Aims

The aim of this double-blind prospective randomised controlled trial was to assess whether low intensity pulsed ultrasound (LIPUS) accelerated or enhanced the rate of bone healing in adult patients undergoing distraction osteogenesis.

We conducted a multicentre two arm double blind randomised controlled trial to assess efficacy of pulsed ultrasound for accelerating the rate of bone healing. Sixty-two skeletally mature adults undergoing limb lengthening, of between 2.5cm to 10cm by distraction osteogenesis, at the proximal tibia using an Ilizarov frame were randomised to either an active or a placebo (control) ultrasound device.

Primary outcome measure was time ready for removal of frame after adjusting for distraction length (days/cm) for both intension to treat (ITT) and per protocol (PP) patients. The time at which the frame was removed was determined by the maturation of the regenerate bone. Secondary outcomes were return to weight bearing and covariates affecting time to frame removal.

The baseline characteristics of the two groups were well balanced, and 90% of patients were managed and followed up as PP. There was no difference in the time to frame removal between the two groups for the ITT (5.0days/cm, p=0.23) or the PP (10.1days/cm, p=0.054). There was no difference in return to weight bearing between the two groups, after adjusting for distraction length, for the ITT or PP patients (p>0.5). Smoking was the only covariate identified to increase the frame removal time (hazard ratio 0.46, 95% confidence interval 0.22 to 0.96; p=0.04).

This trial demonstrated no difference in bone healing between those who underwent pulsed ultrasound and those who did not. Smoking was observed to have a significant inhibitory effect on bone healing.

Objective:

To assess efficacy of pulsed ultrasound for accelerating regenerate consolidation.

Introduction

With an ageing population comes an increased prevalence of osteoporosis and associated fracture. Whilst treatment of the condition following such a fracture is partially effective, primary prevention through screening and appropriate follow-up is the ideal. In order to assess a population's risk of fracture, paper questionnaires would traditionally have to be sent, however this is an wasteful and costly. A more efficient method may be to have patients assess their own FRAX score through a modified computer application.

To analyse the pain distribution in the acute and chronic phase following thoracolumbar fractures.

Prospective observational study

39 patients with fractures between T11 and L2, with no neurological deficit, were treated conservatively. Strict inclusion and exclusion criteria were applied. All had X-rays and MR imaging (whole spine) at post-injury and one-year follow-up.

The patients documented their pain distribution using pain drawing, along with 10 other domains of pain and functional outcomes for a period over 12 months. The pain distribution was analysed. The association of distal pain distribution to - other associated injury, resultant kyphosis, Pre-existing or increase in disc degeneration at the lower non-injured disc levels – were analysed and reviewed

The most common site of the pain distribution in both the acute (90%) and chronic phase (97%) was distal to the fracture (regions - iliac crest, lumbosacral junction and buttock). Factors mentioned above that could be related to distal pain distribution did not show any significant correlation (P>0.5) with different domains of pain outcome.

Some of the commonly believed reasons for distal pain distribution like resultant kyphosis and associated disc/facet pathologies were not supported by our study findings. The distal pain distribution corresponds to the scelerotomal referred pain mapping, which could be the probable explanation. Thoracolumbar pathologies could be the source of pain in patients complaining of low back symptoms. Distal pain distribution of spine pathologies should not be attributed as functional.

Stable thoracolumbar fracture is a common injury. The factors that determine its outcome are unclear. Aspects of injury severity were analysed for their ability to predict outcome by controlling other outcome-affecting factors (patient's pre-injury health status, legal aspects, associated injuries, etc.). No reliable disc injury severity grading system was available and therefore a new system was developed.

A prospective observational study of 44 conservatively treated patients with stable fractures between T11 and L5 was conducted. Bony injury severity was scored based on comminution, apposition and kyphosis parameters. Disc injury severity was scored by the new scale based on variables – Herniation, Indentation, Height decrease and Signal change – seen in MRI. Ten outcome domains (five domains of pain and function each) were assessed at 1 to 2 years from injury. The data was analysed by non-parametric correlation and stepwise-linear regression analysis to assess the predictive value of different variables (patient factors, injury factors and social factor) to outcome.

The correlation coefficients between injury severity and outcome were consistently higher with disc injury severity than bony. Disc injury severity showed highest predictive value for both pain (29%) and functional (16%) outcomes, whereas the bony injury severity parameters (kyphosis, etc.) and the posterior ligament injury severity provided no prediction of outcome. According to AO classification, the fractures were A1, A2, A3 and B1; in this spectrum of injuries, the AO classification had no prediction of outcome. The disc injury score also had a good predictive value for final disc degeneration.

Disc injury severity should be gauged in advising prognosis and treatment. The new disc injury severity grading system showed good construct validity.

Ten percent of fractures end in delayed or non-union. NSAIDs have been linked to an inhibitory action on fracture repair for three decades yet the mechanism of action remains to be elucidated. Cancer research has identified that NSAIDs impede cell proliferation by inhibiting angiogenesis. It is proposed that a similar mechanism occurs in the induction of NSAID induced non-union. We have investigated this hypothesis in a randomised placebo control trial of the NSAID rofecoxib using a murine femoral fracture.

All animals had an open femoral fracture treated using an external fixator. Outcomes measures included x-ray, histology and biomechanical testing, with laser Doppler used to assess blood flow across the fracture gap.

Radiology showed similar healing patterns in both groups; however, at the later stages (day 32) the NSAID group had significantly poorer healing. Histological analysis showed that controls healed quicker (days 24 and 32), with more callus (day 8) and less fibrous tissue (Day 32). Biomechanical testing showed controls were stronger at day 32. Both groups exhibited a similar pattern of blood flow; however NSAIDs exhibited a lower median flow from day 4 onwards (significant at days 4, 16 and 24).

Positive correlations were demonstrated between both histological and radiographic assessments of healing, with increasing blood flow. NSAID animals exhibited lower flows and poorer healing by all outcomes. Regression analysis demonstrates, however, that the negative effect of NSAIDs on fracture repair is independent of its inhibitory action on blood flow.

COX-2 inhibitors are marketed as having cleaner side effect profiles and are widely used in trauma patients. Following development of a novel method of analysing functional vascularity across a fracture gap, we have demonstrated that the COX-2 inhibitor rofecoxib has a significant negative effect on blood flow at the fracture gap alongside inhibiting fracture repair.

Introduction: Conflicting opinions exist as to whether bone healing is affected by the administration of bisphosphonates for osteoporosis. In an animal model, we assessed the effect of bisphosphonates on osteoporotic fracture healing and whether the timing of administration made a difference.

Methods: 36 female Wistar rats underwent a mid-diaphyseal femoral osteotomy six weeks after ovariectomy. They were then divided into 3 groups:

no treatment (control);

Results: Of the 36 rats, 8 were unable to complete the study. Group 3 differed from control in three respects: higher bone mineral content (BMC) and density (BMD); larger callus; lower torsional stiffness. Group 2 did not differ significantly from control. There was a significant positive correlation between stiffness and change in BMC in group 1 (r=0.85, p< 0.001) but not so for group 2 (r=0.2, p> 0.05) and group 3 (r=0.04, p> 0.05). A similar trend existed for all radiographic parameters in the three groups.

Conclusion: The results suggest that, with early bisphosphonate treatment, although there is an increase in the size of the callus, that callus is biomechanically inferior. Furthermore, administration of bisphosphonates at either stage destroys the relationship between radiographic and mechanical parameters used to assess fracture healing.

Introduction: Digital X-rays have become increasingly prevalent in Hospitals throughout the UK and Ireland in the past 10 years. We have devised a semi quantitative analysis of digital radiographs that measures the extent of healing across the fracture gap.

Methods: 48 CD 1 mice underwent a femoral fracture and subsequent fixation with an external fixator. A standardised radiograph was taken. A radiographic analysis was carried out. For each radiograph taken a pixel density graph was generated at five individual points across the fracture gap, along the longitudinal axis of the femur.

A stastical analysis of intra and inter-observer variability was tested using the linearly-weighted kappa statistic for each of the 240 pixel density graphs taken and for the summation total in the 48 radiographs.

Results: For the individual pixel density graphs we expected an agreement of 67.82%. An agreement of 95.42% was recorded showing a kappa statistic of 0.8576 and a standard error of 0.0531.

On analysis of the summation scores we expected an agreement of 75.54% and observed an actual agreement of 96.30%. This showed a kappa statistic of 0.8545 and a standard error of 0.0849.

Conclusion: The results are very similar in the two analyses and indicate excellent agreements. As a result we offer a radiographic, semi-quantative analysis of bone healing across a fracture gap that is highly reproducible. Thus it has the potential for application to future research in this field and possibly to clinical practice with the increased use of digital radiographs in hospital departments

Thrombin related peptide (TP 508) is a 23 amino-acid synthetic peptide that mimics a portion of the receptor-binding domain of the human thrombin molecule.

Thrombin triggers both proteolytic activated receptors and non proteolytic activated receptors to bring about a mixture of responses ranging from tissue breakdown and clot formation, to new vessel formation and tissue repair. TP 508 stimulates only the non proteolytic activated receptors, and this initiates repair and angiogenesis but not clot formation or tissue breakdown Previous studies have shown that TP508 can stimulate repair in the dermal and musculoskeletal tissues by promoting angiogenesis and enhancing the proliferation and migration of cells.

High energy fractures are associated with a delay in healing. We hypothesized that high energy fracture healing would be improved with the use of TP508, and that the dose and site of application would have importance.

Methods: 80 CD 1 Mice were randomised into four groups; all underwent a high energy quadriceps muscle crush and a femoral fracture on the left hind limb. In each case the fracture was reduced and held with an external fixator. At the time of operation Group I received a dose of 100ìg TP 508 into the fracture, Group II 100ìg into the surrounding damaged soft tissue, Group III a dose of 10ìg into the fracture, and group IV (the control group) received PBS carrier into the fracture.

24 animals were sacrificed on day 21 and the remaining 56 mice on day 35. Of the 35 day old animals 8 in each group had both femora harvested and the biomechanical properties were tested using the 3-point bending technique. Specimens from the 21 day old animals and remaining 35 day old animals were used for histological analysis.

All 80 animals had digital radiographs taken each week. Using image analysis software five pixel density graphs were generated across each fracture gap. A validated semi quantitative analysis was used to score each graph and the total accumulated for each radiograph. The width of the fracture calus was measured and expressed as a ratio of the femur diameter.

Results: Mechanical testing showed significantly greater stiffness in group I when compared to control (p < 0.05), and a dose dependent trend of increasing strength.

Radiographic analysis showed greater healing of fracture and callus formation in Group I compared to Groups II, III, and IV, at both three and five weeks post-fracture (P< 0.05).

Histological analysis showed an increase in bone formation in group I compared to the other groups.

Conclusion: This data from this model, suggests that TP508 enhances healing in high energy fractures. The results also suggest that the effects of TP508 are dose dependant, and are greater when delivered into the fracture site.

We investigated the effect of neck dimension upon cervical range of movement. Data relating to 100 subjects healthy subjects aged between 20 and 40yrs was recorded with respect to age, gender and ranges of movement in three planes. Additionally two commonly used methods of measuring neck motion, chin-sternal distance and uniplanar goniometer, were assessed against a validated measurement tool the CROM goniometer (Performance Attainment Associates, Roseville, MN).

Using multiple linear regression analysis it was determined that sagittal flexion (P= 0.0021) and lateral rotation (P< 0.0001) were most closely related to neck circumference alone whereas lateral flexion (P< 0.0001) was most closely related to a ratio of circumference and length. The uniplanar goniometer has some usefulness when assessing neck motion, comparing favourably to chin-sternal distance that has almost no role.

Neck dimension should be incorporated into cervical functional assessment. One should be wary about recorded values for neck motion from non-validated measurement tools.

Background & Objectives: Osteoporosis is one of the most prevalent bone diseases worldwide with fractures its major clinical consequence. Studies on the effect of osteoporosis on fracture repair are contradictory and although it might be expected for fracture repair to be delayed in osteoporotic individuals, a definitive answer still eludes us. Subsequently, the aim of this study was to attempt to clarify any such effect.

Methods: Osteoporosis was induced in 53 female Sprague-Dawley rats by ovariectomy (OVX) at 3 months. A femoral fracture was produced in these animals 12 weeks later {OVX+Fracture group (OVX+F)}. A control group received the fracture only group (F) at 6 months. The fracture consisted of an open osteotomy held with a unilateral external fixator. Outcome measures include histology, motion detector analysis, pQCT, biomechanical strength testing (BST) and digital radiography. Digital radiographs were taken at time of OVX, fracture (confirming satisfactory reduction) and sacrifice from which relative bone density (BMD) measurements were calculated.

Results: OVX+F animals were significantly heavier than F animals at fracture and sacrifice (p< 0.001 for both) and moved significantly less in days 1-4 (p=0.032) and 5-9 (p=0.020) post-fracture. Relative BMD measured in distal femur at fracture and sacrifice was significantly greater in F group (p< 0.001 for both). Furthermore, there was a significant decrease in relative BMD from fracture to sacrifice in OVX+F group (p< 0.001). pQCT showed a significantly greater total BMD {contralateral (p=0.021) and fractured femora (p< 0.001)} and trabecular BMD (p< 0.001 both limbs) in the distal femur of the F group. Histologically, no statistical differences were found, however, the F group generally displayed the most advanced repair. In the contralateral limb, the F group had significantly greater load to failure at 6 (p=0.026) and 8 (p=0.042) weeks and was significantly stiffer at 8 weeks (p=0.050). In the fractured leg, stiffness was significantly greater in the F group at 8 weeks (p=0.001).

Conclusion: OVX was linked to increased body weight, decreased motion, decreased BMD (with particular loss in trabecular BMD), and reduced mechanical properties. OVX did not have a significant effect on fracture healing and although there was no reduction in BMD at the fracture site, histology and reduced stiffness suggest it was delayed.

Background & Objectives: The objective of this study was to develop a rat model of fracture repair. Fixation of experimental fractures is generally internal {Kirschner wire/intramedullary (IM) nail} or external (single/double plane devices). Internal fixation using the IM-fixated model of a standard closed fracture is well described in rats. However, nail insertion can disrupt fracture site morphology and limit x-ray analysis. We planned to create an externally fixated femoral model, to optimise our outcome measures and facilitate the further investigation of bone healing within the department.

Methods: A simple four pin unilateral external fixator was designed and constructed from four stainless steel pins, secured to a stainless steel plate with nuts. Forty-one female Sprague-Dawley rats, (12–18wks), were used. Following anaesthesia the right femur was exposed and a mid-femoral osteotomy made prior to fixator application. Post-operative x-rays were taken to confirm reduction. Animals were assigned to groups for biomechanical strength testing (BST) or histology. Fifteen animals (fractured and contralateral limbs) were sacrificed at 4, 6 or 8 weeks for BST (four-point bending). Maximum load to failure was recorded and stiffness calculated from the load displacement curve obtained. Both parameters were standardised as a percentage of the contralateral limb. Twenty-five fractured limbs were used for histological analysis at day 4, and 1, 2, 4, 6 or 8 weeks.

Results: Satisfactory reduction was confirmed in all animals post operatively and no complications were noted. Histological assessment at day 4 demonstrated a predominantly lymphocytic inflammatory response within the fracture haematoma. This was replaced with endosteal and periosteal new bone between weeks 1 and 2. Bridging of the fracture gap was seen at week 6. Stiffness and load to failure increased with increasing time. There was a statistically significant improvement in the percentage stiffness (p=0.035) and load to failure (p=0.012) between 4 and 8 weeks.

Conclusion: A simple reproducible externally fixated rat model has been established and characterised by radiography, histology and four point bending. This model has since proven to be of value in the study of the role of lipid lowering and anti-inflammatory drugs as well as cell therapy on fracture repair.

Background & Objectives: Statins have been shown to stimulate bone formation in vivo and in vitro in rodent models1 generating interest in the possibility that they may be useful therapeutic agents for osteoporosis. The major clinical consequence of osteoporosis are fractures that occur and although there is no firm evidence, there is a perceived associated delay in fracture repair. We examined the influence of atorvastatin on fracture repair in an ovariectomised rat fracture model.

Methods: 126 Sprague-Dawley rats had an ovariectomy (OVX) at three months and a femoral fracture (F) at six months. The fracture consisted of an open osteotomy held with an external fixator. All animals were randomly assigned into groups 1. OVX+F and early atorvastatin; 2. OVX+F and late atorvastatin; 3. OVX+F. Atorvas-tatin (5mg/kg) was given daily by oral gavage for three months in-group 1 between OVX and fracture and from time of fracture to sacrifice in-group 2. Outcome measures were histology, peripheral quantitative computed tomography (pQCT), biomechanical strength testing (BST) and digital radiography. Digital radiographs were taken at time of OVX, fracture (confirming satisfactory reduction) and sacrifice from which relative bone density (BMD) measurements were calculated.

Results: Non-statin treated animals moved significantly more in 4 days post-fracture (p=0.015), had signifi-cantly more relative (p=0.037) and total BMD (distal femur) than statin treated (p=0.040, early and p=0.036, late treatment). Total BMD at the fracture site was also significantly greater in the OVX+F than the late statin group (p=0.047) while in the adjacent site of the con-tralateral limb, the early statin group had significantly more (p=0.018) than the late statin group. However no differences were found between the early statin and OVX+F groups. Histologically, the rate of repair increased significantly in early statin (p=0.013) and OVX+F (p=0.011) groups. BST data showed no signifi-cant difference in stiffness at six or eight weeks.

Conclusion: Fractures healed in all three groups. Statins did not prevent OVX induced bone loss. Initial evidence suggests that early statin treatment may have a positive effect on early fracture, as shown by x-ray analysis and histology, however this effect was lost by week 8. Overall the evidence suggests that atorvastatin may have impaired fracture repair, particularly with late administration (relative BMD and pQCT results).

The first aim of the study was to investigate if bacteria were implicated in non-union of fractures of the tibia and femur, which had been treated with intramedullary nailing. The second aim was to evaluate the antimicrobial susceptibility of bacteria isolated from the retrieved intramedullary nails.

Forty intramedullary nails removed from tibial and femoral fractures were retrieved for the purpose of the study. Twenty of these nails were from fractures, which had successfully united and 20 were removed from fractures which had failed to unite prior to further operative intervention. There was no evidence of clinical infection in either of the two groups. The nails were subjected to ultrasound in the research laboratory to dislodge adherent bacteria formed as biofilm from the surface of the nail. Using both standard culture techniques and non-culture techniques (Immunofluorescence microscopy and PCR analysis) any dislodged bacteria were isolated and identified.

Isolated bacteria were tested for antimicrobial susceptibility to commonly used antibiotics in orthopaedic practice according to NCCLS guidelines.

Bacteria were detected in 15 out of 20 [75%] of the nails removed from fractures, which had developed a non-union, and in 5 out of 20 [25%] of fractures that had united, using both standard culture techniques and non-culture techniques. The bacterial isolates identified were mainly Staphylococcus epidermidis and the Gram-positive anaerobe Proprionibacterium acnes.

Vancomycin was the most effective antibiotic, with 2 out of 34 [6%] isolates being resistant. Erythromycin was the least effective, with 21 out of 34 [62%] isolates being resistant. Based on overall Minimum Bactericidal Concentrations at which 90% of all strains were killed, Vancomycin was the most active bactericidal agent tested followed in decreasing order by fucidic acid, ciprofloxacin, gentamicin, cefamandole and erythromycin.

Bacteria were detected more commonly in the fracture non-union group than in the union group [p< 0.01]. Of the antibiotic agents tested Vancomycin was the most effective and Erythromycin was the least effective.

Aims An estimated 5–10% of fractures fail to heal adequately. Novel therapies in the treatment of problem fractures include the use of culture expanded cells. An animal model of delayed fracture union is required to parallel the clinical scenario so that variations in cell therapy techniques can be rapidly assessed.

Material and Methods A simple unilateral external fixator was designed for use in the rat. The fixator was applied following open osteotomy of the femur and a reproducible externally fixated femoral fracture model was established (n=41). Fracture union was assessed by digital radiography, histology and biomechanical strength testing (four point bending) at weeks 4, 6 and 8. Histological examination was also undertaken at day 4 and weeks 1 and 2. A delayed union in the fracture model was created by periosteal and endosteal stripping (n=14). Radiography and biomechanical strength testing were performed at week 8. The use of cell therapy was tested in the delayed union model. Osteogenic cells were culture expanded for 6 weeks before re-implantation. Reimplantation was facilitated by the use of a drill hole through the fracture site . Animals were randomized to one of three groups – i) drill hole & cells in a carrier ii) drill hole & carrier only iii) no drill hole, cells or carrier.

Results In the fracture model radiological and histological evidence of fracture union was apparent at week 6. Biomechanical testing showed a significant difference in load to failure and stiffness of the fracture between weeks 4 and 8 (p=0.009 and 0.008 respectively). There was also a significant difference in biomechanical properties between the fracture model and the delayed union model at week 8. Drilling with the injection of a carrier significantly improved the biomechanical properties (p=0.03) of a delayed union at week 14. Surprisingly this effect was negated by the introduction of cells.

Conclusion A fracture and delayed union model in the rat has been established for the testing of cell therapy. The application of cell therapy to a delayed union has been less advantageous in improving union than expected. This prompts the need for further work required in optimising cell culture techniques and cell delivery.

Introduction: The aim of this research project was to establish a simple, reliable and repeatable externally fixed femoral fracture model. The rat was selected, as it was a suitable animal for use in a model of fracture repair and ovariectomy induced osteoporosis, both of which were to be investigated in future experiments. There are femoral fracture models described in the literature based on the insertion of an intramedullary nail prior to inducing a fracture. We felt, based on our experience of the unilateral externally fixed mouse fracture model, that external fixation would allow us to carry out radiographical and histological analysis of fracture healing without any of the tissue trauma caused by the insertion and removal of the intramedullary device.

Materials and Methods: A unilateral external fixator was chosen due to its simplicity. Four threaded stainless steel pins pass through holes in an aluminium plate with nuts placed on the pin above and below the plate. The holes in the plate were 0.1mm bigger than the pins and unthreaded allowing the plate to slide freely over the pins. Tightening of the upper nut compressed the plate against the lower nut holding the pin securely. 41 female Sprague-Dawley rats, aged between 12 and 18 weeks, were used. They were anaesthetised using a standard mixture of hypnorm and midazolam and analgesia, fluids and antibiotic were administered subcutaneously prior to surgery. The femur was exposed through a lateral approach and a standardised osteotomy was made prior to the application of the fixator plate. Accurate reduction was confirmed visually at the time of surgery and also by way of a post-op x-ray. 25 animals were sacrificed at 4 days and 1, 2, 4, 6 and 8 weeks for histology. The fractured limbs were harvested, fixed, decalcified and paraffin embedded as per standard protocol and serial sections were cut. These were stained with H& E and alcian blue and analysed 15 animals were sacrificed at 4,6 or 8 weeks for biomechanical strength testing. Four-point bending was carried out on freshly harvested femurs stored in normal saline between harvest and testing. Both limbs were tested and the fractured limbs were standardised relative to the unfractured limb. Maximum load to failure was recorded and stiffness was calculated from the load-displacement curve.

Results: No post-operative complications of fixation failure or infection occured. On histological assessment at D4 a predominantly lymphocytic inflammatory response was seen within the fracture haematoma. This inflammatory response was replaced with endosteal and periosteal new bone between wks 1 and 2. Bridging of the fracture gap was seen at week 6. Both stiffness and load to failure increased with increasing time. There was a statistically significant improvement in the percentage stiffness and percentage load to failure between 4 and 8 weeks (p=0.03 and p=0.018 respectively). The difference in load to failure between 6 and 8 weeks was also significantly different (p=0.042).

Discussion: A simple, reliable and repeatable externally fixed rat femoral fracture model has been established.

NSAIDs inhibit fracture repair, yet the mechanism behind this effect is unknown. It is recognised that NSAIDs impede tumour growth via an inhibition of angiogenesis, primarily via a COX-2 pathway. We propose that the inhibition of fracture repair is via a similar mechanism and have investigated this hypothesis using a murine fracture model. 225 animals were randomised into either treatment (rofecoxib) or control groups and underwent a standard open femoral fracture treated using an external fixator. Outcomes measures involved assessment of healing using radiographic, histolological and biomechanical means; and measurement of blood flow across the fracture gap using Laser Doppler Flowmetry. X-ray analysis showed a similar healing pattern in both groups, however at days 16 and 32 the NSAID group had significantly poorer healing. Histological analysis showed that controls healed quicker (significant at days 24 and 32); and had more bone but less cartilage at day 8. Biomechanical testing showed controls were statistically stronger and stiffer at day 32, while NSAID animals had a significantly greater rate of fixation failure, leading to loss of pin-bone osseointegration; this occurred primarily before day 16. There was no difference in blood flow between the groups on the day of surgery, and both groups exhibited a similar flow pattern; NSAID animals however, exhibited a lower median flow from day 4 onwards, which was significantly poorer at days 4, 16 and 24. Positive correlations were demonstrated between a higher blood flow and both the histological and radiographic results. While NSAIDs were seen to inhibit fracture repair in all outcome measures; and were also noted to decrease blood flow at the fracture, with strong negative correlations being noted between NSAID prescription and fracture repair; multiple regression analysis suggest that this negative effect of NSAIDs on healing is independent of its inhibitory action on blood flow. COX-2 inhibitors are marketed as having cleaner side effect profiles and prescribing is on the rise. Recently however some of the newer COX-2 specific inhibitors have been removed from the market as their seemingly clean side effect profile has come under scrutiny. We have demonstrated that the COX-2 specific inhibitor rofecoxib does has a significant negative effect on fracture repair; and as hypothesised that it also has a significant negative effect on blood flow at the fracture site. While these outcomes strongly correlate, the mechanism behind the effect remains to be elucidated, as we have also demonstrated that these modalities are independent of each other.

Introduction: Angiogenesis is essential during bone formation. Many studies have looked at the developing vascular network during normal and abnormal bone growth, using histological, immunohistological and contrast-radiological techniques; however all require sacrifice of animals to obtain tissue samples for examination and consequently chronological investigation of angiogenesis is not possible. We have endeavoured to produce an animal model, whereby quantitative assessment of blood flow, and callus formation across a fracture gap, can be repeatedly assessed.

Methods: The model is an adaptation of a 4-pin externally fixated murine femoral fracture previously developed in this department. Three extra conduits have been drilled onto the fixator cross-bar, such that it now links with an x-ray jig and implantable optical cable. The x-ray jig permits repeated lateral x-rays whereas the optical cable which is implanted adjacent to the fracture gap and connected to a laser, measures blood flow using the principle of the Doppler shift of light. Ten mice underwent surgery. Doppler readings and x-rays were taken on the day of surgery and subsequently at days 1, 2, 4, 8, 12, 16, 24 and 32.

Results: Fracture gap pixel density was seen to rise steadily and plateau at day 24, with significant statistical differences between the day of surgery and early time points, and then again between these early time-points (days 2, 4 and 8) and the late time-point day 24. Blood flow was noted to fall following the day of surgery and then slowly increase, with a rapid rise in flow at day 8 until day 16, when levels began to fall again to resting levels.

Conclusion: The data correlates with previous histo-morphological work performed in this department and also with early results from immunohistochemical studies. The above graph for blood flow conforms to that expected in a murine model of fracture healing, with a short initial drop in flow followed by a large rise as angiogenesis follows chondrocyte hypertrophy at the end of the first week, leading to callus formation. This in vivo model may be used to assess the effects on angiogenesis and callus formation of osteogenic compounds and investigate possible antiangiogenic mechanisms of action of medications such as NSAIDs that are known to be detrimental to fracture repair.

Introduction: Sufficient quantity of osteogenic cells is an essential aspect for a successful cell therapy in the treatment of difficult bone fractures and defects. At present, this was achieved by culturing bone marrow and bone-derived cells in a relatively long duration. A large number of the non-adherent mesenchymal stem cells were discarded during medium change. We hypothesize that collecting the non-adherent cells and re-plating them may result in more osteogenic cells in the same duration of cell culture. The aim of this study was to investigate the possibility of enhancing number of osteogenic cells by collecting non-adherent cells in the pull-off media and to examine their osteognic potentials.

Methods: Mononuclear cells were isolated by density gradient centrifugation method from bone marrow washouts in the bone samples obtained from 5 patients undergone total hip replacement. Mononuclear cells were plated at a density of 1 x 10⁶/cm² in a T-75 flask with αMEM medium and 15% FCS. The first medium change was made at day 7 and every 3 days thereafter. For the first three times of medium change, the removed media were centrifuged at 250 g for 10 minutes and plated in a separate T-75 (first time change) and T-25 flask (for the 2nd and 3rd times change). The non-adherent cells from the second and the third puff-off flasks were also collected and plated in separate T-25 flasks. Thus, 1xT-75 flask and 4xT-25 flasks of non-adherent cells resulted from the original T-75 flask. The cells in all flasks were harvested at 21 days from the day when the original flask was set up. The total number of cells in all pull off flasks were counted and compared with that of the original T-75 flask. Rate of cell proliferation with or without osteogenic growth medium were also examined by MTT method for passage 1 of both cells types. Osteogenic differentiation was defined with immunocytochemistry of bone markers: ALP, type I collagen, Osteocalcin and cbfa1. It is planed that cells of passage 2 will be mixed with HA powders and to be implanted into the SCID mice to examine the in-vivo osteogenic potential of these cells.

Results: Mesenchymal stem cells (MSCs) derived from the non-adherent population of human bone marrow culture have demonstrated having similar cell proliferation and differentiation potential in vitro, when compared to the MSCs derived from the adherent cell population. These cells expressed bone markers such as: ALP, type I collagen, osteocalcin and cbfa1. When the non-adherent cells were collected and cultured accumulatively, the total number of MSCs was increased to an average of 39.7% (36.6%–42.9%), compared to the number of cells obtained from the original T-75 flask.

Conclusions: Collecting the non-adherent cell population in the bone marrow culture appeared to result in more MSCs. This harvesting method may be used as a non-invasive way for enhancing MSC numbers in a given period of time. Further in vitro and in vivo studies of these MSCs of non-adherent origins may provide information for optimizing cell culture protocols for rapid expanding the osteogenic cells in vitro. This will facilitate the clinical applications of human osteogenic cell therapy.

Introduction: During the development of an externally fixated femoral fracture model in the rat a single dose of Carpofen (Rimadyl) was administered as part of the pre-operative analgesia regime. The negative effect of a NSAID on fracture repair has been well documented.

Materials and Methods: The external fixator was designed and constructed from threaded stainless steel pins and a semi-cylindrical aluminum plate. The pins were passed through the four drill holes made in the plate and were secured by nuts above and below the plate. Forty-five female Sprague-Dawley rats, aged between twelve and eighteen weeks, were used in the model. Twenty-one animals received a single subcutaneous dose of Carpofen (4mg/kg) pre-operatively. Carpofen was then excluded from the pre-operative analgesia regime and the experiment was repeated. All animals received a dose of Buprenorphine hydrochloride (Temgesic, 0.03mg/kg) and a fluid bolus (40–80ml/ kg) both pre and post operatively and antibiotic pre-operatively. Femoral fractures were created after the animals had been anaesthetised. The right femur was then exposed and a mid femoral osteotomy was made prior to the application of the fixator. Post-operative digital x-rays were taken to confirm reduction. A minimum of four animals were assigned to a group for either biomechanical strength testing or histology. Thirty-one animals in total were sacrificed at 4, 6 or 8 weeks for biomechanical strength testing. The fractured limbs were freshly dissected and stored in saline prior to testing. Both the fractured and contralateral limbs were tested mechanically by four point bending. The maximum load to failure was recorded and stiffness was calculated from the load displacement curve obtained. The bending strength of each fractured femur was expressed as a percentage of the strength of the intact contralateral femur. Fourteen fractured limbs were fixed in formaldehyde, decalcified and paraffin embedded for histological analysis. Serial sections were cut and stained with haematoxylin, eosin and Alcin blue at 4, 6 or 8 weeks.

Results: Satisfactory reduction of the fracture was confirmed post-operatively by faxtitron x-ray imaging in all animals. Preliminary data showed that there was a significant difference in stiffness at 8 weeks between the two groups (p= 0.008). Although not a significant difference, stiffness and load to failure were lower in the NSAID group at each of the three time points.

Conclusion: This data suggests that a single pre-operative dose of a NSAID is sufficient to delay fracture repair. The clinical relevance of this finding is that frequently in acute fracture patients a single dose of NSAID is given peri-operatively as it is felt that this will have no effect on fracture repair. This practice may need to be reviewed. On qualitative histology endosteal and periosteal bridging was evident in the group that did not receive NSAID at 1 and 2 weeks. Healing within the NSAID group at 4 weeks was poor.

Introduction: The existence of peripheral blood (PB) derived mesenchymal stem cells (PB-MSCs) have been documented in different mammalian species including young and adult human. However, the number of PB-MSCs is low in normal adult human blood. We have demonstrated previously that there was an increase in the number of PB-MSCs following long bone fracture and in the patients suffering from fracture non-union. The present study was to compare the biological characteristics of the PB-MSCs from fracture non-union patients, with human bone marrow derived MSCs (BM-MSCs).

Methods: 200 mls PB was collected from 9 patients suffering from fracture non-union. The mononuclear cells (MNCs) were isolated by density gradients centrifugation and cultured in á-MEM containing 15% FBS. The PB-MNCs from normal donors (n=8) and BM-MSCs from patients underwent total hip replacement were used as controls. The colony forming efficiency (CFE) of the PB-MSCs was calculated, and the phenotypes of PB-MSCs and BM-MSCs were compared using immunocytochemistry and flow cytometry methods. Their multipotent differentiation potentials into osteoblasts, chondrocytes, adipocytes, neurogenic and angiogenic cells were examined under specific inductive culture media. The in vivo osteogenic potential of PB-MSCs was examined by implanting the HA-TCP blocks seeded with PB-MSCs into the SCID mice for 12 weeks.

Results: After 28 days in culture, fibroblastic colonies were formed in the PB-MNCs cultures in 5 of 9 fracture non-union patients, with CFE ranging from 2.08–2.86 per 10^8 MNCs. No fibroblastic colony was seen in PB-MNCs cultures of the 8 normal donors. Under flow cytometry examination, PB-MSCs and BM-MSCs were CD34 (low) and CD105+, but PB-MSCs were CD29-, CD44-, and ALP (low), whereas BM-MSCs were CD29+, CD44+, and ALP (high). Under specific differentiation inductions, the PB-MSCs differentiated into osteoblastic cells (ALP+, type I collagen+, osteocalcin+ and Alizarin red+; chondrocytes (type II collagen+ and Alcian Blue nodules formation); adipocytes (Oil red-O positive lipid accumulation). Neurogenic differentiation was confirmed by positive neuro-filament staining, and differentiation into endothelial cells was evident with tube formation in 2D culture, and positive staining for VW factor and CD31. After implantation in the SCID mice for 12 weeks, newly formed woven bones were found in the biomaterials seeded with PB-MSCs, and they were positive for human osteocalcin immunostaining.

Discussion: This study indicated that there were more PB-MSCs in the peripheral circulation of the fracture non-union patients than that in the normal subjects. This may be due to a continous systemic response for recruiting MSCs from remote bone marrow sites, with attempt to repair the fracture(s). The PB-MSCs were clearly multi-potential cells, which had shared some common phenotypic markers with BM-MSCs, as well as many distinguishable makers from the BM-MSCs. The recruitment of the PB-MSCs through circulation might be a general phenomenon of systemic responses in many pathological conditions, such as fracture or wound healing and other systemic diseases. Further understanding the roles of PB-MSCs in diseases and repair may lead to novel therapeutic strategies.

Introduction: Ten percent of fractures end in delayed or non-union. NSAIDs have been linked to an inhibitory action on fracture repair for three decades yet the mechanism of action remains to be elucidated. Cancer research has identified that NSAIDs impede cell proliferation by inhibiting angiogenesis. It is proposed that a similar mechanism occurs in the induction of NSAID induced non-unions. We have investigated this hypothesis in a randomized placebo control trial of the NSAID rofecoxib using a murine femoral fracture model.

Material and Methods: All animals had an open femoral fracture treated using an external fixator. Outcomes measures included x-ray, histology, and biomechanical testing, with laser Doppler used to assess blood flow across the fracture gap.

Results: Radiology showed similar healing patterns in both groups, however at the later stages (day 32) the NSAID group had significantly poorer healing. Histological analysis showed that controls healed quicker (days 24 and 32), with more callus (day 8) and less fibrous tissue (day 32). Biomechanical testing showed that controls were stronger at day 32. Both groups exhibited a similar pattern of blood flow; however NSAIDs exhibited a lower median flow from day 4 onwards (significant at days 4, 16 and 24).

Discussion: Positive correlations were demonstrated between both histological and radiographic assessments of healing, with increasing blood flow. NSAID animals exhibited lower flows, and poorer healing by all outcomes. Regression analysis demonstrates however that the negative effect of NSAIDs on fracture repair is independent of its inhibitory action on blood flow. In conclusion, COX-2 inhibitors are marketed as having cleaner side effect profiles and are widely used in trauma patients. Following development of a novel method of analyzing functional vascularity across a fracture gap, we have demonstrated that the COX-2 inhibitor rofecoxib has a significant negative effect on blood flow at the fracture gap as well as inhibiting fracture repair.

Background context: Stable thoracolumbar spinal fracture is a common injury, yet there remains a relative lack of evidence that would allow reliable prediction of outcome. Variation in outcome in stable thoracolumbar spine fracture without neurological deficit could not be explained by the assessment made from x-rays and CT imaging alone, which measures mainly the bony injury severity. So far, no good classification system has been developed to assess the severity of soft tissue injury (disc).

Objectives: To measure short-term outcome of stable thoracolumbar fracture and analyse aspects of injury severity for their ability to predict outcome. To develop a new disc injury severity grading system in thoracolumbar spine fractures.

Study design: Prospective observational.

Patient sample: 44 patients with stable fractures between T11 and L5 vertebra with no neurological deficit and treated conservatively were selected.

Methods: All had plain x-rays, CT and MRI scans post-injury and at one year post-injury (except CT). Bony injury severity was scored on a seven-point ordinal scale based on (a) communication, (b) apposition and (c) kyphosis. Disc injury severity was scored by the newly developed six-point ordinal scale (none to severe) based on the following variables: (a) Herniation of the disc, (b) Indentation of the end plate, (c) Change in height and (d) Change in signal. Outcome was assessed at one to two years from injury. The following outcome measures were collected: (A) Five domains of pain symptoms – intensity, duration, bothersome, interference and satisfaction. (B) Five domains of function – Physical Component Summary (PSC) measure, Mental Component Summary (MSC) measure, Oswestry disability score, return to pre-injury level of overall activities and return to employment. Non-parametric correlation coefficients were calculated between outcome variables and other variables to look for the predictors of outcome. Stepwise linear regression analysis was performed to compare the predictive values and to look at what proportion of outcome is predicted by different predictors.

Results: According to AO classification, the fractures were A1, A2, A3 and B1. The Spearman correlation coefficients between outcome and injury severity were consistently higher with disc injury severity than bony. For the outcome of pain intensity, the correlation coefficients for disc and bone injury severity respectively were:.63 (p < .0001) and.28 (NS-not significant). Similarly for SF36 PSC were: .41 (p < .01) and.25 (NS). The predictive value of pain at F < .01 was 29% for disc injury severity and all other variable were not significant and excluded. At F < .05, the predictive value of disc injury severity (29%) increased further by 9%, 8% and 6% by addition of variable “Patient’s pre-injury SF36 MSC”, “Legal and Compensation issues pending” and “Physical demand of job” respectively. The predictive value of function at F < .01 was 16% for disc injury severity and it increased to 31% by the addition of “physical demand of the job” variable. At F < 0.05 the predictive value further increased by 5% by addition of variable “Legal and Compensation issues pending”. All other variables were not significant.

Conclusions: A new grading system of disc injury severity was developed and it showed good predictive value for pain and functional outcome. Disc injury severity has a better predictive value for short term outcome than bony injury severity in stable thoracolumbar fractures. In the spectrum of injuries studies, the AO classification and the degree of kyphosis provided no prediction of outcome.

Several studies document what we all know – that, in the vast majority of patients treated in fracture units for low-trauma fractures, there is no attempt to identify and treat factors predisposing to further fractures. We treat this fracture, send ‘em home and wait for the next. How mindless is that?

Equally, it is completely unrealistic to expect orthopaedic surgeons, focused on surgically treating a tide of challenging osteoporotic fractures, to assess the risk in each patient of further falls and the degree to which bone strength is compromised, and be responsible for prescribing treatments which will reduce risk in a cost-effective way. Yet the fracture unit is absolutely the best (and most cost-effective) place to identify the group of patients who will benefit most from preventive measures.

The answer is to work in a system, which connects up the right people to give each patient what they need. Surgeons to heal the current fracture (together with rehabilitationists to restore function and confidence) and physicians to assess and treat falls risk and osteoporosis.

Making this happen in practice requires answers to questions only you can answer:

who are the best physicians for our fracture unit to work with?

This is an issue in which it is worth us investing a lot of effort: we will ourselves soon be old and we must get this right in time for when we need it!

Introduction: Osteoblasts precursors reside in the marrow and small numbers circulate in the blood. Our previous work demonstrated an increase in circulating cells following fracture in humans. Skeletal injury is recognised to stimulate a distant osteogenic response.

We hypothesised that in response to fracture, some integral osteoblasts are recruited via the circulation from remote bone marrow sites.

Method: We established a fracture union model in 3-month-old, male, New Zealand White rabbits and reimplanted labelled autologous osteoblast precursors. At date of submission we have 20 rabbits allocated into 4 groups. Three groups had labelled cells re-implanted, whilst the fourth control group did not receive cells. In groups I, II and III the cells were re-implanted into the fracture gap, into the circulation and into a remote bone marrow cavity respectively. There were six animals in groups I and IV, and four in both II and III.

All animals had bone marrow harvested from their right tibia by saline flush. The mononuclear cells were isolated and culture-expanded in osteogenic medium for 3 weeks. Fluorescent reporter molecules were incorporated into the cell membranes, 24 hours prior to re-implantation of the cells into the fracture model. A 3 mm ulnar defect was preformed in all the animals. In groups I–III this was established 48 hours prior to cell re-implantation.

The animals were sacrificed at least 3 weeks after fracture surgery. Representative samples of the fracture callous, lung, liver, spleen and kidney were harvested from all animals and cryo-sectioned. Using confocal microscopy, the labelled cells were expressed as the average in 5 high power fields for each solid tissue. In addition, cyto-spins were made from blood and marrow and the cell number expressed as a percentage of the total cells.

Results: In group I, labelled cells were identified in the fracture callous, establishing their viability in vivo. Following intravenous re-implantation a smaller number of labelled cells were identified in the callous. When the cells were re-implanted into a remote marrow site, the number of cells in the callous was greater than after venous reimplantation, but less numerous than those in group I.

In all sections, these labelled cells appeared on trabecular surfaces in an osteoblastic fashion, but occasionally they were surrounded by osteoid, corresponding to osteocytes.

A small number of labelled cells were found in the blood, bone marrow, lung, liver and spleen of all animals in groups I–III. No labelled cells were identified in the kidney tissue.

Discussion and Conclusions: We have demonstrated that cells from remote sites are integral in fracture healing. Their presence in callous following venous administration supports recruitment via the circulation. This preliminary data is a proof of concept. This is an exciting new phenomenon, which could provide alternatives for harvesting skeletal progenitor cells and for their delivery in the treatment of bony pathology.

Study Design: Prospective observational study.

Objectives: To score the severity of injury to (a) vertebrae and (b) intervertebral discs following thoraco-lumbar fracture, and compare the two in their ability to predict clinical outcome at 1–2 years.

Methods: 44 patients with fractures between T11 and L5 without neurological deficit were treated conservatively. All had plain X-rays and MRI scans immediately and at one year post-injury. Bony injury severity was scored on a seven-point ordinal scale based on a) comminution, b) apposition and c) kyphosis. Disc injury severity was scored on a six-point ordinal scale based on a) change in signal, b) change in height, c) indentation /herniation. Outcome was assessed at one to two years from injury (av. 18.1 + 5.6 months) Non-parametric correlation coefficients were calculated between injury severity variables and outcome variables.

Outcome measures: Modified Oswestry disability questionnaires, SF-36 questionnaires (physical and mental component summary scores – PCS and MCS), verbal and numeric rating scale of ability to perform pre-morbid activities/work. Detailed analysis of a.) pain (intensity, duration, character, distribution, etc.), b.) early morning stiffness (severity, frequency, and duration).

Results: According to the AO classification, 25% of the fractures were A1 (wedge), 9% were A2 (split), 45% were A3 (burst) and 20% were B1 (flexion-distraction with posterior ligament injury). Disc injuries scored as: grade 3 (mild) in 14%, grade 4 in 36%, grade 5 in 36% and grade 6 (very severe) in 14%. The spearman correlation coefficients between injury severity and outcome were consistently higher with disc injury severity than bony. For the Oswestry disability score the correlation coefficients for disc and bone injury severity respectively were 0.50 (p< .0001) and 0.40 (p< .05), for SF36-PCS: 0.43 (p< .005) and 0.32 (p< .05), for SF36-MCS: 0.43 (p< .005) and 0.06 (NS), for return to pre-morbid activities and work: 0.32 (p< .05) and 0.25 (p< .5), for pain intensity by numeric rating scale: 0.69 (p< .0001) and 0.41 (p< .01), and for pain intensity by verbal rating scale: 0.65 (p< .0001) and 0.28 (p< 0.1).

Conclusion: In all clinical outcomes assessed, there was consistently better prediction by measures of injury severity to the disc than the bone. This study offers possible explanation for previously low or conflicting evidence of correlation between clinical outcome and bony injury in thoraco-lumbar spine fractures uncomplicated by neurological injury. It implies that in selected patients with severe disc injury, treatment focused on eliminating the effects of the disc injury may result in better clinical outcome.

Introduction: Bone mineral density (BMD) has been shown to correlate well with strength and bending stiffness of bone. Following tibial diaphyseal fracture, reduction in the optical density of cancellous bony regions is apparent throughout the postoperative period. As much as 70% loss in BMD in the distal tibia and 45% in the proximal tibia has been reported. The process influencing the extent of such posttraumatic osteoporosis is multifactorial: the severity of injury, age of the patient, the effects of the regional acceleratory phenomenon (RAP), fixation type and onset of weight-bearing have all been implicated. Such loss in BMD in most cases is not fully recoverable and has been shown to increase subsequent fracture risk in the ipsilateral tibia and femur. It has been estimated that a 50% reduction in bone mineral content is required before changes are radiologically observed. Such changes in BDM however can be calculated post operatively from standardised orthogonal tibial digital images, following image density calibration and the utilisation of soft tissue subtraction techniques. Using these image density quantification techniques, a study was performed to examine and compare the effects of fixation of tibial fractures, with either Ilizarov or Intramedullary nail, on BMD in cancellous bone.

Method: Twenty-nine patients were recruited in the context of a randomised controlled trial assessing the radiological outcome following the treatment of closed tibial diaphyseal fractures with either an Ilizarov fixator (n=15) or an intramedullary nail (n=14). Informed consent was obtained for AP and Lat radiograph examination at selected postoperative time intervals (1, 3, 6, 12, 26 and 52 weeks). At each visit the rotation of the patients’ limb was standardised using a position control device (jig). The exposure and image acquisition parameters were standardised and digital images analysed. Serial BMD values were calculated and changes throughout the postoperative period compared between treatment groups.

Results: This study demonstrated considerable differences in the extent of disuse osteoporosis in the cancellous regions of the tibia following either Ilizarov fixation or intramedullary nailing. In the proximal metaphysic patients treated with a tibial nail displayed a reduction in BMD by 18.8% at 26 weeks and 25.7% at 42 weeks. In contrast, patients managed with Ilizarov fixation actually increased the BMD at this region at 26 weeks by 11.7% but with a final overall loss of 5.2% at 52 weeks. Each group demonstrated decreases in BMD at both the distal metaphysic and medial malleolar regions over 26 and 52 weeks. The BMD of the distal metaphysic decreased by 15.9% at 26 weeks and 35.3% at 52 weeks for patient treated with a nail, and reduced by 11.1% at 26 weeks and 0.76% at 52 weeks in patients treated with Ilizarov fixation. The medial malleolar region demonstrated the greatest decreases of all with a reduction in BDM of 43.1% and 66.4% in the nail group, and 34.9% and 61.6% in the Ilizarov group, at 26 and 52 weeks, respectively.

Conclusion: The magnitude of disuse osteoporosis following tibial diaphyseal fractures treated with intramedullary nailing, calculated using digital image analysis, and demonstrates changes similar to those reported previously in the literature. The use of Ilizarov fixation however maintains proximal metaphyseal BMD throughout the review period and promotes remineralisation in the distal metaphysic. No difference is observed in the medial malleolus between the two groups. The benefits of axial loading, stability and preservation of intraosseus vascularity with the use of the Ilizarov fixator are clearly demonstrated in the results; preservation of BMD was also shown to correlate well with improved clinical outcome and will reduce future ipsilateral tibial and femoral fracture risk.

Introduction: Bone mineral density (BMD) is currently the gold standard in predicting osteoporotic fracture, but evidence suggests that over one third of such fractures occur in those with osteopenia or even normal BMD. The level of bone turnover may affect bone quality in these patients independently of BMD. Bone markers have evolved as tools in monitoring anti-resorptive treatment in osteoporosis.

Aims: The aim of this study was to investigate if levels of bone markers in postmenopausal women could be used as an adjunct to BMD measurements in the assessment of fragility fracture risk.

Patients and Methods: 60 postmenopausal women (30 osteoporotic, 30 with normal BDM) were studied. A single BMD measurement by dual energy x-ray absorptiometry (DEXA) enabled categorisation. Serum bone formation markers (bone specific alkaline phosphatase (BSAP) and osteocalcin (OC)), and resorption marker (C-telopetide of type 1 collagen (CTX)), were measured. History of low trauma fracture was documented for each woman.

Results: 36% of the osteoporotic group had experienced at least one fragility fracture. However, the femoral neck and combined spinal BMD in these women was not significantly different from the 64% of osteoporotic women who had no prior fracture. There was also no significant difference in the age of women in both subgroups. Serum bone markers were significantly increased in the osteoporotic fracture subgroup when compared to the non-fracture subgroup and also to the non-osteoporotic controls. The largest increases were seen in the levels of CTX. Smaller increases in all markers were seen when the non-fracture subgroup was compared to the non-osteoporotic control group but these increases did not reach statistical significance.

Conclusions: Bone turnover is significantly increased in postmenopausal osteoporotic women with previous fracture compared to both osteoporotic non-fracture counterparts and non-osteoporotic controls. This suggests higher bone turnover will increase fracture risk in osteoporotic women. It is possible that combining 2 or 3 markers to produce an “index of bone turnover” would be a useful tool when used in addition to BMD to identify those at greatest fracture risk.

Background and Hypothesis: High-energy fractures associated with severe soft tissue injury have a significant incidence of delayed or non-union. The soft tissue envelope may adversely contribute to the healing of a fracture, not only in stripping of the periosteal blood supply, development of compartment syndrome or tissue interposition between the bone ends but also in its ability to generate an intense acute inflammatory response. Inflammation is the initiator of healing; in clinical scenarios of impaired inflammation (immune deficiency, NSAIDs, corticosteroids) healing is delayed; interestingly, in injury with excess inflammation (CVA, MI) healing is also delayed. Would the inflammatory response following high-energy fractures contribute beneficially or adversely to the healing of the underlying fracture? Using an in-house murine femoral fracture model which reliably demonstrated features of delayed fracture healing when associated with a severe overlying muscle crush injury we proposed these hypotheses:

That fracture callus with overlying muscle crush would contain raised expression of acute inflammatory cytokines (IL-1β, IL-6 and TNF-α).

Methods: Total RNA was extracted from normal fracture callus (FO) and muscle crush fracture callus (MC) at day 2, day 4 and day 8. Semi-quantitative RT-PCR was used to compare IL-1β, IL-6 and TNF-α mRNA expression. Histomorpometric analysis of ICC stained sections of the FO and the MC groups was used to estimate IL-1β, IL-6 and TNF-α protein expression within the callus. Positively staining areas for the cytokine within the callus were a semi-quantified and compared between groups. Finally, blocking antibodies to IL-1β and TNF-α were injected into MC fracture callus at day 0, 4 and 8. Control MC group had vehicle only injected. Fracture healing was measured using radiological, histomorphological and biomechanical outcome measures. Following a pilot dosing experiment, the effect of blocking antibodies on fracture healing was compared between MC and MC with antibody groups.

Results: The MC group IL-1β mRNA expression was significantly higher than FO at day 4 and day 8 (p=0.05). ICC for IL-1β protein expression was higher on day 4 and on day 8 in the MC group, significant at day 8 (p=0.03). TNF-α mRNA expression in the MC group at day 8 was significantly higher than the FO group (p=0.05). ICC for TNF-α protein in the MC group peaked at day 8 and was significantly higher than the FO group (p< 0.03). IL-6 mRNA expression was significantly raised in the MC group at day 4 and 8 compared with the FO group (p=0.05). ICC for IL-6 protein showed significantly increased expression at day 8 in the MC group (p=0.05). The patterns of expression of the mRNA and proteins were similar.

Injection of anti-TNF-α antibodies into MC mice caused more new bone formation on day 16 (p=0.03) and day 24 (p=0.06), stiffer calluses at day 24 (p=0.01) and faster fracture gap obliteration at day 16 (p=0.05) and day 24 (p=0.001). IL-1β blockade had slightly less effect, more new bone formationd ay 16 (p=0.01) and day 24 (p=0.03), slightly stiffer (p=0.08), but no significant difference in fracture gap obliteration from controls.

Conclusion: The effect of muscle crush around the fracture callus was to increase and prolong the expression of inflammatory cytokines with the callus. The effect of blocking these excessive inflammatory cytokines in our model was to improve fracture healing. Excessive inflammatory cytokines (IL-1β, IL-6, TNF-α) in bone impair new bone production by osteoblasts, inhibit the recruitment and differentiation of mesenchymal precursors and promote osteoclastogenesis. The mechanism of action of blocking antibodies may be due to inhibition of the antiosteogenic effects of these cytokines.

The burden of non vertebral fractures on the National Health Service is enormous. Osteoporotic fractures have an associated morbidity and mortality and as a consequent incur heavy financial burden with a current cost to the National Health Service of some £1.7 billion per year, hip fractures accounting for the greater part.

We know from our own local experience in the North of Ireland that this previous service had failed to target these fracture patients for secondary prevention of osteoporosis (Northern Ireland Colles Fracture Study). Although hip fractures account for only 7% of all fractures they result in the utilisation of 25% of acute orthopaedic beds. The silent nature of osteoporosis makes a diagnosis prior to fracture difficult and attendance at a fracture clinic may be the first opportunity to diagnose this condition and to intervene with anti-resportive treatment.

An osteoporosis service commenced in Greenpark Health Care Trust in 1996. In 2001, guidelines (Crest guidelines) for the prevention and treatment of osteoporosis were established and in April 2003 a pilot study for the fracture liaison service commenced with the appointment of a Fracture Liaison Nursing Sister. The responsibility of this Nurse included:

Liaison and attendance at Out-Patient Fracture Clinic to ensure that all patients presenting with a low trauma fragility fracture were assessed and referred appropriately for bone densitometry.

Current activity levels include 18 fracture clinics per week at the Royal Victoria Hospital site with approximately 35 patients per clinic. To date, the Fracture Liaison Nurse has been able to attend 54% of these clinics. The patients were identified by Fracture Clinic chart reviews to identify those greater than fifty years of age with a low trauma fracture and approximately 115 charts were reviewed weekly.

At risk patients were interviewed with approximately 35 interviews carried out weekly. Patients were then recruited first for assessment and dexa scanning, measurements were made at both lumbar spine L1-L4 and at the femoral neck with approximately 22 patients weekly recruited. An assessment of osteoporosis risk was made, a plain bed dexa scanner (lunar prodigy scanner) and treatment options were decided depending on the patients T score and according to the CREST Guidelines. The patients were given bone health advice at their scanning visit. Clinic activity was recorded on a database (Gismo) and a computer generated letter to the GP was produced.

Provisional outcomes included arrangements to rescan after 24 months, referral to falls assessment and referral to a Consultant Specialist Osteoporosis Clinic.

Results: To date, 198 patients have been scanned. 28 were male and 170 were female. BMD results were as follows (T score at hip or spine):

- Normal (0 to −1 SD) 16.6%

The mean age for those scanned was 66 years and 3 months.

Osteoporotic risk factors identified include a previous fracture (18%).

Early menopause (19%), fall history (12%), Back pain and height loss (18%), smokers (11%), family history of osteoporosis (13%), alcohol excess (5%).

Outcome – no treatment recommended 26%, 13% were already on treatment, 17% were prescribed treatment, 43% were prescribed Calcium and Vitamin D, 27% a Bisphosphonate, 20% a Bisphosphonate and Calcium and Vitamin D and 12% Evista (serm).

Patient follow-up outcome included a follow-up of dexa scan at 24 months 20%, no hospital review planned 74%, 7% referred to a Specialist Osteoporosis Clinic and 6% were referred for a FALLS assessment.

Conclusion: This service has highlighted the high prevalence of osteoporosis in patients attending a Fracture Clinic. An osteoporosis fracture increases significantly the risk of future fracture. Our current programme for evaluation and managing a patient with osteoporosis fractures is currently being audited to measure quality of service, treatment outcome and trends.

Introduction: 5–10% of all fractures end in delayed or non-union. It has been reported for 3 decades that NSAIDs have an inhibitory action on fracture repair, yet GPs still prescribe these drugs in up to 50% of fracture patients. Not all fracture patients who are treated with this class of medication go on to develop non-union, yet a strong correlation has been shown in clinical studies between long bone fractures and development of delayed and non-union. The mechanism behind this effect has yet to be elucidated. In cancer research it has been shown that NSAIDs, primarily by a COX-2 pathway, can exert an inhibitory action on cell proliferation by inhibiting angiogenesis. It is proposed that a similar mechanism occurs in the induction of NSAID induced delayed fracture repair. We have investigated this hypothesis using an externally fixated murine model of femoral fracture.

Methods: 158 animals were randomised into either treatment (Rofecoxib 5mg/kg/day in a 0.5% methylcellulose carrier) or control (carrier alone). All had a standard surgical regimen involving creating of an open femoral fracture with treatment using a 4-pin external fixator under the isoflurane inhalational anaesthesia. Outcome measures included standardised x-rays (Faxitron MX-20) and Laser Doppler Flow (Oxford Optronics) measurements taken at days 0, 4, 8, 16, 24 and 32, along with biomechanical testing (Lloyd Instruments Ltd) at days 24 and 32. Data was entered into a spreadsheet and analysed using Mann-Whitney U and Wilcoxon Tests for statistical differences (SPSS, Version 9), with statistical significance being attained when p< 0.05.

Results: A greater number of animals in the NSAID group had a failure of treatment with loss fixation due to pin pullout from poor osseointegration (53% NSAID compared to 26% controls). Of those animals that completed the studies, x-ray analysis showed a change in pixel density at the fracture gap suggesting poorer healing of the NSAID animals that was statistically different at days 16, 24 and 32. Biomechanical testing suggested treatment animals had attained statistically less peak loads and stiffness at day 32. Laser Doppler Flow measurements across the fracture gap showed generally less flow at all time points in the NSAID group. This was statistically significant at days 4 and 24.

Conclusions: The new selective and specific COX-2 inhibitors are marketed as having a cleaner side effect profile and are being widely used by primary care practitioners in trauma patients. Not all animals that are treated with NSAIDs go on to develop a delayed union and some are able to heal with similar mechanical properties to animals in a control group. However, we have illustrated that the highly specific COX-2 inhibitor rofexcoxib has a significant negative effect on maintenance of fracture fixation and fracture repair in this model, both in terms of x-ray and biomechanical analysis. We have also shown that the inhibition of fracture healing is associated with a decrease in blood flow at the fracture site leading to the hypothesis that the mechanism behind the effect is via an inhibition of angiogenesis.

Aims: To quantify the complication rate in Ilizarov surgery at an experienced Limb reconstruction Unit. Study Design: A retrospective study of prospectively collected data on complications. Material: Complications in 304 patients, treated between January 1998 and April 2001 were reviewed. Complications relating to the pin site, bones, joints, neurovascular structures, pain, mental status and mechanical failure of the frame were documented. Results: There were 103 complications (34%) in total. Twenty patients (6.6%) required IV antibiotics or curettage of a ring sequestrum. Forty- three (14%) experienced problems with non or delayed union, mal union, incomplete osteotomy, premature consolidation of regenerate or fracture through a pin site. Twelve (4%) developed neural problems in the form of nerve pain or permanent nerve damage. Twenty-one (6.9%) developed loss of joint motion sufþcient to stop distraction or as a permanent sequelae. One (0.3%) suffered from depression during treatment. Three (1%) required referral to a pain team. Despite re-useable hardware mechanical failure was represented by only 3 episodes (1%) of þne wire breakage. Conclusions: Analysis revealed no signiþcant difference between the calendar years and so represents a true complication rate. There was a signiþcant difference in the complication rate for frames applied for acute trauma, late trauma and elective surgery. The difference did not relate to time spent in the frame and seems to represent a separate variable. There was a disproportionate increase in complications for frames applied for upper limb pathology.

Aim: To quantify the complication rate in Ilizarov surgery. This study establishes the complication rate for an experienced Limb Reconstruction Team composed of 3 surgeons, 2 specialist nurses and 2 physiotherapists involved with acute trauma, late trauma reconstruction and elective limb deformity cases.

Study Design: Retrospective analysis of prospectively collected data on complications.

Material: Complications in 304 patients, treated between January 1998 and April 2001 were reviewed. Complications relating to the pin site, bones, joints, neurovascular structures, pain, mental status of the patient and mechanical failure of the frame were documented.

Results: Of the 304 cases treated there were 103 complications (34%) in total. Twenty patients (6.6%) required re-admission for IV antibiotics or curettage of a ring sequestrum secondary to a pin site infection. Forty three patients (14%) experienced problems with non or delayed union, mal union, incomplete osteotomy, premature consolidation of the regenerate or fracture through a pin site. Twelve patients (4%( experienced neural problems in the form of nerve pain during distraction or permanent nerve damage. Twenty-one patients (6.9%) developed loss of joint motion sufficient to stop distraction or as a permanent sequelae of treatment. One patient (0.3%) suffered from depression during the period of treatment. Three patients (1%) required referral to the pain team. Mechanical failure of the frame was represented by three episodes (1%) of fine wire breakage despite re-useable hardware.

Analysis revealed no significant difference in complication rates between the calendar years. However, there was a significant difference between complication rates in frames applied for acute trauma, late presentation of trauma, and elective surgery. This difference did not appear to relate to time spent in the frame, and therefore seems to represent a separate variable. There was a disproportionate increase in complications in Ilizarov frames applied for upper limb problems.

Conclusion: This study provides a baseline for the commonly occurring problems associated with the practice of Ilizarov surgery in the United Kingdom and Ireland.

During the process of distraction osteogenesis new bone is formed rapidly and undergoes remodelling almost immediately. Little is known about the regulatory mechanisms governing the removal of the redundant callus in this process. Tissue homeostasis is achieved by a delicate balance between the processes of cell death (apoptosis) and cell proliferation. The aim of this study was to test the hypothesis that apoptosis is involved during distraction osteogenesis.

Mid-tibial osteotomies were performed in 6 adult male NZW rabbits (age; 24 weeks, weight; 3.0 −3.5 kg), and the tibiae stabilised with unilateral external fixators (Orthofix M-100). 7 days later, twice daily distraction was initiated at rates of 0.7 mm/day for 3 weeks. BrdUrd (40mg/kg) was injected intravenously to the rabbit 1h before killing. The regenerate bone was collected, fixed in 10% buffered formalin and decalcified for paraffin embedding. Some fresh regenerate bone tissues were also prepared for examination under transmission electronic microscopy (TEM). BrdUrd immunohistochemistry has been used to detect proliferating cells and the terminal deoxynucleotidyl transferase (TDT)-mediated dUTP-biotin nick end-labelling (TUNEL) method was used to identify cells undergoing apoptosis. To detect bone-resorbing cells, tartrate-resistant acid phosphatase (TRAP) staining was also performed.

BrdUrd positive cells and TUNEL-positive cells were shown to coexist in most of the areas in the regenerates. In the mineralisation front, the majority of the TUNEL-positive cells were present in the transitional region between the fibrous tissue and the new bone. The TUNEL-positive cells were close to or on bone surfaces, and some of the newly formed osteocytes in the new trabeculae were also positive. The TUNEL-positive cells were also seen in the cartilage region of the regenerate. However, the TUNEL labelling was greatly reduced in the new bone close to the osteotomised bone ends, TUNEL-positive labelling were not detected in the cortical bone of the osteotomised bone ends and in the adjacent surrounding periosteum. TRAP staining in the regenerate revealed similar patterns of distribution to those of the TUNEL staining. There were more TRAP-positive cells in the new bone near the mineralisation front than in that of the new bone region, which was close to the osteotomised bone ends. TEM examinations have demonstrated characteristic signs of apoptotic changes in the fibroblast, osteoblast and osteocytes in the specific regions of the distraction regenerate.

The study provided evidence that in the process of rapid bone formation during distraction osteogenesis, superfluous cells are removed by apoptotic mechanisms. The demonstration of a mixture of proliferative and apoptotic cell populations in the regenerating tissue, indicates that apoptosis and cell proliferation may be regulated by local factors. The neovascularisation of the regenerate and withdrawal of growth factors and cytokines may be responsible for apoptosis occurring in some parts of the regenerating tissue. The changes of distribution of apoptotic cells in the different regions of the regenerate, together with the observed patterns of osteoclast activities, suggest that bone cells undergoing apoptosis may initiate rapid bone remodelling seen during distraction osteogenesis.

Fracture repair is a complex physiological process during which bone shows the remarkable ability to mount a repair process, restoring its mechanical integrity and anatomical configuration by original osseous tissue. Programmed cell death, or apoptosis, is a naturally occurring cell suicide pathway with a homeostatic function in the maintenance of continuously renewing tissues. The present study investigated the relation between cell proliferation and cell death (apoptosis) during fracture healing in a mouse femoral model.

Left femoral osteotomies were performed in 20 male CFLP mice (35–45g), immobilised with uniplanar external fixators. 4 animals were sacrificed on days 2, 4, 8, 16 and 24 post-fracture and fracture callus collected for paraffin embedding. Localisation of cell proliferation was examined using immunohistochemistry with proliferating cell nuclear antigen (PCNA) monoclonal antibody. Apoptotic cells were visualised with the terminal deoxynucleotidyl transferase (TdT)–mediated dUTP-biotin nick end-labelling (TUNEL) method. Random images of each time specific specimen were captured via a digital camera and the positive labelling indices of PCNA and TUNEL labelling were calculated and statically compared.

Cell proliferation and apoptosis were found co-existing during the entire period of fracture healing studied. Cell proliferation was predominant in the early phases of fracture healing (days 2–8). PCNA positive labelling index peaked at day 8 (p< 0.01, t-test) and PCNA-positive cells were not limited to the fracture gap mesenchymal tissues but extended in the periosteum along most of the fractured femur. TUNEL positive labelling was minimal in the early stages (days 2–8). In later stages of fracture healing (days 16–24), PCNA expression declined as intramembranous and endochondral ossification spread within the fracture site and apoptosis was the dominant cell activity with the TUNEL positive labelling index peaked at day 16 (p< 0.05, t-test) and then declined sharply at day 24.

The current study indicated that apoptosis was a normal concomitant during fracture repair, confirming programmed cell death in chondrocytes and bone cells, and that cell proliferation and apoptosis were tempero-spatially dependent. These findings support the view that apoptosis is a natural process, genetically programmed and active during fracture repair. The demonstration of a mixture of proliferative and apoptotic cell populations in the regenerating tissues of fracture callus, suggests that apoptosis and cell proliferation may be regulated by local factors during fracture healing.

Objectives: (i) To compare and correlate outcome in Sanders Type 2 Os Calcis fractures using two disease-specific scores (Kerr-Atkin score & American Orthopaedic Foot and Ankle society score) and a general quality of life score (short form 36 health status questionnaire). (ii) To compare results of operative with non operative treatment, in this group of patients.

Design: Retrospective study using a combination of case notes, plain x-rays and CT scan films review along with current clinical assessment.

Patients: 30 patients with 32 fractures of Os Calcis (Sanders type 2) were identified. These patients were treated during 1994–1997 with mean follow up of 40 months.

Intervention: 16 patients were treated by open reduction and internal fixation using a lateral approach. The remaining 14 patients were managed non operatively. Treatment modality was decided by consultant preference.

Outcome measurements: Kerr-Atkin score, AOFAS score, SF36.

Results: We found an extremely significant correlation (p,.001, Spearman) between the two disease specific scores. AOFAS score showed a stronger correlation with physical component summary score (PCS) of the SF36 than the Kerr-Atkin score.

The age of the patient had little impact on the Kerr-Atkins score but a large effect on PCS. Conversely the pre-op Bohlers angle, a measure of fracture severity, had a large effect on the Kerr-Atkins score but little impact on the PCS. The AOFAS was responsive to both these predictors: 41% of the variance in AOFAS score was explained by Bohlers angle and the age of the patient.

We did not find any significant difference in outcome between operative and non-operatively treated patients.

Conclusion: The AOFAS score was found superior in assessment of outcome for Sanders type 2 fractures, though the Kerr-Atkin score also performed well.

This study does not demonstrate any significant advantage of operative treatment in Sanders type 2 fractures of the Os Calcis.

Objective: To assess the factors which result in increased mortality following a femoral neck fracture.

Design: Patients were sequentially recruited on admission to the fracture units and followed up at 2 weeks, 3 months, 6 months and 1 year.

Setting: The fracture units of two major Belfast teaching hospitals, The Royal Victoria and Belfast City Hospital (which have since amalgamated)

Subjects: All patients over the age of 65 years between 27th October 1997 and 30th November 1998 and who were admitted to the fracture units within 28 days of having sustained a fracture.

Outcome measures: Patients were assessed by: Barthel score, mental score, home circumstances. Mobility and mortality

Results: 748 patients (male/female 153/595). Mean age 82.1 years ± s.d. 7.4 years.

The overall 1-year mortality was 31.4% (235/748) and the sex distribution (male 73/153 [47.7%] female 162/595 [27.2%]).

27/748 patients who did not undergo surgical intervention had a 1-year mortality of 85.2%.

Factors which were associated with an increased 1 year mortality were: male sex (p< 0.0005), High ASA score (p< 0.0005), low Barthel score (p< 0.0005), poor mental score (p< 0.0005), decreased mobility (p< 0.0005), increased dependency in home circumstances (p< 0.0005), increased age (p< 0.0005), increased delay to surgery (p< 0.0005) and living alone (p< 0.0005).

Marital status, fracture type and type of operative intervention had no statistical effect on mortality.

Using logistic regression male sex, high ASA score, increased age, increased delay to surgery and poor mental score all remained independently associated with an increased mortality at 1 year.

Conclusion: The majority of factors which are associated with increased mortality following a femoral neck fracture are outside our control, namely age, sex and mental score. It should however be possible to reduce surgical delay and improve the patients pre-operative medical status (ASA score). A balance has to be struck between optimisation of the patient and delaying surgery unduly. The optimal timing of surgery requires further investigation.

Hypothesis: Early initiation of COX-2 inhibition is more detrimental to fracture healing than later, irrespective of the analgesia-permitted biomechanical stimulation of the fracture by movement.

Model: A validated externally fixated murine femoral fracture model.

Intervention: Left femoral osteotomies, immobilised with sagittal uniplanar external fixators. Treated mice received 4mg/kg meloxicam from the day of surgery, day 4 or day 8 post op until sacrifice, by gavage. Control mice received carrier alone.

Outcome Measurements: Mouse movement was quantified each day until sacrifice. Fracture geometry was determined from post-sacrifice orthogonal x-rays. Animals were sacrificed on day 4,8,16 and 24. Blind computer aided histomorphometric analysis was performed, on six coronal sections per specimen, determining the medial, intramedullary and lateral areas of total callus, mesenchymal tissue, cartilage and new bone.

Results: No difference existed between the treated groups and control fracture fragments overlap or alignment nor in post-operative movement. Meloxicam treated groups showed decreased callus areas on day 4, 8, and 16, although it was noted that callus remodelling had commenced after day 16 in the control specimens only. New bone areas were reduced in all treated groups at all time points examined relative to the controls with the reduction being proportional to duration of COX-2 inhibition. Mesenchymal tissue differentiation was maximally affected in the earliest treatment group.

On day 24, day 0 treated specimens demonstrated significantly more mesenchymal tissue. No correlation was demonstrated between post-operative motion and callus area or new bone area. The care of cartilage present however, was significantly correlated to the amount of post-operative movement in all groups.

Conclusions: COX-2 inhibition inhibits new bone formation in proportion to the proximity of its commencement the fractures occurrence, irrespective of fracture stimulation by motion. Cartilage production in the healing fracture is not altered by COX-2 inhibition but is proportional to fracture stimulation by motion.

Twenty-four cases of complete division of median or ulnar nerves were assessed on two occasions after direct suture, with an interval of three years between assessments. Clinical, electrophysiological and timed functional tests were used. All the operations had been performed by one surgeon, using the operating microscope for approximately half the cases but not for the other half. The results were analysed, and the patient's age, any delay between injury and suture, and the duration of follow-up were all found to exert strong and consistent effects on the scores obtained. After controlling for these factors, there was no consistent difference between the results of the two surgical methods. It is concluded that, at least in the hands of one particular surgeon, the use of the operating microscope gives no better results than careful epineural suture performed without it.

A prospective study was made over a three-year period of 900 consecutive unilateral Colles' fractures. The radiographic features at the time of fracture, after reduction and one week later were measured and correlated with grip strength and range of movement at three years. The most significant radiographic feature to influence the outcome was the presence of shortening of the radius one week after reduction of the fracture. Persistent dorsal tilt, radiocarpal joint involvement and ulnar styloid fracture were each associated with reduced range of movement, but had no effect on grip strength. Extension of the fracture into the distal radio-ulnar joint was associated with reduced grip strength but had no effect on range of movement. Radial tilt of the radial fragment did not correlate with any aspect of the result after three years.