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Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 371 - 371
1 Jul 2008
McCann R Colleary G Geddis C Clarke S Marsh D Dickson G
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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.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 392 - 392
1 Jul 2008
McCann R Colleary G Geddis C Dickson G Marsh D
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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.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 372 - 372
1 Jul 2008
McCann R Colleary G Geddis C Clarke S Marsh D Dickson G
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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).


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 406 - 406
1 Oct 2006
Geddis C McCann R Colleary G Dickson G Marsh D
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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.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 385 - 385
1 Oct 2006
Colleary G McCann R Geddis C Li G Dickson G Marsh D
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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.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_III | Pages 384 - 384
1 Oct 2006
McCann R Colleary G Geddis C Dickson G Marsh D
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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.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 268 - 268
1 Sep 2005
Murnaghan M Watson A Dennison J Colleary G Beverland D
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Introduction: Historically, it has been accepted that the pain associated with arthritis of the hip is usually located in the groin, anterior and lateral thigh with occasional radiation to the anterior knee. Patients complaining of thigh pain that extends below the knee are often considered to have a degenerative lumbar spine as the cause for their lower limb symptoms and total hip replacement (THR) may not be offered.

Following review of data regarding the preoperative distribution of pain in 2000 patients attending for hip replacement, it was noted that 40% of these patients had complained of pain at or below the knee.

We proposed to prospectively investigate the severity and location of pain in patients attending for THR and assessed how this distribution of pain altered following surgery. We also proposed to examine the distribution of radiological wear preoperatively and assess if there is any relationship between localisation of pain, and the severity or distribution of the radiological wear pattern.

Methods: 200 consecutive patients undergoing primary THR completed a questionnaire regarding the location and severity of their pain. Pain was localised to one or more of nine areas extending from low back to the foot. The localisation of pain was quantified as to severity using a visual analogue score. Questionnaires were completed both 4 weeks preoperatively and subsequently at a 3-month review clinic.

All patients underwent a standardised preoperative AP and Lateral x-ray. The AP film was divided into three areas, and the lateral film was divided into 5 areas. Each zone was assessed as to the severity of wear pattern and graded from 1–3 (no change in joint space, decreased joint space, femoral or acetabular destruction).

Results: The 200 patients complained of pain in a total of 980 areas preoperatively and 105 areas postoperative. 70% of the patients had complete relief of all pain at 3 months. The most common area of pain identified by patients was to the anterior aspect of the knee (82%), followed by pain at the greater trochanter and groin. 55% patients complained of pain extending to below the knee, mostly over the anterolateral aspect of the leg. Only 7% of these patients continued to complain of any below knee pain postoperatively, and all of these patients still had some relief of their below knee pain at review.

With regard to the frequencies and severity of x-ray changes, zone-1 (34%) was most commonly severely damaged with femoral and/or acetabular destruction in the AP film, with the anterior and anterolateral areas being most commonly affected areas in the lateral film (20% and 19% respectively).

When the distributions and severities of x-ray changes were correlated with the distribution of pain localised pre and postoperatively we were unable to show any association between the degree of radiological wear in any one zone and the locatin of pain identified by the patient. In fact, there was a normal distribution to the severity of radiological damage between each of the zones and localisation of pain in any of the 9 areas.

Conclusions: A significant number of patients who require hip arthroplasty have pain extending below the knee. This pain is frequently relieved following THR. The commonest area of sever hip joint wear with loss of femoral or acetabular bone is antero-superiorly. It is important to recognise this during surgery, such that action can be taken to ensure appropriate reaming such that subsequent correct tissue tension and leg lengths are achieved. We are unable to show any relationship between area of pain and area of radiological degeneration. We believe that patients who complain of pain in their back, buttock or thigh, which extends below the knee, can still benefit from total hip replacement. Patients who attend complaining of low back pain with radiation of pain down their leg should have their hips as well as their lumbar spine examined and imaged. Careful consideration should be taken before labelling the paid as being referred from degenerative back disease.


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_II | Pages 158 - 159
1 Jul 2002
Crowther S Colleary G Nicholas R McCormack J
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We retrospectively audited outcomes from 97 patients aged over 40 who had undergone arthroscopy in the last 4 years in this orthopaedic unit. The audit was carried out by way of questionnaires which were sent out to patients with the results inputted to a database combined with a review of patients charts, in particular the operative note from the arthroscopy. A standardised proforma was used to record both patient’s details and operative findings.

The questionnaires were sent out to 165 patients. Of that number 102 were returned, five of which were excluded due to inadequate information.

The average wait for surgery was 10 months and 6 patients noticed an improvement in symptoms while waiting for surgery. 80% of those waiting less than 1 year experienced an improvement compared to 73% of those waiting more than 1 year. The results showed that post-operative symptoms in 74 out of the 97 (77%) patients were improved, 12 (12%) remained unchanged with 11 (11%) experiencing a worsening in symptoms.

The age group 60+ had the best outcomes with 23 out of 26 (89%) experiencing some improvement in symptoms; males also experienced a better outcome with 51 out of 63 (81 %) achieving some improvement, compared to females where only 23 out of 34 (67%) showed improvement.

We did not have routine access to an MRI scanner so only 23 of the patients had a pre-operative scan. We have insufficient numbers to comment on the accuracy or otherwise of positive MRI findings.

Pre-operative symptoms of pain, swelling, locking and instability were recorded and their correlation to successful outcome analysed. This showed that the presence of these symptoms did not predict a post-operative improvement in symptoms as an equal number of those with any of these symptoms compared to those without derived benefit from the procedure. This finding is significant in that these symptoms are commonly used in clinical practice to predict the likely benefit from arthroscopy.

A pre-operative history of locking was a specific predictive symptom for meniscal injury in that 27 out of 33 (82%) patients with true locking as a symptom had a meniscal injury but only 27 out of 58 (47%) patients with a meniscal injury experienced locking as a symptom implying that it is not a sensitive indicator of meniscal damage.

We also enquired about the presence of a definite acute injury associated with the onset of symptoms. This also had no predictive value as to the potential benefit of surgery.

A significant negative from the study was the fact that a history of an acute injury gave no indication as to the presence of a meniscal injury and even if a meniscal injury was present the patient’s outcomes were not significantly better than if no injury was present.

In conclusion 77% of patients aged 40+ derived benefit from arthroscopy, possibly due to the effects of washing out the knee rather than any active intervention. A history of locking, pain swelling or an acute injury did not offer an accurate prediction of benefit from arthroscopy, therefore the elderly and those without a history of locking or acute injury should not be dissuaded from undergoing this procedure. This study is confined to those over 40 years of age and the findings are quite different to the findings in younger patients. These findings surprised the surgeons at our unit and therefore we feel may be an interesting and stimulating presentation at the B.A.S.K. meeting.