Can Intermittent Teriparatide Facilitate Supraphysiological-Rate Distraction Osteogenesis? A Feasibility Study in the Rabbit Tibial Lengthening Model.

Abstract

Background: Intermittent teriparatide administration is known to accelerate and promote bone healing. We wanted to investigate if intermittent teriparatide administration could facilitate supraphysiological-rate distraction osteogenesis (DO) in the rabbit tibial lengthening model without compromising on the regenerate quality.

Methods: 24 New Zealand white rabbits underwent tibial lengthening of 10 mm by distraction osteogenesis and were divided into two groups. Group A (n = 12) underwent DO at the physiological (standard) rate of 0.75 mm per day and Group B (n = 12) underwent DO at the supraphysiological (accelerated) rate of 1.5 mm per day. Subgroups A1 and B1 received intermittent teriparatide, whereas subgroups A2 and B2 received saline as the vector control. The latency period (7 days) was equal in both groups. The consolidation phase was 2.5 times the distraction phase. Outcome parameters included mortality, number of failures of DO, regenerate volume, bone mineral density and strength of the regenerate as determined by the three-point bending test parameters (stiffness, work to failure and ultimate load to failure).

Results: There was one mortality in each group. Failure of distraction osteogenesis was noted in one animal in groups A1, A2 and B1, and four animals in Group B2. Kaplan-Meir survival analysis revealed significantly higher failures in Group B2 (log-rank test P value = 0.02). ANOVA revealed significant difference in regenerate stiffness (P = 0.04) among the four groups. However, the total volume, bone mineral density, work to failure and ultimate load to failure parameters were not significantly different among the four groups.

Conclusion: This feasibility study provides proof of concept of using teriparatide to accelerate distraction osteogenesis to supraphysiological levels, without compromising on the regenerate quality.