Objective: To evaluate the effects of a new potent bisphosphonate on the formation, mineralisation, density, and mechanical properties of bone in distraction osteogenesis.

Methods: Thirty immature New Zealand White rabbits had a 10.5 millimetre lengthening of their tibia performed over 2 weeks using an Orthofix M-100 fixator. Ten control rabbits received saline only; 10 received the new bisphosphonate at the time of surgery, and 10 received a second dose at the end of distraction. Bone mineral content (BMC) and density (BMD) measurements were made at two, four and six weeks. Quantitative CT analysis of regenerate, proximal and distal bone, and corresponding segments in the non-operated limb was performed after culling. Mechanical testing was by 4-point bending.

Results: Bone mineral accrual was significantly faster in both treatment groups (ANOVA p< 0.01). BMD increased in all treated animals (ANOVA p< 0.01). Cross sectional area of regenerate at six weeks was increased by 49% in the single dosed group versus controls and by 59% in the re-dosed group. (ANOVA p< 0.01). BMC of the regenerate was increased by 92% in the single dose group and by 111% in the re-dosed group (ANOVA p< 0.01). Moment of inertia of the regenerate was significantly increased in both treated groups (ANOVA p< 0.05). The difference between single dose and controls was significant (p< 0.05), the difference between re-dosed and single dosed was not (p=0.5).

Conclusion: Bisphosphonate therapy significantly increased new bone formation, bone mineralisation and mechanical properties. Osteoporotic effects were reversed. This effect could have wide ranging implications for many orthopaedic practices

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.

The bisphosphonate, pamidronate, has been used successfully in our hospital for the management of osteogenesis imperfecta with an excellent safety profile in growing children. We have performed several research studies on distraction osteogenesis in New Zealand white rabbits showing significant increases in new bone formation and the abolition of stress shielding osteopaenia using both pamidronate and zoledronic acid. Recent studies have shown that bisphosphonates positively effect osteoblasts as well as inhibiting osteoclastic bone resorption.

We present a series of early cases where this research has been used in humans. Two cases of pamidronate assisted distraction osteogenesis are presented, one of which also had congenital pseudarthrosis of the tibia, which united after pamidronate administration.

Two cases of post-traumatic avascular necrosis have been successfully treated such that osteolysis and collapse of the necrotic femoral head did not occur. Bisphosphonates may act to slow bone resorption while simultaneously increasing new bone formation, such that the mechanical integrity of the necrotic segment can be maintained during revascularisation.

A randomised controlled trial of bisphosphonates in distraction osteogenesis at our hospital has now received ethical approval. Newer bisphosphonates have proven their clinical value in osteogenesis imperfecta and adult osteoporosis, but other potential roles are emerging for these compounds, which have extremely potent effects on bone.

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.

We examined the effect on bone mineral density (BMD) of a single dose of 3 mg/kg of the bisphosphonate, pamidronate (Novartis) in distraction osteogenesis in immature rabbits.

Seventeen rabbits (9 control, 8 given pamidronate) were examined by dual-energy x-ray absorptiometry. There was a significant increase in the BMD in the pamidronate group compared with the control animals. The mean areal BMD (g/cm²) in the bone proximal and distal to the regenerate was increased by 40% and 39%, respectively, compared with the control group (p < 0.05). The BMD of the regenerate bone was increased by a mean of 43% (p < 0.05). There was an increase of 22% in the mean area of regenerate formed in the pamidronate group (p< 0.05).

Histological examination of bone in nine rabbits (5 control, 4 pamidronate) showed an increase in osteoblastic rimming and mineralisation of the regenerate, increased formation of bone around the pin sites and an increase in the cortical width of the bone adjacent to the regenerate in the rabbits given pamidronate.

Pamidronate had a markedly positive effect. It reduced the disuse osteoporosis normally associated with lengthening using an external fixator and increased the amount and density of the regenerate bone. Further study is required to examine the mechanical properties of the regenerate after the administration of pamidronate.