Abstract
Introduction: Distraction osteogenesis is a widely utilised orthopaedic procedure; however prolonged treatment time and considerable disuse osteoporosis remain problematic, with decreases of 44% to 61% in bone mineral density reported in adjacent bone. Refracture rates of 10–20% are reported after frame removal.
We set out to examine the role of bisphosphonates in protecting the bone against stress-shielding related osteopaenia during distraction osteogenesis. We used a NZW rabbit model with 2 weeks distraction to 10.5 mm then 4 weeks consolidation. We achieved positive results in the initial trial using the bisphosphonate pamidronate (Novartis). Not only were we able to abolish the decrease in BMD in the surrounding bone, we noted an increase in the mineral properties and strength of the new bone.
Moving on to zoledronic acid (Novartis), a third generation bisphosphonate designed for use in malignant hypercalcaemia and bone metastases, we achieved even more promising results. In a study of thirty rabbits, we gave saline to 10 controls, 0.1 mg/kg zoledronic acid to 10 rabbits at surgery and 10 further rabbits received 0.1 mg/kg zoledronic acid at surgery and at two weeks. The animals were scanned by DXA at 2, 4 and 6 weeks, and by QCT after culling. Mechanical testing was performed by destructive 4-point bend tests.
Second-weekly DXA scans documented faster mineral accrual after distraction between 2 and 4 weeks in both treatment groups (ANOVA p< 0.01). In the control group, the BMD in the segments around the lengthening fell by 0.16 g/cm2 between the 2nd and 6th week. The BMD showed a net increase over the same time period in all treated animals (ANOVA p< 0.01).
The cross sectional area of the regenerate at six weeks as measured by QCT was increased by 49% in the zoledronate group versus controls and by 59% in the re-dosed zoledronate group. (ANOVA p< 0.01). The final (6 week) BMC of the regenerate was increased by 92% in the zoledronate group versus controls and by 111% in the re-dosed zoledronate group (ANOVA p< 0.01). Bone mineral density was increased by a lesser but significant degree to normal values (28% and 34% respectively, ANOVA p< 0.01).
Four point bend testing revealed increases in peak load of 29% in the single dose and 89% in the re-dosed group (ANOVA p< 0.01).
Two patients are presented, one with congenital pseudarthrosis of the tibia, and one who had not united a distraction gap of 5 cm at six months, who were treated with pamidronate. Both showed successful responses in line with our research findings.
A clinical trial is being set up to establish a scientific case for bisphosphonate use in patients undergoing distraction osteogenesis with the aim of possible earlier frame removal and less refractures. Further research in other areas of bone healing is also planned.
The abstracts were prepared by Professor Jegan Krishnan. Correspondence should be addressed to him at the Flinders Medical Centre, Bedford Park 5047, Australia.
