Continuous local infusion of fibroblast growth factor-2 enhances consolidation of the bone segment lengthened by distraction osteogenesis in rabbit experiment

Experimental tibial lengthening was achieved in 61 rabbits to examine the effect of continuous local infusion of recombinant human fibroblast growth factor-2 (rhFGF-2) on bone healing of the lengthened segment. The tibial diaphysis was separated by osteotomy and was subjected to slow progressive distraction (rate: 0.35 mm/12 h) using a monolateral external fixator. There were a lag phase for 1 week, a distraction phase for 2 weeks, and a consolidation phase for 5 weeks in this experiment. At various stages of distraction, rhFGF-2 was infused continuously for 2 weeks into the lengthened segment (rate: 14.28 μg/60 μl/day) using an osmotic pump implanted under the skin. Bone healing was significantly accelerated when rhFGF-2 was infused in the beginning of consolidation phase, but not in the distraction phase or in the lag phase. Infusion of normal saline (N/S) using the same osmotic pump had no effect. Dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computerized tomography (pQCT) studies demonstrated that rhFGF-2-treated tibia had increased bone mineral density (BMD), bone mineral content (BMC) and cortical bone thickness (CBT) when compared with N/S-treated tibia. Three-point bending test demonstrated that rhFGF-2-treated bone had significantly stronger mechanical properties than N/S-treated bone. Finally, distribution of the infused materials was checked by using Indian ink or radio-opaque. The dyes distributed widely but exclusively in the lengthened segment. Based on these results, we conclude that direct delivery of rhFGF-2 into the lengthened segment can shorten the consolidation phase of limb lengthening and the method is applicable to the clinical treatment.