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
