Metal-on-metal Hip Replacements Research Articles

Long-term Follow-up on Revisions of a Recalled Large Head Metal-on-metal Hip Prosthesis: A Single Surgeon Series.

In 2010, a recall was issued for a specific monoblock large head metal-on-metal (MoM) hip prosthesis due to short-term revision rates of 12%-13% (articular surface replacement, DePuy Orthopaedics, Inc., Warsaw, IN). High complication, infection, and rerevision rates for revised MoM implants have been reported. The purpose of the study is to report long-term outcomes and trend metal ion levels of this recalled MoM prosthesis from a single surgeon series. Retrospective chart review was performed on all patients that underwent revision of large MoM hip replacements between 2010 and 2015. Pre- and post-revision Harris Hip Score (HHS), cup abduction angles, anteversion angles, and cup sizes were compared. Survivorship and HHS were the primary outcomes measured; serum cobalt and chromium levels were secondary outcomes. Multivariate linear regression was used to examine the correlation between prerevision serum metal ion levels and HHS. A total of 24 hips (21 patients) met inclusion criteria. Mean time to revision was 4.12 years ± 1.1. Mean follow-up was 10.0 years (7-11.9 years). Mean HHS increased significantly after revision from 48.5 to 89.5 (P < .001). Higher prerevision cobalt levels were correlated with lower prerevision HHS (cobalt R= 0.25; chromium R= 0.3160). There was no correlation with prerevision cobalt (P= .2671) or chromium (P= .3160) with postrevision HHS. Most recent metal ion testing revealed a significant decrease in both cobalt (P= .0084) and chromium (P= .0115). Survival rate is 100%. Our study showed excellent survivorship and outcomes at 10 years. There were no failures for any reason including infection. This differs from previous studies and confirms excellent long-term results are possible with revision of this recalled MoM implant.

REVISION OF METAL-ON-METAL HIP ARTHROPLASTY WITH DUAL MOBILITY BEARINGS AND ACETABULAR COMPONENT RETENTION

In metal-on-metal (MoM) hip replacements or resurfacings, mechanical induced corrosion can lead to a local inflammatory response, pseudo tumours and elevated serum metal ions, requiring revision surgery.The size and diametral clearance of Anatomic (ADM) and Modular (MDM) Dual Mobility bearings matches that of certain MOM components. Presenting the opportunity for revision with exchange of the metal head for ADM/MDM bearings without removal of the acetabular component if it is well-fixed and appropriately positioned.Between 2012 and 2020, across two centres, 94 patients underwent revision of a MoM hip replacement or resurfacing. The mean age was 65.5 (33–87) years. In 53 patients (56.4%), the acetabular component was retained, and dual mobility bearings were used (DM); in 41 (43.6%) the acetabulum was revised (AR). DM was only considered where the acetabular component was satisfactorily positioned and well-integrated into bone, with no surface damage. Patients underwent clinical and radiographic follow-up to at least one-year (mean 42.4 (12–96) months).One (1.1%) patient died before one-year, for reasons unrelated to the surgery. In the DM group, two (3.8%) patients underwent further surgery; one (1.9%) for dislocation and one (1.9%) for infection. In the AR group, four (12.2%) underwent further procedures; two (4.9%) for loosening of the acetabular component and two (4.9%) following dislocations. There were no other dislocations in either group. In the DM group, operative time (68.4 v 101.5 mins, p&lt;0.001), postoperative drop in haemoglobin (16.6 v 27.8 g/L, p&lt;0.001), and length of stay (1.8 v 2.4 days, p&lt;0.001) were significantly lower. There was a significant reduction in serum metal ions postoperatively in both groups (p&lt;0.001 both Cobalt and Chromium) although there was no difference between groups for this reduction (p=0.674 Cobalt; p=0.186 Chromium).In selected patients with MoM hip arthroplasty, where the acetabular component is well-fixed, in a satisfactory position and there is no surface damage, the metal head can be exchanged for ADM/MDM bearings with retention of the acetabular prosthesis. Presenting significant benefits through a less invasive procedure, and a low risk of complications, including dislocation.

False profile view is independently associated with serum metal levels in patients with metal-on-metal hip arthroplasty.

Elevated levels of serum metal ions can be found in some patients with metal-on-metal (MoM) hip replacements. This study seeks to identify whether there is a significant association between the contact patch to rim distance (CPRD) and the anterior center edge angle (ACEA), respectively, and serum cobalt (Co) and chromium (Cr) levels in patients treated with unilateral MoM hip replacements by using standing anteroposterior and false profile view radiographs. This is a retrospective analysis on 53 patients with either unilateral ReCap or M2a-Magnum MoM hip replacements operated in 2006 or 2007. Univariate linear regression and multivariable linear regression (MLR) analyses were performed using the CPRD and ACEA along with risk factors for elevated serum levels of Co and Cr previously suggested in the literature as explanatory variables. Serum Co and Cr were measured using inductively coupled plasma mass spectrometry. The MLR model showed that the same three variables (gender, CPRD and ACEA) were significantly associated with serum levels of both Co and Cr explaining approximately half of the variation. A univariate analysis showed a polynomial association between both anteversion angle and the ACEA with serum levels of Co and Cr. The vertex of the polynomial function was located at approximately 20° and 40°, respectively. Gender, CPRD and ACEA are independently associated with serum levels of Co and Cr. Both ACEA and anteversion angles have optimae associated with low serum metal levels which may be useful for post-surgery evaluation of cup positioning.

Follow-up of Metal-on-Metal Hip Replacements at a Large District Hospital and the Implementation of Medicines and Healthcare Products Regulatory Agency Guidelines: A Review of 297 Patients.

BackgroundMedicines and Healthcare products Regulatory Agency (MHRA) guidance for patients with metal-on-metal (MoM) hip replacements was provided in 2012 and updated in 2017 to assist in the early detection of soft-tissue reactions due to metal wear debris. A large number of MoM hip replacements were undertaken at our hospital trust. A program of recall for all patients with MoM hip replacements was undertaken and MHRA guidelines were implemented. In this study, we aimed to investigate the effectiveness of the revised MHRA guidelines in the detection of early adverse reactions to metal debris and to re-evaluate the indications for metal artifact reduction sequence magnetic resonance imaging (MARS-MRI) and revision surgery.MethodsIdentification and recall of all patients with MoM hip replacements from 2001 were conducted by using theatre logs, patient records, clinical coding information, and consultant logbooks. Two senior arthroplasty consultants reviewed X-rays and patient records. Postal questionnaires were forwarded to patients, together with requests for general practitioners to complete cobalt and chromium blood tests. The two consultant-led review of MOM replacements was undertaken with further radiological investigations (X-rays, MARS-MRI) performed according to the 2017 guidance with support of consultant radiologists.ResultsOf 674 identified patients, 297 were available for review: 26 patients did not have MoM implants, 36 were untraceable, 59 refused follow-up, 87 moved out of area, 147 had died, and 22 already had revision. Of 297 patients, 126 were women and 171 were men; age range was 39 to 95 years (mean age, 69 years); 126 had resurfacing and 171 had MoM replacements. Twenty-six patients had elevated metal ions. Thirty-three patients underwent MARS-MRI: MARS-MRI results were positive in 17 and negative in 16. Of 17 patients with positive MARS-MRI, 10 patients were asymptomatic and seven were waiting revision.ConclusionsPositive MARS-MRI can often occur in the absence of elevated metal ion levels; elevated blood metal ion levels do not mean MARS-MRI will be positive. All patients with MoM replacements were at risk. It is imperative to assess patients regularly for symptoms that may raise clinical suspicion and maintain a low threshold to performing MARS-MRI.

Metal-on-metal hips: current status

One of the greatest technological advances in the history of medicine is the total joint replacement. Hip, knee, and shoulder replacements are routine throughout the world. They reduce pain in a cost-effective way and improve quality of life for millions of patients with end stage arthritis. Total hip replacement (THR) is considered a landmark surgery in modern medical history. The THR has developed with research and experimentation over the last 40–50 years with progressive improvement in materials used, fixation techniques, and peri-operative care. With improving life expectancy and increasing demand at a younger age, clinicians and scientists are always trying to find better performing implants to reduce the revision burden. This paper provides an up-to-date account of the relevant history of metal-on-metal (MoM) hips, problems associated with their use, current status, and guidance about how to continue surveillance of patients with MoM hip replacements.

Longitudinal Followup of Incidentally Detected Pseudotumors in Patients with Metal on Metal Implants: A Retrospective Study.

Background:This study describes the significance and temporal evolution of incidentally detected, presumed, metal-induced reactive periprosthetic masses in patients with metal on metal (MoM) hip arthroplasty and its management. The literature concerning the temporal evolution of these lesions is meagre and so it is still unclear, whether asymptomatic patients with periprosthetic collections should undergo revision.Materials and Methods:Patients with MoM hip replacements fitted with a recalled implant (ASR, DuPuy) often undergo magnetic resonance imaging with metal artifact reduction sequences to look for complications. From a cohort of 136 asymptomatic patients, with 181 MoM hips, hips with a mention of periprosthetic masses in their reports at first presentation, and a repeat scan within 6 months to 3 years were selected for this retrospective study. Patients with complications such as loosening, osteomyelitis, and muscle/tendon tears were excluded from the study, and the final study cohort consisted of 55 MoM hips and 61 periprosthetic masses. Ethics committee approval is not required in our institution for retrospective studies. The followup scans of each patient were compared, and the periprosthetic masses were described to have progressed, regressed, or remained unchanged.Results:Comparison revealed that 29 of the 61 reactive masses remained unchanged, 20 regressed, while only 12 showed progression. The study, therefore, has maximum power as the outcome of interest, i.e., regression or unchanged status of the pseudotumors, was seen in approximately 80% (more than half) of the study group. The P value of the study was < 0.005.Conclusion:Periprosthetic soft tissue masses are not uncommon in patients with MoM hips. The majority of them in asymptomatic individuals remain stable or regress in the short to medium term, and close followup or decisions on revision surgery may not be warranted in asymptomatic patients.

Outcome of revision arthroplasty for failed metal-on-metal total hip replacements; is there a relation with metal ions?

We aimed to assess the early outcome following revision arthroplasty for failed metal-on-metal (MoM) total hip replacements (THR) due to adverse reaction to metal debris (ARMD). We reviewed 106 consecutive revision arthroplasties. Case notes and radiological investigations were reviewed to assess the complications. Oxford Hip Score (OHS) and Euroqol (EQ-5D-3L) scores were used to assess the functional outcome and improvement of quality of life. At a mean follow-up of 20 months (12-48 months), the mean OHS was 28.7. Pain improved in 61% patients. A majority of patients were in level 2 for all the EQ-5D-3L dimensions. The overall complication rate was 16%. Survivorship free from further revision for any cause was 94.3% at 48 months. There was no correlation between pre-revision blood metal ions and the final outcome. Revision surgery for failed MoM hip replacement due to ARMD is associated with a relatively higher rate of complications and risk of chronic pain. There is poor correlation between serum metal ions and development of ARMD and outcome following revision surgery.

Scoring the Current Risk Stratification Guidelines in Follow-up Evaluation of Patients After Metal-on-Metal Hip Arthroplasty: A Proposal for a Metal-on-Metal Risk Score Supporting Clinical Decision-Making.

In the follow-up evaluation of patients with metal-on-metal (MoM) hip replacements, current evidence suggests that orthopaedic surgeons should avoid reliance on any single investigative tool. Current risk stratification guidelines can be difficult to interpret because they do not provide guidance when there are several risk factors in different groups (high and low risk). To improve the clinical utility of risk stratification guidelines, we designed a scoring system to assess the risk of revision. The study population consisted of 1,709 patients (1,912 hips) enrolled in a multicenter follow-up study of a recalled MoM hip replacement. Eleven scoring criteria were determined on the basis of existing follow-up algorithm recommendations and consisted of patient-related factors, symptoms, clinical status, implant type, metal ion levels, and radiographic imaging results. Forward stepwise logistic regression was conducted to determine the minimum set of predictive variables for the risk of revision and to assign variable weights. The MoM risk score for each hip was then created by averaging the weighted values of each predictive variable. Receiver operating characteristic curve analysis yielded good discrimination between all revised and unrevised hips, with an area under the curve of 0.82 (p < 0.001). The odds of revision for the group with a high MoM risk score were increased by 5.8-fold (95% confidence interval [CI], 3.1 to 11.0) relative to the moderate risk group and by 21.8-fold (95% CI, 9.9 to 48.0) compared with the low risk group. Although the use of MoM hip arthroplasty has been limited since 2010, we continue to be faced with the follow-up and risk assessment of thousands of patients who have not had a revision. As more knowledge about risk stratification is gained, the complexity of the algorithms is expected to increase. We propose the use of the MoM risk score as a tool to aid in the clinical decision-making process. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Balancing innovation and medical device regulation: the case of modern metal-on-metal hip replacements.

Due to problems with wear particle generation and subsequent loosening using conventional metal-on-polyethylene total hip replacements, there has been a shift toward alternative bearing systems, including metal-on-metal (MoM), for younger, more active patients with degenerative joint disease. Based on positive results from early short-term clinical studies, MoM hip replacements were readily adopted by orthopedic surgeons with thousands being implanted worldwide over the past decade. Unacceptably high revision rates reported by two national joint registries called into question the rigorousness of the regulatory approval process for these implants, particularly with respect to premarket data requirements to prove safety, effectiveness, and the appropriateness of the regulatory pathway chosen. The purpose of this review was to investigate the balance between facilitating the introduction of new medical technologies and the need to ensure safety and effectiveness through comprehensive regulatory assessment. The case of MoM hip replacement devices was used to frame the investigation and subsequent discussions. The regulatory approval processes and post-market surveillance requirements associated with three common MoM hip replacements (two resurfacings: the Birmingham and articular surface replacement and the articular surface replacement XL total hip replacement) were investigated. With respect to modern MoM hip replacement devices, the balance between facilitating the introduction of these new medical technologies and the need to ensure safety and effectiveness through comprehensive regulatory assessment was not achieved. The lessons learned from these experiences have application beyond joint replacements to the introduction of new medical technologies in general, particularly for those who have a significant potential for harm. In this regard, a series of recommendations have been developed to contribute to the evolution of the medical device regulatory process.

CORR Insights(®): Are Females at Greater Risk for Revision Surgery After Hip Resurfacing Arthroplasty With the Articular Surface Replacement Prosthesis?

Background Female patients undergoing hip resurfacing arthroplasties may be at greater risk of revision surgery than males, but it is unclear whether this is related to sex or other factors. We focused our analysis on data from a prospective multicenter cohort study monitoring the ASRTM hip resurfacing arthroplasty prosthesis on the potential association of sex on patient-reported outcome measures (PROMs), metal ion levels, revision surgery, and presence of adverse local tissue reaction. As thousands of patients with the ASRTM prosthesis are still undergoing followup it is critical to optimize the protocol for monitoring these patients.

Mesures sanguines répétées des ions métalliques chez les patients porteurs d’une prothèse totale de hanche métal-métal (ARS™) bilatérale

BackgroundBlood metal ion measurements have become a cornerstone in the surveillance of metal-on-metal (MoM) hip replacements. Interpretation of these levels in patients with bilateral MoM hip replacements, however, is challenging. We therefore asked (1) if there is a clinically significant change in whole blood (WB) Co or Cr levels in repeated WB assessment in patients operated on with bilateral ASR hip replacements, and (2) what proportion of patients has WB Co or Cr level below the previously established safe upper limits (SUL) (Co<5.0μg/L, Cr<7.4μg/L) in the repeated WB metal ion assessment. HypothesisWe hypothesized that there is a significant difference between repeated Co and Cr level measurement performed within 1 year±4 months interval in patients with bilateral ASR hip replacements. Materials and methodsWe identified all patients (n=139) who had received bilateral ASR hip replacements (278 hips). Patients (n=76, 152 hips) who had undergone two blood metal ion measurements within eight to sixteen months’ time interval were included in the study analysis. Study cohort included 38 patients with bilateral ASR hip resurfacings (mean age: 53 years, median follow-up 4.6 years, median femoral diameter 51mm) and 38 patients with bilateral ASR XL total hip replacements (mean age: 60 years, median follow-up: 3.6 years, median femoral diameter: 49mm). ResultsThere was no significant change in Co and Cr levels between the repeated measurements in the HR cohort. Both Co and Cr was significantly higher in the THR cohort in the repeated measurement (Co: 8.3μg/L vs 12.6μg/L, Cr: 3.15μg/L vs 3.4μg/L, both P<0.001). WB Co and Cr levels remained below SUL and within their initial values during a mean one-year measurement interval in the majority of patients with bilateral high risk HR device. In contrast to this, 21.1 % of patients with THRs had WB Co ion levels exceeding the SUL in the first measurement. WB Co values significantly increased over the measurement interval in the THR group. DiscussionAnnual blood metal ion measurement is not useful in patients with bilateral hip resurfacings who have undergone at least one preliminary screening including both metal ion measurement and cross-sectional imaging. It seems, however, to be beneficial in patients with bilateral high risk MoM THR. Level of evidenceLevel III (retrospective comparative study).

Prevalence of Failure due to Adverse Reaction to Metal Debris in Modern, Medium and Large Diameter Metal-on-Metal Hip Replacements--The Effect of Novel Screening Methods: Systematic Review and Metaregression Analysis.

Metal-on-metal (MoM) hip replacements were used for almost a decade before adverse reactions to metal debris (ARMD) were found to be a true clinical problem. Currently, there is a paucity of evidence regarding the usefulness of systematic screening for ARMD. We implemented a systematic review and meta-analysis to establish the prevalence of revision confirmed ARMD stratified by the use of different screening protocols in patients with MoM hip replacements. Five levels of screening were identified: no screening (level 0), targeted blood metal ion measurement and/or cross-sectional imaging (level 1), metal ion measurement without imaging (level 2), metal ion measurement with targeted imaging (level 3) and comprehensive screening (both metal ions and imaging for all; level 4). 122 studies meeting our eligibility criteria were included in analysis. These studies included 144 study arms: 100 study arms with hip resurfacings, 33 study arms with large-diameter MoM total hip replacements (THR), and 11 study arms with medium-diameter MoM THRs. For hip resurfacing, the lowest prevalence of ARMD was seen with level 0 screening (pooled prevalence 0.13%) and the highest with level 4 screening (pooled prevalace 9.49%). Pooled prevalence of ARMD with level 0 screening was 0.29% and with level 4 screening 21.3% in the large-diameter MoM THR group. In metaregression analysis of hip resurfacings, level 4 screening was superior with regard to prevalence of ARMD when compared with other levels. In the large diameter THR group level 4 screening was superior to screening 0,2 and 3. These outcomes were irrespective of follow-up time or study publication year. With hip resurfacings, routine cross-sectional imaging regardless of clinical findings is advisable. It is clear, however, that targeted metal ion measurement and/or imaging is not sufficient in the screening for ARMD in any implant concepts. However, economic aspects should be weighed when choosing the preferred screening level.

Repeated metal ion measurement in patients with bilateral metal on metal (ASR™) hip replacements

BackgroundBlood metal ion measurements have become a cornerstone in the surveillance of metal-on-metal (MoM) hip replacements. Interpretation of these levels in patients with bilateral MoM hip replacements, however, is challenging. We therefore asked (1) if there is a clinically significant change in whole blood (WB) Co or Cr levels in repeated WB assessment in patients operated on with bilateral ASR hip replacements, and (2) what proportion of patients has WB Co or Cr level below the previously established safe upper limits (SUL) (Co<5.0μg/L, Cr<7.4μg/L) in the repeated WB metal ion assessment. HypothesisWe hypothesized that there is a significant difference between repeated Co and Cr level measurement performed within one year±4 months interval in patients with bilateral ASR hip replacements. Materials and methodsWe identified all patients (n=139) who had received bilateral ASR hip replacements (278 hips). Patients (n=76, 152 hips) who had undergone two blood metal ion measurements within eight to sixteen months’ time interval were included in the study analysis. Study cohort included 38 patients with bilateral ASR hip resurfacings (mean age 53 years, median follow-up 4.6 years, median femoral diameter 51mm) and 38 patients with bilateral ASR XL total hip replacements (mean age 60 years, median follow-up 3.6 years, median femoral diameter 49mm). ResultsThere was no significant change in Co and Cr levels between the repeated measurements in the HR cohort. Both Co and Cr were significantly higher in the THR cohort in the repeated measurement (Co: 8.3μg/L vs. 12.6μg/L, Cr: 3.15μg/L vs. 3.4μg/L, both P<0.001). WB Co and Cr levels remained below SUL and within their initial values during a mean one-year measurement interval in the majority of patients with bilateral high risk HR device. In contrast to this, 21.1% of patients with THRs had WB Co ion levels exceeding the SUL in the first measurement. WB Co values significantly increased over the measurement interval in the THR group. DiscussionAnnual blood metal ion measurement is not useful in patients with bilateral hip resurfacings who have undergone at least one preliminary screening including both metal ion measurement and cross-sectional imaging. It seems, however, to be beneficial in patients with bilateral high risk MoM THR. Level of evidenceLevel III (retrospective comparative study).

Gluteal muscle fatty atrophy is not associated with elevated blood metal ions or pseudotumors in patients with a unilateral metal-on-metal hip replacement

Background and purpose — There are no international guidelines to define adverse reaction to metal debris (ARMD). Muscle fatty atrophy has been reported to be common in patients with failing metal-on-metal (MoM) hip replacements. We assessed whether gluteal muscle fatty atrophy is associated with elevated blood metal ion levels and pseudotumors.Patients and methods — 263 consecutive patients with unilateral ASR XL total hip replacement using a posterior approach and with an unoperated contralateral hip were included in the study. All patients had undergone a standard screening program at our institution, including MRI and blood metal ion measurement. Muscle fatty atrophy was graded as being absent, mild, moderate, or severe in each of the gluteal muscles.Results — The prevalance of moderate-to-severe gluteal muscle atrophy was low (12% for gluteus minimus, 10% for gluteus medius, and 2% for gluteus maximus). Muscle atrophy was neither associated with elevated blood metal ion levels (> 5 ppb) nor with the presence of a clear (solid- or mixed-type) pseudotumor seen in MRI. A combination of moderate-to-severe atrophy in MRI, elevated blood metal ion levels, and MRI-confirmed mixed or solid pseudotumor was rare. Multivariable regression revealed that “preoperative diagnosis other than osteoarthrosis” was the strongest predictor of the presence of fatty atrophy.Interpretation — Gluteal muscle atrophy may be a clinically significant finding with influence on hip muscle strength in patients with MoM hip replacement. However, our results suggest that gluteal muscle atrophy seen in MRI is not associated with either the presence or severity of ARMD, at least not in patients who have been operated on using the posterior approach.

Genetic alterations in periprosthetic soft-tissue masses from patients with metal-on-metal hip replacement

Adverse soft tissue reactions in patients with metal-on-metal (MoM) hip replacement are associated with cobalt (Co) and chromium (Cr) particles released from the implant. Exposing the patients to long periods of increased metal ions concentrations resulting from the wear of these implants poses an increased risk of genotoxicity/mutagenicity. A variable proportion of patients develop periprosthetic soft-tissue masses or pseudotumors at the site of the implant. There is a concern that exposure to increased metal ions could increase the risk of cancer. In order to investigate whether the periprosthetic soft-tissue mass harbours any cancer- related genetic alterations, we studied DNA isolated from periprosthetic tissues of 20 patients with MoM hip replacement, for copy number alterations and mutations in hotspot regions of 50 cancer genes using aCGH and amplicon-based next generation sequencing.Our results showed copy number gains at 12q14.3 and 21q21.1in tumour from patient diagnosed with liposarcoma. Copy number alterations in periprosthetic tissues were seen in three other patients, one had a region of gain at 9q24.1 affecting JAK2 and INSL6, and two patients had region of gain at 6p21.1, affecting RUNX2. Mutation analysis showed V1578del mutation in NOTCH1 in two patients. The copy number alterations and mutations seen in periprosthetic soft-tissue masses are earlier reported in either haematological malignancies or in osteoblast related bone dysplasia. The presence of genetic anomalies was associated with longer in-situ time of the implant. Our findings warrant the need of similar studies in larger patient cohorts to evaluate the risk of development of neoplastic alterations in periprosthetic tissues of patients with MoM hip replacement.

Feasibility of asymmetric flow field-flow fractionation coupled to ICP-MS for the characterization of wear metal particles and metalloproteins in biofluids from hip replacement patients.

Hip replacements are used to improve the quality of life of people with orthopaedic conditions, but the use of metal-on-metal (MoM) arthroplasty has led to poor outcomes for some patients. These problems are related to the generation of micro- to nanosized metal wear particles containing Cr, Co or other elements, but the current analytical methods used to investigate the processes involved do not provide sufficient information to understand the size or composition of the wear particles generated in vivo. In this qualitative feasibility study, asymmetric flow field-flow fractionation (AF(4)) coupled with inductively coupled plasma mass spectrometry (ICP-MS) was used to investigate metal protein binding and the size and composition of wear metal particles present in serum and hip aspirates from MoM hip replacement patients. A well-established HPLC anion exchange chromatography (AEC) separation system coupled to ICP-MS was used to confirm the metal-protein associations in the serum samples. Off-line single particle ICP-MS (spICP-MS) analysis was used to confirm the approximate size distribution indicated by AF(4) of the wear particles in hip aspirates. In the serum samples, AF(4) -ICP-MS suggested that Cr was associated with transferrin (Tf) and Co with albumin (Alb) and an unidentified species; AEC-ICP-MS confirmed these associations and also indicated an association of Cr with Alb. In the hip aspirate sample, AF(4)-ICP-MS suggested that Cr was associated with Alb and Tf and that Co was associated with Alb and two unidentified compounds; AEC analysis confirmed the Cr results and the association of Co with Alb and a second compound. Enzymatic digestion of the hip aspirate sample, followed by separation using AF(4) with detection by UV absorption (280nm), multi-angle light scattering and ICP-MS, suggested that the sizes of the Cr-, Co- and Mo-containing wear particles in a hip aspirate sample were in the range 40-150nm. Off-line spICP-MS was used to confirm these findings for the Co- and Cr-containing nanoparticles. Whilst limited in scope, the results are sufficient to show the interaction of ions with transport proteins and give an indication of particle size, providing useful pathological indices. As such, the methods indicate a new way forward for in vivo investigation of the processes which lead to tissue necrosis and hip loosening in patients with MoM hip replacements.

Good sensitivity and specificity of ultrasound for detecting pseudotumors in 83 failed metal-on-metal hip replacements

Background and purpose — Ultrasound is used for imaging of pseudotumors associated with metal-on-metal (MoM) hips. Ultrasound has been compared with magnetic resonance imaging, but to date there have been no studies comparing ultrasound findings and revision findings. Methods — We evaluated the sensitivity and specificity of preoperative ultrasound for detecting pseudotumors in 82 patients with MoM hip replacement (82 hips). Ultrasound examinations were performed by 1 of 3 musculoskeletal radiologists, and pseudotumors seen by ultrasound were retrospectively classified as fluid-filled, mixed-type, or solid. Findings at revision surgery were retrieved from surgical notes and graded according to the same system as used for ultrasound findings. Results — Ultrasound had a sensitivity of 83% (95% CI: 63–93) and a specificity of 92% (CI: 82–96) for detecting trochanteric region pseudotumors, and a sensitivity of 79% (CI: 62–89) and a specificity of 94% (CI: 83–98) for detecting iliopsoas-region pseudotumors. Type misclassification of pseudotumors found at revision occurred in 8 of 23 hips in the trochanteric region and in 19 of 33 hips in the iliopsoas region. Interpretation — Despite the discrepancy in type classification between ultrasound and revision findings, the presence of pseudotumors was predicted well with ultrasound in our cohort of failed MoM hip replacements.

The relationship between the number of modularities and serum ions across different designs of metal on metal hip arthroplasty

s / International Journal of Surgery 12 (2014) S13eS117 S61 Results: The mechanism of injury was either due to a rugby tackle or fall from a bicycle. The majority of our cohort was male 86% with mean age 38 at time of surgery. All patients received physiotherapy sessions and been followed for 3-6 months. Post-operatively there were no significant difference in mean CC between operated and normal contralateral side. (12.2 vs 11.9 mm) (P<0.5). The median of quick DASH and ASES scores were 15.9 & 79.99 respectively. All the patients were satisfied with no complications recorded. Conclusions: Arthroscopic dog bone tight rope fixation of the ACJ is showing significant promise with minimal scarring and promising functional outcomes, good radiological outcomes, short post-operative stays and a low rate of complications. 0727: THE RELATIONSHIP BETWEEN THE NUMBER OF MODULARITIES AND SERUM IONS ACROSS DIFFERENT DESIGNS OF METAL ON METAL HIP ARTHROPLASTY Samer Mahmoud , Salam Ismael , Ibrahim Malek , D. woodnut , Alun Jones , Steve Jones . Royal National Orthopaedic Hospital, London, UK; University Hospital of Wales, Cardiff, UK; Morriston Hospital, Swansea, UK; 4 St George Hospital, London, UK. Introduction: To assess the relationship between serum ion levels and modularity across different metal on metal (MOM) arthroplasty designs. Methods: A cohort of 616 metal on metal hip replacement patients with similar bearing materials divided based on modularity design (number of articulating surfaces) into 4 groups: resurfacing BHR, Midhead replacements BMHR, Non-cemented stem MOM Hip replacement and the R3 with 3 bearing surfaces (115, 108, 355 and 38 patients respectively). Serum Cobalt and Chromium levels were assessed for each group and multivariant analysis used to create a regression model. Results: Mean time between the procedures and the blood results for the BHR, BMHR, non-cemented stem THR and R3 groups were 40, 35.5, 41.7 and 36.6 months respectively. After adjusting for other potential confounders like head size and gender there was liner relationship between number of articulations and S. Cobalt with positive coefficient values started from 0.25 in BMHR to 0.4 in R3 (P value<0.000:R21⁄411.65). Gender is a positive influence factor, which increases relationship linearity across all designs (P value<0.000:R21⁄413) S. Chromium did not fit the regression model as S. cobalt. Conclusions: There is statistically significant positive proportional relationship between increasedmodularity of MOM hip implants and S. Cobalt accumulation in patients' blood samples. 0731: GETTING TO GRIPS WITH THE BEST PRACTICE TARIFF FOR NECK OF FEMUR FRACTURES, EXPERIENCES FROM A MAJOR TRAUMA CENTRE: A COMPLETED AUDIT LOOP Iain Rankin , Amy Bibby, Reza Jenabzadeh, Dylan Griffiths, Rajarshi Bhattacharya. Department of Trauma and Orthopaedics, St Mary's Hospital, Imperial College Healthcare NHS Trust, London, UK. Introduction: The Best Practice Tariff (BPT) introduced in 2010 aims to financially incentivize hospitals to optimize management of patients with neck of femur (NOF) fractures, utilizing a multidisciplinary approach against set criteria. Major Trauma Centres face challenges in the prioritisation of major trauma patients against fractured NOF patients. This audit examined compliance at a regional Major Trauma Centre, managing acute admissions in conjunction with transfers from a second site within the same trust, prior to and following implementation of a NOF Action Group. Methods: A retrospective audit of our compliance to BPT was conducted for the months of April December 2012, repeated January September 2013 following implementation of a NOF Action Group aimed to improve workflow. Results: 237 patients in 2012 and 236 patients in 2013 were eligible for BPT. Implementation of a NOFAction Group improved outcomes: BPT in all criteria increased from 46.8% to 71.2%; (p<0.001), with the most notable improvement in the rates for time to theatre <36 hours 57.6% to 80.5% (p<0.001). The financial implications were an estimated additional £77,235 for the trust. Conclusions: Implementation of a NOF Action Group improves compliance with BPT in a Major Trauma Centre, despite the challenges faced. 0739: THE ROLE OF EXOGEN IN NON-UNIONS, DOES IT SHOW ANY CLINICAL BENEFIT IN A LARGE DISTRICT GENERAL HOSPITAL? Nader Ibrahim , Devendra Mahadevan, Ramanathan Natarajan, James Rudd, William Groom. Northampton General Hospital, Northampton,

CoCr wear particles generated from CoCr alloy metal-on-metal hip replacements, and cobalt ions stimulate apoptosis and expression of general toxicology-related genes in monocyte-like U937 cells

Cobalt-chromium (CoCr) particles in the nanometre size range and their concomitant release of Co and Cr ions into the patients' circulation are produced by wear at the articulating surfaces of metal-on-metal (MoM) implants. This process is associated with inflammation, bone loss and implant loosening and led to the withdrawal from the market of the DePuy ASR™ MoM hip replacements in 2010. Ions released from CoCr particles derived from a resurfacing implant in vitro and their subsequent cellular up-take were measured by ICP-MS. Moreover, the ability of such metal debris and Co ions to induce both apoptosis was evaluated with both FACS and immunoblotting. qRT-PCR was used to assess the effects on the expression of lymphotoxin alpha (LTA), BCL2-associated athanogene (BAG1), nitric oxide synthase 2 inducible (NOS2), FBJ murine osteosarcoma viral oncogene homolog (FOS), growth arrest and DNA-damage-inducible alpha (GADD45A). ICP-MS showed that the wear debris released significant (p<0.05) amounts of Co and Cr ions into the culture medium, and significant (p<0.05) cellular uptake of both ions. There was also an increase (p<0.05) in apoptosis after a 48h exposure to wear debris. Analysis of qRT-PCR results found significant up-regulation (p<0.05) particularly of NOS2 and BAG1 in Co pre-treated cells which were subsequently exposed to Co ions+debris. Metal debris was more effective as an inducer of apoptosis and gene expression when cells had been pre-treated with Co ions. This suggests that if a patient receives sequential bilateral CoCr implants, the second implant may be more likely to produce adverse effects than the first one.

Effects of cobalt and chromium ions at clinically equivalent concentrations after metal-on-metal hip replacement on human osteoblasts and osteoclasts: Implications for skeletal health

Metal-on-metal hip replacement (MOMHR) using large diameter bearings has become a popular alternative to conventional total hip arthroplasty, but is associated with elevated local tissue and circulating levels of chromium (Cr) and cobalt (Co) ions that may affect bone health. We examined the effects of acute and chronic exposure to these metals on human osteoblast and osteoclast formation and function over a clinically relevant concentration range previously reported in serum and within hip synovial fluid in patients after MOMHR. SaOS-2 cells were cultured with Co(2+), Cr(3+) and Cr(6+) for 3 days after which an MTS assay was used to assess cell viability, for 13 days after which alkaline phosphatase and cell viability were assessed and for 21 days after which nodule formation was assessed. Monocytes were isolated from human peripheral blood and settled onto dentine disks then cultured with M-CSF and RANKL plus either Co(2+), Cr(3+) or Cr(6+) ions for 21 days from day 0 or between days 14 and 21. Cells were fixed and stained for TRAP and osteoclast number and amount of resorption per dentine disk determined. Co(2+) and Cr(3+) did not affect osteoblast survival or function over the clinically equivalent concentration range, whilst Cr(6+) reduced osteoblast survival and function at concentrations within the clinically equivalent serum range after MOMHR (IC(50) =2.2 μM). In contrast, osteoclasts were more sensitive to metal ions exposure. At serum levels a mild stimulatory effect on resorption in forming osteoclasts was found for Co(2+) and Cr(3+), whilst at higher serum and synovial equivalent concentrations, and with Cr(6+), a reduction in cell number and resorption was observed. Co(2+) and Cr(6+) within the clinical range reduced cell number and resorption in mature osteoclasts. Our data suggest that metal ions at equivalent concentrations to those found in MOMHR affect bone cell health and may contribute to the observed bone-related complications of these prostheses.