We investigated the effect of adjuvant and neoadjuvant chemotherapy regimens on the tibial regenerate after removal of the external fixator in a rabbit model of distraction osteogenesis using New Zealand white rabbits.

Forty rabbits were randomly distributed into two groups. In the neoadjuvant group, half of the rabbits received 1mg/kg cisplatinum & 2mg/kg adriamycin at eight weeks of age followed by 1mg/kg cisplatinum & 4mg/kg adriamycin at ten weeks of age. The remaining ten received an identical volume of normal saline using the same regimen. The adjuvant group differed only in the timing of the chemotherapy infusion. Half received the initial infusion ten days prior to the osteotomy, with the second infusion four days following the osteotomy. Again, the remaining ten rabbits received an identical volume of normal saline using the same regimen. This produced an identical interval between infusions and identical age at osteotomy in both groups. All rabbits underwent a tibial osteotomy at 12 weeks of age. Distraction started 24hours after osteotomy at a rate of 0.75mm a day for 10 days, followed by 18 days without correction to allow for consolidation of the regenerate.

At week 16 there was no difference in Bone Mineral Density (BMD), Bone Mineral Content (BMC) or volumetric Bone Mineral Density (vBMD) in the adjuvant group. Neoadjuvant chemotherapy appears to have a significant detrimental effect on BMD, vBMD and BMC. Despite this there were no significant alterations in the mechanical properties of the regenerate. Histologically there was a trend for increased cortical thickness in the control groups compared to intervention however this did not prove statistically significant.

In conclusion, adjuvant chemotherapy may be more beneficial for cases where distraction osteogenesis is being considered to replace segmental bone loss after tumour excision.

Introduction: Enlarging cystic cavitations (syrinxes) form within the spinal cord in up to 28% of spinal cord injured patients. These post-traumatic syrinxes can cause neurological deterioration, and treatment results remain poor. Syrinxes are often found adjacent to regions of arachnoiditis.

The understanding of biological systems is increasingly dependent on modelling and simulations. Numerical simulation is not intended to replace in vivo experimental studies, but to enhance the understanding of biological systems. This study tests the hypothesis that pressure pulses in the SAS are high adjacent to areas of arachnoiditis and investigates the validity of a numerical model by comparison with in vivo experimental findings.

Methods: Experimental Model: Post-traumatic syringomyelia was induced in eight sheep by injection of kaolin into the subarachnoid space (SAS), and excitotoxic amino acid into the spinal cord of the upper thoracic spine. Cerebrospinal fluid (CSF) pressure studies were undertaken at either 3 or 6 weeks. Fibre-optic monitors were used to measure the pressure in the SAS 1 cm rostral and 1 cm caudal to the induced arachnoiditis.

Numerical Model: An axisymmetric fluid-structure interaction model was developed to represent the spinal cord and SAS under normal physiological conditions and in the presence of arachnoiditis. Arachnoiditis was modeled as a porous obstruction in the SAS.

Results: In both models the SAS pressure rostral to the arachnoiditis was found to be higher than the caudal SAS pressure. There was no statistically significant difference between the sheep at 3 and 6 weeks. Under normal conditions, both experimentally and in the numerical model, the pressure drop along the SAS was negligible. In the presence of arachnoiditis, the pressure drop across the arachnoiditis in the experimental model was 1.6 mmHg, whereas the numerical model predicted a pressure difference of 1.3 mmHg.

Discussion: The numerical model accurately predicts CSF pressures in the animal model under both normal and abnormal conditions, allowing predictions to be made to within 20% accuracy. The local increases in SAS CSF pressure demonstrated may act to increase fluid flow through perivascular spaces and be implicated in syrinx formation and enlargement.

Introduction: Post-traumatic syringomyelia typically occurs in the spinal cord adjacent to a region of arachnoiditis. This research tests the hypothesis that pressure pulses in the subarachnoid space (SAS) are higher adjacent to the arachnoiditis than in its absence. A fluid-structure interaction (FSI) analysis has been performed to study this behaviour under both normal physiological conditions and in the presence of arachnoiditis.

Method: A 2-dimensional axisymmetric cylindrical FSI model has been developed to represent the spinal cord and the SAS. CSF flow into the SAS is defined from MRI flow studies. Arachnoiditis is modelled as narrowing of the SAS. This model was based on a patient suffering from post-traumatic syringomyelia. Only the cervical region where arachnoiditis occurs has been modelled, that is from C1 to T1.

Results: Pressures in the SAS adjacent to arachnoiditis are almost 3 times higher (7.2 Pa vs. 21.67 Pa) than without arachnoiditis, with peak pressure occurring at the time of peak fluid inflow from the foramen magnum.

Discussion: The model supports the hypothesis that pressure pulses in the SAS are higher in the presence of the arachnoiditis than in normal unobstructed SAS. This elevated pressure may be implicated in syrinx formation.

INTRODUCTION: Post-traumatic syringomyelia typically occurs in the spinal cord adjacent to a region of arachnoiditis. This research tests the hypothesis that pressure pulses in the subarachnoid space (SAS) are higher adjacent to the arachnoiditis than in its absence. A fluid-structure interaction (FSI) analysis has been performed to study this behaviour under both normal physiological conditions and in the presence of arachnoiditis.

METHOD: A 2-dimensional axisymmetric cylindrical FSI model has been developed to represent the spinal cord and the SAS. CSF flow into the SAS is defined from MRI flow studies. Arachnoiditis is modelled as narrowing of the SAS. This model was based on a patient suffering from post-traumatic syringomyelia. Only the cervical region where arachnoiditis occurs has been modelled, that is from C1 to T1.

RESULTS: Pressures in the SAS adjacent to arachnoiditis are almost three times higher (7.2 Pa vs. 21.67 Pa) than without arachnoiditis, with peak pressure occurring at the time of peak fluid inflow from the foramen magnum.

DISCUSSION: The model supports the hypothesis that pressure pulses in the SAS are higher in the presence of the arachnoiditis than in normal unobstructed SAS. This elevated pressure may be implicated in syrinx formation.

Low intensity pulsed ultrasound (SAFHS, Exogen Inc.) was used to treat 15 immature New Zealand white rabbits following a mid diaphyseal tibial osteotomy and 1cm bone lengthening using an Orthofix M-100 device. Fifteen matched controls underwent an identical procedure but the ultrasound transducer was not switched on. At 4 and 6 weeks postoperatively the tibiae were analysed using DXA, QCT and 4 point bend mechanical testing. There were no differences identified between the active and control groups at 4 or 6 weeks with respect to bone mineral content or cross-sectional area of the regenerate, nor the bone proximal and distal to it. No improvement in strength of the regenerate was identified in either group. We cannot, therefore, support the use of the SAFHS to accelerate bone healing in patients undergoing limb lengthening.

Low intensity pulsed ultrasound has been shown to accelerate fracture healing in animals and humans. The mechanisms of action are discussed and we propose that the intensity of the ultrasound may need to be increased mechanically to stimulate a bone that is rigidly fixed using the M-100 fixator.

Aim: To examine the effect of the low intensity ultrasound stimulation (SAFHS, Exogen) on new bone formation and stress shielding in a distraction osteogenesis model in New Zealand white rabbits.

Methods: Thirty male rabbits underwent a right tibial osteotomy at eight weeks of age. Distraction of the osteotomy by 0.75mm/day was performed for two weeks. Ultrasound stimulation commenced on the seventh day after wound healing. The ‘active’ group was stimulated for 20 minutes daily. The controls had identical dummy stimulators applied. Half of the animals were culled at four weeks and half at six weeks. Dual-energy x-ray absorptiometry scans evaluated BMC and BMD. Quantitative computerised tomography measured the cross-sectional areas. Four-point bend testing of distracted and non-operated tibiae was performed in a standardised fashion.

Results: No differences were identified between the active and control groups at four or six weeks with respect to BMD, BMC or cross-sectional area of the regenerated bone. Stress shielding osteopaenia was unaffected by ultrasound stimulation. No significant improvement in strength of the regenerate was identified in either group – there was a trend towards improved strength at four weeks.

Discussion: Low intensity pulsed ultrasound accelerates fracture healing in humans when immobilised by plaster of Paris. One published study purporting to show improvement in distraction osteogenesis is fatally flawed. We believe the intensity of the ultrasound may need to be increased to stimulate mechanically a bone rigidly fixed by an external fixator. Other interventions such as the use of growth factors or bisphosphonates provide much greater improvements in experimental animals and are much more convenient to apply.

Aim: To examine the effect of the bisphosphonate zoledronic acid in doses of 0.1mg/kg on new bone formation and stress shielding in a distraction-osteogenesis model in New Zealand white rabbits.

Method: Thirty male rabbits underwent a right tibial osteotomy at eight weeks of age. Distraction of the osteotomy by 0.75mm/day was performed for two weeks followed by four weeks for consolidation. Group I was given saline infusions, Group II zoledronic acid at surgery, and Group III received zoledronic acid at surgery and again at two weeks. DXA scans evaluated BMC and BMD. Quantitative computerised tomography measured the cross-sectional areas. Four-point bend testing of both distracted and non-operated tibiae was performed in a standardised fashion.

Results: Bone mineral accretion between two and four weeks was significantly higher in treated versus saline groups, and was better maintained at six weeks (P< 0.01 ANOVA). Stress shielding osteopaenia that was seen in surrounding bone segments in Group I (controls) was abolished in the treated groups. By six weeks there was a 49% and 59% increase in cross sectional area of new bone in Groups II and III respectively (P< 0.01 ANOVA). Group II tibiae were 29% stronger in four-point bending, while Group III were 89% stronger than Group I (P< 0.01 ANOVA). There was little detectable effect on the non-operated tibiae.

Conclusions: Zoledronic acid administration significantly increased the rate and amount of new bone formation and its mineralisation. The increases in bone formation and retention translated to a significant, dose-dependent increase in strength. Further research into the role of zoledronic acid in orthopaedic surgery is indicated.