High complication rates and technical difficulties of intramedullary fixation in children with osteogenesis imperfecta have prompted the modification of existing rod systems. The Sheffield telescoping intramedullary rod system was introduced to reduce the complications. It has a T-piece which is permanently fixed to prevent its separation and is expanded to reduce the migration. This study analyses the outcome of this rod system over a 12-year period in two specialist centres.

Sixty rods were inserted in the lower limbs of 19 children with osteogenesis imperfecta. All children had multiple fractures of the bones before rod insertion. 39 rods were inserted into the femur, of which 3 were exchange and 4 revision procedures. 21 rods were inserted in the tibia. Eight children had intramedullary rodding of all the four lower limb long bones. The outcome was measured in terms of mobility status, incidence of refractures and rod-related complications.

Our series demonstrates that there is significant reduction in refractures and improvement in the mobility status in children with osteogenesis imperfecta following intramedullary fixation. The frequent complication of T-piece separation and the need for reoperation has been overcome with the Sheffield modification of rod design. But the extracortical and metaphyseal migration of the rod continues to be a problem and further improvement in the design is desirable.

Introduction: The limping child poses a diagnostic challenge. The purpose of this study was to create a clinically useful algorithm of presenting variables to allow the exclusion of ‘musculoskeletal sepsis’ as a differential diagnosis in the child presenting with a limp.

Materials & Methods: This study represents the data collected on all limping children admitted to our centre over a 3-year period. Analysis was based on 229 admissions. Comparison was made between the group with septic arthritis or osteomyelitis and the group without infection, using univariate analysis. With logistic regression analysis, a model consisting of three independent multivariate predictors was constructed, to exclude infection.

Results: Patients with septic arthritis or osteomyelitis differed significantly from patients without infection with regard to duration of symptoms, presence of constitutional symptoms, temperature, white cell count and erythrocyte sedimentation rate (ESR), (p-values < 0.05). Multivariate analysis demonstrated that the best model to describe our patient population was based on three variables: duration of symptoms between 1 and 5 days, temperature > 37.0°C and ESR > 35mm/hr. When all three variables were present, the predicted probability of musculoskeletal infection was 0.66. When none of the three were present, the predicted probability of infection was 0.01.

Discussion: Diagnosis of septic arthritis or osteomyelitis is especially difficult in the early phase and there is no single variable that can serve as a definitive test. The significance of constitutional symptoms and duration of symptoms on univariate analysis emphasises the importance of careful history taking. C-reactive protein, while considered for inclusion, was excluded due to its limited availability at our institution.

Conclusion: The multivariate model enables us to rule out musculoskeletal infection with 99% certainty in limping children with none of these three presenting variables.

Background: Aseptic loosening remains the most common cause of failure of total hip arthroplasty. Its pathogenesis is based upon the generation of wear debris particles which trigger synovial macrophage activation.

Statins, inhibitors of 3-hydroxy-3 methylglutaryl coenzyme A (HMG-Co-A) reductase, have revolutionised the treatment of hypercholesterolaemia. More recently statins have been shown to have potent anti inflammatory effects. We investigated the effects of cerivastatin in attenuating the activation of human macrophages by polymethylmethacrylate (PMMA) particles.

Methods: Polymethylmethacrylate-particle-stimulated human macrophages were cultured in vitro with cerivastatin at 75 and 150... mols/litre. TNF-α (tumour necrosis factor alpha) and MCP-1 (monocyte chemotactic protein) expression were determined using ELISA. An ERK1/2 inhibitor, UO126 was utilised to identify the mitogen activated protein kinase (MAP-Kinase) pathway involved and western blotting was used to demonstrate the effect of Cerivastatin on this pathway.

Results PMMA-stimulated TNF-α and MCP-1 expression was consistently attenuated by cerivastatin therapy.

PMMA activation was attenuated by the ERK1/2 inhibitor, UO126.

Western blotting confirmed ERK downregulation by cerivastatin, establishing a mechanism for its anti-inflammatory effects.

Conclusion: We have demonstrated the beneficial effects of statins in suppressing particle mediated activation of macrophages and the potential to prevent or treat periprosthetic osteolysis.

Background: Periprosthetic osteolysis precipitates aseptic component loosening, increases periprosthetic fracture risk and through massive bone loss, complicates revision surgery.

Its pathogenesis is based upon the generation of wear debris particles which trigger synovial macrophage activation. Statins, inhibitors of 3-hydroxy-3 methylglutaryl coenzyme A (HMG-Co-A) reductase, have revolutionised the treatment of hypercholesterolaemia and cardiovascular disease. The antiinflammatory properties of HMG-CoA reductase inhihitors or the statin family are well recognised. We investigated the effects of ceriv-astatin in attenuating the activation of human macrophages by polymethylmethacrylate (PMMA) particles.

Methods: Polymethylmethacrylate-particle-stimulated human macrophages were cultured in vitro with cerivastatin at 75 and 150micromols/litre. TNF- alpha (tumour necrosis factor alpha) and MCP-1 (monocyte chemotactic protein) expression were determined using ELISA. UO126, a Raf/MEK/ERK intracellular transduction pathway inhibitor, was utilised to identify the mitogen activated protein kinase (MAP- Kinase) pathway involved and western blotting was used to demonstrate the effect of cerivastatin on this pathway.

Results Human monocyte/macrophage cultures were activated by PMMA particles evidenced by TNF- alpha and MCP-1 expression(p< 0.05). This activation was consistently attenuated by cerivastatin therapy. Similarily, PMMA activation was attenuated by the Raf/MEK/ERK inhibitor, UO126.

Western blotting confirmed Raf/MEK/ERK down-regulation by cerivastatin, establishing a mechanism for its anti-inflammatory effects.

Conclusion We have demonstrated in vitro, that statins can abrogate particle induced inflammatory responses in a dose dependent manner and this is mediated intra-cellularily through its effect on the Raf/MEK/ERK transduction pathway. We propose that by attenuating this inflammatory response, the associated subsequent osteoclast activation and osteolysis is attenuated. Statins therefore may have role in promoting implant longevity

Aims: Pharmacological modulation of skeletal muscle reperfusion injury after trauma associated ischaemia may improve limb salvage rates and prevent the associated systemic sequelae. Resuscitation with hypertonic saline restores the circulating volume and has favourable effects on tissue perfusion and blood pressure. The purpose of our study was to evaluate the effects of hypertonic saline on skeletal muscle ischaemia reperfusion (I/R) injury and the associated endorgan injury.

Methods: Adult male Sprague Dawley rats (n=24) were randomised into three groups: control group, I/R group treated with normal saline and I/R group treated with hypertonic saline. Bilateral hind-limb ischaemia was induced by rubber band application proximal to the level of the greater trochanters for 2.5 hours. Treatment groups received either normal saline or hypertonic saline prior to tourniquet release. Following twelve hours reperfusion, the tibialis anterior muscle was dissected and muscle function assessed electrophysiologically by electrical field stimulation. The animals were then sacrificed and skeletal muscle harvested for evaluation. Lung tissue was also harvested for measurement of wet-to-dry ratio, myeloperoxidase content and histological analysis.

Results: Hypertonic saline significantly attenuated skeletal muscle reperfusion injury as shown by reduced twitch and tetanic contractions of the skeletal muscle (Table). There was also a significant reduction in lung injury as demonstrated by differences in wet-to-dry ratio, myeloperoxidase content and histological analysis.

Conclusion: Resuscitation with hypertonic saline may have a protective role in attenuating skeletal muscle ischaemia reperfusion injury and its associated systemic sequelae.

Aims: Circulating endothelial precursor cells (CEPs) are thought to play a role in angiogenesis. We investigated the angiogenic stress of musculoskeletal trauma on CEP kinetics in trauma patients and their bone marrow progenitor populations in a murine model. Methods: Peripheral blood mononuclear cells (PB-MNCs) were isolated from patients (n=12) on consecutive days following closed lower-limb diaphyseal fractures. CEP levels, deþned by the surface expression patterns of VEGFR2, CD34 and AC133 were determined and cytokine analysis of collected serum was performed. Bonemarrow precursors deþned byLy-6A/E and c-Kit expression were harvested following the traumatic insult from the murine model and quantiþed on ßow cytometry. Human and murine progenitor populations were cultured on þbronectin and examined for markers of endothelial cell lineage (Ulexeuropaeus- agglutinin-1 binding and acetylated-LDL uptake) and cell morphology. Statistical analysis was performed using variance analysis. Results: A consistent increase in human CEPs levels was noted within 72 hours of the initial insult, the percentage increase over day 1 reaching 300% (p=0.008) and returning to normal levels by day 10. Murine bone marrow precursors were mobilisd within 24 hrs peaking at 48hrs (900% p=0.035). On culture, morphologically characteristic endotheliallike cells binding UEA-1 and incorporating LDL were identiþed. Serum VEGF levels increased signiþcantly within 24 hrs of the insult, (p=0.018) preceeding the peak in CEP mobilisation. Conclusion: We propose that musculoskeletal trauma through the release of chemokines such as VEGF, promotes rapid mobilisation of CEPs from born marrow, which have the potential to contribute to reparative neovascularisation. Strategies to enhance CEPs kinetics may accelerate this process and offer a therapeutic role in aberrant fracture healing.

We retrospectively reviewed medical records and radiographs of 82 children who presented within 12 months of their birth, with unilateral dislocated/subluxed hips and required treatment in from of traction, closed/open reduction, pelvic osteotomy and maintenance. The purpose of the study was to assess if HE angle could be utilized as a prognostic indicator fro assessing reduction of the affected hip. Hilgenreiner epiphyseal angle was measured by two observers for the normal as well as the abnormal side and differences noted. The measurements of the primary presentation and follow-up films were then correlated. Two groups of patients emerged, those in who the difference between the normal and abnormal hips was less than 10 degrees and those in whom was greater than or equal to 10 degrees, on initial presentation. Their management transpired to be quite different (p=0.000), with open reduction/pelvic osteotomy being required in all cases in the latter group.

In late presenting developmental Dysplasia of hip there is controversy as to the most appropriate method of treatment. The purpose of study was to determine the outcome following the non-operative and operative treatment for late presenting developmental dysplasia of hip.

Retrospective study. Inclusion criteria – (1) Unilateral DH (2) Diagnosed 6 months or more after birth (3) Minimum follow up of 2 years after treatment. 41 patients matched the inclusion criteria. 32 patients attended the follow-up clinic. Patients were divided into non-operative and operative group. Outcome instruments used include activities scale for kids (ASK), physical component of SF36 v2, centre edge angle and severin classification system, all validated scoring systems.

32 patients with mean follow-up of 7 (2–12_ years. Mean age at the time of follow-up was 9 (range 2.7 – 15) years. In our series, 15 patients received non-operative and 17 patients received operative treatment. On ASK, conservatively treated hips scored 72% and surgically treated hips scored 69%. (P-Value = > 0.05). On SF36 v2, mean value of physical function score (PFS) for both non-operative and operative group were 57.58 respectively (P Value > 0.05). Centre edge angle (CEA) of non-operative and operative group were compared with their contra-lateral normal sides (P Value > 0.05). According to Severin classification system, 7 hips were grade I, 8 were grade II in the non operative group and in operative group, 10 were grade II, 5 were grade III and 2 were grade IV. There were no major complications and only one (3%) hip developed avascular necrosis of hip.

On a medium term follow-up, despite some radiological abnormalities, most of the patients achieved good functional results following both non-operative treatments for late presenting DDH. There was no statistically significant difference in the development of hips either treated conservatively or surgically. Long term follow up studies are required in order to establish the true outcome of late presenting DDH treated either conservatively or surgically.

Background: Circulating endothelial precursor cells (CEPS) are thought to play a role in postnatal angiogenesis. We investigated the angiogenic stress of musculoskeletal trauma on CEP kinetics in trauma patients and their bone marrow progenitor populations in a murine model.

Methods: Peripheral blood mononuclear cells (PB-MNCs) were isolated from patients (n=12) on consecutive days following closed lower-limb diaphyseal fractures. CEP levels, defined by the surface expression patterns of VEGFR2, CD34 and AC133 were determined and cytokine analysis of collected serum was performed. Bone marrow precursors defined by Ly-6A/E and c-Kit expression were harvested following traumatic insult from the murine model and quantified on flow cytometry. Human and murine progenitor populations were cultured on fibronectin and examined for markers of endothelial cell linage (Ulexeuropaeus- agglutinin- 1 binding and acetylated-LDL uptake) and cell morphology. Statistical analysis was performed using variance analysis.

Results: A consistent increase in human CEPs levels was noted within 72 hours of the initial insult, the percentage increase over day 1 reaching 300%.

Conclusion: We propose that musculoskeletal trauma through the release of chemokines such as VEGF, promotes rapid mobilisation of CEP from born marrow, which have the potential to contribute to reparative neovascularisation. Strategies to enhance CEPs kinetics may accelerate this process and offer a therapeutic role in aberrant fracture healing.

Background: Low molecular weight heparins (LMWH) are of undoubted efficacy as thromboprophylaxis in orthopaedic surgical practice. However, prolonged dosage inhibits bone nodule formation in vitro and we have previously reported that daily dosing significantly delays fracture healing. To further investigate these phenomena we hypothesised that LMWH’s would reduce osteoblast survival and thus bone formation by inducing programmed cell death (apoptosis).

Methods: Primary human osteoblasts were isolated from femoral heads excised during hip arthoplasty and cultured to passage 3–5. These were examined for VEGF receptor expression using a biotinylated binding assay on flow cytometry. Osteoblasts were grown to confluence and then incubated for 24 hours in control medium or medium treated with enoxaparin (200 – 2X10(−4) IU/mL) or combination of enoxaparin (200 – 2X10 (−4) IU/mL) and VEGF (1ng/ml). Apoptosis was determined by measuring cytosolic histone-associated DNA fragmentation using an enzyme linked immunosorbant assay. Results were confirmed by DNA fragmentation analysis on agarose gel electrophoresis. Cell functional viability was measured by a tetrazolium bioreduction colorimetric assay.

Results: Data is expressed as percentage of control apoptosis or viability, illustrates mean ± s.e.m. and n=4 experiments in each case. ANOVA was employed for statistical analysis; *versus control, #versus enoxaparin treated; p< 0.05 was considered significant.

Conclusions: Therapeutic doses of LMWH attenuate osteo-blast survival by inducing significant apoptosis. This effect is partly abrogated by VEGF, which independently enhances osteoblast viability, thus delaying spontaneous and enoxaparin induced apoptosis. These findings may explain the bone resorptive effects of prolonged LMWH therapy and suggest a potential therapeutic role for VEGF in conditions of delayed bone formation.

High complication rates and technical difficulties of intra-medullary fixation in children with osteogenesis imperfecta has prompted the modification of existing rod systems. The Sheffield telescoping intramedullary rod has T-piece which is permanently fixed and is expanded to reduce metaphyseal migration. This study analyses the outcome of this rod system over an 11-year period.

32 rods were inserted in the lower limbs of 11 children with osteogenesis imperfecta. All children had multiple fractures of the bones before rod insertion.24 rods were inserted into femur, of which 3 were exchange procedures for complications. 8 rods were inserted into tibia. 4 children had intramedullary rodding of all the 4 lower limb bones. The outcome was measured in terms of mobility status, incidence of refractures and rod related complications. Complications encountered include 2-rod migrations, one instance each of broken rod, bent rod and valgus drift in the tibia.There was no instance of epiphyseal damage or growth arrest.

Our series demonstrates that there is significant reduction in refractures and improvement in the mobility status in children with osteogenesis imperfecta following intramedullary fixation. The frequent complication of T-piece separation and the need for reoperation has been overcome with Sheffield modification of rod design. Though the incidence of rod related complications remain high, our study concludes that Sheffield rod system compares favourably with the existing intramedullary devices for osteogenesis imperfecta in the literature.