Monsell, F.P.; (2011) The effect of cytotoxic chemotherapy on the structural and material properties of regenerate bone in a rabbit model of limb lengthening. Doctoral thesis , UCL (University College London).

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Abstract

Abstract: A New Zealand White (NZW) rabbit model was used to investigate the effect of cyclical cytotoxic chemotherapy on the structural and material properties of regenerate bone. This attempted to reproduce the biological situation encountered in a human adolescent with a primary malignant bone tumour, treated by surgical resection and either adjuvant or neo-adjuvant cyclical chemotherapy with bone transport to reconstruct the skeletal defect. General Hypothesis It is possible to produce normal bone by distraction osteogenesis in the presence of cyclical cytotoxic therapy. Materials and Methods: Forty immature male rabbits were divided equally into 2 groups. Each received 2 cycles of either cis-platinum / adriamycin or normal saline, with a tibial osteotomy and lengthening at 12-weeks of age. The timing of the cytotoxic drugs differed between groups in an attempt to simulate an adjuvant and neo-adjuvant dose schedule. Results: A reproducible animal model was developed, appropriate doses of cis-platinum and adriamycin were determined and it was demonstrated that surgical lengthening was possible in animals receiving chemotherapy. There were no differences in the physical characteristics of the regenerate or lengthened bone in either arm of the study. In the group that received 2-cycles of chemotherapy before lengthening (neoadjuvant group), there was a significant reduction in bone mineral concentration (BMC), bone mineral density (BMD) and volumetric bone mineral density (vBMD), assessed by dual X- ray absorptiometry (DXA). There was no effect on the structural properties assessed by compression testing In the group that received chemotherapy before and during lengthening (adjuvant group), there was no effect on mineralisation but a reduction in energy to yield and yield strain was demonstrated. Conclusion: These findings should be interpreted with caution, as the animals did not have malignant bone tumours and were given a limited drug regimen. The study did not demonstrate any consistent effect on the properties of regenerate bone but the assessment did not include histological analysis. Further work is needed to investigate the mechanism in which these agents affect distraction osteogenesis and this will require a dynamic assessment of bone formation and more sophisticated analysis of regenerate structure.

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