INTRAVENOUS BISPHOSPHONATE THERAPY AT THE TIME OF SURGERY ENHANCES NEW BONE FORMATION DURING DISTRACTION OSTEOGENESIS IN IMMATURE RABBITS

Abstract

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