We have developed a novel technique to analyse bone, using imaging mass cytometry (IMC) without the constraints of using immunofluorescent histochemistry. IMC can measure the expression of over 40 proteins simultaneously, without autofluorescence. We analysed mitochondrial respiratory chain (RC) protein deficiencies in human bone which are thought to contribute to osteoporosis with increasing age.

Osteoporosis is characterised by reduced bone mineral density (BMD) and fragility fractures. Humans accumulate mitochondrial mutations and RC deficiency with age and this has been linked to the changing phenotype in advancing age and age-related disease. Mitochondrial mutations are detectable from the age of 30 onwards, coincidently the age BMD begins to decline. Mitochondria contain their own genome which accumulates somatic variants at around 10 times the rate of nuclear DNA. Once these mutations exceed a threshold, RC deficiency and cellular dysfunction occur. The PolgD257A/D257A mouse model expresses a proof-reading deficient version of PolgA, a mtDNA polymerase. These mice accumulate mutations 3-5 times higher than wild-type mice showing enhanced levels of age-related osteoporosis and RC deficiency in osteoblasts.

Bone samples were analysed from young and old patients, developing a protocol and analysis framework for IMC in bone tissue sections to analyse osteoblasts in-situ for RC deficiency.

Samples from the femoral neck of 10 older healthy volunteers aged 40 – 85 were compared with samples from young patients aged 1-19. We have identified RC complex I defect in osteoblasts from 6 of the older volunteers, complex II defects in 2 of the older volunteers, complex IV defect in just 1 older volunteer, and complex V defect in 4 of the older volunteers.

These observations are consistent with the PolgD257A/D257A mouse-model and suggest that RC deficiency, due to age-related pathogenic mitochondrial DNA mutations, may play a significant role in the pathogenesis of human age-related osteoporosis.

The most common reason for revision surgery of total hip replacements is aseptic loosening of implants secondary to osteolysis, which is caused by immune-mediated reactions to implant debris. These debris can cause pseudotumour formation. As revision surgery is associated with higher mortality and infection, it is important to understand the pro-inflammatory process to improve implant survival. Toll-like receptor 4 (TLR4) has been shown to mediate immune responses to cobalt ions. Statin use in epidemiological studies has been associated with reduced risk of revision surgery. In-vitro studies have demonstrated the potential for statins to reduce orthopaedic debris-induced immune responses and there is evidence that statins can modulate TLR4 activity. This study investigates simvastatin's effect on orthopaedic biomaterial-mediated changes in protein expression of key inflammatory markers and soluble-ICAM-1 (sICAM-1), an angiogenic factor implicated in pseudotumour formation.

Human macrophage THP-1 cells were pre-incubated with 50µM simvastatin for 2-hours or a vehicle control (VC), before being exposed to 0.75mM cobalt chloride, 50μm3 per cell zirconium oxide or LPS as a positive control, in addition to a further 24-hour co-incubation with 50µM simvastatin or VC. Interleukin −8 (IL-8), sICAM-1, chemokine ligand 2 (CCL2), CCL3 and CCL4 protein secretion was measured by enzyme-linked immunosorbent assay (ELISA). GraphPad Prism 10 was used for statistical analysis including a one-way ANOVA.

Pre-treatment with simvastatin significantly reduced LPS and cobalt-mediated IL-8 secretion (n=3) and sICAM-1 protein secretion (n=2) in THP-1 cells. Pre-treatment with simvastatin significantly reduced LPS-mediated but not cobalt ion-mediated CCL2 (n=3) and CCL3 protein (n=3) secretion in THP-1 cells. Simvastatin significantly reduced zirconium oxide-mediated CCL4 secretion (n=3).

Simvastatin significantly reduced cobalt-ion mediated IL-8 and sICAM-1 protein secretion in THP-1 cells. This in-vitro finding demonstrates the potential for simvastatin to reduce recruitment of leukocytes which mediate the deleterious inflammatory processes driving implant failure.

Aims

Hip fracture commonly affects the frailest patients, of whom many are care-dependent, with a disproportionate risk of contracting COVID-19. We examined the impact of COVID-19 infection on hip fracture mortality in England.

Aims

To identify the responsiveness, minimal clinically important difference (MCID), minimal clinical important change (MIC), and patient-acceptable symptom state (PASS) thresholds in the 36-item Short Form Health Survey questionnaire (SF-36) (v2) for each of the eight dimensions and the total score following total knee arthroplasty (TKA).

Abstract

Hip fracture principally affects the frailest in society, many of whom are care dependent, and are disproportionately at risk of contracting COVID-19. We examined the impact of COVID-19 infection on hip fracture mortality in England.

We conducted a cohort study of patients with hip fracture recorded in the National Hip Fracture Database between 1st February 2019 and 31st October 2020, in England. Data were linked to Hospital Episode Statistics to quantify patient characteristics and comorbidities, Office for National Statistics mortality data, and Public Health England's SARS-CoV-2 testing results. Multivariable Cox regression examined determinants of 90-day mortality. Excess mortality attributable to COVID-19 was quantified using Quasi-Poisson models.

Analysis of 102,900 hip fractures (42,630 occurring during the pandemic) revealed that amongst those with COVID-19 infection at presentation (n=1,120) there was a doubling of 90-day mortality; hazard ratio (HR) 2.05 (95%CI 1.86–2.26), while for infections arising between 8–30 days after presentation (n=1,644) the figure was even higher at 2.52 (2.32–2.73). Malnutrition [1.44 (1.19–1.75)] and non-operative treatment [2.89 (2.16–3.86)] were the only modifiable risk factors for death in COVID-19 positive patients. Patients with previous COVID-19 initially had better survival compared to those who contracted COVID-19 around the time of their hip fracture; however, survival rapidly declined and by 365 days the combination of hip fracture and COVID-19 infection was associated with a 50% mortality rate. Between 1st January and 30th June 2020, 1,273 (99.7%CI 1,077–1,465) excess deaths occurred within 90 days of hip fracture, representing an excess mortality of 23% (20%–26%), with most deaths occurring within 30 days.

COVID-19 infection more than doubled early hip fracture mortality; the first 30-days after injury were most critical, suggesting that targeted interventions in this period may have most benefit in improving survival.

Introduction and Objective

Total joint replacement is indicated for osteoarthritis where conservative treatment has failed, and in the UK the number of patients requiring hip and knee replacements is set to increase with an ageing population. Survival of total hip replacements is around 85% at 20 years with the most common reason for revision being aseptic loosening of the implant secondary to osteolysis, which is caused by immune-mediated reactions to implant debris. These debris can also cause pseudotumour formation. As revision surgery is associated with higher morbidity, mortality, infection rates, venous thromboembolism, resource demand and poorer subsequent function it is important to understand the mechanisms underlying the pro-inflammatory process to improve implant survival. Toll-like receptor 4 (TLR4), an innate immune receptor, has been demonstrated to mediate deleterious immune responses by the Tyson-Capper research group, including inflammatory cytokine interleukin-8 (IL-8) secretion. Statin use in epidemiological studies has been associated with reduced overall risk of revision surgery after hip replacement. In-vitro studies have demonstrated the potential for statins to reduce orthopaedic debris-induced immune responses which can lead to osteolysis and pseudotumour formation. As literature from cardiological investigations demonstrate that statins can reduce the expression and responsiveness of TLR4, this could be an exciting mechanism to exploit to reduce the host immune response to orthopaedic wear debris, thereby improving implant survival by reducing immune mediated osteolysis. This ongoing study investigates simvastatin's effect on cobalt ion-mediated changes in gene and protein expression of interleukin-8 and soluble-ICAM-1 (sICAM-1) which is an angiogenic factor implicated in pseudotumour formation.

Introduction

We aimed to identify genes associated with the development of ALVAL at relatively low levels of wear.

Aims

There are limited published data detailing the volumetric material loss from tapers of conventional metal-on-polyethylene (MoP) total hip arthroplasties (THAs). Our aim was to address this by comparing the taper wear rates measured in an explanted cohort of the widely used Exeter THA with those measured in a group of metal-on-metal (MoM) THAs.

Objectives

We have encountered patients who developed large joint fluid collections with massive elevations in chromium (Cr) and cobalt (Co) concentrations following metal-on-metal (MoM) hip arthroplasties. In some cases, retrieval analysis determined that these ion concentrations could not be explained simply by the wear rates of the components. We hypothesized that these effects may be associated with aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL).

Aims

We sought to determine whether cobalt-chromium alloy (CoCr) femoral stem tapers (trunnions) wear more than titanium (Ti) alloy stem tapers (trunnions) when used in a large diameter (LD) metal-on-metal (MoM) hip arthroplasty system.

Modular un-cemented acetabular components are used in over 50% of UK hip replacements. Mal-seating of hard liners has been reported as a cause of failure which may be a result of errors in assembly, but also could be affected by deformation of the acetabular shell on insertion. Little information exists on in vivo shell deformation. Previous work has confirmed the importance of shell diameter and thickness upon shell behaviour, but mostly using single measurements in models or cold cadavers.

Exploration of deformation and its relaxation over the first twenty minutes after implantation of eight generic metal cups at body temperature.

Using a previously validated cadaveric model at controlled physiological temperature with standardised surgical technique, we tested the null hypothesis that there was no consistency for time dependent or directional change in deformation for a standard metal shell inserted under controlled conditions into the hip joint. Eight custom made titanium alloy (TiAl6V4) cups were implanted into 4 cadavers (8 hips). Time dependent cup deformation was determined using the previously validated ATOS Triple Scan III (ATOS) optical measurement system. The pattern of change in the shape of the surgically implanted cup was measured at 3 time points after insertion.

We found consistency for quantitative and directional deformation of the shells. There was consistency for relaxation of the deformation with time. Immediate mean change in cup radius was 104μm (sd 32, range 67–153) relaxing to mean 96 μm (sd 32, range 63–150) after 10 minutes and mean 92 μm (sd 28, range 66–138) after 20 minutes.

This work shows the time dependent deformation and relaxation of acetabular titanium shells and may aid determining the optimal time for insertion of the inner liner at surgery.

Background

Increased revision rates and early failure of Metal-on-Metal (MoM) hip replacements are often due to adverse reaction to metal debris (ARMD). ARMD describes numerous symptoms in patients such as pain, osteolysis and soft tissue damage. Cobalt is a major component of MoM joints and can initiate an immune response via activation of the innate immune receptor Toll-like receptor 4 (TLR4). This leads to increased secretion of inflammatory cytokines e.g. interleukin-8 (IL-8). This study investigates whether TLR4-specific antagonists inhibit the inflammatory response to cobalt using IL-8 gene expression and protein secretion as a marker of TLR4 activation.

Background

Adverse reactions to metal debris are implicated in the failure of metal-on-metal hip arthroplasty. The peri-implant tissues are often infiltrated by leukocytes which may cause observed immunological effects, including soft tissue necrosis and osteolysis. Cobalt ions from orthopaedic implants aberrantly activate the innate immune receptor human toll-like receptor-4 (TLR4), leading to inflammatory cytokine release including interleukin-8 (IL-8). IL-8 has been shown to increase expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). These factors are essential for leukocyte adhesion to endothelium, which is required for leukocyte migration into tissues. This study investigates cobalt's effect on gene and protein changes in IL-8, ICAM-1 and VCAM-1 to determine their potential role in immune cell infiltration of peri-implant tissues.

Background

Metal-on-metal (MoM) hip arthroplasty has been associated with adverse reactions including pseudotumours, and osteolysis. Tissues surrounding failed MoM hip implants are often infiltrated by inflammatory cells such as monocytes and neutrophils. The mechanisms by which these cells are recruited to the tissues remain unclear. Cobalt from MoM implants activates Toll-like receptor 4 (TLR4), an immune cell surface receptor usually responsible for recognition of bacteria and prevention of sepsis. Activation by bacteria leads to secretion of pro-inflammatory cytokines which guide other immune cells to the site of inflammation. The effect of cobalt on this response is unknown and therefore this study aims to determine the effect of cobalt-mediated TLR4 activation on the migration of inflammatory cells.

Introduction

There is little information available to surgeons regarding how the lateral soft-tissue structures prevent instability in knees implanted with total knee arthroplasty (TKA). The aim of this study was to quantify the lateral soft-tissue contributions to stability following cruciate retaining (CR) TKA.

The pathogenesis of falling bone mineral density (BMD) as a universal feature of advancing age is poorly understood¹. Frequently culminating in the development of osteoporosis, the process is attributable to more than 500,000 fragility fractures occurring every year in the UK Such injuries are associated with great levels of morbidity, mortality and a £3.5 billion cost to the healthcare economy².

With age, humans are known to accumulate somatic mitochondrial DNA (mtDNA) mutations in mitotic and post mitotic tissue, and stem cell precursors³. Compelling evidence in recent years, particularly that provided by animal models suggests that these mutations are intrinsic to the ageing process^4–6. We provide evidence for the first time that mitochondrial dysfunction contributes significantly to the failure of bone homeostasis and falling BMD.

We have utilised a mouse model that accumulates mtDNA mutations at 3–5 times the rate of normal mice, consequently ageing and developing osteoporosis prematurely⁷, to clearly demonstrate that osteoblasts are vulnerable to mtDNA mutations. We have developed a new quadruple immunofluorescent assay to show that mitochondrial respiratory chain dysfunction occurs in osteoblasts as a consequence (p < 0.0001). We show that this mitochondrial dysfunction is associated with reduced BMD in female and male mice by 7 (p = 0.003) and 11 (p = 0.0003) months of age respectively. Using osteoblasts derived from mesenchymal stem cells extracted from male and female mice with mitochondrial dysfunction aged 4, 7 and 11 months, we demonstrate a vastly reduced capacity to produce new mineralised bone in vitro when compared to wild type cell lines (p < 0.0001). Exercise was found to have no beneficial effect on osteoblast and whole bone phenotype in this mouse model. It is likely that mtDNA mutations accumulating over a longer time period in human ageing have significantly detrimental effects on bone biology and diminishing BMD.

INTRODUCTION

Deformation of modular acetabular press-fit shells is of much interest for surgeons and manufacturers. Initial fixation is achieved through press-fit between shell and acetabulum with the shell mechanically deforming upon insertion. Shell deformation may disrupt the assembly process of modular systems and may adversely affect integrity and durability of the components and tribology of the bearing. The aim of the study was to show shell deformation as a function of bone and shell stiffness.

INTRODUCTION

Deformation of modular acetabular press-fit shells is a topic of much interest for surgeons and manufacturer. Such modular components utilise a titanium shell with a liner manufactured from metal, polyethylene or ceramic. Initial fixation is achieved through a press-fit between shell and acetabulum with the shell mechanically deforming upon insertion. Shell deformation may disrupt the assembly process of inserting the bearing liner into the acetabular shell for modular systems. This may adversely affect the integrity and durability of the components and the tribology of the bearing.

Concerns have been raised that deformation of acetabular shells may disrupt the assembly process of modular prostheses. In this study we aimed to examine the effect that the strength of bone has on the amount of deformation of the acetabular shell. The hypothesis was that stronger bone would result in greater deformation. A total of 17 acetabular shells were inserted into the acetabula of eight cadavers, and deformation was measured using an optical measuring system. Cores of bone from the femoral head were taken from each cadaver and compressed using a materials testing machine. The highest peak modulus and yield stress for each cadaver were used to represent the strength of the bone and compared with the values for the deformation and the surgeon’s subjective assessment of the hardness of the bone. The mean deformation of the shell was 129 µm (3 to 340). No correlation was found between deformation and either the maximum peak modulus (r² = 0.011, t = 0.426, p = 0.676) or the yield stress (r² = 0.024, t = 0.614, p = 0.549) of the bone. Although no correlation was found between the strength of the bone and deformation, the values for the deformation observed could be sufficient to disrupt the assembly process of modular acetabular components.

Cite this article: Bone Joint J 2015; 97-B:473–7.

Instability is reported to account for around 20% of early TKR revisions. The concept of restoring the “Envelope of Laxity” (EoL) mandates a balanced knee through a continuous arc of functional movement. We therefore hypothesised that a single radius (SR) design should confer this stability since it has been proposed that the SR promotes normal medial collateral ligament (MCL) function with isometric stability throughout the full arc of motion.

Our aim was to characterise the EoL and stability offered by a SR cruciate retaining (CR)-TKR, which maintains a SR from 10–110° flexion. This was compared with that of the native knee throughout the arc of flexion in terms of anterior, varus/valgus and internal/ external laxity to assess whether a SR CR-TKR design can mimic normal knee joint kinematics and stability.

Eight fresh frozen cadaveric lower limbs were physiologically loaded on a custom jig. The operating surgeon performed anterior drawer, varus/ valgus and internal/external rotation tests to determine ‘maximum’ displacements in 1) native knee and 2) single radius CR-TKR (Stryker Triathlon) at 0°, 30°, 60°, 90° and 110° flexion. Displacements were recorded using computer navigation. Significance was determined by linear modelling (p≤0.05).

The key finding of this work was that the EoL offered by the SR CR-TKR was largely equivalent to that of the native knee from 0–110°. The EoL increased significantly with flexion angle for both native and replaced knees. Overall, after TKR anterior laxity was comparable with the native knee, whilst total varus-valgus and internal-external rotational laxities reduced by only 1°. However, separated varus and valgus laxities at 110° significantly increased after TKR as did anterior laxity at 30° flexion.

In conclusion, the overall EoL offered by the SR CR-TKR is comparable to that of the native knee. In the absence of soft tissue deficiency, the implant appears to offer reliable and reproducible stability throughout the functional range of movement, with exception of anterior laxity at 30° and varus and valgus laxity when the knee approaches high flexion. These shortcomings should offer scope for future work.

Abnormal wear of cobalt-containing metal-on-metal joints is associated with inflammatory pseudotumours. Cobalt ions activate human toll-like receptor 4 (TLR4), which normally responds to bacterial lipopolysaccharide (LPS) in sepsis. Activation of TLR4 by LPS increases the expression of chemokines IL-8 and CXCL10, which recruit leukocytes and activated T-cells, respectively. This study was designed to determine whether cobalt induces a similar inflammatory response to LPS by promoting the expression of IL-8 and CXCL10. A human monocytic cell line, derived from acute monocytic leukaemia, was treated with cobalt ions and expression of IL-8 and CXCL10 measured at mRNA and protein levels. Cobalt-treated macrophages showed a 60-fold increase in IL-8 mRNA, and an eightfold increase in production of the mature chemokine (both p < 0.001); expression of the CXCL10 gene and protein was also significantly increased by cobalt (both p < 0.001). Experiments were also performed in the presence of CLI-095, a TLR4-specific antagonist which abrogated the cobalt-mediated increase in IL-8 and CXCL10 expression.

These findings suggest that cobalt ions induce inflammation similar to that observed during sepsis by the simultaneous activation of two TLR4-mediated signalling pathways. These pathways result in increased production of IL-8 and CXCL10, and may be implicated in pseudotumour formation following metal-on-metal replacement.

Cite this article: Bone Joint J 2014; 96-B:1172–7.

Summary

Metal-on-metal hip replacements have been associated with adverse reactions including inflammatory pseudotumours and soft tissue necrosis. We have shown that cobalt can directly activate toll-like receptor 4, an immune receptor causing pro-inflammatory interleukin-8 secretion. This may contribute to adverse reaction development.

Objectives

Wear debris released from bearing surfaces has been shown to provoke negative immune responses in the recipient. Excessive wear has been linked to early failure of prostheses. Analysis using coordinate measuring machines (CMMs) can provide estimates of total volumetric material loss of explanted prostheses and can help to understand device failure. The accuracy of volumetric testing has been debated, with some investigators stating that only protocols involving hundreds of thousands of measurement points are sufficient. We looked to examine this assumption and to apply the findings to the clinical arena.

Introduction

National Institute for Health and Clinical Excellence (NICE) guidelines recommend the use of total hip replacement (THR) for displaced intracapsular fractured neck of femur (NOF) in cognitively intact patients who were independently mobile prior to the injury. The National Joint Registry for England and Wales (NJR) has collected data on THRs performed since 2003. This retrospective cohort study explores risk factors independently associated with implant failure and perioperative mortality.

Background

Current analysis of unicondylar knee replacements (UKR) by national registries is based on the pooled results of medial and lateral implants. Using data from the National Joint Registry for England and Wales (NJR) we aimed to determine the proportion of lateral UKR implanted, their survival and reason for failure in comparison to medial UKR.

Background

Both surgeon and hospital volume influence patient outcomes following revision knee arthroplasty.

Introduction

Following in-depth analysis of the market leading brand combinations in which we identified implant influences on risk of revision, we compared revision in patients implanted with different categories of hip replacement in order to find implant with the lowest revision risk, once known flawed options were removed.

Introduction

Renal homeostasis has been shown to influence mortality after hip fractures; this is true for patients with both chronic kidney disease, and those who develop acute renal dysfunction after surgery. We have examined the influence of impaired renal function upon mortality and length of stay. We investigated this relationship through accurate mathematical modelling of available biochemistry data on a cohort of hip fracture patients.

Purpose

To determine how patient characteristics; health status and pre-operative knee function effect patient reported satisfaction and operative success following total knee replacement (TKR). We hypothesised that a number of patient factors would influence the reported levels of symptomatic improvement (success) and satisfaction and that these two outcomes would represent different aspects of the patient's perception of outcome.

Background

The most appropriate form of chemical thromboprophylaxis following knee replacement is a contentious issue. Most national guidelines recommend the use of low molecular weight Heparin (LMWH) whilst opposing the use of aspirin. We compared thromboembolic events, major haemorrhage and death after knee replacement in patients receiving either aspirin or LMWH.

Purpose

Although classic teaching holds that the least amount of constraint should be implanted, there is very little in the literature to substantiate this. This study attempts to quantify the influence of constraint and various indications upon functional outcome following aseptic first time revision knee arthroplasty. The null hypothesis was that the level of constraint and indication for surgery would not influence the functional outcome following revision knee replacement.

Introduction

Unlike the NJR, no surgeon driven national database currently exists for ligament surgery in the UK and therefore information on outcome and adverse event is limited to case series.

The aim of this study was to describe the epidemiology of elite youth soccer knee injuries from prospective data collected from forty-one English FA Football Academies over a 5 year period. 12306 players were registered from U9 to the U16 age category.

We studied the incidence of injuries around the knee with particular emphasis upon those causing greater than 28 days time off sport.

There were 609 knee injuries with a mean incidence of 0.71 knee injuries per player per year and a median of 17 training days and 2 matches missed per knee injury. Increased injury rates were seen in older players, in competitive situations and in the latter stages of each half of play. Peaks in injury numbers were seen in early season and subsequent to the winter break. Sprain was the most common diagnosis with the Medial Collateral ligament affected in 23.2% of cases. 609 injuries met the UEFA Model criteria for major injury. In total 60,091 training days and 5,272 match appearances were lost through knee injury.

Knee injuries are common in elite level youth footballers and are often severe in nature, resulting in large amounts of training time lost to injury. Diagnosis of ligament sprain is common leading to prolonged time off, and may mask more serious pathology or inappropriate management.

Introduction

We wished to quantify the influence of constraint and various principal indications upon functional outcome following aseptic first time revision knee arthroplasty.

Purpose of the study

To compare the patellofemoral kinematics and patella stability of a new TKR, with a continuous radius versus an established J shaped knee system and the natural knee. It was hypothesised that the high performance new TKR would be a better match to the natural knee and anatomical patella tracking would provide a more stable patella.

During a retrospective case note analysis, a significant difference was found in prosthesis survival, between two cohorts of patients who underwent different total knee replacements. The first cohort included 70 patients who underwent Kinemax Plus total knee replacement, the second cohort included 58 patients who underwent PFC Total Knee replacement. All patients were under the care of one Consultant Orthopaedic Surgeon. Interestingly, the Kinemax Plus cohort was found to have a higher rate of revision compared to the PFC cohort. A detailed comparison was carried out between the two groups to identify any obvious cause for the disparity.

The two cohorts were found to be well matched with respect to age, sex, ASA grade, underlying pathology and operative technique. Median follow up being 6 years and 5 years for the Kinemax Plus and PFC groups respectively.

There were 11 failed prostheses in the Kinemax Plus cohort, 7 undergoing revision with the remaining 4 patients offered revision but unwilling to have surgery. Wear of the polyethylene tibial insert was the most obvious finding at revision, present in six of the seven revisions. 97% of the Kinemax Plus Prostheses were intact at 5 years but by 8 years only 87% were intact. There were no revisions performed in the PFC cohort.

Post-operative x-ray analysis was undertaken to rule out prosthesis malalignment as a cause for the increased failure rate. The coronal alignment of the prostheses (CAK) was calculated and all post operative x-rays were within the normal limits of 4-10 degrees.

Analysis of the explanted Kinemax Plus polyethylene liners was undertaken. In six cases, the polyethylene bearing surfaces displayed severe surface and subsurface delamination. This suggests massive fatigue and fatigue wear. Only one implant showed localised delamination.

These findings suggest the hypothesis of weak polyethylene particle interface strength.

The posterior drawer is a commonly used test to diagnose an isolated PCL injury and combined PCL and PLC injury. Our aim was to analyse the effect of tibial internal and external rotation during the posterior drawer in isolated PCL and combined PCL and PLC deficient cadaver knee.

Ten fresh frozen and overnight-thawed cadaver knees with an average age of 76 years and without any signs of previous knee injury were used. A custom made wooden rig with electromagnetic tracking system was used to measure the knee kinematics. Each knee was tested with posterior and anterior drawer forces of 80N and posterior drawer with simultaneous external or internal rotational torque of 5Nm. Each knee was tested in intact condition, after PCL resection and after PLC (lateral collateral ligament and popliteus tendon) resection. Intact condition of each knees served as its own control. One-tailed paired student's t test with Bonferroni correction was used.

The posterior tibial displacement in a PCL deficient knee when a simultaneous external rotation torque was applied during posterior drawer at 90° flexion was not significantly different from the posterior tibial displacement with 80N posterior drawer in intact knee (p=0.22). In a PCL deficient knee posterior tibial displacement with simultaneous internal rotation torque and posterior drawer at 90° flexion was not significantly different from tibial displacement with isolated posterior drawer. In PCL and PLC deficient knee at extension with simultaneous internal rotational torque and posterior drawer force the posterior tibial displacement was not significantly different from an isolated PCL deficient condition (p=0.54).

We conclude that posterior drawer in an isolated PCL deficient knee could result in negative test if tibia is held in external rotation. During a recurvatum test for PCL and PLC deficient knee, tibial internal rotation in extension results in reduced posterior laxity.

Introduction and Aims: Morbid obesity (BMI> 40) has been shown to cause increased perioperative morbidity and poorer long-term implant survivorship following total knee arthroplasty (TKA). The aim of this study was to determine the impact of morbid obesity on patient-reported outcomes following TKA.

Methods: Patients undergoing primary TKA were invited to complete questionnaires preoperatively and one year after surgery. Questionnaires include the WOMAC and SF-36 health status measures, demographics, self-reported comorbid medical conditions, height and weight. At follow-up, satisfaction with results of TKA is included. Patients were categorised by their preoperative BMI categories as ideal weight (20–25), overweight (> 25–30), obese (> 30–40) or morbidly obese (> 40). We used multivariate analysis to adjust for known significant correlates of WOMAC and SF-36, namely age, gender and comorbid medical conditions. Adjusted mean scores for each assessment were compared by BMI category.

Results: A total of 769 patients were included in the study which included 27 morbidly obese, 280 obese, 314 overweight and 148 ideal weight patients. Morbidly obese patients when compared with non-obese patients had significantly worse preoperative WOMAC pain and function and a trend for worse SF36 scores (Vitality significantly worse, p=0.04). There was no significant difference between the BMI categories at one year for WOMAC or SF-36 scores (trend for the Physical Functioning score to be lower, p=0.052). Morbidly obese patients were all satisfied with pain relief after surgery but were less satisfied with functional results when compared to the non-obese groups.

Discussion: This study shows that morbidly obese patients report significantly worse health status prior to TKA but their post-operative improvement is greater than the non-obese population. Although morbid obesity should not be an absolute contraindication to TKA, patients should be carefully selected balancing the risk of perioperative complications and earlier failure against the demonstrated marked improvement in quality of life.

There have been marked changes in the management of Juvenile Idiopathic Arthritis (JIA) over recent decades, mainly with earlier use of methotrexate (MTX). Our aim was to describe orthopaedic interventions in a large group of adults with JIA followed up over several decades.

This was a retrospective observational study of adult JIA patients attending a teaching hospital clinic, with information collated on JIA subtype, disease duration, orthopaedic interventions and exposure to MTX.

The study included 144 patients with median disease duration of 19 years. Survival analysis showed that joint surgery was observed in the majority (75%) of patients with disease duration over 40 years with a trend for less joint surgery in patients with oligoarticular JIA. In total 41 patients (28.5%) had received joint surgery and 17/41(41%) have required multiple procedures. Of those who have required joint surgery, 20/41(48%) had started MTX in their adult years, with only 5/41 (12%), starting MTX prior to first joint replacement and none within five years of disease onset. Of the patients who have not had joint surgery to date, most (46/103, 45%) were receiving MTX or another immunosuppressive agent, in the majority of cases MTX was started within two years of disease onset.

Many adults with JIA require joint replacement surgery and ongoing immunosuppressive treatments, emphasising that JIA is not a benign disease. Many patients who have had joint replacement surgery have had exposure to MTX albeit after many years after disease onset; it remains to be seen whether patients who have received MTX therapy early in their disease course will ultimately have less requirement for joint surgery.

Objective: To ascertain the epidemiology of ankle injuries in elite youth football.

Design: Retrospective analysis of prospectively collected injury data from English Football Association Academies.

Setting: Forty-one FA Football Academies, between 1998 and 2006.

Participants: For the complete seasons studied, a total of 14776 players were registered from U9 to the U16 age category – a mean of 2463 players per year. All ankle injuries of sufficient severity to miss 48 hours or more training were studied – 2563 injuries in total.

Main outcome measurements: The incidence and burden of ankle injuries in this population, and factors associated with injury.

Results: There was a mean incidence of one ankle injury per player per year, and a mean of 20 training days and 2 matches were missed per ankle injury. Increased injury rates were seen in older players, in competition and later in each half of match time. Peaks in injury were observed early in the season and after the winter break. In competition, more injuries were associated with a contact situation than in training. Eighty-eight injuries (3.4%) required a lay-off of three months or more and in 18 (0.7%) cases, the player failed to return to training. In total, 52290 training days and 5182 match appearances were lost through ankle injury. The majority of injuries were sprains, but more severe injuries occurred accounted for 3.9% of the total.

Conclusions: Ankle injuries are common in young football players, and are often severe, with prolonged loss of training time. This has potential far reaching implications, both on and off the field. Further syudy in this area is suggested.

We have attempted to quantify the influence of clinical, radiological and prosthetic design factors upon flexion following knee replacement. Our study examined the outcome following 101 knee replacements performed in two prospective randomized trials using similar cruciate retaining implants. Multivariate analyses, after adjusting for age, sex, diagnosis and the type of prosthesis revealed that the only significant correlates for range of movement at 12-months were the difference in posterior condylar offset ratio (p< 0.001), tibial slope (p< 0.001) and preoperative range of movement (p=0.025). We found a moderate correlation between 12-month range of movement and posterior tibial slope (R=0.58) and the difference of post femoral condylar offset (that is, post-operative minus preoperative posterior condylar offset, R=0.65). Posterior condylar offset had the greatest impact upon final range of movement highlighting this as an important consideration for the operating surgeon at pre-operative templating when choosing both the design and size of the femoral component.

Introduction: Correct alignment in both coronal and sagittal planes has been shown to be associated with longevity of total knee arthroplasty. The majority of procedures are performed using an intramedullary rod with a femoral cutting jig, with a 5°–7° offset depending upon the anatomical and mechanical axes. The cutting jig rotates around the rod and therefore the rotational alignment of the jig will also affect the cut and final component position (in addition to the rod entry point). It is interesting that rotational alignment of the femoral component is often assessed after the distal resection has been made. The distal resection plane determines the final position of the femoral component, influences patellar tracking and medial/lateral, flexion/extension balancing. This study measures the resultant effect on the distal femoral resection when entry point and jig rotation are varied.

Materials and Methods: The distal femoral resection was carried out in sawbones with three different entry points (central, inferior and superolateral) in neutral alignment and rotations of 10° (internal and external) about the transepicondylar axis. The resulting plane of the cut was assessed by a graphical method measuring the changes in orientation of the alignment rod in space before and after the distal cut. A computer navigation system was used to measure the varus/valgus and flexion/extension angles of the distal cut. This experiment was done thrice, in a total of 27 sawbones and the average values were recorded.

Results: The results varied considerably in the sagittal plane with central and inferior entry points. Internal rotation of the jig around a central entry point produced hyperextension (mean 3.3°) and external rotation caused flexion (mean 1.8°). Using an inferior entry point, flexion of the distal plane improved from an average 3° in neutral rotation to 1.6° on internal rotation; external rotation worsened flexion to an average of 4.3°. The angles digressed in both sagittal and coronal planes with a superolateral entry point; rotations of the distal cutting jig caused hyperextension (maximum of 7.5°). Coronal alignment ranged from 4.5° of varus to 5° of valgus in neutral alignment and rotations around a superolateral entry point.

Conclusion: The study demonstrates that there is a possibility of a compound error from misplaced entry point and that malrotation prior to distal resection is real. This error would invariably be extrapolated in the subsequent steps of conventional knee arthroplasty. Computer assisted arthroplasty may have a role in avoiding this surgical error.

Surgical reconstruction of the injured Anterior Cruciate Ligament (ACL) is an effective solution to knee instability, but not all grafts incorporate well. The biological environment in the knee that controls graft integration is not well understood, and this study aims to fill that gap as the first step towards a translational approach to optimise outcomes.

Over two stages, tissue samples and knee fluid samples were harvested from patients undergoing ACL reconstruction. These samples were cultured and stored to allow batch analysis for a variety of cytokines, growth factors and collagenases.

Stage 1 (n=14) identified the presence of specific pro-inflammatory cytokines, growth factors and latent collagenase. Information gathered allowed a more targeted approach to be used in stage 2 (n=18). Stage 2 data from tissue cultures suggest that collagenase activity peaks later than 6 hours post-op. The relationships between collagenase activity and levels of TNF-alpha, IL-1beta and bFGF are of potential interest, and the profiles of patients will be compared with longer term follow-up data to determine any effects on outcomes.

Further detailed assessment of the biology of ACL graft incorporation is required, but these preliminary data have clarified some of the details worthy of further study.

The Kinemax Plus knee replacement has a reported 10 year survival of around 96%. However we found the survival rate of this implant in our cohort to be 75% at 9 years. No abnormalities were found for clinical and radiological parameters. At reoperation the most striking feature was that of significant ultra-high molecular weight polyethylene (UHMWPE) failure. Oxidative and structural analysis of the polyethylene components was therefore undertaken.

Ten Kinemax Plus tibial inserts were analysed; one was a shelf-aged unused implant, the others were explants. An FTIR analysis of the data showed that oxidation is present in all samples. The degree of oxidation however varied with depth and location. Except for a sharp oxidative peak approximately half way into the sample, the shelf aged samples had a fairly constant level of oxidation. The retrieved implants had an overall higher level of oxidation in both bearing and non-bearing regions. The latter had less of a variation in oxidation which implies that in vivo loading exaggerates the degree of oxidation. In the non-articulating regions oxidation of the explants was found to peak often at the region of about 40% from the bottom surface in all retrieved samples. By contrast, most articulating region had two oxidative peaks; one occurring at approximately 1–1.5mm from the surface, which is consistent with findings on subsurface oxidation, and another occurring about 2–3mm from the bottom surface.

SEM imaging provided evidence for the presence of fusion defects by indicating grain boundaries through-out the explants. This indicates a compromised material which is more susceptible to damage. Fatigue loading of the implant has also been seen to produce a subsurface stress maximum at approximately 1 to 2mm below the articulating surface. It is thought that maximum contact stresses within this region cause Type 1 and Type 2 defects to open or become more pronounced. This in turn will increase the local concentration of oxygenating material as it will be present in these defects and voids where surface areas are greater for oxidative reaction. We therefore hypothesise that these fusion defects are the cause for the early failure of the Kinemax implants.

We aim to explain the significant difference in survivor-ship found between two cohorts of patients who underwent different total knee replacements. The first cohort included 70 patients who underwent Kinemax Plus total knee replacement, the second cohort included 58 patients who underwent PFC Total Knee replacement. All patients were under the care of one Consultant Orthopaedic Surgeon.

Interestingly, the Kinemax Plus cohort was found to have a higher rate of revision as compared to the PFC cohort. A detailed comparison was then carried out between the two groups to identify any obvious cause for the disparity.

The two cohorts were found to be well matched with respect to age, sex, ASA grade, underlying pathology and operative technique. Median follow up being 6 years and 5 years for the Kinemax and PFC groups respectively. There were 11 failed prostheses in the kinemax cohort, 7 undergoing revision with the remaining 4 patients offered revision but unwilling have surgery. Wear of the polyethylene tibial insert was the most obvious finding at revision, present in six out of the 7 revisions. 97% of the Kinemax Plus Prostheses were intact at 5 years but by 8 years only 87% were intact.

There were no revisions performed in the PFC cohort.

Post operative x-ray analysis was undertaken to rule out prosthesis misalignment as a cause for the increased failure rate. The coronal alignment of the prostheses (CAK) was calculated and all post operative x-rays were within the normal limits of 4–10 degrees.

Analysis of the explanted Kinemax Plus polyethylene liners was undertaken. In six cases, the polyethylene bearing surfaces displayed severe surface and subsurface delamination at both medial and lateral sides. This suggests massive fatigue and fatigue wear. Only one inplant showed localised delamination. The surface characterisation suggests the hypothesis of weak UHMWPE particle interface strength.

Objective: The aim of the study was to test the hypothesis that insertion of a total knee replacement (TKR) may effect range of motion as a consequence of excessive stretching of the retinaculae.

Methods: 8 fresh frozen cadaver knees were placed on a customised testing rig. The femur was rigidly fixed allowing the tibia to move freely through an arc of flexion. The quadriceps were loaded to 175N in their physiologic lines of action using a cable, pulley and weight system. The iliotibial tract was loaded with 30N. Tibiofemoral flexion and extension was measured using an optical tracking system. Monofilament sutures were passed along the fibres of the medial patellofemoral ligament (MPFL) and the deep transverse band in the lateral retinaculum with the anterior ends attached to the patella. The posterior suture ends were attached to ‘Linear Variable Displacement Transducers’. Thus small changes in ligament length were recorded by the transducers. Ligament length changes were recorded every 10° from 90° to 0° during an extension cycle. A transpatellar approach was used when performing the TKR to preserve the medial and lateral retinaculae. Testing was conducted on an intact knee and following insertion of a cruciate retaining TKR (Genesis II). Statistical analysis was performed using a two way ANOVA test.

Results: The MPFL had a mean behaviour close to isometric, while the lateral retinaculum slackened by a mean of 6mm as the knee extended from 60 degrees (Fig 1). After knee replacement there was no statistically significant difference seen in ligament length change patterns in the MPFL, however the lateral retinaculum showed significant slackening from 10 to 0°.

Conclusion: The data does not support the hypothesis that insertion of a TKR causes abnormal stretching of the retinaculuae. This result relates specifically to the TKR design tested.

Background: The determinants of range of movement following knee replacement may be surgically modifiable (tibial slope, posterior condylar offset or the level of the joint line) or non modifiable (pre-operative range of movement, sex or BMI). We aimed to quantify the influence of these factors upon restoration of flexion in the arthritic knee following knee replacement

Methods: Patients were included from two prospective trials for three different designs of knee replacement. Range of movement was recorded using a standard measuring technique preoperatively and 12 months after surgery. Radiological measurement was done by an independent observer and included the preoperative posterior condylar offset and the postoperative tibial slope, posterior condylar offset, posterior condylar offset ratio, varus-valgus alignment and Insall ratio. Multivariate analysis using stepwise selection was performed to determine the significant predictors of the range of movement at 12 months.

Results: The study includes 133 knee replacements performed on 125 patients. Complete clinical and radiographic data for preoperative and 12-month assessment was available for 101 knees and only these were included for the analyses. There was no significant difference between the three groups in terms of postoperative range of movement or the radiological parameters measured. Multivariate analysis after adjusting for age, sex, diagnosis and the type of prosthesis revealed that the only significant correlates of range of movement at 12-months were the difference in posterior condylar offset ratio, tibial slope and preoperative range of movement. Moderate correlation was noted between range of movement at 12 months and posterior tibial slope (R=0.58) and the difference of post femoral condylar offset (that is, post-operative minus preoperative posterior condylar offset, R=0.65). Preoperative range of movement had only a weak correlation with post-operative range of movement (R=0.20).

Conclusions: We found that the posterior femoral condylar offset had the greatest impact upon final range of movement. We would encourage the operating surgeon at pre-operative templating to take this into account when choosing size and design of femoral component.

Objective: The aim of this study was to test the hypothesis that malrotation of the femoral component following total knee replacement (TKR) may lead to patellofemoral complications as a consequence of excessive stretching of the retinaculae.

Methods: 8 fresh frozen cadaver knees were placed on a customised testing rig. The femur was rigidly fixed allowing the tibia to move freely through an arc of flexion. The quadriceps and iliotibial tract were loaded to 205N in their physiologic lines of action using a cable, pulley and weight system. Tibiofemoral flexion and extension was measured using an optical tracking system. Monofilament sutures were passed along the fibres of the medial patellofemoral ligament (MPFL) and the deep transverse band in the lateral retinaculum with the anterior ends attached to the patella. The posterior suture ends were attached to ‘Linear Variable Displacement Transducers’. Thus small changes in ligament length were recorded by the transducers. Ligament length changes were recorded every 10° from 90° to 0° during an extension cycle. A transpatellar approach was used when performing the TKR to preserve the medial and lateral retinaculae. Testing was conducted following insertion of a cruciate retaining TKR (Genesis II). The femoral component was rotated using a custom built intramedullary device. Ligament length changes were measured at neutral rotation, 5° internal and 5° external rotation. Statistical analysis was performed using a two way ANOVA test.

Results: Internal rotation resulted in the MPFL slackening a mean of 1.7mm from 70-0° extension (p< 0.001). External rotation resulted in the MPFL tightening a mean of 1.5mm over the same range (p< 0.01). The lateral retinaculum showed less significant differences.

Conclusion: External rotation resulted in smaller length changes than internal rotation. Patellar tilting as a result of internal rotation may be caused by MPFL slackening and not lateral retinacular tension, contrary to popular understanding.

Objective: This study tested the hypothesis that complications resulting from overstuffing the patellofemoral joint after total knee replacement (TKR) may be a consequence of excessive stretching of the retinaculae.

Methods: 8 fresh frozen cadaver knees were placed on a customised testing rig. The femur was rigidly fixed and the tibia moved freely through an arc of flexion. The quadriceps and iliotibial tract were physiologically loaded to 205N using a cable, pulley and weight system. Tibiofemoral flexion/extension was measured using an optical tracking system. Monofilament sutures were passed along the fibres of the medial patellofemoral ligament (MPFL) and the deep transverse band in the lateral retinaculum with the anterior ends attached to the patella. The posterior suture ends were attached to ‘Linear Variable Displacement Transducers’. Thus, small changes in ligament length were recorded by the transducers. Length changes were recorded every 10° from 90°- 0° during an extension cycle. A transpatellar approach was used when performing the TKR to preserve the medial and lateral retinaculae. Testing was conducted following insertion of a cruciate retaining TKR (Genesis II). The patella was resurfaced and various patellar thicknesses were achieved by placing 2mm thick nylon washers behind the ‘onlay’ button. The thicknesses measured were 2mm understuff, pre-cut thickness, 2 and 4mm overstuff. Statistical analysis was performed using a two way ANOVA test.

Results: Patellar understuff resulted in the MPFL slackening an average of 1.6mm from 60 to 0° (p< 0.05). Overstuffing the patella 2mm resulted in no significant length changes whereas 4mm overstuff resulted in a mean increase in MPFL length of 2.3mm throughout extension (p< 0.001). No significant length changes seen in the lateral retinaculum

Conclusion: Overstuffing the PFJ stretches the MPFL, because it attaches directly between two bones. The lateral retinaculum attaches to the relatively mobile ITT, so overstuffing does not stretch it.