breaks and alkali labile sites) induced by culturing human fibroblasts in synovial fluid retrieved at revision arthroplasty. All six samples from revision cobalt-chromium metal-on-metal and four of six samples from cobalt-chromium metal-on-polyethylene prostheses caused DNA damage. By contrast, none of six samples from revision stainless-steel metal-on-polyethylene prostheses caused significant damage. Samples of cobalt-chromium alloy left to corrode in phosphate-buffered saline also caused DNA damage and this depended on a synergistic effect between the cobalt and chromium ions. Our results further emphasise that epidemiological studies of orthopaedic implants should take account of the type of metal alloy used


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 2 | Pages 145 - 151
1 Feb 2012
Henderson RA Lachiewicz PF

Persistent groin pain after seemingly successful total hip replacement (THR) appears to have become more common. Recent studies have indicated a high incidence after metal-on-polyethylene and metal-on-metal conventional THR and it has been documented in up to 18% of patients after metal-on-metal resurfacing. There are many causes, including acetabular loosening, stress fracture, and iliopsoas tendonitis and impingement. The evaluation of this problem requires a careful history and examination, plain radiographs and an algorithmic approach to special diagnostic imaging and tests. Non-operative treatment is not usually successful. Specific operative treatment depending on the cause of the pain usually involves revision of the acetabular component, iliopsoas tenotomy or other procedures, and is usually successful. Here, an appropriate algorithm is described.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 12 | Pages 1610 - 1616
1 Dec 2011
Pegg E Pandit H Gill HS Keys GW Svard UGC O’Connor JJ Murray DW

Since the Oxford knee was first used unicompartmentally in 1982, a small number of bearings have fractured. Of 14 retrieved bearings, we examined ten samples with known durations in situ (four Phase 1, four Phase 2 and two Phase 3). Evidence of impingement and associated abnormally high wear (> 0.05 mm per year) as well as oxidation was observed in all bearings. In four samples the fracture was associated with the posterior radio-opaque wire. Fracture surfaces indicated fatigue failure, and scanning electron microscopy suggested that the crack initiated in the thinnest region. The estimated incidence of fracture was 3.20% for Phase 1, 0.74% for Phase 2, 0.35% for Phase 3, and 0% for Phase 3 without the posterior marker wire. The important aetiological factors for bearing fracture are impingement leading to high wear, oxidation, and the posterior marker wire. With improved surgical technique, impingement and high wear should be prevented and modern polyethylene may reduce the oxidation risk. A posterior marker wire is no longer used in the polyethylene meniscus. Therefore, the rate of fracture, which is now very low, should be reduced to a negligible level.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 9 | Pages 1292 - 1297
1 Sep 2005
Lietman SA Inoue N Rafiee B Deitz LW Chao EYS

We used a canine intercalary bone defect model to determine the effects of recombinant human osteogenic protein 1 (rhOP-1) on allograft incorporation. The allograft was treated with an implant made up of rhOP-1 and type I collagen or with type I collagen alone.

Radiographic analysis showed an increased volume of periosteal callus in both test groups compared with the control group at weeks 4, 6, 8 and 10. Mechanical testing after 12 weeks revealed increased maximal torque and stiffness in the rhOP-1 treated groups compared with the control group.

These results indicate a benefit from the use of an rhOP-1 implant in the healing of bone allografts. The effect was independent of the position of the implant. There may be a beneficial clinical application for this treatment.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 9 | Pages 1306 - 1311
1 Sep 2010
Patten EW Atwood SA Van Citters DW Jewett BA Pruitt LA Ries MD

Retrieval studies of total hip replacements with highly cross-linked ultra-high-molecular-weight polyethylene liners have shown much less surface damage than with conventional ultra-high-molecular-weight polyethylene liners. A recent revision hip replacement for recurrent dislocation undertaken after only five months revealed a highly cross-linked polyethylene liner with a large area of visible delamination. In order to determine the cause of this unusual surface damage, we analysed the bearing surfaces of the cobalt-chromium femoral head and the acetabular liner with scanning electron microscopy, energy dispersive x-ray spectroscopy and optical profilometry. We concluded that the cobalt-chromium modular femoral head had scraped against the titanium acetabular shell during the course of the dislocations and had not only roughened the surface of the femoral head but also transferred deposits of titanium onto it. The largest deposits were 1.6 μm to 4.3 μm proud of the surrounding surface and could lead to increased stresses in the acetabular liner and therefore cause accelerated wear and damage.

This case illustrates that dislocations can leave titanium deposits on cobalt-chromium femoral heads and that highly cross-linked ultra-high-molecular-weight polyethylene remains susceptible to surface damage.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 11 | Pages 1528 - 1533
1 Nov 2007
Jeffcote B Nicholls R Schirm A Kuster MS

Achieving deep flexion after total knee replacement remains a challenge. In this study we compared the soft-tissue tension and tibiofemoral force in a mobile-bearing posterior cruciate ligament-sacrificing total knee replacement, using equal flexion and extension gaps, and with the gaps increased by 2 mm each. The tests were conducted during passive movement in five cadaver knees, and measurements of strain were made simultaneously in the collateral ligaments. The tibiofemoral force was measured using a customised mini-force plate in the tibial tray. Measurements of collateral ligament strain were not very sensitive to changes in the gap ratio, but tibiofemoral force measurements were. Tibiofemoral force was decreased by a mean of 40% (sd 10.7) after 90° of knee flexion when the flexion gap was increased by 2 mm. Increasing the extension gap by 2 mm affected the force only in full extension. Because increasing the range of flexion after total knee replacement beyond 110° is a widely-held goal, small increases in the flexion gap warrant further investigation.