To investigate whether elective joint arthroplasty performed
at the weekend is associated with a different 30-day mortality We examined the 30-day cumulative mortality rate (Kaplan-Meier)
for all elective hip and knee arthroplasties performed in England
and Wales between 1st April 2003 and 31st December 2014, comprising
118 096 episodes undertaken at the weekend and 1 233 882 episodes
performed on a weekday. We used Cox proportional-hazards regression
models to assess for time-dependent variation and adjusted for identified
risk factors for mortality.Aims
Patients and Methods
Wear particles cause aseptic loosening by stimulating macrophages to produce inflammatory cytokines. Recent studies indicate that Toll-like receptor 2 (TLR2) and TLR4 mediate macrophage responses to the wear particles [1–3]. TLR2 and TLR4 uniquely activate MyD88-dependent signaling via an additional adapter protein known as TIRAP/Mal [4]. Del Vescovo et al reported that three single nucleotide polymorphisms (SNPs) within the TIRAP/Mal gene associate with aseptic loosening in THA patients [5]. The goal of the current study was therefore to determine whether TIRAP/Mal mediates responses to orthopaedic wear particles. Immortalized wild type (WT) and TIRAP/Mal knockout (KO) murine macrophages (Mfs) were incubated in the presence or absence of titanium (Ti) particles (1 × 108 particles/cm2 [2]. Three types of particles were used as described previously [1,2]: Ti particles with adherent bacterial debris (38.3 Endotoxin Units/109 particles), endotoxin-free Ti particles (<0.1 EU/109 particles), and Ti particles with adherent lipopolysacharide (LPS, 32.8 EU/109 particles). TNFa, IL-1b, and IL-6 mRNAs were measured by real-time PCR and the secreted cytokines were measured by ELISA. Particle-induced osteolysis in calvaria of TIRAP/Mal KO and WT mice was measured 7 days after particle implantation [1,2]. Introduction:
Methods:
Between 1988 and 1998 we implanted 318 total hip replacements (THRs) in 287 patients using the Plasmacup (B. Braun Ltd, Sheffield, United Kingdom) and a conventional metal-on-polyethylene articulation. The main indications for THR were primary or secondary osteoarthritis. At follow-up after a mean 11.6 years (7.6 to 18.4) 17 patients had died and 20 could not be traced leaving a final series of 280 THRs in 250 patients. There were 62 revisions (22.1%) in 59 patients. A total of 43 acetabular shells (15.4%) had been revised and 13 (4.6%) had undergone exchange of the liner. The most frequent indications for revision were osteolysis and aseptic loosening, followed by polyethylene wear. The mean Kaplan-Meier survival of the Plasmacup was 91% at ten years and 58% at 14 years. Osteolysis was found around 36 (17.1%) of the 211 surviving shells. The median annual rate of linear wear in the surviving shells was 0.12 mm/year and 0.25 mm/year in those which had been revised (p <
0.001). Polyethylene wear was a strong independent risk factor for osteolysis and aseptic loosening. The percentage of patients with osteolysis increased proportionately with each quintile of wear-rate. There is a high late rate of failure of the Plasmacup. Patients with the combination of this prosthesis and bearing should be closely monitored after ten years.
The adjusted odds ratios for pelvic osteophytes and HO with carriage of the rare FRZB 200 variant were 4.34 (1.01–18.7 p=0.048) and 1.64 (1.05 to 2.54, p=0.028) respectively. The adjusted odds ratio for osteolysis was 0.62 (0.38 to 0.99 p=0.049). There were no bone phenotype associations with the FRZB Arg324Gly variants.
Bleeding is a major complication of revision total hip replacement. We report a case where the inflated balloon of a urinary catheter was used to temporarily control intrapelvic bleeding from the superior gluteal artery, while definitive measures for endovascular embolisation were made.
The aims of this study were to examine the repeatability of measurements of bone mineral density (BMD) around a cemented polyethylene Charnley acetabular component using dual-energy x-ray absorptiometry and to determine the longitudinal pattern of change in BMD during the first 24 months after surgery. The precision of measurements of BMD in 19 subjects ranged from 7.7% to 10.8% between regions, using a four-region-of-interest model. A longitudinal study of 27 patients demonstrated a transient decrease in net pelvic BMD during the first 12 months, which recovered to baseline at 24 months. The BMD in the region medial to the dome of the component reduced by between 7% and 10% during the first three months, but recovered to approximately baseline values by two years. Changes in BMD in the pelvis around cemented acetabular components may be measured using dual-energy x-ray absorptiometry. Bone loss after insertion of a cemented Charnley acetabular component is small, transient and occurs mainly at the medial wall of the acetabulum. After two years, bone mass returns to baseline values, with a pattern suggesting a uniform transmission of load to the acetabulum.
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.
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.
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.
The Sheffield Expanding Intramedullary Rod System was developed after experiencing problems with existing rod systems in the management of osteogenesis imperfecta. Between 1986 and 1996 we treated 74 bones in the lower limb in 28 children at a median follow-up of 5.25 years. We have reviewed 24 children with a total of 60 rods. Before surgery, all children had had multiple fractures of the lower limb. At review eight patients had experienced no further fractures, but three had suffered five or more subsequently. Before initial stabilisation, 15 children had never walked, and only three (13%) used walking as their main means of mobility. After surgery, half of those who showed motor arrest were able to walk (p = 0.016). The number of patients able to walk, with or without aids, increased to 17 (p = 0.0001). We have experienced no evidence of epiphyseal damage after the procedure, and complication rates requiring rod exchange have been low (7%).