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Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_I | Pages 60 - 60
1 Jan 2003
Wilkinson JM Wilson AG Stockley I Scott IR Macdonald DA Hamer AJ Eastell R
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Tumour necrosis factor-α (TNF) is thought to play a role in aseptic loosening, the major cause of implant failure after total hip arthroplasty (THA). Natural sequence variations at –238 and –308 in the promoter region of the TNF gene are associated with differences in the susceptibility and severity of several TNF-mediated diseases. We tested whether carriage of the [less common] ‘A’ allele at –238 and –308 are associated with aseptic loosening after THA.

481 Caucasians (214 with failed implants versus 267 with radiologically intact implants) were recruited 11.7± 4.1 years after cemented THA for osteoarthritis. Genomic DNA was extracted from peripheral blood and genotyped for the –238 and –308 polymorphisms using the Taqman® 5′ nuclease method. 500 subjects from the local population were also genotyped using Taqman® to establish the background prevalence of the ‘A’ allele at each site.

The carriage rate of –238A was 8.8% in the background population and 10.9% in the THA controls (P> 0.05). –238A carriage in the loosening group was 17.3% (odds ratio 1.72, 95% confidence interval 1.02 to 2.90). Carriage was highest (20.5%) in subjects with loosening of both the femoral and pelvic implant components (odds ratio 2.12; 1.17 to 3.83). The association of –238A with aseptic loosening was independent of age, sex, and amount of implant wear (Cox hazard ratio 1.49 (1.04 to 2.13; P=0.03)). Carriage of –308A was not associated with aseptic loosening.

Genetic, as well as environmental factors, influence implant failure after THA. Whether the –238 polymorphism causes the biological change that predisposes to loosening, or is in linkage disequilibrium with such a locus, is not yet known.


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_I | Pages 34 - 34
1 Jan 2003
Wilkinson J Stockley I Peel N Hamer A Elson R Barrington N Eastell R
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An acute phase of periprosthetic bone loss occurs following total hip arthroplasty (THA). Periprosthetic bone loss undermines implant support, may contribute to its failure, and complicates revision surgery as allograft may be required to replace lost bone. We assessed the effect of a single 90mg dose of the bisphosphonate pamidronate on early periprosthetic bone mineral density (BMD), biochemical markers of bone turnover, and clinical outcome in 47 men and women undergoing hybrid THA in a randomised, double-blinded, placebo-controlled trial.

The mean (± 95% CI) differences in BMD (area under BMD change.time curve) between those receiving pamidronate and those receiving placebo was 0.91(± 0.51) g.weeks/cm2 for the proximal femur (P=0.002), and 0.80 (±0.60) g.weeks/cm2 for the pelvis (P=0.009). Patients in the pamidronate group had suppression of all biochemical markers of bone turnover compared to placebo (P< 0.05), except for urinary free deoxypyridinoline. Both treatment groups experienced similar improvement in Harris hip and SF-36 UK outcome scores. The frequency of adverse events was similar in each treatment group (placebo 7/24, pamidronate 8/23, P> 0.05).

Acute periprosthetic bone loss following THA is due to a transient increase in bone turnover. A single dose infusion of pamidronate in the early post-operative period significantly reduces this bone loss, and is well tolerated.


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_I | Pages 59 - 59
1 Jan 2003
Wilkinson JM Stockley I Hamer AJ Elson RA Eastell R
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Factors that allow the generation or ingression of wear particles at the implant-host interface after total hip arthroplasty (THA) may include early migration and periprosthetic bone loss. We have previously shown that a single 90mg dose of the bisphosphonate pamidronate prevents bone loss over 6 months after THA. In this 2 year randomised trial extension study we assessed the longer term effects of this intervention on bone loss and implant migration.

Twenty-two patients received 90mg of pamidronate and 22 received placebo at randomisation 5 days after surgery. Femoral and pelvic bone mineral density (BMD) was measured by dual energy x-ray absorptiometry (DXA) and implant migration was measured using the EBRA-Digital method over a 104 week period.

In the placebo group rapid periprosthetic bone loss occurred over the first 6 months. After this period a partial recovery in bone mass occurred in most regions. Patients in the pamidronate group had significantly less femoral, but not pelvic, bone loss than those give placebo (ANOVA P=0.02). Pamidronate was most effective in preventing bone loss in Gruen zones 6 and 7 (ANOVA P=0.004, and P=0.014, respectively). At week 104 the mean total stem migration was 1.77mm±0.27 and 1.62mm±0.37 for the placebo and pamidronate groups, respectively (P> 0.05). Total cup migration was 0.75mm±0.26 and 0.76mm±0.14, respectively (P> 0.05). Age at surgery accounted for 26% (linear regression r=−0.65, P=0.02) and 38% (r=−0.51, P=0.007) of the variability in stem and cup migration at week 104, with younger subjects experiencing greater migration. Stem migration at week 104 was also inversely related to the Barrack cement mantle grade (r=−0.66, r2 41%, P=0.0003). Implant migration was not significantly related to changes in periprosthetic bone mass.

Pamidronate therapy has a significant effect on bone mass, but not implant stability, after THA.Our findings suggest that the major determinants of early migration after THA are young patient age and poor cementing technique.


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_II | Pages 151 - 151
1 Jul 2002
Wilkinson JM Stockley I Peel NFA Hamer AJ Barrington NA Eastell R
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We aimed to determine whether acute periprosthetic bone loss at 1 year following THA may be predicted by early changes in markers of bone turnover, and prevented by a single 90 mg dose of pamidronate in a randomized trial of 46 men and women undergoing primary THA.

Femoral BMD was measured at postoperative baseline, and 6, 12, 26, and 52 weeks later using an Hologic 4500-A densitometer. Markers of bone turnover were measured at preoperative baseline and at 1, 6, 12, and 26 weeks.

Patients in the placebo group lost significantly more periprosthetic bone than those in the pamidronate group. The mean (±95% CI) difference in proximal femoral BMD (area under BMD change.time curve) between those receiving pamidronate and those receiving placebo was 1.84 (±1.29) g.weeks/cm2 (P=0.02). A transient increase in all markers of bone turnover was seen in the placebo group, with peaks in osteoclast activity at 6 weeks, and peaks in osteoblast activity 12 weeks. Pamidronate therapy was associated with suppression of all markers of bone turnover with the exception of the resorption marker iFDpd (P< 0.05).

Using a multiple regression analysis model the AUC changes in bone markers predicted 42% of proximal femoral BMD change at 1 year (P=0.006). Using only change in 2 of the markers (PINP and iFDpd) at 6 weeks 28% of proximal femoral BMD change at 1 year could be predicted (P=0.01).

THA is associated with a transient increase in bone remodelling units and bone loss. The relationship between femoral bone loss and turnover markers in the placebo group suggests that the transient increase in these markers reflects local changes in BMD, and that pamidronate reduces bone loss by preventing increased local bone turnover.


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_II | Pages 152 - 152
1 Jul 2002
Phillips NJ Wilkinson JM Stockley I
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We aimed to determine whether the EBRA method had greater precision and sensitivity for measuring implant migration following total hip arthroplasty (THA) than direct plain radiographic techniques using modern measuring tools.

Short-term precision was evaluated in 20 subjects following THA. Consecutive, standardised radiographs of the hip were performed on the same day after repositioning. Prosthetic cup and stem migration were measured from the plain radiographs using a digital calliper following methods described by Ianotti, Malchau, Nunn, Sutherland and Wetherall, and compared to those made using EBRA. Precision was expressed as 95% confidence interval (95%CI = 1.96x Std.dev.). 10 subjects were then followed prospectively with standardised plain radiographs at baseline, 6,12 and 26 weeks after THA. Migration measurements made using EBRA were compared to those made using the most precise plain radiographic method.

The 95%CI of all EBRA cup and stem measurements was ±1mm or smaller. Only the Sutherland method had a similar level of precision (95%CI ±1.11 to 1.28 mm: F-Test P> 0.05; all other method comparisons with EBRA P< 0.05). In the longitudinal study cup cranial migration of 0.53 mm (SEM 0.19) and stem subsidence of 1.53 mm (SEM 0.19) were detected using EBRA (2-way ANOVA by rank; P< 0.05 and P< 0.001 respectively). No statistically significant migration of the cup or stem was detected using the Sutherland method.

The EBRA method is a precise method for describing implant migration in small groups of patients in the early period following THA, and manual methods lack sufficient precision to be used for this purpose.


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_II | Pages 152 - 152
1 Jul 2002
Wilkinson JM Stockley I Barrington NA Eastell R
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We aimed to determine whether development of heterotopic ossification (HO) following THA might be predicted by early changes in biochemical markers of bone turnover.

The study cohort consisted of 21 men and women taking part in a randomised trial of the bisphosphonate pamidronate in the prevention of bone loss following THA. All had under gone unilateral THA using the same design of implant and all were assigned to placebo in the trial. The osteoblast activity markers bone-specific alkaline phosphatase (bAP), osteocalcin (Oc), and N-terminal propeptide of type-I procollagen (PINP); and the osteoclast activity markers deoxypyridinoline (iFDpd) and N-telopeptide of type-I collagen (NTx) were measured at baseline, and at 1, 6, 12, and 26 weeks following unilateral THA. The presence of HO was assessed using the Brooker grading by a musculoskeletal radiologist from plain AP radiographs of the hip taken at week 26.

A transient increase in all turnover markers occurred following surgery, with peaks in iFDpd, NTx, and PINP at 6 weeks, and peaks in bAP and Oc at 12 weeks. 10 subjects had HO at week 26 (all Brooker grade 1 or 2). Subjects with HO had higher mean peak rises (SEM) in PINP and Oc than those without HO (PINP 81% (10) versus 43% (10), P=0.01; Oc 26% (5) versus 9% (6), P=0.04). Using area under the curve ‘ROC’ analysis, PINP and Oc were equally discriminatory in predicting HO formation (P< 0.05). The optimal cut-off peak rise of > 57% in PINP at 6 weeks following THA had a sensitivity and specificity of 90 and 82, respectively for predicting the development of HO.

An increase in PINP of more than 57% 6 weeks following THA is predictive of the development of HO at 26 weeks. This early prediction might allow identification of patients in whom early therapeutic measures could be taken.


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_II | Pages 152 - 152
1 Jul 2002
Taggart T Kerry RM Stockley I Norman P
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The incidence of infection after primary arthroplasty is low. However, with the increasing number of arthroplasties being performed the prevalence of infection is increasing. The pattern of infecting organisms following total joint arthroplasty has changed and gentamicin resistant organisms are becoming increasingly common. Vancomycin added to bone a cement carrier can, with adequate surgical debridement be very effective in the eradication of established resistant infection. We report the results of its use in 33 patients with 26 infected hip and 7 infected knee arthroplasies. 32 patients remain clinically and radiologically free of infection after a mean follow-up of 67 months. There was one recurrence of infection and there were three positive second stage cultures of uncertain significance. Vancomycin is potentially a very useful tool in the management of deep infection following arthroplasty surgery.


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_II | Pages 154 - 154
1 Jul 2002
Graham NM Stockley I
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In Sheffield the senior author has a long experience in the use of massive circumferential proximal femoral allografts in complex revision hip arthroplasty. Sheffield has a well established bone harvesting and banking service, essential for this type of work.

We wish to present the early experience with this technique in the UK.

Between April 1992 and November 1998 a total of 33 circumferential proximal femoral allografts were used by one senior surgeon. They were all fresh frozen, cadaveric grafts. This time period was selected to allow a reasonable minimum follow-up period. Seven patients had died and two were lost to follow up, leaving a total of 24 patients to review.

A step cut osteotomy was utilised and augmented with a cerclage wire and strut allograft where deemed necessary. The proximal femur was retained where possible. The component was cemented into the allograft only, in the majority of the cases. A cemented, collared prosthesis was used in over 85% of cases.

Average follow up was 53 months. By the time of review 2 had undergone further revision, one for sepsis, one for aseptic loosening. A further patient had had revision of the acetabular component in isolation. One patient had recurrent sepsis but is currently being managed non–operatively. One patient required secondary surgery with plate and graft for symptomatic junctional non-union.

Other complications included wound drainage, delaying discharge, in three patients and one chronic sciatic nerve palsy.

The trochanter was considered radiologically united in 18 patients. Junctional union was considered to have occurred in 17 patients. Allograft resorption of 100% cortical thickness was seen in only 9 patients and in only one zone in 6 of these.

Oxford hip scores were collected at follow-up.

We recommend this technique in cases where bone loss is catastrophic and in specialist hands only.