Synthetic bone substitutes provide an alternative to autograft but do not give equivalent clinical results. Their performance may be enhanced by adding osteogenic growth factors. In this study, TGFβ1 was absorbed on to a carrier of β tricalcium phosphate and Gelfoam® and used to fill a defect around a tibial implant in a rat model of revision arthoplasty.

We added 0.0, 0.02 μg, 0.1 μg or 1.0 μg of TGFβ1 to the carrier and then implanted it around an hydroxyapatite-coated stainless-steel pin in the proximal tibia of rats. The tibiae were harvested at three, six or 26 weeks and the amount of bone formation and ceramic resorption were assessed.

TGFβ1 had no effect on the amount of bone in the defect, the amount of fluorescent label incorporated or the rate of mineral apposition. The growth factor did not significantly affect the amount of β TCP remaining in the tissue at any of the time points.

Aims: After Total Hip Replacement (THR), bearing surface pistoning during the gait cycle can affect wear rates. This ‘micro-separation’ has been shown clinically by video-fluoroscopy to be greater with a Metal-on-Polyethylene (MOP) bearing than a Metal-on-Metal (MOM) one. In this study, we quantified the suction forces that these bearings generate during the swing phase of the gait cycle as a result of interfacial tension from the thin fluid film present at the bearing surface. Methods: We used a servo-hydraulic universal testing machine with 250N load cell and programmed a sinusoidal waveform that could vary the loads and frequencies applied to MOP or MOM bearings submerged in 25% serum. We measured the bearing separation (±1μm) at tensile loads of 10N to 100N lasting 0.1s to 0.5s per 1Hz cycle.

Results: MOM bearings resisted tensile loads of up to 35N when applied for 0.1s to 0.5s of the simulated gait cycle. Bearing separation was measured at a maximum of 198 microns. Above 50N, the MOM bearing was unable to prevent separation occurring even when applied for only 0.1s of the simulated gait cycle (p< 0.001). The MOP bearing could not resist separation at any of the applied tensile loads (p< 0.0001).

Conclusions: The suction-fit of the MOM bearing used in this study is insufficient to prevent bearing separation due to gravity (110N). However, it may reduce the total bearing separation distance by delaying the time point at which separation occurs during the finite period of the swing phase (< 0.5s) during the gait cycle. This effect is crucially dependent upon the bearing clearance, bearing diameter, weight of the leg, speed of walking and soft tissue tension around the hip. This ultimately relies upon prosthetic design, patient selection and surgical technique.

Aim: Evaluate a novel horseshoe shaped cup designed by the senior authors to minimise the resection of healthy bone in total hip arthroplasty.

Method: Fifty female patients with a displaced, subcapital, femoral neck fractures were chosen for the study. In half of the group of patients, the composite support shell was coated with HA, with the other half remaining uncoated. Clinical and radiological assessments were undertaken regularly for 5 years.

Results: To date 20 patients have died and 13 have withdrawn from the study due to poor medical health unrelated to the study. Charnley modified Merle d’Aubigne score at 5 years was as good as the preoperative score with 80% of patients having full range of movement, no pain and walking unaided.

Radiographic results showed no evidence of loosening of HA coated cups, in contrast to non HA coated cups which migrated significantly in 80% of cases. Four patients with loose non HA coated cups underwent revision surgery.

Conclusion: It replaces the cartilage and underlying sub-chondral bone of the acetabulum socket with a cup that is designed to flex in harmony with the surrounding bony structure. This trial has demonstrated success at 5 years with the HA coated Cambridge Acetabular Cup. Cups from which HA coating has been removed have migrated significantly in 80% of cases. There is an advantage of the HA fixation which will be taken into account before wider clinical usage is advocated.

The novel horseshoe shaped cup was designed by the senior authors to minimise the resection of healthy bone in total hip arthroplasty. It replaces the cartilage and underlying sub-chondral bone of the acetabulum socket with a cup that is designed to flex in harmony with the surrounding bony structure.

Fifty female patients with a displaced, subcapital, femoral neck fractures were chosen for the study. In half of the group of patients, the composite support shell was coated with HA, with the other half remaining uncoated. Clinical and radiological assessments were undertaken regularly for five years.

To date 20 patients have died and 13 have withdrawn from the study due to poor medical health unrelated to the study. Charnley modified Merle d’Aubigne score at five years was as good as the preoperative score with 80% of patients having full range of movement, no pain and walking unaided.

Radiographic results showed no evidence of loosening of HA coated cups, in contrast to non HA coated cups which migrated significantly in 80% of cases. Four patients with loose non HA coated cups underwent revision surgery.

This trial has demonstrated success at 5 years with the HA coated Cambridge Acetabular Cup. Cups from which HA coating has been removed have migrated significantly in 80% of cases. There is an advantage of the HA fixation which will be taken into account before wider clinical usage is advocated.

Radio-pacifiers in bone cements are an accepted part of every-day practice. They have, however, been shown to be a potential cause of an increase in third body wear and to excite bone resorption in vitro and in vivo studies.

We reviewed the results of 228 consecutive Stanmore Total Hip Replacements performed between 1981 and 1985 in 211 patients. All were inserted with radiolucent bone cement. Information regarding whether the prosthesis had been revised was available for all patients. 73 patients (83 hips) were still alive and 41 patients (44 hips) were sufficiently healthy to attend clinic. Information regarding pain level was obtained from the remaining 32 patients. When revision of the implant was taken as the end-point, there was 95% ten-year survival, 91% fifteen-year survival and 75% eighteen-year survival. These long-term results of Stanmore THRs, performed in a district general hospital, with radiolucent bone cement, compare favourably with the other published series for this implant. We did not find the inability to see the bone cement a particular disadvantage when reviewing x-rays for signs of loosening.

Differentiating cases of aseptic loosening of total hip arthroplasty (THA) from loosening due to low-grade infection can often be difficult. It is possible that some cases of ‘aseptic’ loosening may be related to unidentified bacterial infection.

Using Polymerase Chain Reaction (PCR), this study attempted to identify the frequency with which bacterial DNA could be observed at revision arthroplasty for what was considered ‘aseptic’ loosening.

All revision cases had to fulfil strict criteria to be considered aseptically loose In all cases operative specimens from the synovial fluid, synovium, femoral and acetabular membranes where possible were sent for analysis by histology, bacteriology and by PCR to identify the presence of the 16S bacterial ribosomal fraction, an indicator of bacterial DNA. Ten bacteria per millilitre of tissue/fluid were the threshold for detection. As a control for environmental contamination, specimens from primary THA were also sent for analysis in the same manner as revisions.

The identification of bacterial DNA in at least one sample from a patient was considered a positive case result.

45 revision THA were identified over a 3-year period (1998–2001). From those 45 revision cases, 163 specimens were sent for analysis by PCR. These specimens were compared to the control group of 34 primary THA from which 91 specimens were sent for analysis by PCR. When analysed by specimens positive by PCR, bacterial DNA was identified in 55 of 163 specimens sent from the 45 revision THA. This compared with 21 of 91 specimens positive by PCR sent from the 34 primary THA (p=0. 07).

When analysed by cases positive by PCR, bacterial DNA was identified in 29 of 45 revision THA and in 8 of 34 primary THA (p< 0. 001).

PCR is a sensitive test for detecting infection in revision THA. Results from the primary THA cases would suggest there is at least a 23% false positive rate even with negative bacterial culture. The increased frequency with which bacterial DNA has been identified in ‘aseptically’ loose revision THAs, however, is unlikely to be due solely to environmental contamination. These results may have relevance for our interpretation and understanding of aseptic loosening as well for the diagnosis of prosthetic infection.

The use of musculo-skeletal MRI is increasing at spectacular rate, however there have been few rigorous evaluations of its’ clinical effectiveness. This study was conducted to assess the impact of MRI of the wrist on clinical diagnosis and patient management.

A controlled observational study was performed, in which referring clinicians completed questionnaires on diagnosis and intended management before and after wrist MRI. We analysed 118 consecutive patients referred for MRI of the wrist, to the magnetic resonance imaging units at a regional teaching hospital and a large district general hospital. We assessed: changes in clinicians’ leading and subsidiary diagnoses after MRI; their certainty of these diagnoses; and changes in intended patient management.

Five patients had incorrectly completed requests, ten cancelled their appointments and two could not tolerate the MR examination. Complete follow up data is available for 98/101 patients with correctly completed request forms who were examined. The clinical diagnosis changed in 55 of 98 patients (56%). Diagnostic certainty increased in 23 of the remaining 43 patients (53%). Clinicians reported that MRI had substantially improved their understanding of the patients’ disease in 67/98 (68%) patients. There was a change in management in 46/98 (47%) patients, with a shift away from operative treatment. 28 out of 98 (29%) patients were discharged without further investigation. MRI was similarly effective in a regional teaching centre and a district general hospital.

Magnetic resonance imaging of the wrist influences clinicians’ diagnoses and management plans. These results demonstrate the clinical effectiveness of MRI of the wrist in both a regional teaching centre and a district general hospital.

Introduction: Aseptic loosening of THR has a multifactorial aetiology. Differentiating such cases from loosening due to low-grade infection can often be difficult. It is possible that at least some cases of ‘aseptic’ loosening may be related to unidentified bacterial infection. This study attempted to identify the frequency with which bacterial DNA could be observed in the periprosthetic membrane and synovial fluid of patients undergoing revision surgery for what was considered ‘aseptic’ loosening.

Methods: Specimens from 39 revision and 31 primary hip replacements were obtained. The latter were used as a control for environmental contamination. All revision THR cases were investigated pre-operatively for infection by CRP, ESR, WCC, Gallium Scan. Operative specimens were analysed by bacteriological culture as well as by PCR to identify the presence of the 16S bacterial ribosomal fraction. Results were analysed by Chi square test.

Results: By PCR, bacterial DNA was identified in 22 of 39 revision hip surgery specimens and 6 of 31 primary hip replacement specimens (p=0.002). By culture none of these specimens had any bacterial growth.

Conclusions: The increased frequency with which bacterial DNA has been identified in ‘aseptically’ loose revision THR is unlikely to be due solely to environmental contamination although this remains a concern. These results may have relevance for our interpretation and understanding of aseptic loosening as well for the diagnosis of prosthetic infection.

There is evidence to suggest that fractures heal more rapidly in patients with a head injury as a result of systemic factors released from the site of this injury. We have measured the circulating level of insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP-3) in serum because of their known involvement in the stimulation of the activity of osteoblasts and the healing of fractures.

The serum level of IGF-1 was significantly lower in patients with both head injury and fracture and fracture only compared with that in healthy volunteers (p < 0.01 and p < 0.02, respectively). The level of IGFBP-3 was also significantly lower in patients with both head injury and fracture (p < 0.01).

Our findings showed, however, that the level of IGF-1 and IGFBP-3 varied from week to week in both the patients and healthy control subjects. These results indicate that the levels of circulating IGF-1 and IGFBP-3 are unlikely to be responsible for the altered healing of fractures seen in conjunction with head injury.

Particulate prosthetic materials are often studied by adding them to monocytic cells in vitro and measuring the release of cytokines as an indicator of their inflammatory potential. Endotoxin is known to be a contaminant of particle preparations and also stimulates the release of cytokines. It is usual to use a proprietary endotoxin test to avoid erroneous results.

Four different formulations of cement were found to be free from endotoxin using standard, gelclot tests but stimulated different levels of release of cytokines from macrophages. These differences were explained when a more sensitive, kinetic endotoxin assay showed that release correlated with minor contamination with endotoxin. In a repeat experiment using cement particles with low or undetectable levels of endotoxin by kinetic assay, differences in the ability of the formulations to stimulate the release of cytokines were not seen.

Endotoxin is adsorbed on to the surface of particles and it is this combination which stimulates increased release of cytokines. In both the above methods for determination of endotoxin, the water in which the particles had been soaked was examined rather than the particles directly. Further investigations showed that a kinetic assay directly on a particle suspension is the most sensitive method to measure contamination with endotoxin.

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.

We used a rat model in vivo to study the effects of particulate bone cements at the bone-implant interface. A ceramic pin was implanted into the tibiae of 48 rats. Three types of particle of clinically relevant size were produced from one bone-cement base without radio-opacifier, with zirconium dioxide (ZrO₂) and with barium sulphate (BaSO₄). The rats were randomly assigned to four groups to receive one of the three bone cements or normal saline with 2% v/v Sprague-Dawley serum as the control. A total of 10⁹ particles was injected into the knee at 8, 10 and 12 weeks after the original surgery. The animals were killed at 14 weeks and the tibiae processed for histomorphometry. The area of fibrous tissue and the gap between the implant and bone were measured using image analysis.

All three types of particle were associated with a larger area of bone resorption than the control. Only in the case of the BaSO₄-containing cement did this reach statistical significance (p = 0.01). Particles of bone cement appear to promote osteolysis at the bone-implant interface and this effect is most marked when BaSO₄ is used as the radiopaque agent.

We have investigated whether the particle-stimulated release of inflammatory cytokines from human primary macrophages in vitro was dependent upon the type of bone cement used. Particles of clinically relevant size were produced from Palacos R without radio-opacifier, Palacos R with BaSO₄, Palacos R with ZrO₂ and from CMW3 which contains BaSO₄. All four preparations produced significantly greater release of tumour necrosis factor alpha, interleukin-6 and interleukin-1 beta than a negative control but there were no significant differences between them. The differences in the ability to stimulate bone resorption and in clinical performance between proprietary bone cements previously recorded are not explained by the release of the cytokines most commonly implicated in osteolysis.