Following hip arthroplasty carried out using the Slooff-Ling impaction grafting technique micro-motion of the acetabular cup is frequently seen within the bone graft bed. In some cases this can lead to gross migration and rotation of the acetabular cup, resulting in failure of the arthroplasty. The movement of the cup is thought to be due to the irrecoverable deformation of bone graft under shear and compressive forces. Previous experimental studies have addressed ways in which the behaviour of the bone graft material may be improved, for example through washing and the use of improved particle size distribution. However there has been a limited amount of research carried out into assessing the behaviour of the acetabular construct in-vivo.

This study presents a 3D finite element model of the acetabular construct and hemi-pelvis following impaction grafting of a cavitory defect. A sophisticated elasto-plastic material model was developed based on research carried out by the group to describe the bone graft bed. The material model includes the non-linear stiffness response, as well as the shear and consolidation yield response of the graft. Loading associated with walking, sitting down, and standing up is applied to the model. Distinct patterns of migration and rotation are observed for the different activities. When compared in a pseudo-quantitative manner with clinical observations results were found to be similar. Walking is found to account for superior migration, and rotation in abduction of the acetabular cup, while sitting down and standing up are found to account for posterior migration, and lateral rotation. The developed 3D model can be used in the assessment of cup designs and fixation devices to reduce the rate of aseptic failure in the acetabular region.

Introduction: Cement pressurisation is key to achieving good cement-bone interdigitation in THR. To obtain adequate pressurisation the medullary canal must be sealed distally using a cement restrictor. The cement restrictor must remain stable in the femoral canal.

Methods: Five different cement restrictors were evaluated, namely the Exeter Cement Plug, Biostop G, Hardinge, Rex CementStop and a preinjected cement plug. The restrictor was deployed in a sawbone that had been reamed to produce a distal flare, based on radiographic measurements. Low viscosity bone cement pressurised using a cement ram connected to a 10bar air supply. An electronic pressure valve increased the pressure in the cement. Cement pressure and cement restrictor displacement were continuously measured. The pressure valve and recording of measurements was controlled by a customised computer package.

Results: The Rex CementStop withstood the greatest pressures (mean 565.8kPa). This was a significantly greater pressure than any of the other cement restrictors (p< 0.001). Pre-injected cement plugs were able to resist the next highest pressures (mean 350.4kPa). They did not displace but leaked cement and were technically difficult to deliver in the distal femur. Cement restrictors that function well above the isthmus were ineffective (Biostop mean 118.7kPa) or could not be deployed below the isthmus (Exeter). The Hardinge recorded a mean 162.3kPa.

Discussion: During pre-operative templating it is important to consider where the cement restrictor will sit in the femur. When the cement restrictor is going to be deployed beyond the femoral isthmus, an alternate method of cement restriction may need to be used. Universal sized plugs (e.g. Hardinge) function poorly in this situation. Press-fit plugs such as Biostop and Exeter are severely compromised when inserted past the femoral isthmus. Pre-injected cement plugs are variable in efficacy. The expandable Rex CementStop reliably occluded the femur, allowing the highest pressures to be generated.

Previous experimental studies of the pelvis have been carried out on cadaveric samples stripped of soft tissue. Investigations of the stress concentrations present in the pelvis due to the application of force through the hip joint have been conducted with the superior iliac crests cast in resin or cement. Thus stress concentrations are observed towards the superior iliac crests, and to some extent the pubic symphysis (these being the areas in which force transfer can occur). Due to the rigid fixing of the pelvis in these experiments, the pelvic bone has become viewed as a ‘sandwich beam’ acting between the sacro-iliac and the pubic joints. Numerical models employing similar fixed conditions have shown good agreement with the experimental studies.

However it is clear that these experiments, and the accompanying computational models are not representative of the in-vivo situation, in which the muscles and ligaments of the pelvis and hip joint provide resistance to movement, and in the case of muscles place additional forces on the pelvis, not addressed in the experimental studies. This study presents a finite element model of the pelvis in which novel techniques have been used to include the pelvic ligaments, and hip joint muscles using realistic attachment areas on the cortex, providing a more realistic comparison to the in-vivo environment. Joint interactions at the pubic symphysis and sacro-iliac joints are also simulated. A fixed boundary condition model is also presented for comparison.

The resulting stress concentrations in the pelvis for single leg stance observed in the in-vivo boundary condition model are dramatically different to those presented in studies in which the pelvis is rigidly fixed in place. The abductor muscles are seen to play a significant role in reducing stress concentrations towards the sacro-iliac joints and superior to the acetabulum, in comparison to fixed boundary condition analyses. Stress reductions away from the acetabulum are also observed in the underlying trabecular bone for the in-vivo boundary condition model. Similar stresses are observed within the acetabular region for the fixed, and in-vivo boundary condition models.

An estimated 10% of patients have problems with fracture healing. Initial studies have revealed that it is likely that both the innate and specific immune systems play a role in fracture repair, but this has not been attributed to particular components, cells or their products. It is known that the functionality of the immune system is impaired with age and this may account for the higher rate of delayed union in elderly patients.

We used a validated mouse model of a reproducible closed tibial fracture. In order to prevent any foreign body inflammatory/immune response no artificial internal fracture fixation was used and instead external support was provided using a Plaster of Paris cast. The role of the specific immune system was studied using an immunodeficient Balb/c SCID (Severe Combined Immuno Deficient) mutant mouse. The SCID mice were matched for age, sex (all males) and weight to the control, wild type Balb/c mice. Mechanical (4 point bending) and radiographic (Radiographs scanned and calculations of callus area, index and density made with image analysis software) measures were used to assess fracture repair at 21 days.

Mechanical measurements revealed an enhancement of fracture healing in the SCID mouse strain compared to the control strain, with stress at yield and Young’s modulus higher in SCID mice than controls. (Stress at yield: 4.2 +/− 0.23MPa in Controls, 7.1 =/− 0.6MPa in SCIDs, P< 0.01; Young’ Modulus: 22.1 +/− 2.99MPa in Controls, 60+/− 9.9MPa in SCIDs P< 0.01). There were no significant differences seen in mechanical properties of unfractured bone between the two strains. Radiographic analysis revealed no significant differences in callus area or index (both measurements of callus size) but callus density was significantly higher (P< 0.01) in the SCID subjects compared to controls (2.6 +/− 0.06E5 Greyscale in SCIDs vs. 2.2 +/− 0.09E5 in controls).

We conclude that an abnormality of the immune system due to either lack of the specific immune system (T and B cells) or an enhancement of the innate system results in increased mineralization, stiffness and strength of fracture healing, and that further investigation might result in novel therapies directed toward avoidance of non/delayed-union.

Bone substitutes have emerged as a promising alternative in surgeries requiring bone grafting, with a large array of materials available for today’s surgeon. Unfortunately, there is currently no definitive method for comparing the potential bone-healing potential of these different materials. We have developed a novel technique for assessing the osteogenic capacity of different bone substitutes in a mechanically-stimulating perfusion bioreactor.

The Zetos(TM) bioreactor system consists of individual flow chambers connected to a low-flow perfusion pump, which recirculates media through samples. The Zetos can be programmed to apply a controlled stress or a controlled strain to each individual sample inside the flow chamber. Since bone formation has been shown to be optimal with short doses of high amplitude strains, test samples were subjected to daily loading corresponding to physiological strain experienced during a jumping exercise (maximum 3000 microStrain).

Three substitute materials representing the range of materials available clinically were tested in the Zetos system; these included collagen, calcium phosphate, and a synthetic polymer. Primary human osteoblasts were seeded onto the substitutes, which were then placed inside the Zetos system and maintained under load or non-load conditions for 14 days. No supplementary osteogenic factors were provided to the cells. The degree of bone formation in the samples was assessed using Von Kossa staining and quantified in terms of the area of new mineral relative to the surface area of the substitute.

No mineralisation was detected in the non-loaded samples. However, in the loaded samples, mineralisa-tion was detected in some of the substitutes. The degree of mineralisation depended on the material: in collagen, an average of 0.22 mm2/mm2 was mineralised; in calcium phosphate, mineralisation averaged 0.0013 mm2/ mm2; but in the loaded polymer samples, no mineralisation was detected.

This indicates that mechanical loading is a sufficient stimulus for bone formation in some materials, even in the absence of other known osteogenic factors. Further, commercial substitutes differ in their ability to support bone formation under conditions of physiological loading. Further development of this technique could allow it to be used as a screening tool for predicting the efficacy of commercial products.

Micro level finite element models of bone have been extensively used in the literature to examine its mechanical behaviour and response to loads. Techniques used previously to create these models involved CT attenuations or images (e.g. micro-CT, MRI) of real bone samples. The computational models created using these methods could only represent the samples used in their construction and any possible variations due to factors such as anatomical site, sex, age or degree of osteopo-rosity cannot be included without additional sample collection and processing. This study considers the creation of virtual finite element models of trabecular bone, i.e. models that look like and mechanically behave like real trabecular bone, but are generated computationally.

The trabecular bone is anisotropic both in terms of its micro-architecture and its mechanical properties. Considerable research shows that the key determinants of the mechanical properties of bone are related to its micro-architecture. Previous studies have correlated the apparent level mechanical properties with bone mineral density (BMD), which has also been the principal means of diagnosis of osteoporosis. However, BMD alone is not sufficient to describe bone micro-architecture or its mechanical behaviour. This study uses a novel approach that employs BMD in conjunction with micro-architectural indices such as trabecular thickness, trabecular spacing and degree of anisotropy, to generate virtual micro-architectural finite element models. The approach permits generation of several models, with suitable porous structure, for the same or different levels of osteoporosity. A series of compression and shear tests are conducted, numerically, to evaluate the apparent level orthotropic elastic properties. These tests show that models generated using identical micro-architectural parameters have similar apparent level properties, thus validating this initial bone modelling algorithm. Numerical tests also clearly illustrate that poor trabecular connectivity leads to inferior mechanical behaviour even in cases where the BMD values are relatively high. The generated virtual models have a range of applications such as understanding the fracture behaviour of osteoporotic bone and examining the interaction between bone and implants.

Morsellised cortico-cancellous bone (MCB) is used extensively in impaction grafting procedures, such as the filling of cavitory defects on the femoral and acetabular sides during hip arthroplasty. Several experimental studies have attempted to describe the mechanical behaviour of MCB in compression and shear, and it has been found that it’s properties can be improved by washing and rigorous impaction at the time of surgery. However their focus has not been on the development of constitutive models that can be used in computational simulation.

The results of serial confined compaction tests are presented and used to develop constitutive models describing the non-linear elasto-plastic behaviour of MCB, as well as its time dependent visco-elastic behaviour. It is found that the elastic modulus, E of MCB increases linearly with applied pressure, p, with E achieving a value of around 30 MPa at a pressure of around 1 MPa. The plastic behaviour of MCB can be described using a Drucker Prager Cap yield criterion, capable of describing yielding of the graft in shear and compression. The time dependent visco-elastic behaviour of MCB can be accurately modelled using a spring and dashpot model that can be numerically expressed using a fourth order Prony series. The role of impaction in reducing subsequent plastic deformation was also investigated. The developed relationships allow the constitutive modelling of MCB in finite element simulations, for example of the acetabular construct following impaction grafting. The relationships also act as a gold standard against which to compare synthetic graft and graft extender materials.

Introduction: In hereditary multiple exostosis (HME) the synthesis of the polysaccharide heparan sulphate (HS) is disrupted. HS-proteoglycans are low affinity receptors involved in fibroblast growth factor signaling. Activation of FGF receptor 3 (FGFr3) on mature chondrocytes leads to growth attenuation rather than stimulation. We tested the hypothesis that in HME chondrocytes with absent or reduced HS-PG synthesis there is impaired response to the FGFr3 ligand and loss of control of chondrocyte proliferation.

Materials and methods: Chondrocytes were harvested from normal growth plate (epiphyseodesis) or HME osteochondroma cartilage cap obtained as surgical discard and cultured to 70% confluence in growth media. Cells were re-plated for experimentation. Growth curves were obtained for cells over a period of 5 days. In addition proliferative responses of healthy and HME chondrocytes were determined after low serum synchronization followed by challenge with FGF 9 (10 and 100ng/ml) and incorporation of BrdU for 2hours every two hours over a twenty eight hour period. Using these techniques it is possible to describe in detail the time dependent entry of cells into S-phase of the cell cycle and compare cell lines and treatment.

Results: Significant differences were observed in the growth characteristics over a five-day period (p< 0.05). Under baseline growing conditions the chondrocytes derived from osteochondroma had a more rapid doubling time when compared with the normal growth plate chondrocyte (2.6+/− 0.6 vs 4.9+/−1.0, p< 0.05). In response to incubation with FGF-9 cells from normal growth plate have a lower peak proportion of cells entering the s-phase than with media alone (7% vs 25%). This inhibition is not observed in chondrocytes from osteochondroma.

Conclusions: It would appear that osteochondroma chondrocytes are resistant to the normal regulatory effect of FGF-9 on cell proliferation. The differential response to FGF may be responsible for the growth differences observed both in-vitro and in-vivo.

A descriptive study of osteoporotic fractures and the evaluation of the relative risk of hip fracture following a minor fracture were done on 2.5 million individuals from 1980 to 1997. People aged forty-five years old and older have a risk for hip fracture after a minor fracture of 2.3–17.3 time the risk of people without previous fracture. Given the availability of pharmaceuticals that decrease the fracture risk dramatically within the first 18 months of therapy, the average four to six years time between minor and hip fracture represents a perfect window of opportunity for preventive treatment.

Osteoporotic fractures, especially hip fractures, represent a major health problem in terms of morbidity, mortality and cost. Since the availability of new treatments for osteoporosis, a better understanding of the disease is needed to define the indications for treatment.

A descriptive study of osteoporotic fractures and the evaluation of the relative risk of hip fracture following a minor fracture were done on a population aged fortyfive years old and older from 1980 to 1997 (2.5 million individuals).

During the follow-up period, 220,120 fractures (hip, wrist, proximal humerus and ankle) were recorded. Wrist fractures were the most frequent (42.2%) followed by hip fractures (32.5%). Although the proportions of fracture sites were similar for both sexes, 75% of the fractures occurred in females. The mortality rate 1 year after a hip fracture is increased by 14–27% for men and 9–13% for women. Men and women aged fortyfive years old and older have a risk for hip fracture after a humerus or a wrist fracture of 2.3–17.3 time the risk of people without previous fracture. The average time between a wrist or humerus fracture and a hip fracture was four to six years.

Wrist and humerus fractures represent a major risk for future hip fracture. Given the availability of pharmaceuticals that decrease the risk of hip fracture dramatically within the first eighteen months of therapy, the interval between minor and hip fracture represents a perfect window of opportunity for preventive treatment to decrease the risk of future hip fracture.

Autologous osteochondral cylinder transfer is a treatment option for small articular defects, especially those arising from trauma or osteochondritis dissecans. There are concerns about graft integration and the nature of tissue forming the cartilage-cartilage bridge. Chondrocyte viability at graft and recipient edges is thought to be an important determinant of quality of repair. The aim was to evaluate cell viability at the graft edge from ex vivo human femoral condyles, after harvest using conventional technique. With ethical approval and patient consent, fresh human tissue was obtained at total knee arthroplasty. Osteochondral plugs were harvested using the commercially available Acufex 4.5mm diameter mosaicplasty osteotome from regions of the lateral femoral condyle (anterior cut) that were macroscopically non-degenerate and microscopically non-fibrillated. Plugs were assessed for chondrocyte viability at the graft edge using confocal laser scanning microscopy (CLSM), fluorescent indicators and image analysis. The central portions of the plugs remained healthy, with > 99% cell viability (n=5). However, there was substantial marginal cell death, of thickness 382 ± 68.2 microm in the superficial zone (SZ). Demi-plugs were created by splitting the mosaicplasty explants with a fresh No. 11 scalpel blade. The margin of SZ cell death was 390.3 ± 18.8 microm at the curved edge of the Acufex, significantly (Mann-Whitney; P= 0.0286; n =4) greater than that at the scalpel cut (34.8 ± 3.2 microm). Findings were similar when the cartilage was breached but the bone left intact. In time-course experiments, the SZ marginal zone of cell death after Acufex harvest showed no increase over the time period 15 minutes to 2 hours. Mathematical modelling of the mosaicplasty surface shows that cell death of this magnitude results in a disturbing 33% of the superficial graft area being non-viable. In conclusion, mosaicplasty, though capable of transposing viable hyaline cartilage, is associated with an extensive margin of cell death that is likely to compromise lateral integration. There would appear to be considerable scope for improvement of osteochondral transplant techniques which may improve graft-recipient healing and clinical outcomes.

Measuring strain in biological specimens has always been inherently difficult due to their shape and surface properties. Traditional methods such as strain gauges require contact and therefore have reinforcing effects, also the surface preparation can be time consuming and if proper fixation is not achieved the results will be inaccurate. Using a non contact method to measure strain such as photogrammetry has several advantages. The strain over the whole surface of a specimen can be mapped, depending on the field of view of the camera used. It has a large dynamic range, from microns to millimetres which can be decided upon at the post processing stage. Specimens can be tested to destruction without damaging any measurement equipment. Also there is considerably less set up time involved between testing different specimens once the system is in place. We aimed to test speckle photogrammetry, a method used in industry and fluid dynamics as a tool for assessing proximal femur fracture stability and repair techniques. A Zwick Roell materials testing machine was used to axially apply a staircase loading pattern to sawbones femora, simulating the load experienced by the femur when standing. Firstly an intact bone was tested then a set of three identical fractures of each of three common fracture configurations were produced by osteotomy. The first femur of each configuration was loaded un-repaired to failure; the remaining two were repaired using common techniques for that particular fracture type then also loaded to failure. The bone and fixation device were covered with stochastic, high contrast paint speckle prior to testing. This speckle pattern was recorded at regular load intervals by a digital camera which was attached to the materials testing machine via a rigid frame to eliminate any camera movement. These images were then transferred to a computer where they were converted to 8 bit bitmap images. Matlab was used to process the data from subsequent images to produce vector and colour maps of the displacements and strains over the entire visible surface of the proximal femur and to show the comparative displacements and strains experienced by the individual bone fragment and the fixation devices. Non contact optical strain measurement has proved itself to be a useful tool in assessing the stability of fractures and the repair techniques of these fractures. Additionally it can also be used to validate finite element models to compare theoretical and experimental results due to the similar data and graphic visualisation outputs which are produced by both techniques.

Introduction: It has been suggested that statins may influence bone turnover via an effect on bone morphogenic protein 2 (BMP-2). While the effect on statins in the prevention of osteoporosis remains controversial there is some evidence that they may exert a significant effect on fracture healing.

Using a newly developed fracture model of the proximal tibia of the rat, the effect of simvastatin on osteoporotic and non-osteoporotic fracture healing was investigated. The fracture model was used as it provided a useful model of metaphyseal fracture healing which is particularly relevant to osteoporotic fracture.

Methods: Four groups of 20 3-month-old female Wistar rats were used. Half underwent ovariectomy (ovx) while the remainder had a sham procedure. 8 weeks later a fracture was created in the proximal tibia of each animal by three point bending. The fractures were supported by a narrow intramedullary k-wire. 20 sham and 20 ovx animals were then fed 20mg/kg simvastatin by gavage for 14 days while the rest received placebo. 10 animals from each group were sacrificed at 2 weeks post surgery while the rest were sacrificed at 4 weeks.

X-rays of the healing fractures were taken. Both the intact and fractures tibiae were then taken for mechanical testing by four point bending.

Results: Six animals (7.5%) were excluded because of fracture comminution (5) or loss of stabilisation (1). There was a similar radiological appearance in all 4 groups at each time point. At two weeks: there was no difference in the mechanical properties of the healing bone between the groups. At 4 weeks the fractured and intact tibiae from the sham animals had an equal ultimate load at failure to their intact tibiae. However, the fractured tibiae from the ovx animals remained weaker (ovx & placebo 68%, ovx & statin 60.5% of ultimate load at failure compared with intact tibia). The difference between the fractures ultimate load in ovx and sham animals was statistically significant (p=0.0105). No difference was seen between the statin and placebo group.

Discussion: This work provides evidence that a metaphyseal fracture in the osteoporotic rat model is able to withstand significantly less load at 4 weeks than a fracture from a sham ovx animal suggesting fracture healing is slower in osteoporotic individuals. Simvastatin at 20mg/kg had no effect on the mechanical properties of normal or osteoporotic fracture healing in this study.

Introduction: Emerging therapies for regenerating skeletal tissues are focused on the repair of pathologically altered tissue by the transplantation of functionally competent cells and supportive matrices. Stem cells have the potential to differentiate into musculoskeletal tissue and may be the optimal cell source for such therapies. In vitro studies have demonstrated the ability of adult bone marrow stromal cells (MSC) and human embryonic stem cells (hES) to generate bone, but little is known regarding their potential to repair bone in vivo. Preclinical studies in animal models will allow investigation into the extent that regenerated tissue resembles functional and healthy tissue, and its potential clinical application.

Aim: To assess whether adult and embryonic stem cells maintained their ability to form musculoskeletal tissues in vivo using diffusion chambers implanted into the peritoneal cavity of nude mice. Currently, ongoing experiments are assessing the use of MSCs and hES cells to regenerate bone in a rodent preclinical model.

Methods: MSC cells and embryoid body-derived H9 hES cells were prepared as previously described (Haynesworth et al Bone 1992; Sottile et al Cloning Stem Cells 2003). Groups of cells were left untreated or pre-treated with osteogenic (OS) media for 5 days. Study 1: Single cell suspensions of untreated or pre-treated cells were injected into diffusion chambers which were implanted intraperitonealy into nude mice and left for 79 days. Study 2: OS pre-treated cells were implanted into an experimentally created full thickness calvarial defect in adult male Wistar rats. The defect area was left empty or filled with demineralised bone matrix (DBM: Allosource®) alone or with DBM/MSCs or DBM/hES composite. Tissues were collected 4 weeks after surgery.

Analysis: Histological and immunochemical techniques were used to evaluate cell phenotypes and the contribution of transplanted cells to tissue repair.

Results: Study 1: Both hES (in 2/3 chambers) and MSC (3/3) cells pre-treated with OS media formed only mineralised bone. No cartilage was detected in these OS pre-treated cells. Untreated hES cells formed both mineralised bone and cartilage within the chambers (2/3). In contrast, untreated MSC cells (3/3) produced no mineralised bone or cartilage. Preliminary analysis demonstrated the absence of any other tissue type in the diffusion chambers. Study 2: Active bone regeneration was observed at the edges of the calvarial defect after 4 weeks, with a high density of cells present within the MSC or hES/DBM composite. No signs of local cellular immunological response were seen.

Summary: OS pre-treatment restricted differentiation towards the osteoblast lineage in both hES and MSC cells indicating successful directed differentiation in vivo. Untreated hES and MSC cells produce a different range of cell phenotypes suggesting that the two cell sources represent cells at a different stage of commitment in a common cell lineage or cells derived from two distinct cell lineages. New bone formation was seen at the site of the calvarial defect in the presence OS pre-treated MSC and hES cells suggesting that these cells may support in vivo bone repair in a preclinical model. Funded by Geron Corporation

Introduction: The concept of cell senescence has been described as the mechanism responsible for the ageing of tissues, that is a finite ability to replicate and produce new tissue. The senescent cell population is separate and distinct from the cells which are undergoing programmed cell death (apoptosis), and those which are necrosing acutely. Cells reaching the senescent state have an increase in β-galactosidase activity, which is detectable using an established technique for soft tissues including fibroblasts and epithelial tissues. Senescence has not previously been investigated in bone. We have investigated this and hypothesise that new bone formed by distraction osteogenesis will have fewer senescent cells than the adult cortical “old” bone.

Methods: Eight New Zealand white rabbits underwent application of a M100 Orthofix external fixator to the tibia and creation of a mid-diaphyseal osteotomy, using a hand saw. After a seven day latency period, distraction was commenced (0.5mm twice daily) to twenty percent lengthening. After 3 weeks consolidation, the tibae were harvested for histological analysis.Senescent Staining:The sections were stained using a technique described by Faragher, using an X-gal based stain. Sections were incubated for 16 hours at 37 degrees centigrade before counter staining with DAPI. Sections underwent histological analysis and total cell and senescent cell counts performed.

Results: Surprisingly, large numbers of cells within the bone regenerate stained for cell senescence. A mixture of multinucleate and mononucleate cells were present. The location and appearance of the multinucleate cells prompted the use of TRAP staining. This provided support for these cells being osteoclasts.

Discussion: Previously, a high percentage of apoptotic cells and a high rate of cell division has been reported in bone regenerate. The surprisingly high numbers of cells within the newly formed bone staining positively for senescence suggest that there may also be a high senescent cell population. Alternatively, the positive TRAP staining may indicate that the stain is less specific than reported and may be staining osteoclasts and mature macrophages within the bone regenerate.

Introduction: Tibial component loosening is a common mode of failure in modern total knee arthroplasty and is thus a common cause for revision knee surgery. Direct bone ingrowth of press fit knee prosthesis has been deemed an important prerequisite for long-lasting implant fixation and thus clinical success in both primary and revision TKA whether for cemented or uncemented stems. To achieve good long term biological stabilization, initial secure mechanical stability, (i.e. minimising tibial tray and stem motion with respect to the tibia,) is vital. A lack of initial stability can lead to resorption of bone at the implant-tissue interface and can consequently result in loosening and failure of the prosthesis. Obtaining adequate tibial fixation is difficult in revision patients as often there is insufficient bone stock in the proximal tibia. A longer stem is often recommended with revision surgery as a central stem should guide the migration of the tibial component so that it occurs predominantly along the vertical axis, thus minimising the risk of recurrent malalignment and loosening due to tilting of the tibial tray. It is also thought that the presence of a third rigid peg helps to reduce inducible displacements by anchoring the new implant in robust cancellous bone. However there is no consensus on the length of central stem should be to achieve the best load transfer and fixation and although the use of long stems on the tibial component is advocated, in revision TKA involving bone grafting and augmentation. The effect of the tibial stem length in other cases has received contradictory evaluations. This research deals with an experimentally evaluate the effect that central stem lengths on the initial micromotion of the tibial tray in two revision tibial defects. This is being investigated by measurement of the bone-implant interface motion of the tibial stem.

Method: Composite bones were resected with an extramedullary jig. Three common revision defects were compared 1) no defect requiring no repair(primary); 2) T1 defect requiring bone impaction grafting; 3) T2A requiring augmentation. Three stem configurations were analysed in conjunction with these defects 1) no stem; 2) short 40mm stem; 3) long 80mm stem. Four LVDTs were positioned anteriorly, posteriorly, medially and laterally around the tray and were used to measure the movement of the tibial tray with respect to the tibia. The bones were potted and subjected to axial loading simulating 1– 6 times body weight for 3500 cycles at 1 Hz.

Results: The longer stemmed press fit implants were associated with slightly higher levels of micromotion compared to the “no stem press fit” trays in the primary and T2A defects. This could be due to the fact that cutting errors are accentuated by a longer stem and can cause increased levels of posterior lift off. For bone impaction grafting it seems that a stem sufficiently long to by-pass the defect should be used. The proximal surface cemented trays presented more stable fixation with the inducible displacement between the no stem and stemmed groups being negligible. Subsidence of the tibial tray was reduced marginally by using a longer stem.

If an arthroplasty patient presents with wound breakdown, sinus formation or a hot, red joint the diagnosis of infection is straightforward. However, most total joint replacement (TJR) infections are difficult to distinguish from aseptic loosening. It is imperative to know if a painful TJR is infected to plan appropriate management.

In this prospective study of 204 patients we analysed the diagnostic accuracy of various tests for infection: Inflammatory Markers (CRP/ESR); Aspiration Microbiology; and the Polymerase Chain Reaction (PCR) – a novel technique in this situation. We used international criteria as the gold standard for infection, applied at the time of revision surgery. Any of – a sinus; frank pus in the wound; positive intra-operative microbiology; positive histology – classified the patient as infected. The sensitivity (Sens), specificity (Spec), positive predictive value (PPV) and negative predictive value (NPV) of each test were calculated.

52 patients with an original diagnosis of inflammatory arthritis were excluded, as histology may be inaccurate. The results for the remaining 152 patients are: CRP > 20mg/l: Sens 77%; Spec 76%; PPV 49%; NPV 92%. ESR > 30 mm/hr: Sens 61%; Spec 86%; PPV 57%; NPV 87%. Aspiration Microbiology: Sens 80%; Spec 83%; PPV 71%; NPV 88%. PCR: Sens 71%; Spec 78%; PPV 43%; NPV 89%.

Few patients with negative CRP/ESR were found to be infected; if positive, there was a 50/50 chance that the joint was infected. Positive aspiration microbiology was associated with underlying infection 3 times out of every 4, and negative results were correct 9 times out of 10. PCR was no more accurate than existing tests.

All patients with painful TJR’s should have inflammatory markers checked – if negative the clinician can be relatively reassured that the implant is not infected. If positive or suspicion remains, further investigation should be undertaken. Joint aspiration for microbiology is currently the best available second line investigation.

Introduction If an arthroplasty patient presents with wound breakdown, sinus formation or a hot, red, painful joint replacement the diagnosis of infection is relatively straightforward. However, most total joint replacement (TJR) infections present in an indolent fashion and are impossible to distinguish from aseptic loosening. It is imperative to know if pain in a TJR is due to infection to plan appropriate further management.

Methods In this prospective study of 204 patients we analysed the diagnostic accuracy of various tests for infection in the setting of TJR: Inflammatory Markers (CRP/ESR); Aspiration Microbiology; and the Polymerase Chain Reaction (PCR) – a novel technique in this situation. We used internationally agreed criteria as the gold standard for infection. The patient was deemed to be infected if any of the following were found at the time of revision surgery: a sinus; frank pus in the wound; positive microbiology or positive histology on intra-operative specimens. The sensitivity (Sens), specificity (Spec), positive predictive value (PPV) and negative predictive value (NPV) of each test were calculated.

Results 52 patients with an original diagnosis of inflammatory arthritis were excluded, as histology may be inaccurate. Their results have been presented elsewhere. The results for the remaining 152 patients are: CRP > 20mg/l: Sens 77%; Spec 76%; PPV 49%; NPV 92%. ESR > 30 mm/hr: Sens 61%; Spec 86%; PPV 57%; NPV 87%. Aspiration Microbiology: Sens 80%; Spec 83%; PPV 71%; NPV 88%. PCR: Sens 71%; Spec 78%; PPV 43%; NPV 89%.

Findings and Conclusions Only a few of the patients with negative inflammatory markers later turned out to be infected. If the inflammatory markers were positive, there was roughly a 50/50 chance that the joint was infected. Positive aspiration microbiology was associated with underlying infection approximately 3 times out of every 4, and negative results were correct 9 times out of 10. PCR was no more accurate than existing tests.

We recommend that all patients with painful TJRs have inflammatory markers checked as a screening test – if negative then the clinician can be relatively reassured that the implant is not infected. If positive, further investigation should be undertaken. Joint aspiration for microbiology is currently the best available second line investigation.

Introduction: Diminished adult stature is a key feature of Hereditary Multiple Exostoses (HME). Current debate on the pathogenesis of skeletal abnormalities in HME centres on whether there are ‘field-change’ effects which might retard bone-growth, or whether exostoses themselves distort normal bone development locally. The latter theory allows for surgical excision of exostoses to improve prospects for local normal bone development whereas the former does not. No study has previously investigated patterns of height disturbance in HME. Such an analysis in a cohort of children and adults with HME may provide evidence for or against either pathogenesis theory, and throw light on the chance of success of lower limb surgery in improving final height.

Methods: Between 1996 and 2000, 172 individuals from 78 families with HME had clinical measurement of standing height and leg length (anterior superior iliac spine to medial malleolus. 71 were skeletally immature (1st and 2nd decades). Surgical intervention in anatomical areas affecting stature (lower limb, pelvis and spine) were recorded. Centile heights were calculated from Tanner Whitehouse charts.

Results: 25/172 (15%) exhibited severe short stature (< 3rd centile height). Overall, Statural retardation was not apparent up to age 10; thereafter progressive diminution in centile height was recorded (figure 1). Before age 10, 25/37 (68%) were over the 50th centile. Beyond this age, 98/35 (73%) were less than the 50th centile (X2=22.42, p< 0.001). 101 patients who had surgery did not achieve a greater stature than those who had not. In the normal population lower limb contribution to height increases with age, whereas in HME it remains static suggesting that the retardation of stature seen between ages 10 and 20 in HME is mainly due to lower limb, not spinal growth retardation. Leg length discrepancy of > 1% of centile height was seen in 35/167 (21%), encompassing all age groups without significant difference.

Discussion: The pattern of height retardation observed in this study is consistent with a progressive linear disturbance which is not apparent in early childhood, but progresses significantly in the second decade. Overt spinal exostoses are rare; and the spine’s contribution to growth retardation in HME appears be far less than that due to the lower limb. Although the genetics of HME allow for a field-change effect as well as a local osteo-chondroma effect, these results reinforce the possibility that solutions to severe short stature in HME may be achieved through lower limb surgery.

We investigated the use of PCR (the Polymerase Chain Reaction) to detect the presence of infection in a group of patients undergoing revision arthroplasty for loose TJR (total joint replacement), compared to internationally agreed criteria used as the ‘gold standard’ for infection.

We prospectively tested samples taken from 108 patients undergoing revision arthroplasty (76 hips, 32 knees). Antibiotics were omitted prior to obtaining samples. DNA was extracted by 2 methods – a previously published technique (reference) and a commercial extraction kit (Qiagen^®). PCR involved amplification of an 882 base pair segment of the universal bacterial 16S RNA gene. During revision arthroplasty multiple specimens were taken from around the joint for microbiological and histological examination and the presence or absence of pus was noted. The patient was deemed to be infected if one of the following criteria was found: presence of a sinus pre-operatively; 2 or more intra-operative cultures positive for the same organism; an acute inflammatory response on histology; pus in the joint at revision.

Using the published DNA extraction technique PCR had a sensitivity of 50%, specificity of 93%, positive predictive value of 67% and negative predictive value of 88%. Using commercial extraction the sensitivity improved to 60%, specificity to 98%, positive predictive value to 90% and negative predictive value to 90%.

The previous report stated that PCR had a high sensitivity but a low specificity for detecting low grade infection. However, when using the published technique we found the opposite results – a moderate sensitivity and a high specificity. Introduction of a new DNA extraction technique improved the sensitivity. The refined PCR technique had a high accuracy, but further work is needed to improve sensitivity before we would recommend this method for routine clinical use.

Detection of infection in total joint replacements (TJR) is notoriously difficult. Ideally the diagnosis should be known before revision arthroplasty is undertaken. The level of C-reactive protein (CRP) is one readily available test. Sanzen et al. reported sensitivity of 78% and specificity of 100% for CRP in distinguishing infection in 23 infected TJRs and 33 non-infected TJRs undergoing revision, using a cut off of 2mg/dl¹. However, they used only intra-operative cultures as the standard to compare the CRP against. We have analysed the reliability of CRP to diagnose infection pre-operatively in a group of patients undergoing revision arthroplasty, using the following criteria as the reference standard for infection: 2 or more intra-operative cultures positive for the same organism; presence of acute inflammatory response on histology; presence of pus in the joint at revision (1/3 positive indicates true infection), as described by Hanssen et al.²

The results of CRP and the operative investigations of 26 patients undergoing revision arthroplasty (15 hips and 11 knees) were studied prospectively. In our unit CRP is assayed in mg/dl serum by an automated machine. During revision arthroplasty, multiple specimens were taken from around the joint for microbiological and histological examination. Microbiological cultures were carried out on solid media and broth in aerobic and anaerobic conditions. Histological analysis assessed the level of neutrophils present in the tissue. The presence or absence of pus was noted. The results were analysed graphically and a cut off level of CRP was then chosen for analysis of reliability.

Thirteen patients were infected and 13 were not. Eleven of the 13 infected patients had a CRP greater than 2 mg/dl, and 10 of the 13 non-infected patients had a CRP less than 2 mg/dl. Using 2 mg/dl as a cut off, CRP had a sensitivity of 85% and a specificity of 77%. If 4mg/dl is taken as the threshold for infection, then CRP is 100% specific but only 61% sensitive.

CRP is a useful investigation in the diagnosis of infection in joint replacements. However we have shown that a cut off of 2mg/dl is not 100% specific for non-infected patients. Increasing the threshold improves the specificity, but reduces the sensitivity. Unfortunately there is no single investigation that is 100% accurate in this setting. CRP results must be interpreted in the light of the clinical picture and other investigations. These patients are part of an ongoing study to identify the most reliable criteria for diagnosing the presence of infection in total joint replacement.