Objectives. Modular dual-mobility (MDM) constructs are used to reduce dislocation rates after total hip replacement (THR). They combine the advantages of dual mobility with the option of supplementary acetabular screw fixation in complex revision surgery. However, there are concerns about adverse reaction to metal debris (ARMD) as a result of fretting corrosion between the metal liner and shell. Methods: The aim of this systematic review was to find and review all relevant studies to establish the outcomes and risks associated with MDM hip replacement. All articles on MDM THRs in the Medline, EMBASE, CINAHL, Cochrane Library, and Prospero databases were searched. A total of 14 articles were included. A random intercept logistic regression model was used for meta-analysis, giving estimated average values. Results: There were 6 cases of ARMD out of 1312 total. Estimated median incidence of ARMD from meta-analysis was 0.3% (95% CI 0.1 – 1.4%). Mean postoperative serum Cobalt was 0.81 μg/L (95% CI 0.33 – 1.29 μg/L), and Chromium was 0.77 μg/L (95% 0.35 – 1.19 μg/L), from 279 cases in 7 studies. Estimated median incidence of a serum cobalt or chromium ion measurement ≥1 μg/L was 7.9% (95% CI 3.5 – 16.8%), and ≥7 μg/L was 1.8% (95% CI 0.7 – 4.2%). Conclusions: ARMD is a rare but significant complication following total hip replacement using a MDM construct. Its incidence appears higher than that reported in non-metal-on-metal (MoM) hip replacements but lower than that of MoM hip replacements. MDM hip replacements are associated with raised serum metal ion levels postoperatively, but there was no correlation with worse clinical hip function within studies. Studies were poor quality and at high risk of confounding. Pending further work, MDM constructs should be used with caution, reserved for select cases at particularly high risk of dislocation

Abstract. Objectives. Modular dual-mobility (MDM) constructs are used to reduce dislocation rates after total hip replacement (THR). They combine the advantages of dual mobility with the option of supplementary acetabular screw fixation in complex revision surgery. However, there are concerns about adverse reaction to metal debris (ARMD) as a result of fretting corrosion between the metal liner and shell. Methods. The aim of this systematic review was to find and review all relevant studies to establish the outcomes and risks associated with MDM hip replacement. All articles on MDM THRs in the Medline, EMBASE, CINAHL, Cochrane Library, and Prospero databases were searched. A total of 14 articles were included. A random intercept logistic regression model was used for meta-analysis, giving estimated mean values. Results. There were 6 cases of ARMD out of 1312 total. Estimated median incidence of ARMD from meta-analysis was 0.3% (95% CI 0.1 – 1.4%). Mean postoperative serum Cobalt was 0.81 μg/L (95% CI 0.33 – 1.29 μg/L), and Chromium was 0.77 μg/L (95% 0.35 – 1.19 μg/L), from 279 cases in 7 studies. Estimated median incidence of a serum cobalt or chromium ion measurement ≥1 μg/L was 7.9% (95% CI 3.5 – 16.8%), and ≥7 μg/L was 1.8% (95% CI 0.7 – 4.2%). Conclusions. ARMD is a rare but significant complication following total hip replacement using a MDM construct. Its incidence appears higher than that reported in non-metal-on-metal (MoM) hip replacements but lower than that of MoM hip replacements. MDM hip replacements are associated with raised serum metal ion levels postoperatively, but there was no correlation with worse clinical hip function within studies. Studies were poor quality and at high risk of confounding. Pending further work, MDM constructs should be used with caution, reserved for select cases at particularly high risk of dislocation. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Adverse reaction to metal debris (ARMD) is well recognised as a complication of large head metal on metal total hip replacement (THR) leading to pain, bone and tissue loss and the need for revision surgery. An emerging problem of trunnionosis in metal on polyethylene total hip replacements leading to ARMD has been reported in a few cases. Increased metal ion levels have been reported in THR's with a titanium stem and a cobalt chrome head such as the Accolade-Trident THR (Stryker). We present 3 cases of ARMD with Accloade-Trident THR's with 36mm cobalt chrome head and a polyethylene liner. Metal ion levels were elevated in all three patients (cobalt 10.3 – 161nmol/l). Intraoperative tissue samples were negative for infection and inflammatory markers were normal. Abnormal fluid collections were seen in all three cases and bone loss was severe in one patient leading to a proximal femoral replacement. Histology demonstrated either a non-specific inflammatory reaction in a case which presented early or a granulomatous reaction in a more advanced case suggesting a local foreign body reaction. All patients had improved symptoms post-operatively. 1 patient who had staged bilateral Accolade-Trident THR's required revision of both THR's. ARMD in metal on polyethylene THR's with a titanium stem represents a potential emerging problem. Further studies are required to assess whether these occurrences are rare or represent the tip of an iceberg

Introduction:. When having to remove broken or embedded metal implants using high speed burrs, the consequence is often a significant amount of metal debris which becomes embedded in the soft tissues. This may then act as a source for a foreign body inflammatory reaction or as a third body wear in the situation of joint arthroplasty. We describe a simple, cheap and effective method of reducing this debris using only a sterile water-based lubricating gel. Materials & Methods:. Several experimental surgical models consisting of porcine muscle over a polyethylene tube with a large fragment titanium locking plate and screw secured to it were constructed. In 8 separate models a screw head locked within the plate was subjected to 90 seconds of high speed burring to create debris. On 4 models no water-based lubricating gel was utilized and on the remaining 4 the surrounding soft tissues were coated in the water-based lubricating gel (AQUAGEL, Halliburton – 42g £1.98). All models were then irrigated with NaCl 500mls using a 20mlsl syringe under manual pressure. Images were then captured after irrigation. The amount of debris was quantified by processing with ImageJ (a public domain, Java-based image processing program developed at the National Institutes of Health and is a computer automated program for counting particles.) The results were then statistically analysed using a student t test (IBM Corp. Released 2011. IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp.). Results:. the images from the models with water-based gel were shown to have a statistically significant difference in particle number and area within the soft tissues (p=0.001). Conclusion:. We have shown that using a safe, cheap and easily available water-based lubricating gel reduces the amount of embedded debris when burring metal implants using a high-speed burr

Wear products of metal implants are known to induce biological events which may have profound consequences for the microcirculation of skeletal muscle. Using the skinfold chamber model and intravital microscopy we assessed microcirculatory parameters in skeletal muscle after confrontation with titanium and stainless-steel wear debris, comparing the results with those of bulk materials.

Implantation of stainless-steel bulk and debris led to a distinct activation of leukocytes combined with a disruption of the microvascular endothelial integrity and massive leukocyte extravasation. While animals with bulk stainless steel showed a tendency to recuperation, stainless-steel wear debris induced such severe inflammation and massive oedema that the microcirculation broke down within 24 hours after implantation. Titanium bulk caused only a transient increase in leukocyte-endothelial cell interaction within the first 120 minutes and no significant change in macromolecular leakage, leukocyte extravasation or venular diameter. Titanium wear debris produced a markedly lower inflammatory reaction than stainless-steel bulk, indicating that a general benefit of bulk versus debris could not be claimed. Depending on its constituents, wear debris is capable of eliciting acute inflammation which may result in endothelial damage and subsequent failure of microperfusion. Our results indicate that not only the bulk properties of orthopaedic implants but also the microcirculatory implications of inevitable wear debris play a pivotal role in determining the biocompatibility of an implant.

Abstract. Objective. The aim of our systematic review was to report the latest evidence on the effects of CoCr particles on local soft tissue with a focus on its clinical relevance. Methods. PubMed, Embase, and Cochrane Library databases were screened to perform an extensive review. Inclusion criteria were studies of any level of evidence published in peer-reviewed journals reporting clinical and preclinical results written in English. Relative data were extracted and critically analyzed. PRISMA guidelines were applied, and the risk of bias was assessed, as was the methodological quality of the included studies. Results. 30 studies were included after applying the inclusion and exclusion criteria. Of these, 24 were preclinical studies (18 in vitro human studies, 6 animal modal studies, including 3 in vitro and 3 in vivo), 5 were clinical studies and 1 was previous review on similar topic. The presence of metal ions causes cell damage by reducing cell viability, inducing DNA damage, and triggering the secretion of cytokines. Mechanisms of apoptosis, autophagy and necrosis are responsible for the inflammatory reaction observed in ALTR. Conclusion. The available literature on the effects of CoCr particles released from MoM implants shows that metal debris can cause damage to skeletal muscle, the capsule, and provoke osteolysis and inflammation. Therefore, the cytotoxic and genotoxic damages, as well as the interaction with the immune system, affect the success of the arthroplasty and lead to a higher rate of revision surgeries. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Increased revision rates and early failure of Metal-on-Metal (MoM) hip replacements are often due to adverse reaction to metal debris (ARMD). Cobalt is a major component of MoM joints and can initiate an immune response via activation of the innate immune receptor Toll-like receptor 4 (TLR4). This leads to increased secretion of inflammatory cytokines/chemokines e.g. CCL3 and CCL4. The aim of this study was to evaluate whether TLR4-specific neutralising antibodies can prevent cobalt-mediated activation of TLR4. MonoMac 6 (MM6) cells, a human macrophage cell line, were treated with two different TLR4-specific monoclonal antibodies followed by 0.75mM of cobalt chloride (CoCl2). Lipopolysaccharide (LPS), a known TLR4 agonist was used as a positive control. Enzyme-linked immunosorbent assay (ELISA) was used to assess CCL3/CCL4 protein secretion and real time- polymerase chain reaction (RT-PCR) allowed quantification of CCL3/CCL4 gene expression. MM6 cells treated with cobalt and LPS up-regulate CCL3 and CCL4 gene expression and protein secretion. MM6 cells pre-treated with both monoclonal antibodies prior to stimulation with 0.75mM CoCl2 for 16 hours demonstrated significant inhibition of both CCL3 and CCL4 secretion as well as gene expression (both p=<0.0001). One of the antibodies failed to inhibit chemokine expression and secretion in LPS treated cells. This study identifies for the first time the use of TLR4-specific monoclonal antibodies to prevent cobalt activation of TLR4 and subsequent inflammatory response. This finding demonstrates the potential to exploit TLR4 inhibition in the context of MoM joint replacements by contributing to the development of novel therapeutics designed to reduce the incidence of ARMD

Background. Adverse reactions to metal debris are implicated in the failure of metal-on-metal hip arthroplasty. The peri-implant tissues are often infiltrated by leukocytes which may cause observed immunological effects, including soft tissue necrosis and osteolysis. Cobalt ions from orthopaedic implants aberrantly activate the innate immune receptor human toll-like receptor-4 (TLR4), leading to inflammatory cytokine release including interleukin-8 (IL-8). IL-8 has been shown to increase expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). These factors are essential for leukocyte adhesion to endothelium, which is required for leukocyte migration into tissues. This study investigates cobalt's effect on gene and protein changes in IL-8, ICAM-1 and VCAM-1 to determine their potential role in immune cell infiltration of peri-implant tissues. Methods. TLR4-expressing human dermal microvascular endothelial cells (HMEC-1) were treated with a range of clinically relevant cobalt ion concentrations. IL-8 protein secretion was measured by enzyme-linked immunosorbent assay (ELISA). Gene expression changes were quantified by TaqMan-based real time polymerase chain reaction. Results. Stimulation with cobalt ions significantly increases IL-8 secretion (n=3) in HMEC-1 cells. This is a TLR4-specific effect as a small molecule TLR4 antagonist inhibited cobalt-induced IL-8 secretion. Following cobalt treatment (0.75mM cobalt chloride) there is a 12-fold increase in ICAM-1 (p-value=0.0004) and a 6-fold increase in VCAM-1 (p-value<0.0001) gene expression. Work will be undertaken to determine the role of TLR4 in these responses. Conclusion. Cobalt increases IL-8 secretion and adhesion molecule gene expression in HMEC-1 cells. This in vitro finding demonstrates the potential for cobalt ions to increase leukocyte adhesion to the endothelial surface. This may contribute to leukocyte infiltration of peri-implant tissues in metal-on-metal hip arthroplasty failure

Background. Increased revision rates and early failure of Metal-on-Metal (MoM) hip replacements are often due to adverse reaction to metal debris (ARMD). ARMD describes numerous symptoms in patients such as pain, osteolysis and soft tissue damage. Cobalt is a major component of MoM joints and can initiate an immune response via activation of the innate immune receptor Toll-like receptor 4 (TLR4). This leads to increased secretion of inflammatory cytokines e.g. interleukin-8 (IL-8). This study investigates whether TLR4-specific antagonists inhibit the inflammatory response to cobalt using IL-8 gene expression and protein secretion as a marker of TLR4 activation. Methods. MonoMac 6 (MM6) cells, a human macrophage cell line, were treated with TLR4-specific antagonists followed by 0.75mM of cobalt chloride. Lipopolysaccharide (LPS), a known TLR4 agonist was used as a positive control. Enzyme-linked immunosorbent assay (ELISA) was used to assess IL-8 protein secretion and real time- polymerase chain reaction (RT-PCR) allowed quantification of IL-8 gene expression. Results. MM6 cells treated with cobalt and LPS up-regulate IL-8 gene expression and protein secretion (n=3). The addition of TLR4-specific antagonists significantly inhibits this up-regulation suggesting the observed effects are TLR4-mediated. MM6 cells stimulated with cobalt (0.75mM) for 16 hours demonstrated a 27-fold increase in IL-8 gene expression (p-value = < 0.0001). When pre-treated with 10μg/ml of a TLR4-specific antagonist fold increase decreased to 6-fold (p-value = < 0.0001). IL-8 secretion decreased from 5000pg/ml to 3000pg/ml (p-value = < 0.0001). Conclusion. TLR4-specific antagonists inhibit cobalt-mediated IL-8 gene expression and protein secretion in MM6 cells. This finding demonstrates the potential to exploit this inhibition in the context of MoM joint replacements by contributing to the development of novel therapeutics designed to improve MoM implant longevity, reduce the incidence of ARMD and prevent subsequent revision surgery

We report the survival, functional and radiological outcome of a series of Birmingham hip resurfacing procedures performed by a single surgeon at a district general hospital. The aim of this study was to retrospectively report the medium term outcome and survival of our patients. There were 45 hip resurfacings performed in 38 patients between 2004 and 2010. Patients were followed for a mean duration of four years. Mean age of 52.6 years (range 26 to 65). Although no patients were lost to follow up, four did not complete the oxford hip scoring assessment. The median Oxford hip score was 16.25 points (range 12–39 points, standard deviation 5.9) at 48 months follow up (range 11.5–84.2 months). The mean acetabular inclination was 46.9 (range 40.9–59.9) in the 45 hip resurfacings post operatively. There was one patient with varus subsidence of the prosthesis and one patient with persistent hip pain post operatively under investigation currently. There was no definite radiological evidence of loosening or of narrowing of the femoral neck. No cases were revised and no cases developed any other complications. These medium-term results from a district general hospital are comparable to the other studies performed. Few independent studies have reported the outcome of resurfacing arthroplasty of the hip in a district general hospital. Further evaluation and follow up of these patients is required to address the concerns raised by other centers related to fracture and metal debris

The aim is to report a rare technique for correction of intramedullary nail acute angular deformity. Intramedullary tibial nail fixation of diaphyseal tibial fractures is the gold standard treatment allowing early mobilisation whilst preserving the soft tissues around the fracture site. Most commonly, intramedullary nails fail by metal fatigue secondary to non union, without significant deformity of the metalwork. Plastic deformity of the nail can result following new acute trauma, particularly before bone union has occurred. This is a clinical challenge as a reamed intramedullary nail is designed to achieve three point fixation with close anatomical fit, such that removal of a bent nail is technically difficult and also risks further damage to bone and soft tissues. We report a case of a 20 year old patient treated with intramedullary nail fixation of a diaphyseal right tibial fracture who was subsequently assaulted 4 weeks post operatively. This produced an unacceptable deformation of the nail into 25 degrees valgus and procurvatum. To remove the nail, the authors used a previously reported but rare technique of partial (up to 50%) nail division on the convex surface of the apex using Midas Rex High Speed Drill to weaken the nail then manipulation to correct deformity with minimal stress. The technique produced minimal metal debris and allowed simple exchange nail replacement without further complication. The authors believe this is the first reported use of the technique from the United Kingdom

Particulate wear debris can induce the release of bone-resorbing cytokines from cultured macrophages and fibroblasts in vitro, and these mediators are believed to be the cause of the periprosthetic bone resorption which leads to aseptic loosening in vivo. Much less is known about the effects of particulate debris on the growth and metabolism of osteoblastic cells. We exposed two human osteoblast-like cell lines (SaOS-2 and MG-63) to particulate cobalt, chromium and cobalt-chromium alloy at concentrations of 0, 0.01, 0.1 and 1.0 mg/ml. Cobalt was toxic to both cell lines and inhibited the production of type-I collagen, osteocalcin and alkaline phosphatase. Chromium and cobalt-chromium were well tolerated by both cell lines, producing no cytotoxicity and no inhibition of type-I collagen synthesis. At the highest concentration tested (1.0 mg/ml), however, chromium inhibited alkaline phosphatase activity, and both chromium and cobalt-chromium alloy inhibited osteocalcin expression. Our results clearly show that particulate metal debris can modulate the growth and metabolism of osteoblastic cells in vitro. Reduced osteoblastic activity at the bone-implant interface may be an important mechanism by which particulate wear debris influences the pathogenesis of aseptic loosening in vivo

This study reports the mid-term results of a large bearing hybrid metal on metal total hip replacement (MOMHTHR) in 199 hips (185 patients) with mean follow up of 62 months. Clinical, radiological outcome, metal ion levels and retrieval analysis were performed. Seventeen patients (8.6%) had undergone revision, and a further fourteen are awaiting surgery (defined in combination as failures). Twenty one (68%) failures were females. All revisions and ten (71%) of those awaiting revision were symptomatic. Twenty four failures (86%) showed progressive radiological changes. Fourteen revision cases showed evidence of adverse reactions to metal debris (ARMD). The failure cohort had significantly higher whole blood cobalt ion levels (p=0.001), but no significant difference in cup size (p=0.77), inclination (p=0.38) or cup version (p=0.12) in comparison to the non revised cohort. Female gender was associated with an increased risk of failure (chi squared p=0.04). Multifactorial analysis demonstrated isolated raised Co levels in the absence of either symptoms or XR changes was not predictive of failure (p=0.675). However both the presence of pain (p<0.001) and XR changes (p<0.001) in isolation were both significant predictors of failure. Wear analysis (n=5) demonstrated increased wear at the trunnion/head interface (mean out of roundness measurements of 34.5 microns +/−13.3 (+/−2SD, normal range 8-10 microns) with normal levels of wear at the articulating surfaces. There was evidence of corrosion at the proximal and distal stem surfaces. The cumulative survival rate, with revision for any reason was 92.4% (95%CI: 87.4-95.4) at 5 years. Including those awaiting surgery, the revision rate would be 15.1% with cumulative survival at 5 years of 89.6% (95% CI: 83.9-93.4). This MOMHTHR series has demonstrated unacceptable high failure rates with evidence of high wear at the head/trunnion interface and passive corrosion to the stem surface. This raises concern with the use of large heads on conventional 12/14 tapers. Female gender was an independent risk factor of failure. Metal ion levels remain a useful aspect of the investigation work up but in isolation are not predictive of failure

Background. The worldwide withdrawal of the DePuy Articular Surface Replacement (ASR) device in both its resurfacing and total hip replacement (THR) form on 26 August 2010, after 93,000 were implanted worldwide, has had major implications. The 2010 National Joint Registry for England and Wales quoted figures of 12-13% failure at five years; however these figures may be an underestimate. Patients and methods. In 2004 a single surgeon prospective study of the ASR bearing surface was undertaken. Presented are the Adverse Reaction to Metal Debris (ARMD) failure rates of the ASR resurfacing and ASR THR systems. The diagnosis of ARMD was made by the senior author and was based on clinical history, examination, ultrasound findings, metal ion analysis of blood and joint fluid, operative findings and histopathological analysis of tissues retrieved at revision. Acetabular cup position in vivo was determined using EBRA software. Mean follow up was 52 months (24-81) and 70 patients were beyond 6 years of the procedure at the time of writing. Kaplan Meier survival analysis was carried out firstly with joints designated ‘failure’ if the patient had undergone revision surgery or if the patient had been listed for revision. A second survival analysis was carried out with a failure defined as a serum cobalt concentration > 7microgrammes/L (MHRA guideline from MDA-2010-069). Full explant analysis was carried out for retrieved prostheses. Results. There were 505 ASR hips in total (418 resurfacings and 87 THRs). 657 metal ion samples were available at the time of writing including 152 repeats. Survival analysis using revision/listed for revision as end point (at 6 years): ASR resurfacing: 26.1% failure; ASR THR: 55.5% failure. Survival using ion analysis (at 5 years): ASR resurfacing: 50.1% failure; ASR THR: 66.5% failure. The median (range) volumetric wear rate of failed prostheses was 8.23mm3/year (0.51-95.5). Failure and high ion concentrations are linked to acetabular cup size, anteversion and inclination. Increased failure rates in THRs were due to wear at the taper junction of head and stem. Conclusion. Design flaws in the ASR have led to excessive wear and consequently catastrophic failure rates secondary to ARMD

Summary Statement. Fretting and corrosion has been identified as a clinical problem in modular metal-on-metal THA, but remains poorly understood in modern THA devices with polyethylene bearings. This study investigates taper damage and if this damage is associated with polyethylene wear. Introduction. Degradation of modular head-neck tapers was raised as a concern in the 1990s (Gilbert 1993). The incidence of fretting and corrosion among modern, metal-on-polyethylene and ceramic-on-polyethylene THA systems with 36+ mm femoral heads remains poorly understood. Additionally, it is unknown whether metal debris from modular tapers could increase wear rates of highly crosslinked PE (HXLPE) liners. The purpose of this study was to characterise the severity of fretting and corrosion at head-neck modular interfaces in retrieved conventional and HXLPE THA systems and its effect on penetration rates. Patients & Methods. 386 CoCr alloy heads from 5 manufacturers were analyzed along with 166 stems (38 with ceramic femoral heads). Metal and ceramic components were cleaned and examined at the head taper and stem taper by two investigators. Scores ranging from 1 (mild) to 4 (severe) were assigned in accordance with the semi-quantitative method adapted from a previously published technique. Linear penetration of liners was measured using a calibrated digital micrometer (accuracy: 0.001 mm). Devices implanted less than 1 year were excluded from this analysis because in the short-term, creep dominates penetration of the head into the liner. Results. The majority of the components were revised for instability, infection, and loosening. Mild to severe taper damage (score ≥2) was found in 77% of head tapers and 52% of stem tapers. The extent of damage was correlated to implantation time at the head taper (p=0.0004) and at the stem taper (p=0.0004). Damage scores were statistically elevated on CoCr heads than the matched stems (mean score difference=0.5; p<0.0001) and the two metrics were positively correlated with each other (ρ=0.41). No difference was observed between stem taper damage and head material (CoCr, ceramic) (p=0.56), nor was a correlation found between taper damage and head size (p=0.85). The penetration rate across different formulations of HXLPE was not found to be significantly different (p=0.07), and therefore grouped together for further analysis. Within this cohort, penetration rate was not found to be associated with head size (p=0.08) though a negative correlation with implantation time was noted (ρ=−0.35). When analyzed along with taper damage scores, a correlation was not observed between head taper damage scores and HXLPE penetration rates (p=0.51). Discussion. The results of this study do not support the hypothesis that 36+ mm ceramic or CoCr femoral heads articulating on HXLPE liners are associated with increased risk of corrosion among HXLPE liners when compared with smaller diameter heads. A limitation of this study is the semi-quantitative scoring technique, heterogeneity of the retrieval collection and short implantation time of the larger diameter heads. Because corrosion may increase over time in vivo, longer-term follow-up, coupled with quantitative taper wear measurement, will better assess the natural progression of taper degradation in modern THA bearings

Wear debris induced osteolysis is a recognized complication in conventional metal-on-polyethylene hip arthroplasty. One method of achieving wear reduction is through the use of metal-on-metal articulations. One of the latest manifestations of this biomaterial combination is in designs of hip resurfacing which are aimed at younger, more active patients. But, do these metal-on-metal hip resurfacings show low wear when implanted into patients?. Using a Mitutoyo Legex 322 co-ordinate measuring machine (scanning accuracy less than 1 micron) and a bespoke computer program, volumetric wear measurements for retrieved Articular Surface Replacements (ASR, DePuy) metal-on-metal hip resurfacings were undertaken. Measurements were validated against gravimetric calculations for volumetric wear using a sample femoral head that was artificially worn in vitro. At 5mm3, 10mm3, and 15mm3 of material removal, the method was shown to be accurate to within 0.5mm3. Thirty-two femoral heads and twenty-two acetabular cups were measured. Acetabular cups exhibited mean volumetric wear of 29.00mm3 (range 1.35 - 109.72mm3) and a wear rate of 11.02mm3/year (range 0.30 - 63.59mm3/year). Femoral heads exhibited mean wear of 22.41mm3 (range 0.72 - 134.22mm3) and a wear rate of 8.72mm3/year (range 0.21 - 31.91mm3/year). In the 22 cases where both head and cup from the same prosthesis were available, mean total wear rates of 21.66mm3/year (range 0.51 - 95.50mm3/year) were observed. Revision was necessitated by one of five effects; early femoral neck fracture (4 heads), avascular necrosis (AVN) (2 heads, 1 cup), infection (1 head, 1 cup), adverse reaction to metal debris (ARMD) (19 heads, 18 cups) or ARMD fracture (6 heads, 2 cups). Mean paired wear rates for the AVN and infection retrievals were 0.51mm3/year and 3.98mm3/year respectively. In vitro tests typically offer wear rates for metal-on-metal devices in the region of 2-4mm3. Mean paired wear rates for ARMD and ARMD fracture were 17.64mm3/year and 68.5mm3/year respectively, significantly greater than those expected from in vitro tests. In the 4 cases of early fracture, only the heads were revised so a combined wear rate calculation was not possible. The heads exhibited mean wear rate of 8.26mm3/year. These high wear rates are of concern

Background. Investigations into the response to implant debris tend to concentrate on how a population of cells proliferate in the presence of implant material, and how the regulation of cytokines change. For the problem of cobalt-chromium (CoCr) implants this has been done for osteoblasts and osteoclasts to understand how bone resorption, leading to aseptic loosening, is occurring. However, investigating the formation of the extracellular-matrix (ECM) may give a better indication of the mechanisms occurring. ECM is excreted from cells and is important for adhesion, structure, signaling and growth. Type I collagen is the most abundant protein in the ECM and is known to direct tissue development and is therefore a key part of understanding the mechanism behind aseptic loosening. Methods. 3T3-fibroblasts were seeded in Dulbecco's Modified Eagle Medium (DMEM) and supplemented with 100mM ascorbic acid. Every 48hours cells were fed with DMEM and doped with Co and Cr ions until fixation. Sirius Red dye was used to bind to the type I collagen, then removed using NaOH and analysed using UV absorption to show relative amounts of collagen. Type I collagen gel was formed in the presence of Co and Cr ions with and without DMEM and the fibers were imaged using AFM. Results and Conclusions. Studies show a decrease in the collagen output of 3T3-fibroblasts with increasing concentration of Co ions, and low concentrations of Cr ions. Precipitation was also seen for Cr ions in the presence of DMEM which may explain the reduced effect of higher concentration of Cr ions in comparison to Co ions. Co and Cr ions do influence the ECM which will affect the bone re-modelling process. Further work will be performed to link these results to mineralisation mechanisms to quantitatively determine the impact of metal ion debris on the ECM and collagen fiber formation

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

Second-generation metal-on-metal (MoM) articulations in total hip arthroplasty (THA) were introduced in order to reduce wear-related complications. The current study reports on the serum cobalt levels and the clinical outcome at a minimum of 20 years following THA with a MoM (Metasul) or a ceramic-on-polyethylene (CoP) bearing.

Proponents of the biological theory of aseptic loosening have in recent years tended to concentrate on the production and distribution of particulate ultra-high-molecular-weight polyethylene (UHMWPE) debris around the potential joint space. However, mechanical loading of cemented implants with the differing elastic moduli of metal stems, polymethylmethacrylate (PMMA) cement and bone can result in relative micromotion, implying the potential for production of metal and PMMA particles from the stem-cement interface by fretting wear. In order to investigate the production and biological reactivity of debris from this interface, PMMA and metal particulate debris was produced by sliding wear of PMMA pins containing barium sulphate and zirconium dioxide against a Vaquasheened stainless steel counterface. This debris was characterised by SEM, energy-dispersive analysis by X-ray (EDAX) and image analysis, then added to cell cultures of a human monocytic cell line, U937, and stimulation of pro-osteolytic cytokines measured by ELISA. Large quantities of PMMA cement debris were generated by the sliding wear of PMMA pins against Vaquasheened stainless steel plates in the method developed for this study. Both cements stimulated the release of pro-osteolytic TNFα from the U937 monocytic cell line, in a dose-dependent fashion. There was a trend towards greater TNFα release with Palacos cement than CMW cement at the same dose. Palacos particles also caused significant release of IL-6, another pro-osteolytic cytokine, while CMW did not. The particulate cement debris produced did not stimulate the release of GM-CSF or IL1β from the U937 cells. These results may explain the cytokine pathway responsible for bone resorption caused by particulate PMMA debris. Radio-opaque additives are of value in surgical practice and clinical studies to quantify the relevance of these in vitro findings are required before the use of cement containing radio-opacifier is constrained