to determine the prevalence of asymptomatic pseudotumours after MoMHRA; and to measure Co and Cr ion levels as well as lymphocyte proliferation responses to Ni, Co and Cr (the principal elements in the CoCr alloy used in MoMHRA) in MoMHRA patients with and without asymptomatic pseudotumours.
Metal Ion Levels – The presence of pseudotumour was associated with significantly higher median serum cobalt levels (9.2mg/L vs. 1.9mg/L, p<
0.001), chromium levels (12.0mg/L vs. 2.1mg/L, p<
0.001), hip aspirate cobalt levels (1182 mg/L vs. 86.2mg/L, p=0.003), and aspirate chromium levels (883mg/L vs. 114.8mg/ L, p=0.006), as well as with inferior functional scores (OHS 41 vs. 47 p<
0.001). There was no significant difference in acetabular cup inclination angle (p=0.51). Lymphocyte Reactivity: A higher incidence and level of enhanced lymphocyte reactivity to Ni (p=0.001), but not to Co or Cr (the principal elements in the CoCr alloy used in metal-on-metal hip resurfacing implants), was found in patients with MoMHRA compared to the patients without MoM implants. However, lymphocyte reactivity to Co, Cr and Ni did not significantly differ in patients with pseudotumours compared to those patients without pseudotumours. Conclusion: The prevalence of asymptomatic pseudotumours in females was high, especially in females with bilateral MoMHRA implants (30%). The patients with ‘asymptomatic’ pseudotumours were in fact mildly symptomatic. Lymphocyte reactivity to Co, Cr and Ni did not differ in patients with pseudotumour compared to those patients without pseudotumours, suggesting that systemic hypersensitivity type IV reactions, mediated by lymphocyte reactivity to these metals, is not the dominant mechanism in pathogenesis of the soft tissue pseudotumours. Furthermore, pseudotumours were not detected in those patients who had normal levels of cobalt and chromium ions. This suggests that pseudotumours do not occur if MoM articulations are well functioning. Therefore, pseudotumours are likely to be a biological consequence of the large amount of metal debris generated in vivo due to excessive wear.
Our aim was to investigate the molecular features of progressive severities of cartilage damage, within the phenotype of Anteromedial Gonarthrosis (AMG). Ten medial tibial plateau specimens were collected from patients undergoing unicompartmental knee replacements. The cartilage within the area of macroscopic damage was divided into equal thirds: T1(most damaged), to T3 (least damaged). The area of macroscopically undamaged cartilage was taken as a 4th sample, N. The specimens were prepared for histological (Safranin-O and H&
E staining) and immunohistochemical analysis (Type I and II Collagen, proliferation and apoptosis). Immunoassays were undertaken for Collagens I and II and GAG content. Real time PCR compared gene expression between areas T and N. There was a decrease in OARSI grade across the four areas, with progressively less fibrillation between areas T1, T2 and T3. Area N had an OARSI grade of 0 (normal). The GAG immunoassay showed decreased levels with increasing severity of cartilage damage (p<
0.0001). There was no significant difference in the Collagen II content or gene expression between areas. The Collagen I immunohistochemistry showed increased staining within chondrocyte pericellular areas in the undamaged region (N) and immunoassays showed that the Collagen I content of this macroscopically and histologically normal cartilage, was significantly higher than the damaged areas (p<
0.0001). Furthermore, real time PCR showed a significant increase in Collagen I expression in the macroscopically normal areas compared to the damaged areas (p=0.04). In AMG there are distinct areas, demonstrating progressive cartilage loss. We conclude that in this phenotype the Collagen I increase, in areas of macroscopically and histologically normal cartilage, may represent very early changes of the cartilage matrix within the osteoarthritic disease process. This may be able to be used as an assay of early disease and as a therapeutic target for disease modification or treatment.
Despite the satisfactory short-term implant survivor-ship, there is an increasing concern that the metal-on-metal hip resurfacing arthroplasty (MoMHRA) release large amount of very small wear particles and metal ions. The periprosthetic soft-tissue masses such as pseudotumours are being increasingly reported. These were found be locally destructive, requiring revision surgery in most patients. It has been suggested that either an immune reaction or cytotoxic effect of chromium(Cr) or cobalt(Co) may play a role in its aetiology. However, the effect of the phagocytosis of implant-associated metal nanoparticles on macrophages has not been elucidated. The aim of this study was to investigate the in vitro viability and proliferative response of murine macrophages to clinically relevant metal nanoparticles and ions.
At the end of day 1 and 4, two methods were used to quantify cell proliferation and viability. The AlamarBlue assay(Invitrogen) incorporates a fluorimetric growth indicator and the fluorescence signal correlates with metabolic activity of the cells. LIVE/DEAD stain kit(Molecular Probes) contains two fluorescent dyes to stain living cells green and dead cells red. The viability was calculated by the number of live cells divided by total cell numbers. Inter-group comparisons were performed using one-way ANOVA with Tukey post hoc test. Differences at p<
0.05 were considered to be significant.
Recently, a series of locally destructive soft tissue pseudotumour has been reported in patients following metal-on-metal hip resurfacing arthroplasty (MoMHRA), requiring revision surgery in a high percentage of patients. Based on the histological evidence of lymphocytic infiltration, a delayed hypersensitivity reaction to nickel (Ni), chromium (Cr) or cobalt (Co) has been suggested to play a role in its aetiology. The aim of this study was to investigate the incidence and level of hypersensitivity reaction to metals in patients with pseudotumour.
Group 1: MoMHRA patients with pseudotumours, detected on the ultrasound and confirmed with MRI (n=6, 5 F:1 M, mean age 53 years); Group 2: MoMHRA patients without pseudotumours (n=13, 7 F:6 M, mean age 55 years); and Group 3: age-matched control subjects without metal implants (n=6, 4 F:2 M, mean age 54 years). Lymphocyte transformation tests (LTT) were used to measure lymphocyte proliferation responses to metals. Peripheral blood mononuclear cells were isolated from heparinized blood samples using standard Ficoll–Hypaque® (Pharmacia). The PBMC were cultured at a cell density of 106 cells/mL. Culture was set up in the presence of either:
medium alone; nickel chloride (Sigma; 10-4M-10-6M); cobalt chloride (10-4M-10-6M); and chromium chloride (10-4M-10-6M). After 5 days of culture, cells were pulsed with [3H]-thymidine and proliferation was assessed by scintillation counting. The stimulation index (SI) was calculated by the ratio of mean counts per minute of stimulated to unstimulated cultures. A SI value of greater than 2.0 was interpreted as a positive result.
Tribological studies of hip arthroplasty suggest that larger diameter metal-on-metal (MOM) articulations would produce less wear than smaller diameter articulations. Other advantages using these large femoral heads implants include better stability with lower dislocation rates and improved range of motion. The aim of the present study was to compare chromium (Cr), cobalt (Co) and titanium (Ti) ion concentrations up to 1-year after implantation of different large diameter MOM total hip arthroplasty (THA).
Statistical group comparison revealed significant difference for Cr (p=0.006), Co (p=0.047) and Ti (p=<
0.001). With Biomet implants presenting the best results for Cr and Co and Zimmer the highest Ti level.
Metal on Metal Hip Resurfacing Arthroplasty (MoMHRA) has gained popularity due to its perceived advantages of bone conservation and relative ease of revision to a conventional THR if it fails. Known MoMHRA-associated complications include femoral neck fracture, avascular necrosis/collapse of the femoral head/neck, aseptic loosening and soft tissue responses such as ALVAL and pseudotumours. This study’s aim was to assess the functional outcome of failed MoMHRA revised to THR and compare it with a matched cohort of primary THRs.
Patello-femoral instability (PFI) affects 40 individuals per 100,000 population and causes significant morbidity. The causes of patello-femoral instability are multi-factorial, and an isolated anatomical abnormality does not necessarily indicate instability. Patello-femoral subluxation ranges from 0% (stable patella tracking) to 100% (dislocation) and there is an established relationship between the amount of subluxation and anterior knee pain. Traditionally, magnetic resonance (MR) imaging and standard radiographs are used to guide the clinician towards a suitable corrective procedure for PFI. The multi-factorial nature of patello-femoral instability is not addressed with current imaging techniques. This study aims to address which anatomical variables assessed on MR images are most relevant to patello-femoral subluxation. This information will aid surgical decision making, particularly in selecting the most appropriate reconstructive surgery. A retrospective analysis of MR studies of 60 patients with suspected patello-femoral instability was performed. All patients were graded for degree of subluxation using a dynamic MR scan. The patient scans were assessed for the presence of a specific range of anatomical variables:
patella alta, (modified Insall-Salvatti) patella type (Wiberg classification) trochlea sulcus angles for bone and cartilage surfaces the distance of the vastus medialis obliquis (VMO) muscle from the patella trochlea and patella cartilage thickness the horizontal distance between the tibial tubercle and the midpoint of the femoral trochlea (TTD) patella engagement – the percentage of the patella height that is captured in the trochlea groove in full extension. The Wilk’s Lambda test for multi-variate analysis was used to establish whether any relationship was present between the degree of patello-femoral instability and bony or soft tissue anatomical variables. Non-parametric statistical tests were applied across the groups and within the groups to assess their relative significance. The following variables showed a significant relationship with patellofemoral subluxation; distance of the VMO from the patella (<
0.001), TTD (<
0.001), patella engagement (0.001), sulcus angles (0.004) and patella alta (0.005). This study agrees with previous work showing a significant correlation between subluxation and trochlea sulcus angle and TTD. This is the first study to establish a significant correlation between patella engagement and radiological instability. The lower the percentage engagement of the patella in the trochlea, the greater the degree of patello-femoral instability. Patella engagement showed a more significant relationship with subluxation than patella alta. We report a new method of predicting patello-femoral instability by measuring the overlap of the patella in the trochlea groove.
100% of medial compartments showed full thickness anteromedial loss with preservation of the posteromedial cartilage. When present, the meniscus was extruded in 96% of cases. 90% of lateral compartments were normal and none had full thickness cartilage loss. However 10% showed high signal in the tibial plateau. There was a highly reproducible pattern of osteophyte formation; 94% posteromedial and posterolateral aspect of medial femoral condyle; 90% medial tibial; 80% medial femoral and 84% lateral intercondylar notch.
patients’ pre-operative demographics for age, weight, height, BMI, intraoperative variables such as the operating surgeon (n=2), insert and component sizes, and clinical assessment criteria including pre-operative and five-year post-operative Oxford knee (OKS) and Tegner (TS) scores.
In finite element (FE) analysis of long bones it is now common practice to calculate the material properties based on CT data. Although a unique material property is calculated for each element, assigning each element an individual material property results in excessively large models. To avoid this, it is usual to group the elements based on their material properties and to assign each group a single material property (Zannoni 1998). No study has analysed the effect the number of material properties used in a long bone FE model has on the accuracy of the results. The aim of this study was to evaluate the variation in the calculated mechanical environment as a function of the number of material properties used in an FE model. An FE mesh of a cadaveric human tibia containing 47,696 ten-node tetrahedron elements and 75,583 nodes was created using CT scans. Material properties were calculated for each element of the mesh based on previous work (Rho 1995, 1996). Eleven FE models were created by varying the number of groups (1, 2, 4, 8, 16, 32, 64, 128, 256, 512, 1024) the elements were divided into. A single material property was assigned to each group. All models were subject to an axial point load of 300N applied on the medial condyle of the tibial plateau while the distal end was fixed. The variation in maximum and minimum principal strains and deflections, at 17 well distributed surface nodes and at 65 randomly distributed nodes within the bone were plotted against the number of element groups. The total strain energy was also plotted against the number of groups. The errors for strain, deflection, and total strain energy were calculated for each model assuming that the model using 1024 element groups was accurate. The parameter to converge with the least number of element groups was the total strain energy. At 512 element groups the error was less than 0.001% (0.7% for the two material model). The next to converge were the displacements. Using 512 materials the maximum error in displacement at the surface nodes was 0.001% (4.7% for the 2 material model), while for the internal nodes the maximum error was 0.53% (36.7% for the 2 material model). The least convergence occurred for principal strains. The maximum errors when 512 materials were used were 1.06% (57.7% for the 2 material model) and 3.02% (104.5% for the 2 material model) for the surface and the internal nodes respectively. This study demonstrates the relationship between the accuracy of calculated mechanical environment and the number of material properties assigned to the model. While this study will allow the analyst to make an informed decision on the number of material properties for modelling the human tibia it also helps examine the validity of previous studies which, usually due to limited resources, used fewer material properties.
Metal-on-metal (MoM) bearing technology, made of cobalt-chromium (Co-Cr) alloys, is being used in anticipation of extending the durability of hip replacements. Increasingly, concern has been expressed that long term exposure to Co2+ and Cr3+ could cause DNA damage and immune dysfunction; specifically a reduction in the circulating number of CD8+ cytotoxic cells. More recently, we reported that Co2+ and Cr3+ affected the differentiation of osteoclast precursors into bone-resorbing osteoclasts. Despite these observations the effects of metal ions on osteoblast activity have been poorly investigated. The aim of the current study was to elucidate the effects of various metal ions on osteoblast activity in vitro. Cells of the human osteosarcoma cell line SaOS-2 were cultured in the presence of 0, 1, 10 and 100 μM Co2+ and Cr3+. The morphology, viability, cytokine release (TNFalpha, IL-1beta, IL-6, LIGHT, MIP-1alpha and VEGF) and alkaline phosphatase activity were investigated after 24h and 48h in contact with metal ions. Finally the capacity of SaOS-2 to produce and mineralize a new bone matrix was assessed by the Alizarin red method. All experiments were repeated at least 5 times and the differences between each were determined using non-parametric Mann-Whitney test. Compared to untreated cultures, although the morphology looked normal after 48h, the viability indicated that Co2+ and Cr3+ ions at high concentrations induced some significant and irreversible damages to the osteoblast cells. Interestingly, any of the cytokines investigated were released in contact with metal ions after 24h or 48h. The alkaline phosphatase activity was significantly increased by low concentrations of Co2+ and decreased by high concentrations of Cr3+ after 24h and 48h. Moreover, the degree of mineralization of a new bone matrix in vitro was significantly reduced when the SaOS-2 cells were exposed to high concentrations of Cr3+, but significantly increased when they were exposed to Co2+. Our results indicated that irreversible damages are caused to the cells as soon as 24h with high concentrations of metal ions. For osteoblasts cells, Co2+ appeared to be less toxic than Cr3+ at high concentrations. This study was supported by Furlong Research Charitable Foundation
Kinematic data from in-vivo fluoroscopy measurements during a step-up activity was used to determine the relative tibial-femoral position as a function of knee flexion angle for each model. Medial and lateral force distribution was adapted from loads measured in-vivo with an instrumented implant during a step-up activity. The affect that varying the bearing thickness has on the stresses in the bearing was investigated. In addition, varus-valgus mal-alignment was investigated by rotating the femoral component through 10 degrees.
Tibial lesion: In lateral OA, the midpoint of lesions was 2.0mm (SD:6.5) posterior to the reference line passing through the mid-coronal plane of the resected tibia. This was located significantly more posterior (p=0.038) than midpoint in medial OA, which was 2.2mm (SD:5.7) anterior to the reference line. Knee Flexion Angle: In lateral OA, the midpoint of lesions was on average at 40° flexion and sites of smaller lesions were very variable. The lesion expanded both anteriorly and posteriorly. In medial OA, smaller femoral lesions occurred in full extension and extended further posteriorly with disease progression. No significant difference was demonstrated in medial and lateral localisation of the lesions.