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 loosening^1,2 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

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.

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.

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.

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.

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.