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.

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.

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.

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.

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.

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.

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.

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.

Although the incidence of infection associated with hip and knee prostheses is low, with the increasing number of arthroplasties being carried out, the total number of such cases is increasing. The pattern of infecting organisms after total joint arthroplasty has changed and gentamicin-resistant organisms are becoming increasingly common. In conjunction with surgical debridement, vancomycin added to a bone-cement carrier can be very effective in the treatment of infection caused by such organisms.

We report the results of its use in proven deep infection in 26 hip and seven knee arthroplasties. After a mean follow-up of 67 months, 32 patients remained clinically and radiologically free from infection. There was one recurrence and positive second-stage cultures of uncertain significance in three other patients. Vancomycin is potentially very useful in the management of deep infection after arthroplasty.

We aimed to evaluate the precision and longitudinal sensitivity of measurement of bone mineral density (BMD) in the pelvis and to determine the effect of bone cement on the measurement of BMD in femoral regions of interest (ROI) after total hip arthroplasty (THA).

A series of 29 patients had duplicate dual-energy x-ray absorptiometry (DXA) scans of the hip within 13 months of THA. Pelvic analyses using 3- and 4-ROI models gave a coefficient of variation (CV) of 2.5% to 3.6% and of 2.5% to 4.8%, respectively. Repeat scans in 17 subjects one year later showed a significant change in BMD in three regions using the 4-ROI model, compared with change in only one region with the 3-ROI model (p < 0.05).

Manual exclusion of cement from femoral ROIs increased the net CV from 1.6% to 3.6% (p = 0.001), and decreased the measured BMD by 20% (t = 12.1, p < 0.001). Studies of two cement phantoms in vitro showed a small downward drift in bone cement BMD giving a measurement error of less than 0.03 g/cm²/year associated with inclusion of cement in femoral ROIs.

Changes in pelvic periprosthetic BMD are best detected using a 4-ROI model. Analysis of femoral ROI is more precise without exclusion of cement although an awareness of its effect on the measurement of the BMD is needed.

We report two cases of fungal infection of prosthetic joints which were successfully treated by the incorporation of fluconazole into polymethylmethacrylate beads inserted at the time of debridement.

Secondary sterilisation of allograft bone by gamma irradiation is common, but the conditions under which it is performed vary between tissue banks. Some do so at room temperature, others while the bone is frozen. Bone is made brittle by irradiation because of the destruction of collagen alpha chains, probably mediated by free radicals generated from water molecules. Freezing reduces the mobility of water molecules and may therefore decrease the production of free radicals. We found that bone irradiated at −78°C was less brittle and had less collagen damage than when irradiated at room temperature. These findings may have implications for bone-banking.

There have been conflicting reports on the effects of gamma irradiation on the material properties of cortical allograft bone. To investigate changes which result from the method of preparation, test samples must be produced with similar mechanical properties to minimise variations other than those resulting from treatment.

We describe a new method for the comparative measurement of bone strength using standard bone samples. We used 233 samples from six cadavers to study the effects of irradiation at a standard dose (28 kGy) alone and combined with deep freezing. We also investigated the effects of varying the dose from 6.8 to 60 kGy (n = 132).

None of the treatments had any effect on the elastic behaviour of the samples, but there was a reduction in strength to 64% of control values (p < 0.01) after irradiation with 28 kGy. There was also a dose-dependent reduction in strength and in the ability of the samples to absorb work before failure

We suggest that irradiation may cause an alteration in the bone matrix of allograft bone, but provided it is used in situations in which loading is within its elastic region, then failure should not occur.

We report a series of 17 exchange arthroplasties for infected knee prostheses, ten one-stage and seven two-stage procedures. The method proved successful in controlling infection and restoring function. In two-stage exchanges the interval between the stages was managed by using a prosthesis as a spacer, and acrylic cement beads containing the appropriate antibiotic to provide high local concentrations. Three one-stage procedures had recurrence of infection, but were successfully treated by further exchange operations. All patients had satisfactory function and there have been no serious complications. We recommend this modified two-stage technique for the management of infected knee arthroplasties.

We reviewed 32 deep-frozen irradiated allografts used for the reconstruction of bone defects in 20 knees. They were subdivided into bulk grafts, cortical strut grafts, and morsellised bone. The average follow-up was 4.2 years (2 to 7.2). Radiographs showed union of the allograft to the host in all cases. Two allografts later fractured and three knees required further surgery because of infection. The allografts effectively filled large bone defects around the knee, lessening the need for custom-made and constrained prostheses.

Five patients with Boyd type II congenital pseudarthrosis of the tibia underwent excision of the pseudarthrosis and double onlay bone grafting. Stability was maintained by extending intramedullary rods. Clinical union was achieved in all cases at a mean of 8.6 months (range six to 11). The rods extended by 15.7% (range 2% to 31.4%) as growth occurred. One rod was removed because of infection and a vascularised free fibular graft was subsequently performed. The extending rods provided stability while union occurred and did not require revision as the legs grew. The rods can be removed easily and have not jeopardized further surgical options.

In a prospective study of 100 knee arthroplasties in patients with rheumatoid arthritis, simultaneous bilateral surgery was compared with staged bilateral replacements. All patients had improved function following their operations but those who had staged surgery only achieved maximum benefit after the second knee had been replaced. The complication rate was no greater for simultaneous surgery and we therefore advocate the method for those patients who require bilateral replacements.

The relationship between hindfoot deformity and forefoot pressure was assessed in 28 rheumatoid patients who had undergone forefoot reconstruction four years previously. Patients with valgus hindfoot deformities tended to have high forefoot pressures whereas those with a normal hindfoot recorded normal pressures on the dynamic pedobarograph. All patients with residual forefoot pain recorded abnormal forefoot pressures. We believe that orthotic control of hindfoot deformities should be considered for those patients who require forefoot surgery as a combination of surgical and orthotic management may offer the best chance of success.

We report the results of using 83 expanding intramedullary rods in 24 children with osteogenesis imperfecta after a mean follow-up of five years three months. In all, 62% of the rods have expanded after one primary operation. Thirty-four additional operations were necessary; 11 for the correction of rotation or angulation deformities and 23 for revision of the rod or T-piece. All these revisions were successful. Complications were more frequent in children who required very small rods. Problems with Bailey-Dubow rods led to the development of the Sheffield rod system; 17 bones treated with these rods are included in the series. Before surgery only eight of the 24 children were able to walk but at review 20 children were walking, 15 without walking aids. Elongating intramedullary rods should be available to all children with osteogenesis imperfecta as they improve walking capability, reduce the number of fractures, prevent deformity and allow integration of the child into society.