ARMD (Adverse Reaction to Metal Debris) is an increasingly recognised complication of metal on metal hip replacements. The MHRA (Medical and Healthcare Related Devices Agency) have advised a blood cobalt or chromium level above 7 mg/L is a threshold for further investigation, stating that “low levels are reassuring and strongly predict not having an adverse outcome”. Cross-sectional imaging should be performed when levels are above 7 mg/L. We have performed a study investigating the specificity and sensitivity of chromium and cobalt metal ion levels as a screening measure for ARMD. 79 ASR hip replacements were performed at our hospital and 75 (95%) of these underwent a Metal Artefact Reduction Sequence (MARS) MRI scan. All patients (64 hips) who had not undergone revision were invited to take part in this study. 57 patients with 62 hip replacements completed hip and activity scores, had blood cobalt and chromium ion level measurements and 3D-CT to measure acetabular component position. Acetabular component inclination (>50 degrees), small head size (< 51mm) and female gender were significantly correlated with raised chromium (Cr) and cobalt (Co) ion levels. An ARMD was detected using MRI in 18 (29%) of the hips in this study. The incidence of ARMD was significantly higher when chromium concentration was above 7 mg/l (p = 0.02). Chromium ion levels >7 mg/L had a sensitivity of 56% and specificity of 83% for ARMD, and cobalt ion levels >7 mg/L 56% and 76% respectively. 40 patients had cobalt levels <7 mg/L and 33 had chromium levels <7 mg/L, but 8 of these had an ARMD on MRI. All 8 patients had minimal symptoms (Oxford Hip Score ≥ 44 out of 48). The Medicines and Healthcare Products Regulatory Agency (MHRA) has recommended that cobalt and chromium levels be measured in patients with a metal-on-metal hip replacement and cross-sectional imaging performed when these levels are above 7 μg/L. This study has shown that by using this threshold, in patients with this implant combination, the sensitivity and specificity for the detection of ARMD is low and patients with soft tissue disease may be missed. Furthermore the presence of MRI detected ARMD, in the absence of significant clinical symptoms and with metal ion levels <7 μg/L is of concern. MoM implants at risk of failure are associated with raised cobalt and chromium levels. However metal ion analysis alone is not reliable as a screening tool for ARMD, which is often clinically “silent”. We recommend the routine use of MARS MRI as the safest method of ARMD diagnosis in patients with MoM implants.
Of the 76 hips that were MRI scanned, 27 (36%) had typical features of a MOM reaction. These were classified as mild in 10 (13%), moderate in 13 (17%) and severe in 4 (5%). 78 patients completed an OHS and the mean score was 21. The mean OHS was 29 pre-operatively in those that had been revised, 25 in patients with abnormal MRI findings and 20 in those with a normal MRI. 10 patients with abnormal MRIs had a near perfect OHS (15 or less)
Classification of osteoarthritis of the hip is fraught with difficulty Although different patterns of disease are recognised, there is no accepted classification or grading system. We aim to develop a classification system that reflects both the radiological changes, and the local disease process within the joint. After ethical permission and consent tissue was taken from 20 patients undergoing primary hip replacement surgery. Intra-operative tissue samples were taken from each patient and the steady state gene expression of several cytokines (TNF-α, IL1-β, IFN-γ, IL-6, RANKL and OPG) measured quantitatively using Taqman RT-PCR. Relative expression was calculated for each sample using standard curves and normalised to 18S expression. The technique was consistent with high correlations for repeated measures from the same tissue type (κ=0.99) and from different tissue types in the same joint (κ=0.92). Intra-observer (κ=0.93) and inter-observer (κ=0.89) reliability for the technique were also found to be high. Preoperative radiographs were scored by two independent observers and joint space narrowing, cysts, osteophytes and sclerosis noted in each of the DeLee-Charnley zones on the femoral and acetabular side. Based on these scores patients were then classified to either lytic or sclerotic type and subclassified into either hypertrophic or atrophic. Subgroup analysis of cytokine expression by radiographic type was performed. There were statically significant differences in expression of macrophage stimulating cytokines (IL-1γ and OPG) in the lytic group as compared to the sclerotic group (p<
0.05). Conversely, the sclerotic group expressed significantly higher levels of IL-6. Individuals with atrophic subtype demonstrated significantly higher levels of IL-1β and IL-6, but lower levels of IFN-γ Our results demonstrate greatly differing patterns of disease within osteoarthritic hip joints. These changes are reflected in radiographic appearances of osteoarthritis. Our proposed classification system can be used grade and classify osteoarthritis in a manner that reflects the disease process.
60 out of total series of 643 metal-on-metal hip replacements, carried out over the last nine years, have so far required revision, 13 for peri-prosthetic fracture and 47 for extensive, symptomatic, peri-articular soft-tissue changes. Dramatic corrosion of generally solidly fixed, cemented stems has been observed and is believed to have resulted in the release of high levels of cobalt chrome ions from the stem surface. The contribution of the metal-to-metal articulation is, as yet, unclear. Not including the fracture cases, plain films have demonstrated little or no abnormality to account for patients’ progressive symptoms. MRI scanning, on the other hand, utilising a technique designed to minimise implant artefact, has correlated very closely with findings at the time of revision surgery. The histological changes, typified by extensive lymphocytic infiltration and a severe vasculitis leading to, in some cases, extensive tissue necrosis are demonstrated and discussed. The failure of any of the existing protective mechanisms or regulatory restrictions to identify and limit the exposure of large numbers of patients to unsatisfactory implants has again been demonstrated.
In relation to the conduct of this study, one or more of the authors is in receipt of a research grant from a non-commercial source.
This study investigated the effects of wear particles, produced from a number of implant materials, at the bone-implant interface using a small animal model. Particles were prepared from metal, ceramic and polymer replacement joint components or implant grade stock by grinding the materials against a diamond embedded grinding pad. The mean diameter of the particles ranged from 1.5mm to 3.2mm. Sterilised particles were suspended in sterile saline containing 2% v/v male Sprague-Dawley serum at a concentration of 109 particles per ml. Seventy-two male Sprague-Dawley rats were assigned to twelve groups of six animals. A ceramic pin was inserted into the right tibia of each animal. Six groups were assigned a particle type with one group acting as vehicle control. 100ml of particle suspension or vehicle was injected into each knee joint at 8, 10 and 12 weeks following implantation and the animals were killed 2 weeks later. Of the remaining five groups, four were assigned a particle type and one was the vehicle control. These animals were injected with 100ml of particle suspension or vehicle at 20, 22 and 24 weeks following pin implantation and were killed 2 weeks later. The tibia and femora were removed, disarticulated and processed for histology. The total gap between pin and bone, including fibrous tissue, was measured. Specimens showed no signs of infection either clinically or in the histopathology. All materials tested produced lesions at the bone-implant interface. A significant difference was seen between metal injected vs. vehicle control animals and aluminium oxide injected vs. vehicle controls. Particles of stainless steel produced the greatest response and this finding may have implications for the use of metal on metal articulations aimed at eliminating polyethylene wear.
This study investigated the relationship between histological, clinical and radiological features of aseptically loose total joint replacements (TJRs) and synovial fluid levels of interleukin (IL)-1b, IL-6, IL-8 and IL-10. Tissue and synovial fluid samples were retrieved from patients undergoing primary (hip; n=15: knee; n=13), or revision of aseptically loose TJRs (hip; n=14: knee; n=9). The presence of inflammatory cells, blood vessels and wear debris in the tissue were assessed on a relative scale. Revision TJRs were assessed for sepsis, migration of the implant, gross loosening and the degree of radiolucency. Cytokine levels in the synovial fluid samples were determined by ELISA. All cytokines were increased in synovial fluid from revision TJRs compared to primary replacements, as were the degree of macrophage and giant cell infiltration (p<
0.01). There was a significant positive correlation between the presence of macrophages and giant cells with the levels of IL-1b, IL-8 and IL-10 (p<
0.05) but not IL-6. The amount of wear debris was related to the presence of macrophages and giant cells (p<
0.01) but not to any of the cytokines. There were no relationships between any of the clinical parameters and the presence of wear debris or the levels of any cytokine with the exception of IL-6 and gross loosening (p<
0.01). Similarly there were no differences between hips and knees for any of the parameters except IL-6, for which higher levels were found in hips (p<
0.05). The results suggest that macrophages and giant cells are responsible for the majority of IL-1b, IL-8 and IL-10 production but another cell type is contributing to IL-6 production. Furthermore, IL-6 does not fit the pattern of the other cytokines as it is upregulated in hip joints compared to knees and correlates with the presence of gross loosening. This may suggest a unique role for IL-6 that requires further investigation.