EFFECTS OF RH-BMP-7 ON BONE HEALING IN A RABBIT MODEL OF DISTRACTION-INDUCED OSTEOGENESIS

Abstract

Purpose of the study: We conducted an experimental study of the effects of rh-BMP-7 on healing rate in the tibia of the immature rabbit exposed to bone distraction. As seen in previous models using bone stock loss or lumbar fusion, we hypothesized that rh-BMP-7 accelerates osteogenesis of the distracted segment.

Material and methods: Twenty-eight immature male New Zealand rabbits weighing 2 to 3 kg were randomly selected from a homogeneous population. Two groups of 14 rabbits were constituted by random selection: the control group (group I) and the BMP group (group II). An Orthofix M-103 external fixator was installed on the left tibia in all rabbits before performing a mid-shaft osteotomy. 70 g rh-BMP-7 was applied to the osteotomy surfaces in group II animals. After a postoperative latency period of 7 days, bone distraction was instituted at the rate of 0.5 mm/12 hr for 21 days in all animals. Radiographic qualitative grading, ultrasonography, and bone mineral density measurements on the callus were performed each week on each animal from the second week to sacrifice. After sacrifice, the distracted callus was removed and embedded in resin for histomorpho-metric analysis without decalcification.

Results: Two animals from each group were excluded from the analysis because of a fracture on the pin line of the operated tibia. There were no wound or pin track infections. The radiographic grade noted in group I was constantly greater than in group II. Bone mineral content was significantly higher in group I animals compared with group II. The ultrasound examination of the callus revealed more rapid distraction gap filling in group I than group II. An liquid-filled cyst was noted early in 92% of the rabbits in group II, which retarded osteogenesis. This type of cyst was not observed in any of the group I animals. At the time of sacrifice, the ultrasound and bone density measurements tended toward similar values in the two groups, the results for group II catching up with those for group I. This trend was concomitant with resolution of the cysts within the callus in group II animals. The histological examination demonstrated earlier osteogenesis and remodeling in group I animals.

Discussion: Early formation of cysts would be the only factor causing late maturation of the callus in group II. The fact that the results tended toward similar values for the ultrasound and bone density studies late in the study (when the cysts were being resorbed) favors this hypothesis. Interposing rh-BMP-7 in solid form between the osteotomy surfaces may have inhibited the formation of the primary callus and caused an inflammatory reaction with cyst formation. The rh-BMP-7 may have been applied to early or may in itself had a negative effect, which might explain the absence of the expected acceleration of healing.

Conclusion: Early local application of 70 g rh-BMP-7 on osteotomy section surfaces in a rabbit model of tibial distraction did not lead to expected accelerated healing rate. The application of this compound after formation of a primary callus or in another formulation (liquid) might avoid the development of cysts within the callus and allow the active substance to play is potential role as an accelerator of bone healing.