Successful estimation of postoperative PROMs prior to a joint replacement surgery is important in deciding the best treatment option for a patient. However, estimation of the outcome is associated with substantial noise around individual prediction. Here, we test whether a classifier neural network can be used to simultaneously estimate postoperative PROMs and uncertainty better than current methods.

We perform Oxford hip score (OHS) estimation using data collected by the NJR from 249,634 hip replacement surgeries performed from 2009 to 2018. The root mean square error (RMSE) of the various methods are compared to the standard deviation of outcome change distribution to measure the proportion of the total outcome variability that the model can capture. The area under the curve (AUC) for the probability of the change score being above a certain threshold was also plotted.

The proposed classifier NN had a better or equivalent RMSE than all other currently used models. The threshold AUC shows similar results for all methods close to a change score of 20 but demonstrates better accuracy of the classifier neural network close to 0 change and greater than 30 change, showing that the full probability distribution performed by the classifier neural network resulted in a significant improvement in estimating the upper and lower quantiles of the change score probability distribution. Consequently, probabilistic estimation as performed by the classifier NN is the most adequate approach to this problem, since the final score has an important component of uncertainty.

This study shows the importance of uncertainty estimation to accompany postoperative PROMs prediction and presents a clinically-meaningful method for personalised outcome that includes such uncertainty estimation.

Increased collection of patient-reported outcome measures (PROM) in registries enables international comparison of patient-centered outcomes after knee and hip replacement. We aimed to investigate 1) variations in PROM improvement, 2) the possible confounding factor of BMI, and 3) differences in comorbidity distributions between registries.

Registries affiliated with the International Society of Arthroplasty Registries (ISAR) or OECD membership countries were invited to report aggregate EQ-5D, OKS, OHS, HOOS-PS and KOOS-PS values. Eligible patients underwent primary total, unilateral knee or hip replacement for osteoarthritis within three years and had completed PROMs preoperatively and either 6 or 12 months postoperatively, excluding patients with subsequent revisions. For each PROM cohort, Chi-square tests were performed for BMI distributions across registries and 12 predefined PROM strata (male/female, age 20-64/65-74/>75, high or low preoperative PROM scores). Comorbidity distributions were reported for available comorbidity indexes.

Thirteen registries from 9 countries contributed data, n~130000 knee (range 140 to 79848) and n~113000 hip (range 137 to 85281). Mean EQ-5D index values (10 registries) ranged from 0.53 to 0.71 (knee) and 0.50 to 0.70 (hips) preoperatively and 0.78 to 0.85 (knee) and 0.83 to 0.87 (hip) postoperatively. Mean OKS (6 registries) ranged from 19.3 to 23.6 preoperatively and 36.2 to 41.2 postoperatively. Mean OHS (7 registries) ranged from 18.0 to 23.2 preoperatively and 39.8 to 44.2 postoperatively. Four registries reported KOOS-PS and three reported HOOS-PS. Proportions of patients with BMI >30 ranged from 35 to 62% (10 knee registries) and 16 to 43% (11 hip registries). For both knee and hip registries, distributions of patients across six BMI categories differed significantly among registries (p30 were for patients in the youngest age groups (20 to 64 and 65 to 74 years) with the lowest baseline scores. Additionally, females with lowest preoperative PROM scores had highest BMI. These findings were echoed for the OHS and OKS cohorts. Proportions of patients with ASA scores ≥3 ranged from 7 to 42% (9 knee registries) and 6 to 35% (8 hip registries).

PROM-score improvement varies between international registries, which may be partially explained by differences in age, sex and preoperative scores. BMI and comorbidity may be relevant to adjust for.

Data of high quality are critical for the meaningful interpretation of registry information. The National Joint Registry (NJR) was established in 2002 as the result of an unexpectedly high failure rate of a cemented total hip arthroplasty. The NJR began data collection in 2003. In this study we report on the outcomes following the establishment of a formal data quality (DQ) audit process within the NJR, within which each patient episode entry is validated against the hospital unit’s Patient Administration System and vice-versa. This process enables bidirectional validation of every NJR entry and retrospective correction of any errors in the dataset. In 2014/15 baseline average compliance was 92.6% and this increased year-on-year with repeated audit cycles to 96.0% in 2018/19, with 76.4% of units achieving > 95% compliance. Following the closure of the audit cycle, an overall compliance rate of 97.9% was achieved for the 2018/19 period. An automated system was initiated in 2018 to reduce administrative burden and to integrate the DQ process into standard workflows. Our processes and quality improvement results demonstrate that DQ may be implemented successfully at national level, while minimizing the burden on hospitals.

Cite this article: Bone Jt Open 2022;3(9):716–725.

Aims

Our main aim was to describe the trend in the comorbidities of patients undergoing elective total hip arthroplasties (THAs) and knee arthroplasties (KAs) between 1 January 2005 and 31 December 2018 in England.

Aims

A recent report from France suggested an association between the use of cobalt-chrome (CoCr) femoral heads in total hip arthroplasties (THAs) and an increased risk of dilated cardiomyopathy and heart failure. CoCr is a commonly used material in orthopaedic implants. If the reported association is causal, the consequences would be significant given the millions of joint arthroplasties and other orthopaedic procedures in which CoCr is used annually. We examined whether CoCr-containing THAs were associated with an increased risk of all-cause mortality, heart outcomes, cancer, and neurodegenerative disorders in a large national database.

Abstract

Abstract

Aims

Debate remains whether the patella should be resurfaced during total knee replacement (TKR). For non-resurfaced TKRs, we estimated what the revision rate would have been if the patella had been resurfaced, and examined the risk of re-revision following secondary patellar resurfacing.

Abstract

Aims

To develop and validate patient-centred algorithms that estimate individual risk of death over the first year after elective joint arthroplasty surgery for osteoarthritis.

The use of cementless acetabular components is currently the gold standard for treatment in total hip arthroplasty (THA). Porous coated cups have a low modulus of elasticity that enhances press-fit and a surface that promotes osseointegration. Monoblock acetabular cups represent a subtype of uncemented cup with the liner moulded into the metal shell, minimizing potential backside wear and eliminating the chance of mal-seating. The aim of this study was to compare the short-term clinical and radiographic performances of a modular cup with that of a monoblock cup, with particular interest in the advent of lucent lines and their correlation with clinical outcomes.

In this multi-surgeon, prospective, randomized, controlled trial, 86 patients undergoing unilateral THA were recruited. Participants were randomized to either a porous-coated, modular metal-on-polyethylene (MoP) acetabular component (n=46) or a hydroxyapatite (HA)- and titanium-coated monoblock shell with ceramic-on-ceramic (CoC) bearing (n=42). The porous-coated cup had an average pore size of 250 microns with an average volume porosity of 45%, whereas the monoblock shell had an average pore size of 300 microns with an average volume porosity of 48% and a HA coating thickness of 80 nm. There were no baseline demographic differences between both groups regarding sex, age, body mass index (BMI), or American Society of Anaesthesia (ASA) class (p>0.05). All of the sockets were under-reamed by 1 mm. Radiographs and patient-reported outcome measures (PROMs), including modified Harris Hip Score (mHHS), Western Ontario and McMaster Universities Arthritis Index (WOMAC) and University of California at Los Angeles (UCLA) Hip Score, were available for evaluation at a minimum of 2 years of follow-up. A radiolucent distance between the cup and acetabulum of ≥0.5 mm was defined as gap if it was diagnosed from outset or as radiolucency if it had sclerotic edges and was found on progressive x-ray analyses.

Thirty-two gaps (69%) were found in the modular cup group and 28 (6%) in the monoblock one (p=0.001). Of the former, 17 filled the gaps whereas 15 turned into a radiolucency at final assessment. Of the latter, only 1 of the gaps turned into a radiolucency at final follow-up (p 0.05) in both groups. Only the porous-coated cup was an independent predictor of lucent lines (OR:0.052, p=0.007). No case underwent revision surgery due to acetabular loosening during the study period. Only 2 cases of squeaking were reported in the CoC monoblock shell.

Both porous-coated modular and hydroxyapatite-coated monoblock cups showed successful clinical results at short-term follow-up, however, the former evidenced a significantly higher rate of radiolucent line occurrence, without any association with PROMs. Since these lines indicate the possibility of future cup loosening, longer follow-up and assessment are necessary.

Local and systemic concentrations of cobalt (Co) and chromium (Cr) ions may be elevated in patients with accelerated tribo-corrosion at prosthesis bearing surfaces and modular taper junctions. Previous studies by us and others have shown that exposure to these metals negatively affect the viability and function of osteoblasts and osteoclasts in vitro, with implications for bone health. More recently, we have observed an increase in total bone mineral density and reduced bone turnover (TRAP5b and osteocalcin) in patients with well-functioning metal-on-metal hip resurfacing (MOMHR). Here, we provide data to support the hypothesis that osteoclast differentiation and function is altered in this patient population, and that this effect is transferrable through their serum.

Patients with well-functioning MOMHR (n=18) at median follow-up of 8 years were individually matched for gender, age and time-since-surgery to a low-exposure group consisting of patients with metal-on-polyethylene total hip arthroplasty (THA). The median circulating concentrations of Co and Cr for the MOMHR group were 2.53µg/L and 2.5µg/L respectively, compared to 0.02µg/L and 0.03µg/L for the THA group. Monocyte fraction of peripheral blood was isolated from these patients, seeded onto dentine wafers and differentiated into osteoclasts using media supplemented with RANKL and M-CSF (osteoclastogenic media, OM). Cultures were monitored for the onset of resorption, following which they were treated with OM, autologous serum or serum from the other individual within the matched MOMHR - THA pair, all supplemented with RANKL and M-CSF. At the end of the culture, cells were TRAP stained and quantified for total osteoclast number, number of resorbing osteoclasts and percentage resorption using the CellD Software Package (Olympus, Southend-on-Sea, U.K.).

For cells differentiated in osteoclastogenic media, the resorbing ability of osteoclasts derived from MOMHR patients was reduced by 30% (P=0.046) compared to THA. Correlation analyses showed that chronic exposure to Co and Cr trends towards negative association with resorption ability of these osteoclasts (r = −0.3, P=0.06). Furthermore, the resorbing ability of osteoclasts generated from MOMHR patients and differentiated in autologous serum was reduced 33% (p < 0 .0001), whilst matched THA serum caused a smaller reduction of 14% (p < 0 .01). When cells derived from THA patients were differentiated in autologous serum, the resorbing ability of osteoclasts was similarly reduced by 35% (p < 0 .0001), whilst the matched MOMHR serum also caused a reduction of 21% (p < 0 .0001).

Reduced osteoclastogenic response of precursor cells from patients with higher circulating Co and Cr suggests an inherent change in their potential to differentiate into functional osteoclasts. The data also suggests that functional response of mature osteoclasts generated from patient precursor cells are dependent on the prior systemic metal concentrations and the presence of higher circulating CoCr in patients with MOMHR. These effects are modest, but may explain the subtle increase in systemic bone mineral density and decreased bone turnover observed in patients after 8 years exposure compared to age, sex, and exposure-time matched patients who received a conventional THA.

In conventional DXA (Dual-energy X-ray Absorptiometry) analysis, pixel bone mineral density (BMD) is often averaged at the femoral neck. Neck BMD constitutes the basis for osteoporosis diagnosis and fracture risk assessment. This data averaging, however, limits our understanding of localised spatial BMD patterns that could potentially enhance fracture prediction. DXA region free analysis (RFA) is a validated toolkit for pixel-level BMD analysis. We have previously deployed this toolkit to develop a spatio-temporal atlas of BMD ageing in the femur. This study aims first to introduce bone age to reflect the overall bone structural evolution with ageing, and second to quantify fracture-specific patterns in the femur.

The study dataset comprised 4933 femoral DXA scans from White British women aged 75 years or older. The total number of fractures was 684, of which 178 were reported at the hip within a follow-up period of five years. BMD maps were computed using the RFA toolkit. For each BMD map, bone age was defined as the age for which the L2-norm between the map and the median atlas at that age is minimised. Next, bone maps were normalised for the estimated bone age. A t-test followed by false discovery rate (FDR) analysis was applied to compare between fracture and non-fracture groups.

Excluding the ageing effect revealed subtle localised patterns of loss in BMD oriented in the same direction as principal tensile curves. A new score called f-score was defined by averaging the normalised pixel BMD values over the region with FDR q-value less than 1e–6. The area under the curve (AUC) was 0.731 (95% confidence interval (CI)=0.689–0.761) and 0.736 (95% CI=0.694–0.769) for neck BMD and f-score. Combining bone age and f-score improved the AUC significantly by 3% (AUC=0.761, 95% CI=0.756–0.768) over the neck BMD alone (AUC=0.731, 95% CI=0.726–0.737).

This technique shows promise in characterizing spatially-complex BMD changes, for which the conventional region-based technique is insensitive. DXA RFA shows promise to further improve fracture prediction using spatial BMD distribution.

Ageing is associated with a gradual and progressive bone loss, which predisposes to osteoporosis. Given the close relationship between the involutional bone loss and the underlying mechanism of osteoporosis, improving the understanding of the bone ageing process can lead to enhanced preventive and therapeutic strategies for osteoporosis. To facilitate this understanding, we develop a spatio-temporal atlas of ageing bone in the femur.

We applied our method to a cohort of 11,576 Caucasian women (20–97 years). We amalgamated data from three different studies: 5095 women from the UK Biobank study, 1609 women from the OPUS study, and 5112 women from the MRC-Hip study. The scans are collected using either a Hologic QDR 4500A (Waltham, MA), a Lunar GE iDXA (Madison, WI), or a Lunar GE Prodigy (Madison, WI). Pixel BMD maps were exported using APEX v3.2 and Encore v16 for scans collected on Hologic Inc. and Lunar Corp., respectively. The method utilises a thin plate spline (TPS) registration to warp each scan to a reference mean shape. This image warping, termed Region Free Analysis (RFA), aims to eliminate morphological variation and establish a correspondence between pixel coordinates. At each pixel coordinate, the BMD evolution with ageing was modelled using smooth quantile curves. We deployed the R-package ‘VGAM’ to fit the smooth quantile curves.

Cortical thinning was observed consistently with ageing around the shaft from the 60th onwards. A widespread bone loss was also observed in the trochanteric area. Quantile regression curves demonstrated different rates of bone loss at different anatomic locations. For example, bone loss was observed consistently in the mid-femoral neck, while bone mass was preserved the most in the inferior cortex. The developed atlas provides new insights into the spatial bone loss patterns, for which the conventional DXA analysis is insensitive.

The development of an algorithm that provides accurate individualised estimates of revision risk could help patients make informed surgical treatment choices. This requires building a survival model based on fixed and modifiable risk factors that predict outcome at the individual level. Here we compare different survival models for predicting prosthesis survivorship after hip replacement for osteoarthritis using data from the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man.

In this comparative study we implemented parametric and flexible parametric (FP) methods and random survival forests (RSF). The overall performance of the parametric models was compared using Akaike information criterion (AIC). The preferred parametric model and the RSF algorithm were further compared in terms of the Brier score, concordance index (C index) and calibration.

The dataset contains 327 238 hip replacements for osteoarthritis carried out in England and Wales between 2003 and 2015. The AIC value for the FP model was the lowest. The averages of survival probability estimates were in good agreement with the observed values for the FP model and the RSF algorithm. The integrated Brier score of the FP model and the RSF approach over 10 years were similar: 0.011 (95% confidence interval: 0.011–0.011). The C index of the FP model at 10 years was 59.4% (95% confidence interval: 59.4%–59.4%). This was 56.2% (56.1%–56.3%) for the RSF method.

The FP model outperformed other commonly used survival models across chosen validation criteria. However, it does not provide high discriminatory power at the individual level. Models with more comprehensive risk adjustment may provide additional insights for individual risk.

Heterotopic ossification (HO) is lamellar bone formation that occurs within tissues that do not normally have properties of ossification. The pathoaetiology of HO is poorly understood. We conducted a genome wide association study to better understand the genetic architecture of HO.

891 patients of European descent (410 HO cases) following THA for primary osteoarthritis were recruited from the UK. HO was assessed from plain AP radiographs of the pelvis. Genomic DNA was extracted, genotyped using the Illumina 610 beadchip and referenced using the 1000 Genome Project panel. HO susceptibility case-control analysis and an evaluation of disease severity in those with HO was undertaken using SNPTESTv2.3.0 on>10 million variants. We tested variants most strongly associated with HO in an independent UK THA replication cohort comprising 209 cases and 211 controls. The datasets were meta-analysed using PLINK.

In the discovery cohort 70 signals with an index variant at p<9×10–5 were suggestively associated with HO susceptibility. The strongest signal lay just downstream of the gene ARHGAP18 (rs59084763, effect allele frequency (EAF) 0.19, OR1.87 [1.48–2.38], p=2.48×10–8), the second strongest signal lay within the long non-coding (LNC) RNA gene CASC20 (rs11699612, EAF 0.25, OR1.73 [1.1.40–2.16, p=9.3×10–8). In the discovery cohort 73 signals with an index variant at p<9×10–5 were associated with HO severity. At replication, 12 of the leading 14 susceptibility signals showed a concordant direction of allelic effect and 5 replicated at nominal significance. Following meta-analysis, the lead replicating susceptibility signal was the CASC20 variant rs11699612 (p=2.71×10–11).

We identify consistent replicating association of variation within the LNC RNA CASC20 with HO susceptibility after THA. Although the function of CASC20 is currently unknown, possible mechanisms include transcriptional, post-transcriptional and epigenetic regulation of downstream target genes. The work presented here provides new avenues for the development of novel predictive and therapeutic approaches towards HO.

Commonly used alterations of prosthetic surfaces include grit-blasting (GB), plasma-sprayed titanium (Ti) or hydroxyapatite (HA) coating. Systemic concentrations of cobalt (Co) and chromium (Cr) are elevated in patients with metal-on-metal hip replacement, but can occur for all modular hip replacements. Here, we use whole genome microarrays to assess differential gene expression in primary human osteoblasts grown in vitro and on these prosthesis surfaces following exposure to clinically relevant concentrations of Co and Cr.

Mesenchymal cells obtained from bone-fragments of 3 patients undergoing joint replacement surgery were differentiated into osteoblasts. Subsequently, cells were cultured in vitro on tissue-culture plates (TCP), or on GB, Ti and HA surfaces (JRI Orthopaedics Ltd, Sheffield, UK). Following 24hr exposure to a combination of clinically equivalent concentrations of Co2+:Cr3+, RNA was extracted and hybridized to SurePrint-G3 Gene Expression Microarray. Probe signals were normalised using ‘Limma’ package on R-Bioconductor and differential gene expression assessed with empirical Bayes approach (Log2FC>1.00, P<0.001 for differentially expressed genes).

For cells grown on TCP, 11 genes were upregulated with 500μg/L Co2+:Cr3+. Of these, 4 were associated to HIF-1 signalling based on KEGG pathway analysis (P=5.4e-5). Exposure to 1000μg/L Co2+:Cr3+ altered expression at 164 loci for HA surfaces, and a separate 50 loci for Ti surfaces compared to GB surfaces. Genes for osteoblast differentiation (BMP2 and RGS2) were downregulated on HA surfaces compared to GB, whilst genes for cell-adhesion (ESAM), vesicular trafficking (RAB37) and protection against oxidative damage (NRF2) were upregulated. Ti surfaces caused an upregulation in ERBB3 and CNTF, which are associated with inhibition of osteoblast differentiation and mineralisation, when compared to GB surfaces.

This study confirms the role of HIF-1 signalling in response to prosthesis generated metal ions, and is the first to provide a comprehensive genome-wide insight into transcriptional response of osteoblasts at prosthesis surface to clinically equivalent metal exposure.

Aims

The aim of this study was to describe temporal trends and survivorship of total hip arthroplasty (THA) in very young patients, aged ≤ 20 years.

Aims

The aim of this study was to determine whether patients with metal-on-metal (MoM) arthroplasties of the hip have an increased risk of cardiac failure compared with those with alternative types of arthroplasties (non-MoM).

Aims

To investigate whether elective joint arthroplasty performed at the weekend is associated with a different 30-day mortality versus that performed between Monday and Friday.

Introduction:

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.

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.

Introduction: Between 1987 and 1997 we implanted 319 primary hybrid total hip arthroplasties in 289 patients using the ‘Plasmacup’ (B. Braun Ltd, Sheffield) with a conventional metal on polyethylene articulation. We have observed a high revision rate with this implant recently and therefore undertook a clinical review of this cohort.

Patients and Methods: The indications for surgery were osteoarthritis (223), secondary arthritis (83), inflammatory arthritis (10), and others (3). 17 patients have died and 20 have been lost to follow up. Survival analysis was calculated using implant failure defined as revision (including liner exchange), and includes the censored patients outlined above. Assessment of complications in surviving implants was made using AP radiographs of the hip.

Results: The cup survival rate (Kaplan-Meier method) was 91% at 10 years (95%CI ± 4%) and 67% at 13 years (95%CI +/−9%). The stem survival rate was 96% at 10 years (95%CI +/−3%) and 87% at 13 years (95%CI +/−7%). The median wear in cup revisions for osteolysis was 2.4mm (IQR 1.0–3.2mm), and the median wear in surviving cups was 1.3 mm (IQR 0.8 1.9mm), and was an independent predictor of failure (Cox: p=0.001). There have been 57 revisions (35 cup only, 18 cup and stem, 4 stem only). Indications for revision were osteolysis or loosening (34), wear (18), and infection (5). In surviving cups (214), 29 have expansile acetabular osteolysis and 8 have linear osteolysis. In surviving stems (244), 14 have expansile osteolysis and 23 have linear osteolysis.

Conclusions: There is a high late failure rate of the plasma cup using a conventional metal on polyethylene articulation. Patients with this implant/bearing combination should be closely monitored, particularly after 10 years.

Introduction: The concept that aseptic loosening is a function of polyethylene wear has led to the introduction of cross-linked polyethylene in THA. We studied the relationship between polyethylene wear rate and aseptic loosening 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); isolated femoral stem looseners (n=43); and isolated cup looseners (n=34). Polyethylene 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 (OR ).

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 OR of cup loosening increased 4.7 times per standard deviation (SD) increase in wear rate above the reference (control) population (p< 0.001). The OR 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 predicted mean z-score wear rates of modified versus conventional polyethylene. 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 reduce by 7% and 17%, respectively.

Discussion: The use of cross-linked-polyethylene has the potential for a major impact on the incidence of cemented cup loosening. However their effect on femoral stem loosening may be limited.

Introduction: Bone phenotype, such as osteoarthritis (OA) pattern and development of osteolysis or heterotopic ossification (HO) after THA, may be governed by genetic and environmental factors. We investigated whether single nucleotide polymorphisms within the gene encoding secreted-Frizzled Related Protein-3, FRZB Arg200Trp and FRZB Arg324Gly influence bone phenotype.

Methods: Genomic DNA was extracted from 609 subjects at a mean of 11 years following cemented THA for idiopathic osteoarthritis. Pre-operative OA was defined using The American College of Rheumatology criteria and post operative HO after primary THA was assessed using Brooker’s classification

Results: For FRZB Arg200Trp, minor allele carriage (MAC) was greater in subjects with pre-operative pelvic osteophytes (n=267) versus those without osteophytes (n=34) (MAC 27.9% versus 6.3%, Fisher’s exact test p=0.037). There were no associations with other radiographic criteria of OA. MAC was also higher in HO+ve subjects (n=291) versus HO-ve subjects (n=341), (MAC 21.7% versus 12.0%, χ² test p=0.063). Finally MAC was 14.2% in osteolysis +ve subjects (n=268) and 21.7% in osteolysis –ve subjects (n=341) (χ² test p=0.041).

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.

Discussion: Carriage of the FRZB 200Trp allele is positively associated with osteophyte and HO formation and negatively associated with osteolysis, suggesting this locus may be a marker for pro-osteoblastic activity.

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

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.

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.

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%).