header advert
Results 21 - 40 of 48
Results per page:
Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_III | Pages 549 - 549
1 Aug 2008
White G Gordon A Stockley I Hamer A Wilkinson JM
Full Access

Introduction: Aseptic loosening due to periprosthetic osteolysis is the main cause of implant failure after total hip arthroplasty (THA). Some previous studies have suggested a link between pattern of pre-operative osteoarthritis (OA) and subsequent aseptic loosening. Specifically, atrophic OA may predict implant loosening1,2 however this remains controversial.3

Methods: We retrospectively assessed the survival of 301 cemented THAs inserted for idiopathic osteoarthritis to determine whether pre-operative patterns of osteoarthritis predict subsequent risk of osteolysis. There were 204 control subjects and 97 subjects with osteolysis. The mean age of patients at insertion of primary implant was 63.4 years and lysis free survival or follow up was 10.6 years. The osteoblastic response in OA was assessed using Bombelli’s classification. The American College of Rheumatology criteria for radiographic evidence of OA was used to assess the pattern of OA prior to primary THA

Results: Atrophic OA was not a risk factor for osteolysis. Atrophic OA in osteolysis group was 16% versus 14% in the control group (χ2 test p> 0.05). There was no association between osteolysis and joint space narrowing, femoral or pelvic osteophytes, femoral or pelvic sclerosis, femoral or pelvic cysts and femoral head collapse (χ2 test p> 0.05 all comparisons).

Conclusion: The morphological pattern of OA does not predict osteolysis after THA


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_III | Pages 538 - 538
1 Aug 2008
Manning V Buckley SC Kerry RM Stockley I Hamer AJ
Full Access

Aims: Dislocation is one of the commonest complications following total hip arthroplasty. A significant proportion of these patients go on to have recurrent dislocations. Many factors have been identified as contributing to the risk of dislocation but treatment of recurrent dislocation is challenging. The use of semicaptive acetabular components is a potential solution to the problem of recurrent dislocation but there are few studies into the efficacy of these implants.

Methods: Patients who underwent revision of their total hip arthroplasty to a semi-captive socket at the Lower Limb Arthroplasty Unit, Northern General Hospital, Sheffield between 2001 and March 2006 were studied. A proforma was designed and data was obtained from patients’ medical records. The number of dislocations both prior to revision to a semi-captive component and the following revision to a semi-captive acetabular component were recorded including the method of reduction Reasons for revision and the number and reasons for previous revisions were noted.

Results: Average time of follow up was 22 months (range 2 months – 5 years 1 month). Following revision of total hip arthroplasty to a semi-captive component, 78% suffered no further dislocations. Of those patients who went on to redislocate, three went on to have recurrent dislocations and all were reduced by closed reduction. One patient redislocated and underwent a second revision to a semi-captive acetabular component, which was successful and underwent no further dislocations.

Discussion. The results of this study show the use of semicaptive acetabular components in revision surgery for dislocation following total hip arthroplasty to be a highly effective solution to the problem of recurrent dislocation.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 379 - 379
1 Jul 2008
G A Hamer A Stockley I Eastell R Wilkinson J
Full Access

Introduction: The concept that aseptic loosening is a function of polyethylene wear has led to the use of cross-linked polyethylene in total hip arthroplasty (THA). We studied the relationship between polyethylene wear rate and aseptic loosening in order to model the potential effects of wear-reducing strategies on the failure rate for each prosthetic component.

Methods: 350 subjects who had previously undergone Charnley THA were divided into 3 groups: Controls (n=273); those with loosening of only the femoral stem (n=43); and those with only cup loosening (n=34). Poly-ethylene wear was measured using a validated method (EBRA). The relationship between wear rate and loosening was examined using logistic regression analysis, and estimates of the effect of wear rate modulation made using odds-ratios.

Results: The median annual wear rate in the controls (0.07mm) was lower than both stem looseners (0.09mm, p=0.002) and cup looseners (0.18mm, p< 0.001). The odds of cup loosening increased 4.7 times per standard deviation (SD) increase in wear rate above the reference (control) population (p< 0.001). The odds of stem loosening increased 1.7 times per SD, but was not independent of other risk factors (p> 0.05). The potential reduction in risk of loosening was calculated using the following formula: (OR^SD2)/(OR^SD1), where 1 and 2 are the new and old mean z-score wear rates. Thus, for a 25% or 50% reduction in wear rate, the incidence of cup loosening may reduce by 71% and 293%, respectively. The rate of stem loosening may, at best, reduce by 7% and 17%, respectively.

Discussion: Wear reduction strategies, such as cross-linked polyethylene, have the potential for a major impact on the incidence of cemented cup, but not stem, loosening.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 316 - 316
1 Jul 2008
Bridgens J Norman P Stockley I
Full Access

Introduction: It is common practice to use additional antibiotics in bone cement for revision hip surgery. Ideally antibiotic elution would initially be rapid and then reduce to zero in order to reduce the risk of antibiotic resistance developing. There is evidence that the addition of antibiotics to bone cement leads to deterioration in mechanical properties. We have carried out a study to see if the addition of vancomycin to Palacos R40G and Smartset GHV affects their in-vitro antibiotic elution and mechanical properties.

Methods: Palacos R40G (contains 0.5g gentamycin per 40g mix) and Smartset GHV (contains 1g gentamycin per 40g mix) were used. 40g samples of the two cements with no additional vancomycin, 1g and 2g vancomycin were prepared by a standard method using vacuum mixing in a syringe. Antibiotic elution over a five week period was measured using an immunoassay method. Standard mechanical testing was carried out according to methods defined in ISO 5833.

Results: Smartset GHV eluted double the quantity of gentamycin as Palacos R40G, as would be expected. Both cements eluted more gentamycin when vancomycin was added. Smartset appears to elute more vancomycin than Palacos initially and then shows a more rapid tailing off. The mechanical properties of the two cements were the same with no statistical differences found between them. Both showed deterioration in flexural strength with addition of increasing vancomycin.

Discussion: Smartset may have improved qualities of antibiotic elution as compared with Palacos with similar mechanical properties. The presence of higher initial quantities of gentamycin does not lead to reduced mechanical properties.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 311 - 311
1 Jul 2008
Revell M Stockley I Davies S Norman P
Full Access

Introduction: The correct identification of the infecting micro-organism in prosthetic joint infections is difficult and there is no single method that is wholly reliable. We report a novel method intended to improve accuracy by disrupting the biofilm surrounding the prosthesis and transferring samples rapidly to culture medium.

Method: Explanted prostheses from 20 revision operations were sampled by pressing a microbiology swab or by passing a No.10 surgical blade along it. The sample so obtained was plated immediately in the operating theatre onto horse-agar petri dishes. These were incubated in aerobic conditions in the laboratory. Culture results were compared with those obtained from our standard detection method using multiple tissue samples with are plated or grown in prolonged aerobic and anaerobic culture broth.

Results: The method proved practical to perform in practice. When compared with multiple tissue samples as the standard, the Positive Predictive Value was 90%, Negative Predictive Value 80%, sensitivity 82%, specificity 89%. In 4 of the 10 true positive samples, the theatre-inoculated samples yielded early results within 3 days, while conventional method yielded positives only later on prolonged culture.

Discussion: The above pilot is to continue and has started to alter our practice in sample taking. Blade-scrape does appear to penetrate the biofilm successfully. Growing confidence in interpretation and ease in reading the plates mean that in certain cases, we consider the results to be more reliable than traditional tissue culture. Direct plating also reduces the chance of bacterial overgrowth in broth inhibiting colonies of secondary infective organisms. Further refinement is needed, particularly with regard to anaerobic bacteria. Inaccuracies have resulted when agar plates are allowed to go out of date.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 312 - 312
1 Jul 2008
Gordon A Hamer A Stockley I Eastell R Wilkinson J
Full Access

Introduction: Activated peri-prosthetic macrophages release pro-inflammatory cytokines, including interleukin-6 (IL-6), that stimulate osteoclast activation and aseptic loosening. Natural sequence variations (polymorphisms) within the IL-6 gene promoter region are associated with diseases characterised by increased osteoclast activity, including osteoporosis, and affect IL-6 production in-vitro. We tested whether polymorphisms in the IL-6 gene promoter influence the risk of aseptic loosening after total hip arthroplasty (THA).

Methods: 614 Caucasians, 292 men and 322 women, mean age 75.8 years who had undergone primary cemented THA for idiopathic osteoarthritis a mean of 13.4 years previously were recruited. Peripheral blood was taken and DNA extracted using standard techniques. Subjects were genotyped for the IL-6 -174, -572, and -597 promoter single nucleotide polymorphisms using the Taqman 5′ nuclease method.

Results: The allele frequencies and carriage rates for both alleles at promoter positions −174, −572, and −597 were similar between controls and aseptic loosening subjects (Table, χ2 P> 0.05 all comparisons).

Discussion: Although Il-6 has been implicated in the pathogenesis of aseptic loosening and the −174, −572, and −597 polymorphisms are associated with bone loosing pathologies, they do not appear to play a major role in aseptic loosening after THA.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 411 - 411
1 Oct 2006
Shetty N Hamer A Stockley I Eastell R Wilkinson J
Full Access

Dual energy X-ray absorptiometry (DXA) is a precise tool for measuring bone mineral density (BMD) around total joint prostheses. The Hologic ‘metal-removal hip’ analysis package (Hologic Inc, Waltham, Massachusetts) is a DOS-based analysis platform that has been previously validated for measurement of pelvic and proximal BMD after total hip arthroplasty (THA). This software has undergone a change in the operating platform to a Windows-based system that has also incorporated changes to DXA image manipulation on-screen. These changes may affect the magnitude of random error (precision) and systematic error (bias) when compared with measurements made using the previously validated DOS-based system. These factors could influence interpretation of longitudinal studies commenced using the DOS system and later completed using the Windows system. The aims of this study were to compare the precision and bias of pelvic and femoral periprosthetic BMD measurements made using the Windows versus the DOS analysis platform of the Hologic ‘metal-removal hip’ software. A total of 29 subjects (17 men and 12 women) with a mean age of 51years (SD±10), who had undergone hybrid THA using a cemented stem and uncemented cup. Subjects underwent duplicate DXA scans of the hemipelvis and proximal femur taken on the same day after a period for repositioning.. Scans were obtained with the patient lying supine in the scanner with the legs in extension and the foot in a neutral position. Scans were carried out using the same Hologic QDR 4500-A fan-beam densitometer in ‘metal-removal hip’ scanning mode. The DXA scan acquisitions were analysed using both the DOS and the Windows versions of the analysis software. The same observer made all analyses (NRS). Pelvic scans were analysed using a four region of interest model and femoral scans were analysed using a seven region of interest model. Precision was expressed as coefficient of variation (CV%) and compared between methods using the F-test. Systematic bias was examined using the Bland and Altman method and paired t-test. The CV% for the pelvic regions of interest (n=4) varied from 3.92 to 8.54 and from 2.36 to 5.96 for the Windows and DOS systems, respectively. The CV% for the net pelvic region was 3.04 and 2.36 for Windows versus DOS, respectively (F- test, p> 0.05). The CV% for the femoral regions of interest (n=7) varied from 1.58 to 4.14 and from 1.84 to 4.65 for the Windows and DOS systems, respectively. The CV% for the net femoral region was 1.75 and 1.51 for Windows versus DOS, respectively (F- test, p> 0.05). Absolute BMD values for the net pelvic region were similar (Bland-Altman, Windows minus DOS value mean = -1.0%, 95% CI −7.5 to 5.6; t-test p.0.05). Absolute BMD values for the net femoral region were also similar (Bland-Altman, Windows minus DOS value mean = 1.3%, 95% CI −8.3 to 10.8; t-test p.0.05). In summary precision of the measurements using the 2 operating systems was similar and there was no systematic bias between methods. These data suggest that scans analysed using each platform may be used interchangeably within the same study subjects, without the need of a calibration correction.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_II | Pages 238 - 238
1 May 2006
Shetty N Hamer A Stockley I Eastell R Wilkinson J
Full Access

Peri-prosthetic bone loss may contribute to aseptic loosening after THA. The aims of this randomised controlled trial extension study were to study the effect of pamidronate therapy on Peri-prosthetic bone mineral density (BMD) and Peri-prosthetic osteolysis over 5 years after primary THA.

50 patients were enrolled in the study in 1998. All received a hybrid THA (Ultima-TPS stem, Plasmacup) for osteoarthritis. Subjects were randomised to receive either 90mg of pamidronate or placebo by intravenous infusion on the 5th post-operative day. At 5 years 36 patients (41 Hips: placebo n=21, pamidronate n=20) returned for measurement of BMD and clinical and plain radiographic assessment. Five patients had died and nine had withdrawn from the study.

The effect of pamidronate in maintaining femoral bone mass in the region of the calcar previously reported at 2 years was maintained at 5 years (Gruen zone 6 pamidronate versus placebo ANOVA P=0.038; Gruen zone 7 ANOVA P=0.048). No differences in pelvic BMD were found between treatment groups at 5 years. Harris hip scores used to evaluate clinical outcome did not show any significant difference between the 2 groups over the 5-year period. (Mann Whitney p> 0.05). Isolated expansile osteolytic lesions were identified on AP radiographs of the hip at 5 years in 4 patients (2 placebo, 2 pamidronate; P> 0.05). One patient had a 5x9mm lytic lesion in the region of the femoral calcar, and 3 patients had pelvic lytic lesions in the region of the acetabular dome (largest measuring 20x10mm).

Single-dose peri-operative pamidronate therapy preserves femoral calcar bone mass over a 5 year period after THA. However, although the number of subjects with osteolysis is small, we have seen no difference in the rate of osteolytic lesions between treatment groups. Long term study of this patient group is required to examine the rate of aseptic loosening between the treatment groups.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_II | Pages 235 - 235
1 May 2006
Hoad-Reddick DA Stockley I
Full Access

Aims and Objectives Hybrid hip replacement became popular in some centres for younger patients with expected lower rates of acetabular loosening and subsequent revision. We have previously reported our 5 year results and now have further follow-up data on the same cohort of patients.

Materials and Methods 86 uncemented acetabular components of the same design were implanted into 68 patients between 1992 and 1997 who were prospectively followed with respect to clinical outcome, polyethylene wear and intention to revise as a definition of failure.

Results Data is available on 73 acetabular cups with a mean follow-up of 9.5 years. The failure rate is 22%. 9 patients have been revised and 7 further patients await revision for polyethylene wear and osteolysis which in some cases has been very aggressive. Further patients have advanced wear and early lysis which is under close observation.

Conclusion The prosthesis studied has a high failure rate. Patients often report few symptoms until advanced osteolysis has occurred. We recommend that all patients with this type of prosthesis be recalled for frequent radiological review and report on an implant which seems to be failing unacceptably early.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_II | Pages 256 - 256
1 May 2006
Hoad-Reddick DA Evans CR Norman P Stockley I
Full Access

The use of prolonged courses of parenteral or oral antibiotic therapy in the management of two stage revision of infected total knee arthroplasty is reported by all major series.

We present a series of 59 consecutive patients, all with microbiologically proven deep infection managed at our unit where a prolonged course of antibiotic therapy has not been routinely used. The mean follow-up is 56.4 months (range 24–114 months). Of the 38 patients undergoing a staged exchange, infection was successfully eradicated in 34 patients (89%) with recurrent or persistent infection in 4 (11%). The infection cure rate in our series is similar that reported elsewhere.

A prolonged course of antibiotic therapy does not seem to alter the incidence of recurrent or persistent infection. The costs of antibiotic administration are high, both to the patient and care facility. It may be unnecessary.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_II | Pages 249 - 249
1 May 2006
Gordon A Southam L Loughlin J Stockley I Hamer A Macdonald D Eastell R Wilkinson M
Full Access

In-vitro evidence suggests that wear debris can alter osteoblast function resulting in decreased bone matrix production and negative remodelling balance. FRZB encodes for Secreted Frizzled-Related Protein 3 which may play a role in bone formation and osteoarthritis. This study was undertaken to investigate whether the recently described single nucleotide polymorphisms (SNPs) at positions [+6] and [+109] of the FRZB gene are associated with osteolysis after THA.

Genomic DNA was extracted from 481 North European Caucasians at a mean of 12 years following cemented THA for idiopathic osteoarthritis. The control group consisted of 267 subjects and the osteolysis group 214 subjects. The [+6] and [+109] FRZB SNPs were genotyped using standard techniques.

For the FRZB [+6] SNP, the rare T allele was significantly over-represented in control versus the osteolysis group (χ2 test for trend, p=0.02,). The odds ratio for osteolysis associated with carriage of the [+6] T-allele versus the [+6] C-allele was 0.58 (95%CI 0.36 to 0.94), p=0.03. The odds ratio for osteolysis associated with carriage of the [+109] G-allele versus the [+109] C-allele was 0.66 (0.38 to 1.12), p=0.15. A number of covariates have previously been described in this cohort and after adjustment for the effects of these covariates, the odds ratio for osteolysis with carriage of the [+6] T-allele was 0.69 (0.42–1.16).

We found that the FRZB [+6] T-allele is less common in subjects with osteolysis after THA versus controls, suggesting that allelic variants of genes associated with bone formation pathways may have a role in modulating the risk of osteolysis. However its loss of significance after correction for other factors suggests an interaction between this allele and other risk factors in osteolysis.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_II | Pages 248 - 248
1 May 2006
Shetty N Hamer R Kerry A Stockley I Eastell R Wilkinson J
Full Access

The pattern and magnitude of pelvic periprosthetic bone loss around cementless metal-backed acetabular implants have previously been described. The pattern of periprosthetic BMD change around cemented all-polyethylene acetabular implants is unreported. The aims of this study were to determine the precision of pelvic BMD measurements around the Charnley cup and to examine the longitudinal pattern of BMD change over the first 2 years after surgery.

19 subjects who had previously received a Charnley cup for osteoarthritis underwent duplicate measurements of pelvic BMD after repositioning using an Hologic QDR 4500A densitometer. Scan analysis was carried out using a 4-region of interest model according to a protocol previously described. In-vivo precision was expressed as coefficient of variation (CV%) for each region of interest. The precision of pelvic periprosthetic BMD measurements were 7.7%, 9.8%, 10.8%, and 9.9% for regions 1 to 4, respectively.

Longitudinal BMD changes were measured over a 2 year period in 32 patients (mean age 74 years; 22 women) undergoing cemented THA for unilateral osteoarthritis (17 right-sided). Transient decreases in BMD were observed in regions 2 and 3 (behind the dome of the implant) at 3 months (−9.0% and −13.2%, respectively; P< 0.05) and at 1 year (−8.1% and −9.3%; P< 0.05). By 2 years there had been some recovery in bone mass (BMD−6.9% and −2.6% respectively). No significant changes in BMD for regions 1 and 4 (located at the rim of the implant) were found.

The precision of pelvic periprosthetic BMD measurements for the cemented Charnley cup are poorer than those we have previously reported for cementless cups and may be due, in part, to cement artifact. The pattern of BMD change observed for the Charnley implant suggests that load transfer between the implant and the pelvis occurs principally at the implant rim. The magnitude of bone loss is similar to that we have previously reported for cementless metal-backed acetabular implants.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_II | Pages 248 - 248
1 May 2006
Shetty N Hamer A Kerry R Stockley I Wilkinson J
Full Access

The Exeter (Howmedica Ltd) and Ultima-TPS (Depuy Ltd) implants are both collarless, polished, double-tapered, cemented femoral implants. The Exeter is manufactured in stainless steel and has an excellent long-term survivorship. The Ultima-TPS is manufactured in cobalt-chrome and has been recently introduced. The aim of this study was to compare the early performance of these implants in a 2-year randomised clinical trial.

65 patients with unilateral hip osteoarthritis were randomised to receive either the Exeter or TPS stem. All received a Charnley Cup. Outcome measures included the Oxford Hip Questionnaire, proximal femoral bone mineral density (BMD) measured by dual energy x-ray absorptiometry, and implant subsidence measured using EBRA. At 2 years 43 patients (66%) were reviewed. 22 patients (mean age 70 years, 16 female, BMI 27.9Kg/m2) received the TPS implant, and 21 patients (mean age 70 years, 15 female, BMI 28.9Kg/m2) received the Exeter implant. 19 patients withdrew for reasons unrelated to the study, 2 died, and 1 was withdrawn after deep wound infection.

Complete Oxford hip scores were available pre-operatively and at 2 years in 37 patients (n=20 TPS). Median (IQR) pre-operative hip scores were 51 (43 to 54) and 48 (36 to 53) for the TPS and Exeter implants, respectively. At 2 years the hip scores improved to 24 (18 to 31) and 22 (16 to 31), respectively. There were no differences in scores between groups at each time-point. There were no differences in BMD between groups at pre-operative baseline, 3 months, 1 and 2 years (Gruen zones 1–7, all time-points; n=19 TPS, n=13 Exeter implants: P> 0.05). Maximum bone loss was seen in Gruen zone 7 at 2 years for bone implants (TPS-11%, Exeter -14%, P> 0.05). Measurement of subsidence over 2 years using EBRA was possible in 20 patients (n=7 TPS, n=13 Exeter). Mean subsidence at 2 years was 1.62mm for the TPS implant and 1.60mm for the Exeter implant (P> 0.05). There was no plain radiographic evidence of osteolysis in either group.

These data suggest that the early performance of the two implants studied is similar. However, long-term survivorship data is required to confirm their equivalency.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_II | Pages 248 - 249
1 May 2006
Gordon A Kiss-Toth E Stockley I Hamer A Eastell R Wilkinson J
Full Access

Phagocytosis of wear particles by perimplant macrophages results in cytokine release and osteoclast activation and osteolysis. Some investigators have proposed that this response may be mediated by adherent endotoxin. The aim of this study was to determine the role of endotoxin in modulating pro-inflammatory cytokine mRNA expression of macrophages when stimulated with titanium particles using relative quantitative real-time polymerase chain reaction (rqRT-PCR)

Human peripheral blood mononuclear cells were isolated from healthy subjects and plated in chamber slides. Three types of titanium particles were prepared; commercially pure titanium particles (cpTi), endotoxin stripped particles and endotoxin stripped particles with endotoxin (LPS) added back. Endotoxin levels of 450, 0 and 140 Eu/ml respectively were confirmed by high sensitivity Limulus Amebocyte Lysate assay. Macrophages were stimulated with particle concentrations of 0, 8.3, 83 and 830 particles per cell at time points 0 and 3 hours. LPS (200ng/ml) was used as a positive control. rqRT-PCR was performed using standard techniques.

Stimulation of human macrophages with cpTi demonstrated a significant dose dependent increase in TNFα, IL-1A, IL-1B and, IL-6. (Kruskal-Wallis p=0.01, p=0.017, p=0.001 and p=0.013 respectively). IL-18 mRNA levels were not increased (P> 0.05). The expression of mRNA following stimulation with the highest dose of titanium particles was similar to that following LPS stimulation. Endotoxin-free cpTi particles did not elicit any increase in mRNA expression above base line levels (P > 0.05, all cytokines). This lack of response was rescued in endotoxin-stripped particles with LPS added back. Particle dose dependent increases in cytokine mRNA levels were observed for TNFα, IL-1A, IL-1B and, IL-6 mRNA but not IL-18 (p=0.01, p=0.01, p=0.01, p=0.05 and p=0.> 0.05 respectively).

Our results show that adherent endotoxin plays a role in modulating particle induced pro-inflammatory cytokine mRNA expression in-vitro. Further study is required in evaluating the role of adherent endotoxin in vivo


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_II | Pages 236 - 236
1 May 2006
Gordon A Kiss-Toth E Stockley I Hamer A Eastell R Wilkinson J
Full Access

Cytokine mediated activation of osteoclasts can lead to peri-implant osteolysis and aseptic loosening. The aim of this study was to determine the IL-1β and TNFα mRNA cytokine expression profile of human macrophages when stimulated with polyethylene particles using relative quantitative real-time polymerase chain reaction (rqRT-PCR).

Human peripheral blood monocytes or human monocytes from the cell line THP-1 were used in this study. rqRT-PCR conditions were optimized by stimulating human macrophages with 200ng/ml lipopolysaccharide (LPS). The median CV% value for duplicate measures was 12.6 (range 4.5–54). Stimulation assays were performed using unfractionated endotoxin-free commercial polyethylene particles (median size 7μm); or fractionated particles (size range 0.1–1.2μm). Human macrophages were stimulated with high dose unfractionated polyethylene particles at 0, 3500 or 10500 mm3/cell or with fractionated polyethylene particles at 0 and 100mm3/cell at time points 0 and 3 hours. Low dose unfractionated polyethylene stimulation was performed on THP-1 cells at 0, 50, 100, 1000 and 10000 mm3/cell. In all experiments LPS stimulation was used as a positive control. RNA was extracted and rqRT-PCR was performed using standard techniques

High dose unfractionated polyethylene stimulation did not result in a significant difference in cytokine mRNA levels between groups. Using fractionated polyethylene, a small increase in IL-1β mRNA was identified (21% versus maximal stimulation using LPS). Low dose unfractionated polyethylene stimulation of THP-1 cells demonstrated dose dependent decreases in TNFα and IL-1β mRNA expression that was not due to inhibition of RNA extraction or a decrease of cell viability.

Endotoxin-free polyethylene particles do not appear to be a major stimulus for IL-1β and TNFα mRNA production as measured by rqRT-PCR. We did observe a small positive effect on IL-1β mRNA expression using a fractionated polyethylene stimulus. However it remains unclear whether this effect is due to fractionation of particles into the submicron range or is due to introduction of endotoxin during the filtration process.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_I | Pages 70 - 70
1 Jan 2004
Gordon A Wilson AG Stockley I Hamer AJ Macdonald DA Eastell R Wilkinson JM
Full Access

Aseptic loosening due to periprosthetic bone loss is a major cause of implant failure after total hip arthroplasty (THA). Interleukin 1-B (IL-1B) is thought to play a role in aseptic loosening by stimulating the activity of osteoclasts, the main bone resorbing cell type. A restriction fragment length polymorphism due to a C/T single base variation at +3954 in exon 5 of the IL-1B gene has been associated with differences in susceptibility to chronic periodontitis, a condition associated with bone loss. In this study we tested whether carriage of the C and T alleles at this site resulted in differential risk of aseptic loosening in 481 Caucasians (214 failed versus 267 radiologically intact implants) at 11.7± 4.1 years following primary cemented THA for osteoarthritis. Genomic DNA extracted from peripheral blood was genotyped using the Taqman 5′ nuclease method. Carriage rates were calculated and analysed using the 2 test.

In the intact implant group the frequency of the T allele was 0.253. The distribution of the C and T alleles was 147:105:15 (CC:CT:TT, respectively). In the failed implant group the frequency of the T allele was 0.241). The distribution of the C and T alleles was 124:77:13. The carriage rate of the T alleles in each group was 44.9% and 42.1%, respectively (odds-ratio P> 0.05). The genotype frequencies were in Hardy-Weinberg equilibrium for both intact and loose implant populations (Chi-squared P> 0.05).

Using the multivariate Cox proportional hazards model significant risk factors for loosening of both implant components included gender and age at THA (P< 0.05). However, carriage of the +3954 allele was not a significant independent risk factor for aseptic loosening (P> 0.05). Our data suggests that the IL-1B gene restriction fragment length polymorphism at +3954 does not influence the risk of aseptic loosening after THA.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_I | Pages 69 - 69
1 Jan 2004
Ali F Kerry RM Cooper R Wilkinson JM Norman PA Stockley I
Full Access

Purpose: The role of hip aspiration as a preoperative investigation for the painful hip remains controversial. Since 1999, we have performed hip aspiration under local anaesthetics in the X-ray department. This paper reviews our experience with this technique.

Results: Hip aspirations were carried out subsequently on 182 patients from November 1999 to November 2002. Out of 68 patients that underwent revision hip surgery, 63 were included in the study. Three of the five patients excluded had received antibiotics at induction prior to obtaining the operative samples and two did not have any operative samples taken at the time of surgery. Fifteen (23.8%) of the 63 hips were found to be infected based on operative tissue cultures. The sensitivity and specificity of the test were 80% and 87.5%, respectively. Positive and negative predictive values were 66.6% and 93.3% respectively and the accuracy was 85.7%.

Conclusion: Hip aspiration in the Radiology department is a simple, cost effective and reliable preoperative test when used selectively. When used in combination with other laboratory and radiological investigation it can act as an important preoperative investigation in the diagnosis of sepsis. There is an added advantage of identifying the microorganism along with its antibiotic sensitivities. This can guide clinicians in choosing the correct antibiotic for the cement and also for the postoperative antibiotic therapy.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_I | Pages 72 - 72
1 Jan 2004
Aspinall GR Nicholls A Kerry RM Hamer AJ Stockley I
Full Access

The Huckstep ( Bbraun Medical) interlocking hip prosthesis has been used in the Sheffield Lower Limb Arthroplasty Unit in cases of complex primary and revision hip arthroplasty since 1996. We reviewed the outcomes in cases performed prior to October 2001.

Eighty cases were identified. Of these, eight died within one year of surgery, four of which were in the peri operative period. A further thirteen were lost to follow up in the first year due to medical deterioration, move from area or refusal to attend. The remaining 57 patients had a mean time to follow up of 34 months (12–81m).

As a primary prosthesis the Huckstep was used to allow corrective osteotomy. In revision cases it was employed to bypass periprosthetic fractures and fragile proximal femoral bone, in cases requiring extended trochanteric osteotomy to facilitate cement removal, and to enable use of bulk proximal femoral allograft. The use of the Huckstep was planned pre operatively in 67 cases and as a salvage option in 13.The design of the implant allowed a stable construct without the need for bone cement which could interpose and prevent bone healing or graft incorporation. It avoids problems incurred in pressurising cement or impaction grafting against fragile bone.

Complications included infection requiring further surgery (5), dislocation (5), periprosthetic fracture (2), screw breakage (4), and mechanical failure (2). Eleven patients required further revision surgery. The apparently high complication rate reflects the complex nature of the surgery and the high degree of co morbidity in the elderly patient group.

In conclusion, we have found the Huckstep hip prosthesis to be a useful option in cases of complex hip surgery. Whilst the long term outcome is as yet unknown, our short term results show it to have allowed healing of fractures, osteotomy sites and cortical defects, allograft incorporation and replenishing of bone stock, hence facilitating further arthroplasty surgery.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_I | Pages 68 - 68
1 Jan 2004
Buckley S Hamer A Kerry R Stockley I
Full Access

One of the major surgical challenges at revision arthroplasty is the management of bone stock loss in the acetabulum.

There are several options available for reconstruction; cemented sockets within thick cement mantles, custom sockets jumbo uncemented sockets, support rings and bone grafting. Slooff and others have shown good results with impaction grafting.(JBJS 80B 1998)

If one is to use bone graft, does the preparation of the graft have any effect on the graft itself? There are a number of ways bone can be presented, freeze dried, fresh frozen or frozen irradiated. Concerns have been raised that irradiated bone has an altered and weakened structure. There is a paucity of clinical results on this subject. In this study we present a series of patients using gamma irradiated bone for reconstruction.23% of the cases reconstructions secondary to failure due to sepsis.

Between 1987 and 2000 192 revision arthroplasties in 165 patients were performed with irradiated morcellised bone allograft for acetabular reconstruction. Only those patients with a minimum follow up of 24 months were reviewed. Clinical and radiological follow up was achieved in 130 hips in 115 patients. 9 patients had died at a range of 1 to 66 months after surgery. There were 23 (17%) re-revisions of the acetabular component. Of these 13 were for deep sepsis, 5 for persistent early dislocation and 4 for aseptic loosening. Of those hips revised for infection there was a 13% re-revision rate for reinfection. There was only one catastrophic failure of the graft and only three re-revisions for aseptic loosening to date.

We feel that impaction grafting of the acetabulum is a useful technique for reconstruction even when the index arthroplasty failed for sepsis. We have found no evidence to show that gamma irradiated bone performs any worse than other types of allograft bone.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_I | Pages 71 - 71
1 Jan 2004
Gordon A Kiss-Toth E Wilson AG Stockley I Hamer AJ Eastell R Wilkinson JM
Full Access

Polyethylene wear particle-induced osteolysis is a major cause of implant failure after total hip arthroplasty (THA). Tumour necrosis factor (TNF) is a pro-inflammatory cytokine that is thought to play a pivotal role in this process. We have recently shown that carriage of the −238 ‘A’ allele in the TNF gene promoter is associated with a higher rate of osteolysis after THA versus carriage of the [more common] ‘G’ allele. The aim of this study was to determine the effect of this polymorphism on TNF gene transcriptional activation in response to polyethylene particle stimulation using a luciferase reporter gene assay.

A 691 bp fragment (−585 to +106) of the TNF gene was amplified by polymerase chain reaction and directionally cloned into the PGL3.basic vector (Promega, Madison, WI). Insert sequences were checked using an ABI 377 DNA sequencer (PE Applied Biosystems, Foster City, CA). RAW264.7 murine macrophage-like cells in rapid growth phase were transfected with plasmids containing either the TNF-238G allele or the TNF-238A allele. pTK-RL (Promega), that expresses the Renilla luciferase gene under the control of Herpes simplex virus minimal promoter, was used as a transfection control. The cells were then either left unstimulated or were induced using polyethylene particles generated from a hip simulator. Lipopolysaccharide (LPS) and LTA (Lipoteichoic acid) were used as positive controls. Luciferase reporter activity was measured after 4 hours (Dual luciferase assay, Promega Corp., Southampton, U.K.) and the relative firefly luciferase activity was calculated. Results were analysed using repeated measures ANOVA.

Polyethylene particle stimulation at concentrations of 0, 1, 15, and 30mg/mL resulted in relative luciferase activities (mean (SD)) of 21.4 (2.9), 36.2 (8.2), 45.9 (11.1), and 40.7 (5.1) for the −238A allele; and 19.7 (5.0), 26.4 (8.0), 35.9 (2.3), and 32.4 (2.4) for the −238G allele (ANOVA P=0.01). LPS and LTA stimulation also resulted in increased reporter activity for −238A versus −238G (ANOVA P=0.02 and P=0.04, respectively).

The promoter allele TNF-238A results in higher levels of transcriptional activation versus the TNF-238G allele in response to a clinically relevant stimulus, and provides functional evidence for the significance of this polymorphism in the development of osteolysis after THA.