Currently, the cement being used for hemiarthroplasties and total hip replacements by the authors and many other surgeons in the UK is Palacos® (containing 0.5g Gentamicin). Similar cement, Copal® (containing 1g Gentamicin and 1g Clindamycin) has been used in revision arthroplasties, and has shown to be better at inhibiting bacterial growth and biofilm formation. We aim to investigate the effect on SSI rates of doubling the gentamicin dose and adding a second antibiotic (clindamycin) to the bone cement in hip hemiarthroplasty.

We randomised 848 consecutive patients undergoing cemented hip hemiarthroplasty for fractured NOF at one NHS trust (two sites) into two groups: Group I, 464 patients, received standard cement (Palacos®) and Group II, 384 patients, received high dose, double antibiotic-impregnated cement (Copal®). We calculated the SSI rate for each group at 30 days post-surgery. The patients, reviewers and statistician were blinded as to treatment group.

The demographics and co-morbid conditions (known to increase risk of infection) were statistically similar between the groups. The combined superficial and deep SSI rates were 5 % (20/394) and 1.7% (6/344) for groups I and II respectively (p=0.01). Group I had a deep infection rate 3.3 %(13/394) compared to 1.16% (4/344) in group II (p=0.082). Group I had a superficial infection rate 1.7 % (7/394) compared to 0.58% (2/344) in group II (p=0.1861). 33(4%) patients were lost to follow up, and 77 (9%) patients were deceased at the 30 day end point. There was no statistical difference in the 30 day mortality, C. difficile infection, or the renal failure rates between the two groups.

Using high dose double antibiotic-impregnated cement rather than standard low dose antibiotic-impregnated cement significantly reduced the SSI rate (1.7% vs 5%; p=0.01) after hip hemiarthroplasty for fractured neck of femur in this prospective randomised controlled trial.

Deep surgical infections are a serious complication of total knee arthroplasty (TKA). Various protocols exist for treating these infections, each with its own advocates. In this series we report the one to five year follow-up of infected TKA that were treated with a two-stage revision knee replacement at the Glasgow Royal Infirmary between December 2003 and March 2009.

48 patients were identified from the hospital database. 6 of these were excluded as they did not meet the stipulated infection criteria. Another patient was excluded as no notes were available thereby the infection status could not be determined. Another 8 patients were excluded as these only had a first stage.

33 patients (16 male) average age 67y (49–88) met the inclusion criteria. Mean BMI was of 31.62 (19–47) and 8 patients suffered from rheumatoid arthritis. At presentation, the median for the ESR, CRP and WCC were 70.5, 133 and 8.5 respectively. The infective organism was identified in 22 patients. Following the first stage, the patients were treated with antibiotics (initially intravenous followed by oral) for an average of 11.8 weeks (4–52 weeks). This procedure failed to eliminate the infection in 6 patients (18.18%) who had further re-admissions for infection of the affected prosthesis. The resultant success rate is of over 80% which is comparable to literature data (success rates of 41% to 96% quoted). For these patients, the average time to review was 25.13 months (12–67months). At review these patients had a mean extension of 2.17° (0–10°) and a mean flexion of 98.26 (70–120°). These patients were all satisfied with their outcome.

Our results show a high successful rate of elimination of infection when a two-stage revision is used for infected knee prosthesis with over 80% of patients free of infection.

Background

Intervertebral disc cells exist in a challenging physiological environment. Disc degeneration occurs early in life implying that disc cells may no longer be able to maintain a functional tissue. We hypothesise that disc cells have a stress response different from most other cells because of the disc environment. We have compared the stress response of freshly isolated and cultured bovine nucleus pulposus (NP) cells with bovine dermal fibroblasts, representative of cells from a vascularised tissue.

Introduction

Total Knee Arthroplasty (TKA) aims to deliver relief from pain and restore normal function. Unfortunately, a significant cohort of patients report poor outcomes.

The internal fixation of osteochondral fragments in fractures normally utilizes intra-articular screws inserted through a pilot hole drilled into cartilage/bone. This trauma causes cartilage injury leading to chondrocyte death. We have quantified the cell death following cartilage drilling and identified irrigation conditions that can protect chondrocytes. Articular cartilage of bovine metacarpophalangeal joints of 3yr-old cows was irrigated in the presence/absence of saline of various compositions. Holes were then made using a standard 1.5mm drill (Ortho Solutions Ltd.) at 18,000 rpm through the articular cartilage into bone. Osteochondral explants were then harvested and cultured in Dulbecco's Modified Eagle's Medium containing chloromethylfluorescein-di-acetate and propidium iodide (10uM each), to label living chondrocytes green and dead cells red, respectively. Axial images were taken by confocal microscopy and the width of the zone of cell death (ZCD) around the hole determined. With no irrigation, new drills caused a ZCD of 171±25um, which was increased when drills used 50+ times were tested (279±31um;p=0.03). With saline irrigation, the ZCD was reduced for old drills (150±6um;p=0.016) but not for new drills (124±8um) suggesting the heating effect of the old drills caused additional chondrocyte death. However for new drills, the ZCD was further reduced significantly to 82±7um when the osmolarity of the saline irrigation solution was raised to 480mOsm using sucrose. Data are mean±s.e.m., from at least 5 separate experiments each with a minimum of 3 replicates. The results demonstrate a chondroprotective effect of raising the osmolarity of saline used during drilling of cartilage which could be clinically beneficial.

The aim of this study was to determine whether the clinical outcome of autologous chondrocyte transplantation was dependent on the timing of a high tibial osteotomy in tibio-femoral mal-aligned knees. Between 2000 and 2005, forty-eight patients underwent autologous chondrocyte implantation with HTO performed at varying times relative to the second stage autologous chondrocyte implantation procedure. 24 patients had HTO performed simultaneously with their second stage cartilage transplantation, (the HTO Simultaneous Group). 5 patients had HTO prior to their cartilage procedure, (the HTO pre-ACI Group) and 19 had HTO performed between 1 to 4 years after their second stage cartilage implantation, (the HTO post-ACI Group). There were 29 men and 19 women with a mean age of 37 years (Range 28 to 50) at the time of their second stage procedure.

With average follow-up of 72 months we have demonstrated a significant functional benefit in performing the HTO either prior to or simultaneously with the ACI procedure in the mal-aligned knee. The failure rate in the Post-ACI group was 45% compared to the Pre-ACI and Simultaneous group, with failure rates of 20% and 25%, respectively.

An HTO performed prior to or simultaneously with an autologous chondrocyte implantation procedure in the mal-aligned knee, provides a significant protective effect by reducing the failure rate by approximately 50%.

Recent approaches have sought to harness the potential of stem cells to regenerate bone lost as a consequence of trauma or disease. Bone marrow aspirate (BMA) provides an autologous source of skeletal stem cells (SSCs) for such applications, however previous studies have demonstrated that the concentration of SSCs present in iliac crest BMA is below that required for robust bone regeneration. Here we present a novel acoustic-facilitated filtration strategy to concentrate BMA for SSCs, clinically applicable for intra-operative orthopaedic use.

The aim of this study was to demonstrate the efficacy of this strategy in concentrating SSCs from iliac crest bone marrow, as well as femoral canal BMA from older patients.

Iliac crest BMA (Lonza, Rockville, MD, USA) and femoral canal BMA was obtained with informed consent from older patients during total hip replacement. 5 to 40ml of BMA was processed via the acoustically-aided exclusion filtration process to obtain 2-8 fold volume reductions. SSC concentration and function was assessed by flow-cytometry, assays for fibroblastic colony-forming units (CFU-F) and multi-lineage differentiation along chondrogenic, osteogenic and adipogenic pathways examined. Seeding efficiency of enriched and unprocessed BMA (normalised to cell number) onto allograft was assessed.

Iliac crest BMA from 15 patients was enriched for SSCs in a processing time of only 15 minutes. Femoral BMA from 15 patients in the elderly cohort was concentrated up to 5-fold with a corresponding enrichment of viable and functional SSCs, confirmed by flow cytometry and assays for CFU-F. Enhanced osteogenic (P<0.05) and chondrogenic (P<0.001) differentiation was observed using concentrated aspirate, as evidenced by biochemical assay and semi-quantitative histological analysis. Furthermore, enhanced cell seeding efficiency onto allograft was seen as an effect of SSC concentration per ml of aspirate (P<0.001), confirming the utility of this approach for application to bone regeneration.

The ability to rapidly enrich BMA demonstrates potential for intra-operative application to enhance bone healing and offers immediate capacity for clinical application to treat many scenarios associated with local bone stock loss. Further in vivo analysis is ongoing prior to clinical tests.

Background

Skeletal stem cells can be combined with human allograft, and impacted to produce a mechanically stable living bone composite. This strategy has been used for the treatment of femoral head avascular necrosis, and has been translated to four patients, of which three remain asymptomatic at up to three year follow-up. In one patient collapse occurred in both hips due to widely distributed and advanced AVN disease, necessitating bilateral hip arthroplasty. However this has provided the opportunity to retrieve the femoral heads and analyse human tissue engineered bone.

Background and objectives

Fracture healing represents a physiological process regulated by a variety of signalling molecules, growth factors and osteogenic progenitor cells. Bone healing following trauma is associated with increased serum concentrations of several pro-inflammatory and angiogenic growth factors1. Platelet-derived growth factor (PDGF) has been shown to stimulate mesenchymal stem cell (MSC) proliferation in vitro. However, the in vivo relationship between the levels of PDGF and the numbers of MSCs in humans has not yet been explored. The aim of this study was to investigate PDGF release in the peripheral circulation following trauma and to correlate it with the numbers of MSCs in iliac crest bone marrow (BM) aspirate and in peripheral blood.

Periprosthetic femoral fractures can occur as a complication of total hip arthroplasty and are often challenging to treat as the mechanical scenario is influenced by the presence of the metal prosthesis within the bone. This research focuses on finding the optimum fixation for transverse, Vancouver type B1 periprosthetic fractures, stabilised using locking plates and secured using screws. The aim of this study was to experimentally validate a computer model of a human femur, develop that model to represent a periprosthetic femoral fracture fixation and show how the model could be used to indicate differences between plating techniques.

In the first development stage, both a laboratory model and a finite element model were developed to evaluate the mechanical behaviour of an intact composite femur under axial loading. Axial strains were recorded along the medial length of the femur in both cases and compared to provide validation for the computational model predications. The computational intact femur model was then modified to include a cemented total hip replacement, and further adapted to include a periprosthetic fracture stabilised using a locking plate, with unicortical screws above, and bicortical screws below the transverse fracture.

For the intact femur case, the experimental and computational strain patterns correlated well with an average difference of 16%. Following the inclusion of the stem, there was a reduction in the strain in the region of the prosthesis reducing by an average of 45%. There was also a large increase in bulk stiffness with the introduction of the prosthesis. When the fracture and plate fixation were included, there was little difference in the proximal strain where the stem dominated, and the strains in the distal region were found to be highly sensitive to the distribution of the screws.

The results of this study indicate that screw configuration is an important factor in periprosthetic fracture fixation. A laboratory model of the periprosthetic facture case is now under development to further validate the computational models and the two approaches will then be used to determine optimum fixation methods for a range of clinical scenarios.

Long bone fractures are a commonly presented paediatric injury. Whilst the possibility of either accidental or non-accidental aetiology ensures significant forensic relevance, there remain few clinical approaches that assist with this differential diagnosis. The aim of this current study was to generate a reproducible model of spiral fracture in immature bone, allowing investigation of the potential relationship between the rotational speed and the angle of the subsequent spiral fracture.

Seventy bovine metacarpal bones were harvested from 7 day old calves. Sharp dissection ensured removal of the soft tissue, whilst preserving the periosteum. The bones were then distributed evenly before eleven groups, before being aligned along their central axis within a torsional testing machine. Each group of bones were then tested to failure at a different rotational speed (0.5, 1, 15, 20, 30, 40, 45, 60, 75, 80 and 90 degrees s-1). The angle of spiral fracture, relative to the long axis, was then measured, whilst the fracture location, the extent of comminution and periosteal disruption, were all recorded.

Sixty-two out of 70 specimens failed in spiral fracture, with the remaining tests failing at the anchorage site. All bone fractures centred on the narrowest waist diameter, with 5 specimens (all tested at 90 degrees s-1) demonstrating comminution and periosteal disruption. The recorded spiral fracture angles ranged from 30 - 45 degrees, and were dependant on the rotational speed.

This study has established a relationship between the speed of rotation and the angle of spiral fracture in immature bovine bone. It is anticipated that further study will enable investigation of this trend in paediatric bone, ultimately providing an additional diagnostic tool for clinicians trying to verify the proposed mechanism of injury.

Total knee arthroplasty is an established and successful operation. In up to 13% of patients who undergo total knee arthroplasty continue to complain of pain. Recently computerised tomography (CT) has been used to assess the rotational profile of both the tibial and femoral components in painful total knee arthroplasty.

We reviewed 56 painful total knee replacements and compared these to 56 matched patients with pain free total knee replacements. Patients with infection, aseptic loosening, revision arthroplasties and gross coronal malalignment were excluded. Datum gathered from case notes and radiographs using a prospective orthopaedic database to identify patients. The age, sex, preoperative and postoperative Oxford scores, visual analogue scores and treatments recorded. The CT information recorded was limb alignment, tibial component rotation, femoral component rotation and combined rotation.

The two cohorts of patients had similar demographics. The mean limb alignments were 1.7 degrees varus and 0.01 degrees valgus in the painful and control groups respectively. A significant difference in tibial component rotation was identified between the groups with 3.2 degrees of internal rotation in the painful group compared to 0.5 degrees of external rotation in the control group (p=0.001). A significant difference in femoral component rotation was identified between the groups with 3.8 degrees of internal rotation in the painful group compared to 1.1 degrees of external rotation in the control group (p=0.001). A significant difference in the combined component rotation was identified between the groups with 6.8 degrees of internal rotation in the painful group compared to 1.7 degrees of external rotation in the control group (p=0.001).

We have identified significant internal rotation in a patient cohort with painful total knee arthroplasty when compared to a control group with internal rotation of the tibial component, femoral component and combined rotation. This is the largest comparison series currently in the literature.

Frictional resistance to tendon gliding is minimised by surrounding loose areolar tissues. During periods of prolonged immobilisation, for example post tendon-repair, adhesions can form between the two adjacent tissues, thereby limiting function. Whilst agents applied during surgery are recognised to succeed in adhesion prevention, they have also been reported to provide some reduction in friction during in vitro tendon-bony pulley investigations. This study investigated the effectiveness of common anti-adhesion agents in lubricating the tendon-surrounding tissue contact by comparison with a control study. By using a validated apparatus and with reference to the Stribeck curve, it was determined that the natural in vivo contact is likely to be lubricated by a film of synovial-like fluid. Application of all anti-adhesives generated a similarly efficient lubricating system, and hence administration of these agents should be encouraged to all regions of the tendon disrupted during surgery. Minimising frictional resistance to gliding will reduce the likelihood of tendon ‘gapping’ - and subsequently failure - at the repair site.

Introduction

Anteromedial osteoarthritis of the knee (anteromedial gonarthrosis-AMG) is a common form of knee arthritis. In a clinical setting, knee arthritis has always been assessed by plain radiography in conjunction with pain and function assessments. Whilst this is useful for surgical decision making in bone on bone arthritis, plain radiography gives no insight to the earlier stages of disease. In a recent study 82% of patients with painful arthritis had only partial thickness joint space loss on plain radiography. These patients are managed with various surgical treatments; injection, arthroscopy, osteotomy and arthroplasty with varying results. We believe these varying results are in part due to these patients being at different stages of disease, which will respond differently to different treatments. However radiography cannot delineate these stages. We describe the Magnetic Resonance Imaging (MRI) findings of this partial thickness AMG as a way of understanding these earlier stages of the disease.

AIM

Avascular necrosis (AVN) of the femoral head is a potentially debilitating disease of the hip in young adults. Impaction bone grafting (IBG) of morcellised fresh frozen allograft is used in a number of orthopaedic conditions. This study has examined the potential of skeletal stem cells (SSC) to augment the mechanical properties of impacted bone graft and we translate these findings into clinical practice.

Introduction

Iliac crest bone marrow aspirate (ICBMA) is frequently cited as the ‘gold-standard’ source of MSCs. MSCs have been shown to reside within the intramedullary (IM) cavities of long-bones [Nelea, 2005] however a comparative assessment with ICBMA has not yet been performed and the phenotype of the latter compartment MSCs remains undefined in their native environment.

Femoral stem varus has been associated with poorer results. We report the incidence of varus/valgus malalignment of the Exeter polished, double taper design in a multicentre prospective study. The surgical outcomes at a minimum of five year and complication rates are also reported.

A multicentre prospective study of 987 total hip replacements was undertaken to investigate whether there is an association between surgical outcome and femoral stem malalignment. The primary outcome measure was the change in the Oxford hip score (OHS) at five years. Secondary outcomes included the rate of dislocation and revision.

The incidence of varus and valgus malignment were 7.1% and 2.6% respectively. There was no significant difference in OHS between neutral and malaligned femoral stems at 5 years (neutral, mean = 40.2; varus, mean 39.3, p = 0.465; valgus, mean = 40.9, p = 0.605). There was no significant difference in dislocation rate between the groups (p = 0.66). There was also no significant difference in revision rate (p = 0.34).

This study provides evidence that the Exeter stem is extremely tolerant of varus and valgus malalignment, both in terms of outcome and complication rate.

Background, Context and Motivation

“Increases in reconstructive orthopaedic surgery, resulting from advances in surgical practice and the ageing population, have lead to a demand for bone graft that far exceeds supply.”…Traditional bone grafting methods have been linked with a number of negative issues including increased morbidity due to secondary operation site and action as a vector for spread of disease. (Hing 2004). A solution to these insufficiencies would be the creation of a synthetic osteoinductive bone graft material. This would vastly improve bone graft surgery success rates and expedite post-op recovery times. The aim of this study was to classify then explore the dissolution rates of three experimental hydroxyapatite/silicate apatite synthetic bonegrafts in physiological solutions, (phosphate buffered saline, (PBS) +/− serum proteins, (PBS +FCS). The overall objective being to identify whether there is an explainable significant difference in ion exchange that could be behind the osteoinductive phenomena.

Introduction

Therapeutic exploitation of MSCs in orthopaedics has been tempered by their scarcity within ‘gold-standard’ iliac crest bone marrow aspirate (ICBMA) and the resulting need to expand cells in vitro. This is time-consuming, expensive and results in cells with a reduced differentiation capacity. [Banfi 2000] The RIA is a device that provides continuous irrigation and suction during reaming of long bones. Aspirated contents pass via a filter, trapping bony-fragments, before moving into a ‘waste’ bag, from which MSCs have been previously isolated. [Porter 2009] We hypothesised that ‘waste’ RIA bag contains more MSCs than a standard aspirated volume of ICBMA (30 ml). We further hypothesised than a fatty solid phase within this ‘waste bag’ contains many MSCs trapped within the adipocyte-rich stromal network and hence requiring an enzymatic digestion for their efficient release [Jones 2006].

Bone marrow is an environment rich in its diversity of cell types and niches. Both hematopoietic and osteogenic stromal cells are present and have been studied extensively. Less is known about the function of one of the most abundant cell types in the bone marrow: adipocytes. There are several hypotheses that have been proposed including: passive role as a space filler; active role in the body's general lipid metabolism; role in providing a localized energy reservoir for emergency situations affecting the bone or hematopoiesis; support of differentiation or function of other cell types (such as bone, endothelial, and other stromal cells).

There are several human pathologies associated with increases in adipocyte hypertrophy or proliferation including changes associated with aging, osteoporosis, and osteonecrosis. The reasons for these changes are poorly understood. One etiology associated with both osteoporosis and osteonecrosis, corticosteroid therapy, has been shown to increase the lipid content of osteoblasts and adipocytes.

With osteonecrosis, several pathogenetic mechanisms involving adipocytes have been proposed:

Mechanical - increased size and number cause increased intraosseous pressure and decreased venous outflow

The possibility that adipocytes may actually play an active role in propagating specific pathologic features has only recently been discussed. This is in part due to our increasing understanding that adipocytes have an endocrine role in metabolism.

Only recently have scientists tried to identify specific cellular mechanisms that may be involved in the pathogenesis of osteonecrosis. Results from these studies will not only contribute to our understanding of the disease of osteonecrosis (and other diseases such as osteoporosis) but will also help us to appreciate the multiple functionalities of the heretofore unappreciated adipocyte.