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Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_I | Pages 202 - 202
1 Mar 2010
Quinlan J Watson R Kelly G Kelly P O’Byrne J Fitzpatrick J
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Patients with spinal cord injuries have been seen to have increased healing of attendant fractures. While the benefits are obvious, this excessive bone growth also causes unwanted side effects, such as decreased movement around joints, joint fusion and renal tract calculi. However, the cause for this phenomenon remains unclear.

This paper evaluates two groups with spinal column fractures – those with neurological compromise (n=10) and those without (n=15), and compares them with a control group with isolated long bone fractures (n=12). Serum was taken from these patients at five specific time intervals post injury (1 day, 5 days, 10 days, 42 days (6 weeks) and 84 days(12 weeks)). These samples were then analysed for levels of Transforming Growth Factor-Beta (TGF-.) using the ELISA technique. This cytokine has been shown to stimulate bone formation after both topical and systemic administration.

Results show TGF-.; levels of 142.79±29.51 ng/ml in the neurology group at 84 days post injury. This is higher than any of the other time points within this group (.0.009 vs. all other time points, ANOVA). Furthermore, this level is also higher than the levels recorded in the no neurology (103.51±36.81 ng/ml) and long bone (102.28±47.58 ng/ml) groups at 84 days post injury (p=0.009 and p=0.04 respectively, ANOVA).

In conclusion, the results of this work, carried out for the first time in humans, offers strong evidence of the causative role of TGF-.; in the increased bone turnover and attendant complications seen in patients with acute spinal cord injuries.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_I | Pages 73 - 73
1 Mar 2010
Butcher A Parsons P Ellis K Milner R Carter2 P Watson T Horner A
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Introduction: There is controversy regarding the effectiveness of PRC for bone healing. A possible explanation is the different bone graft substitutes (BGSs) used with PRC. Here we investigated the effect of combining different BGSs with PRC on hBMSCs differentiation and growth factor release from the BGS/PRC composites.

Method: hBMSCs, DBM and allograft were prepared from femoral heads donated by patients undergoing total hip replacement. Growth factor release (TGF-â, VEGF, PDGF-AB, BMP-2) was measured by ELISA. The effect of PRC on hBMSC differentiation was determined by ALP activity and mineralisation. PRC was produced using the CAPTION device (S& N) from 10 healthy volunteers.

Results: Combining PRC with BGSs increased hBMSC proliferation (p< 0.05) and decreased ALP activity (p< 0.05) compared to DBM or â-TCP (GenOS, S& N) alone, but had no effect on allograft following 3 and 5 days treatment. After 21 days PRC enhanced mineralisation compared to all BGSs alone (16%–56%). Compared to PRC alone addition of DBM and allograft increased proliferation (p< 0.05), decreased ALP activity (p< 0.005) and decreased mineralisation (p< 0.005). TGF-â, VEGF and BMP-2 release from PRC was unaffected when combined with DBM but PDGF-AB release was reduced by 50%.

Conclusions: Combining PRC with the majority of BGSs enhanced cell proliferation and decreased osteoblastic differentiation at early time points but increased total mineralisation compared to the BGSs alone. However, compared to PRC alone combining DBM or allograft with PRC reduced mineralisation. One potential explanation for the effects of combining PRC with DBM is altered growth factor release profiles compared to the components alone.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 350 - 350
1 May 2009
Williams G Callon K Watson M Naot D Wang Y Xu A Reid I Cornish J
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Adiponectin, a hormone secreted by adipocytes, regulates energy homeostasis and glucose and lipid metabolism. Plasma levels of adiponectin are negatively correlated with body fat mass. Adiponectin inhibits the formation and activity of osteoclasts and increases the proliferation and differentiation of osteoblasts in vitro. The aim of our study was to determine the bone phenotype of adiponectin knockout mice.

Male adiponectin-deficient (Ad-KO) and wild-type (WT) C57BL/6J mice were sacrificed at 8, 14 and 22 weeks of age. Body weights did not differ between Ad-KO and WT mice. We scanned the left proximal tibia using micro-CT at 5μm resolution and analysed bone microarchitecture by 3D analysis.

We found significant increases in trabecular bone volume (BV/TV) (15.9±1.63 vs. 12.2±0.72%, p=0.02) and trabecular number (3.20±0.18mm-1 vs. 2.32±0.12mm-1, p=0.0009) in 14-week old Ad-KO mice compared to controls. Similar differences between WT and Ad-KO were present in 8 and 22-week old animals but these did not reach statistical significance. Trabecular thickness was significantly greater (0.053±0.001mm vs. 0.048±0.002mm, p=0.04) in 22-week old Ad-KO mice compared to WT.

Ad-KO mice have increased number and volume of trabeculae at 14 weeks of age indicating that the net effect of adiponectin on bone accrual in vivo is inhibitory. These effects are age-dependent. Our data concur with the observations from epidemiological studies in humans that adiponectin negatively correlates with both fat mass and bone mass. Therefore, adiponectin may be a contributor to the link between fat and bone mass.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 352 - 352
1 May 2009
Gray S Watson M Callon K Williams G Reid I Cornish J
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Leptin is a major hormonal product of the adipocyte which regulates appetite and reproductive function through its hypothalamic receptors. It has now become clear that leptin receptors are much more widely distributed than just the hypothalamus, and the skeleton has emerged as an important site of action of leptin.

The signalling form of the leptin receptor has been found in several cell types including human osteoblasts, rat osteoblasts and human chondrocytes. In vitro we have shown leptin to an anabolic factor, stimulating osteoblast proliferation and inhibiting osteoclastogenesis. Leptin increases bone mass and reduces bone fragility when administered peripherally but has an indirect inhibitory effect on bone mass via the hypothalamus when administered directly into the central nervous system.

Data from animal models where there is an absence of either leptin production (ob/ob) or its receptor (db/db) have been contradictory. In this study we compared the bone phenotype of leptin receptor-deficient (db/db) and wild-type (WT) mice. Micro-CT analysis was done on proximal tibiae using a Skyscan 1172 scanner. Db/db mice had significantly reduced trabecular bone volume, trabecular thickness and trabecular number and a higher degree of trabecular separation. Cortical bone was also significantly lower in db/db animals in volume, cross-sectional thickness and perimeter.

These results demonstrate that in the absence of leptin signalling there is reduced bone mass indicating that leptin indeed acts in vivo as a bone anabolic factor, mimicking the in vitro results.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 244 - 244
1 May 2009
Goel DP Chan D Mohtadi N Watson K
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The current standard of care in Calgary, Alberta for management of a ruptured Achilles tendon is surgical repair, typically performed following admission to hospital. The primary objective of this study was to compare the costs of hospital treatment and complications associated with the surgical repair of Achilles tendon ruptures between two groups of patients: Group One = patients enrolled in the randomised clinical trial (RCT) Multicentre Achilles Tendon Treatment Study (MATTS), Group Two = all other non-study patients.

This observational cohort study analyzed all patients surgically treated for Achilles tendon ruptures at Calgary area hospitals over a three-year period (October 2002–September 2005). Inclusion criteria: age eighteen to seventy years, acute rupture.

A total of two hundred and eighty-two patients met the inclusion criteria; thirty-three patients were included in Group One, two hundred and forty-nine patients in Group Two. In Group One, twenty-seven patients (82%) were treated as outpatients, five patients (15%) were ADOP-24hr, and one patient (3%) was admitted. In Group Two, twenty-seven patients (11%) were treated as outpatients, ninety-five patients (38%) were ADOP-24hr, and one hundred and twenty-seven patients (51%) were admitted. The total costs for patients treated as outpatients and requiring overnight stays in Group One were $18,408 and $7,419, respectively. In Group Two, the total cost for outpatients was $18,071 compared to $379,496 for non-study patients requiring overnight stay. If all overnight patients in each group were treated as outpatients, the total savings would be $235,545. There were no serious complications in Group One. In Group Two, complications included two cases of pulmonary embolus, and one case of compartment syndrome requiring readmission. All complications resolved.

Surgical treatment of Achilles tendon rupture can be performed safely and at less cost on an outpatient basis. Participation in this RCT has allowed us to recommend a change in the standard of care in Calgary.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_I | Pages 37 - 37
1 Mar 2009
Taneja T Mandal D Sood L MahaluxmiVala J Natali C Achan P Goodier D Curry S Watson A
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Intramedullary Nailing is now accepted as the standard treatment for most femoral diaphyseal fractures. Most intramedullary nails are designed for proximal and distal locking with screws. We describe our experience with the Brooker Wills femoral nail. This nail is unique as distal fixation is achieved with as transverse fixator deployed through slots in the nail, a concept first enunciated by deCamargo in 1952. The fins of the fixator pierce the distal cortex when deployed thereby conferring rotational stability. The entire nail (including the proximal and distal fixation devices) can be inserted through a single proximal incision in the skin.

We treated 17 patients with femoral shaft fractures using this system. 93% of the patients were males. Motor vehicle accidents accounted for 80 % of the fractures. Most fractures involved the middle third of the femur (54%), followed by distal third (33%) and proximal third (13%). 67 % of the fractures showed Winquist and Hansen Grade 3 or 4 comminution.

All the nailings were performed in the supine position. Static locking was done in 16 cases. Post operative weight bearing was individualized with 86% of the patients bearing full weight before the end of 16 weeks. The average time to full weight bearing was 14 weeks.

The mean time to union was 17.1 weeks, with proximal, middle and distal third fractures showing average healing times of 19, 15.6 and 18.8 weeks respectively. All the fractures united. There was one case of delayed union. Intra-operative complications included–inability to deploy the distal fixator in one case and unwinding of the reamer in another case. There was one case of superficial infection where a patient developed a sinus over the metallic fin of the distal fixation device, which had penetrated the cortex. This healed after the distal fixation device was removed. There was one case of proximal nail migration, but the fracture went onto union with some limb shortening.

Results were evaluated using the scoring system devised by Sanders etal (1991). The functional criteria in their scoring system include- knee flexion, presence of pain, femur deformity, walking distance, stair climbing and pre injury functional status. We achieved excellent results in 53% of patients, good- 27%, fair–13 % and poor-7%.

We feel that the main advantage of the Brooker Wills Nail is the ease of distal locking. This saves time and also leads to lower level of radiation exposure, as the image intensifier is sparingly used for distal locking. In fact, this nail is an attractive option in centres which lack an image intensifier. We achieved good results with this nailing system and feel that it is an acceptable alternative to other nailing systems with conventional locking systems with screws.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_III | Pages 573 - 573
1 Aug 2008
Godey S Watson J
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Introduction and aims: Soft tissue defects after total knee arthroplasty (TKA) are difficult problems to treat. Flap surgery has been successful in salvaging the prostheses. We present results of flap surgery for exposed TKAs over a 10 year period performed by single surgeon.

Material and Methods: Between 1996 and 2005, 31 patients (32 knees) underwent flap surgeries for TKAs. Four of these procedures were done prophylactically in patients with previous knee surgeries. Gastrocnemius, medial fasciocutaneous and anterior compartment flaps were used either solely or in combination based on the size of the defect. The data was collected retrospectively from case-notes and correspondence from the treating orthopaedic surgeons.

Results: The patients were aged between 50 and 94 years. Indication for primary TKA was osteoarthritis in 25 patients and rheumatoid arthritis in 5. Coagulase negative Staph. aureus was the most commonly isolated organism. In patients using steroids, 4 of 6 (71.4%) knees had good or satisfactory outcome compared to 22 of 24 (91.7%) knees in patients not on steroids. Smoking did not influence the outcome of flap surgery . The average duration between the TKA and flap surgery was 11 weeks (range 1 – 52). Successful soft tissue cover was achieved in 30 of 32 knees (94%). Overall, TKA was salvaged in 20 of 28 knees (71.4%) knees, 3 knees (9.7%) underwent arthrodesis and above knee amputation was performed in 4 (12.4%). The information gathered from case notes and orthopaedic surgeons was insufficient to use a knee score for evaluating the functional outcome of the procedure.

Conclusion: Local flap surgery for providing soft tissue cover for exposed TKA is a viable and successful procedure with good results.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 215 - 215
1 Jul 2008
Cloke D Watson H Purdy S Steen I Williams J
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The aim of this randomised, controlled trial is to compare subacromial steroid injections, physiotherapy and both interventions with a control treatment in early painful arc of the shoulder.

Over a six-month period patients with “painful arc”, of less than six months duration, were recruited via their GPs. Eligible patients were consented to enter the trial and were then randomised, by sealed envelopes, to one of four arms of the study: control (normal analgesia and/or non-steroidal anti-inflammatory medication), a specified and repeatable Exercise and Manual Therapy Package (EMTP), a course of up to three subacromial steroid injections or both the EMTP and the steroid injections. The interventions and clinic follow-ups were over an 18-week period. A final postal questionnaire was sent out at one year. The progress of the patients was monitored using the Oxford Shoulder Score (OSS) and the SF36 general health questionnaire.

Seventy-nine GPs referred 186 patients, of whom 112 were randomised (Control=27, EMTP=29, Injections=28, Both=28). 64 patients were female and 48 male. The mean age was 54.5 years (range 23–88 years). Ninety patients completed the trial (Control=20, EMTP=22, Injections=26, Both=22). Sixty-two returned the follow-up questionnaire. By paired sample t-tests, no significant differences were found between the OSS scores or SF-36 (physical health total) at the beginning and end of the intervention period, or at one year. Two patients in the injection group went on to surgery, along with one each in the control and EMTP groups.

We have found no significant differences in outcome between steroid injections, a physiotherapy package, both treatments, or symptomatic treatment in our group of patients presenting with symptoms of painful arc of the shoulder.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 217 - 218
1 Jul 2008
Johnson R Roberts C Jones G Wiles N Chaddock C Potter R Watson P Symmons D Macfarlane G
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Background: Each year, 7% of the adult population consult their General Practitioner (GP) with low back pain (LBP). Approximately half of these patients still experience disabling pain after three months. Evidence suggests a biopsychosocial approach may be effective at reducing long-term pain and disability. This study aimed to evaluate, for persistent disabling LBP, the effectiveness of an exercise, education and cognitive behavioural therapy intervention compared to usual GP care plus educational material, and to investigate the effect of patient preference.

Method: Design: randomised controlled trial. Patients, aged 18–65yrs, consulting their GP with LBP were recruited. After 3 months those still reporting disabling LBP (≥20mm on 100mm pain visual analogue scale (VAS) and ≥5 Roland and Morris Disability Questionnaire (RMDQ) points) were randomised, having first established preference, to 2 groups. VAS and RMDQ were assessed at 0, 6, and 12-months post-intervention.

Results: 234 patients were randomised; 116 to the intervention. The intervention showed small non-significant effects at reducing pain (3.6mm) and disability (0.6points RMDQ) over one year. Preference showed significant interaction with treatment effect at one-year; patients had better outcomes if they received their preferred treatment.

Conclusion: The above intervention program produces only a modest effect in reducing LBP and disability over a one-year period. These results add to accumulating evidence that interventions for LBP produce, at best, only moderate benefits. The challenge for future research is to evaluate interventions tailored for specific LBP sub-populations. These results suggest that if patients receive treatment which they believe is beneficial their outcome can be optimised.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 343 - 343
1 Jul 2008
Cloke MD Watson H Purdy S Steen I Williams J
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Introduction: Shoulder pain represents a significant burden of disease in the general population, yet there is a lack of evidence about the effectiveness of routinely used interventions such as corticosteroid injection and physiotherapy.

Methods: Over a six-month period patients with “painful arc” of less than six months duration were recruited via their GPs.

Eligible patients randomised to one of four arms of the study: control (normal analgesia and/or non-steroidal anti-inflammatory medication), a specified and repeatable Exercise and Manual Therapy Package (EMTP), a course of up to three subacromial steroid injections or both the EMTP and the steroid injections. Follow-up was for 18 weeks, with postal questionnaire at one year.

The primary outcome measure was the Oxford Shoulder Score (OSS).

Results: 186 patients were referred, 112 were randomised. Mean age was 54.5 years. Ninety patients completed the trial. Sixty-two returned the follow-up questionnaire.

By analysis of covariance, no significant differences were found between the OSS scores or SF-36 (physical health total) at the beginning and end of the trial, or at one year. Two patients in the injection group went on to surgery, along with one each in the control and EMTP groups. No significant differences were found between treatment groups.

Conclusion: We have found no significant differences in outcome between steroid injections, physiotherapy, both treatments, and symptomatic treatment in a group of patients with early painful arc of the shoulder. Further, larger studies may be needed to find small differences in outcome between these treatments.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 4 | Pages 451 - 454
1 Apr 2008
Amin A Watson A Mangwani J Nawabi DH Ahluwalia R Loeffler M

We undertook a prospective randomised controlled trial to investigate the efficacy of autologous retransfusion drains in reducing the need for allogenic blood requirement after unilateral total knee replacement. We also monitored the incidence of post-operative complications. There were 86 patients in the control group, receiving standard care with a vacuum drain, and 92 who received an autologous drain and were retransfused postoperatively. Following serial haemoglobin measurements at 24, 48 and 72 hours, we found no difference in the need for allogenic blood between the two groups (control group 15.1%, retransfusion group 13% (p = 0.439)). The incidence of post-operative complications, such as wound infection, deep-vein thrombosis and chest infection, was also comparable between the groups. There were no adverse reactions associated with the retransfusion of autologous blood.

Based on this study, the cost-effectiveness and continued use of autologous drains in total knee replacement should be questioned.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 9 | Pages 1158 - 1164
1 Sep 2007
Lusty PJ Watson A Tuke MA Walter WL Walter WK Zicat B

We studied 33 third generation, alumina ceramic-on-ceramic bearings retrieved from cementless total hip replacements after more than six months in situ. Wear volume was measured with a Roundtest machine, and acetabular orientation from the anteroposterior pelvic radiograph. The overall median early wear rate was 0.1 mm3/yr for the femoral heads, and 0.04 mm3/yr for the acetabular liners. We then excluded hips where the components had migrated. In this stable subgroup of 22 bearings, those with an acetabular anteversion of < 15° (seven femoral heads) had a median femoral head wear rate of 1.2 mm3/yr, compared with 0 mm3/yr for those with an anteversion of ≥15° (15 femoral heads, p < 0.001). Even under edge loading, wear volumes with ceramic-on-ceramic bearings are small in comparison to other bearing materials. Low acetabular anteversion is associated with greater wear.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_II | Pages 319 - 319
1 May 2006
O’Grady P Watson R Redmond H Bouchier-Hayes D
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The mechanism by which cells die is important in an immune response and its resolution. The role of apoptosis in sepsis and trauma, and its regulation by cytokines is unclear. During the systemic inflammatory response, rates of human neutrophil apoptosis are decreased. Peritoneal macrophage apoptosis has been induced by nitric oxide and Lipopolysaccharide (LPS) in vitro but this has not as yet been demonstrated in vivo.

We examined the induction and effects of macrophage apoptosis in a model of trauma and sepsis.

One hundred female CD-I mice were randomised into four groups: Control, Septic model, challenged with intraperitoneal LPS (1.Img/200ul/mouse), Traumatic model, received hind limb amputation (HLA) and a Combined trauma/septic model. After 24 hrs mice were sacrificed and peritoneal macrophages were assessed for apoptosis by morphology and DNA fragmentation by flow cytometry and DNA gel electrophoresis

Peritoneal lavage from septic models had a decreased percentage of macrophages in comparison to control and trauma groups. The septic model also had a significantly increased incidence of apoptosis in comparison to control and trauma levels. There was no significant difference between control and traumatic groups.

These findings demonstrate that in a murine model of sepsis, lipopolysaccharide induces macrophages apoptosis. Modulation of this immune response may have important roles in the management of trauma patients.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 5 | Pages 606 - 613
1 May 2006
Abu-Rajab RB Watson WS Walker B Roberts J Gallacher SJ Meek RMD

We compared peri-prosthetic bone mineral density between identical cemented and cementless LCS rotating platform total knee arthroplasties. Two matched cohorts had dual energy x-ray absorptiometry scans two years post-operatively using a modified validated densitometric analysis protocol, to assess peri-prosthetic bone mineral density. The knee that was not operated on was also scanned to enable the calculation of a relative bone mineral density difference. Oxford Knee and American Knee Society scores were comparable in the two cohorts.

Statistical analysis revealed no significant difference in absolute, or relative peri-prosthetic bone mineral density with respect to the method of fixation. However, the femoral peri-prosthetic bone mineral density and relative bone mineral density difference were significantly decreased, irrespective of the method of fixation, particularly in the anterior distal portion of the femur, with a mean reduction in relative bone mineral density difference of 27%.

There was no difference in clinical outcome between the cemented and cementless LCS total knee arthroplasty. However, both produce stress-shielding around the femoral implants. This leads us to question the use of more expensive cementless total knee components.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_II | Pages 316 - 316
1 May 2006
O’Grady P Watson R O’Bryne J O’Brien T Fitzpatrick J
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Aseptic loosening is the single most important long-term complication of total joint arthroplasty. Wear debris induced inflammation stimulates osteoclastic resorption of bone. Cellular mechanisms involved in osteoblast viability in PWD induced inflammation is poorly understood.

Wear induced inflammation increases osteoblast necrosis and susceptibility to death by apoptosis. PMMA cement has a detrimental effect on osteoblast resistance to apoptosis, and that this is via an receptor mediated pathway. Osteoblast cell cultures (Human and MG63) were grown with and without PMMA cement and assessed for apoptosis and necrosis. TNF-α or Fas antibody simulated inflammation. Viability and apoptosis with PI exclusion, flow cytometry and western blotting assessed response.

Cement induced osteoblast necrosis up to 1 hour. This effect was negated after 24 hours. Culture of osteob1asts on cement had no direct effect on spontaneous apoptosis but susceptibility to inflammation was increased.

Polymerised cement has no direct effect on osteoblast cell death. Effects are mediated by inhibiting expression of anti-apoptotic protein (Bcl-2), and increasing susceptibility to inflammatory. Osteoblast resistance to death may represent a novel and important factor in aseptic loosening. The role of gene therapy is explored.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 3 | Pages 406 - 410
1 Mar 2006
Quinlan JF Watson RWG Kelly G Kelly PM O’Byrne JM Fitzpatrick JM

Injuries to the spinal cord may be associated with increased healing of fractures. This can be of benefit, but excessive bone growth can also cause considerable adverse effects.

We evaluated two groups of patients with fractures of the spinal column, those with neurological compromise (n = 10) and those without (n = 15), and also a control group with an isolated fracture of a long bone (n = 12). The level of transforming growth factor-beta (TGF-β), was measured at five time points after injury (days 1, 5, 10, 42 and 84).

The peak level of 142.79 ng/ml was found at day 84 in the neurology group (p < 0.001 vs other time points). The other groups peaked at day 42 and had a decrease at day 84 after injury (p ≤ 0.001).

Our findings suggest that TGF-β may have a role in the increased bone turnover and attendant complications seen in patients with acute injuries to the spinal cord.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 131 - 131
1 Mar 2006
Quinlan J Watson R Kelly P OByrne J Fitzpatrick J
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Increased bone turnover and fracture healing is associated with acute spinal cord injuries. Experimental work to date has been confined to animal models. While the benefits in relation to quicker fracture healing are obvious, this excessive bone growth (heterotopic ossification) also causes unwanted side effects, such as decreased movement around joints, joint fusion and renal tract calculi.

This paper evaluates two groups of patients with spinal column fractures – those with neurological compromise and those without, and compares them with a control group with isolated long bone fractures. Serum was taken from these patients at 10 days post injury and was analysed for the known osteogenic cytokines Insulin-like Growth Factor-1 (IGF-1) and Transforming Growth Factor-b1 (TGF-b1) as well as being added to an osteoblast cell culture line to analyse cell proliferation.

The results for the IGF-1 show a higher level in the neurology group compared to the no neurology group (p=0.038). In the TGF-B1 assay, the neurology group has a lower level than the other two groups (p< 0.0001 and p=0.002 respectively). However, when this group is subdivided into patients with complete and incomplete neurology, it can be seen that the levels of the complete group are elevated, although not significantly so (p=0.228).

All three groups stimulated markedly increased osteoblast cell proliferation versus a control group (p=0.086, p=0.005 and p=0.002 respectively). However, the neurology group is significantly lower than the other two groups (p=0.007 and p=0.001 respectively). Furthermore the complete group causes a lower proliferation rate than the incomplete group (p=0.539).

In conclusion, at 10 days post injury when the acute inflammatory reaction is subsiding and new bone is being laid down, patients with acute spinal cord injuries have increased bone turnover. This increase is being indirectly mediated by IGF-1, and more elevated levels with more severe neurological compromise suggest a contributory role of TGF-b1. Direct stimulation of osteoblasts does not appear to have any role to play in this accelerated bone healing.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 143 - 143
1 Mar 2006
Quinlan J Watson R Kelly P OByrne J Fitzpatrick J
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Patients with spinal cord injuries have been seen to have increased healing of attendant fractures. This for the main has been a clinical observation with laboratory work confined to rats. While the benefits in relation to quicker fracture healing are obvious, this excessive bone growth (heterotopic ossification) also causes unwanted side effects, such as decreased movement around joints, joint fusion and renal tract calculi. However, the cause for this phenomenon remains unclear.

This paper evaluates two groups with spinal column fractures – those with neurological compromise (n=10) and those without (n=11), and compares them with a control group with isolated long bone fractures (n=10). Serum was taken from these patients at five specific time intervals post injury (1 day, 5 days, 10 days, 42 days (6 weeks) and 84 days(12 weeks)). These samples were then analysed for levels of Transforming Growth Factor-Beta (TGF-b) using the ELISA technique. This cytokine has been shown to stimulate bone formation after both topical and systemic administration.

Results show TGF-b levels of 142.79+/−29.51 ng/ml in the neurology group at 84 days post injury. This is higher than any of the other time points within this group (p< 0.001 vs. day 1, day 5 and day 10 and p=0.005 vs. 42 days, ANOVA univariate analysis). Furthermore, this level is also higher than the levels recorded in the no neurology (103.51+/−36.81 ng/ml) and long bone (102.28=/−47.58 ng/ml) groups at 84 days post injury (p=0.011 and p=0.021 respectively, ANOVA univariate analysis). There was statistically significant difference in TGF-b levels seen between the clinically more severely injured patients i.e. complete neurological deficit and the less severely injured patients i.e. incomplete neurological deficit.

In conclusion, the results of this work, carried out for the first time in humans, offers strong evidence of the causative role of TGF-b in the increased bone turnover and attendant complications seen in patients with acute spinal cord injuries.


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. 87-B, Issue SUPP_III | Pages 261 - 261
1 Sep 2005
Quinlan JF Watson RWG Kelly PM O’Byrne JM Fitzpatrick JM
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Patients with spinal cord injuries have been seen to have increased healing of attendant fractures. This for the main has been a clinical observation with laboratory work confined to rats. While the benefits in relation to quicker fracture healing are obvious, this excessive bone growth (heterotopic ossification) also causes unwanted side effects, such as decreased movement around joints, joint fusion and renal tract calculi. However, the cause for this phenomenon remains unclear.

This paper evaluates two groups with spinal column fractures – those with neurological compromise (n=10) and those without (n=11), and compares them with a control group with isolated long bone fractures (n=10). Serum was taken from these patients at five specific time intervals post injury (1 day, 5 days, 10 days, 42 days (6 weeks) and 84 days (12 weeks)). These samples were then analysed for levels of Transforming Growth Factor-Beta (TGF-ß) using the ELISA technique. This cytokine has been shown to stimulate bone formation after both topical and systemic administration.

Results show TGF-ß levels of 142.79+/−29.51 ng/ml in the neurology group at 84 days post injury. This is higher than any of the other time points within this group (p< 0.001 vs day 1, day 5 and day 10 and p=0.005 vs 42 days, ANOVA univariate analysis). Furthermore, this level is also higher than the levels recorded in the non neurology (103.51+/−36.81 ng/ml) and long bone (102.28=/−47.58 ng/ml) groups at 84 days post injury (p=0.011 and p=0.021 respectively, ANOVA univariate analysis). There was statistically significant difference in TGF-ß levels seen between the clinically more severely injured patients, ie complete neurological deficit and the less severely injured patients, ie incomplete neurological deficit.

In conclusion, the results of this work, carried out for the first time in humans, offers strong evidence of the causative role of TGF-ß in the increased bone turnover and attendant complications seen in patients with acute spinal cord injuries.