Expression of osteocalcin and callus reaction during distraction osteogenesis with recombinant human bone morphogenic protein-7 injection

Cho, Yeong Cheol; Sung, Iel Yong; Byun, June Ho; Park, Bong Uk; Kim, Uk Kyu; Shin, Sang Hun; Kim, Jong Ryoul

Abstract

PURPOSE
The aim of this study was to evaluate the effect of recombinant human bone morphogenetic protein-7 (rhBMP-7) injected on the rate of new-bone formation for distraction osteogenesis on dogs.
MATERIALS AND METHODS
Twelve adult dogs were randomly selected into two groups of six dogs on each. Unilateral osteotomies were performed on the body of the mandible and an intraoral distractor was mounted to the mandible on dogs. One group was treated with injection of rhBMP-7 and the other group served as the control. RhBMP-7 was administered on the day of surgery by single injection into the medullary bone at the osteotomy gap. Distraction was performed five days after osteotomy as a rate of 0.5 mm twice per day for 10 days. The animals were then sacrificed at 2, 4, and 8 weeks after completion of the distraction. Two dogs in each group, totaling four dogs, were killed at 2 weeks, 4 weeks, and 8 weeks after completion of distraction, respectively. The lengthened mandibles were harvested and processed for radiographic and histological examinations. In addition, immunohistochemical examination using osteocalcin expression was studied.
RESULTS
Radiographs showed accelerated regenerate ossification with maturation of new bone in the rhBMP-7 group comparing with the control group at the 4 weeks of the consolidation. There was no significant difference in the radiographic findings at the 2 weeks and 8 weeks of the consolidation period. Histological findings demonstrated increased bone healing pattern in the rhBMP-7-treated group during all observation period. The expression of osteocalcin immunoreactivity was hardly detected in the normal mandible of dog, but the expression was detected in all experimental rhBMP-7 treated specimens. There were also significant increasing in number of positive immunostaining cells and staining intensity of osteocalcin expression in the rhBMP-7 treated group compared with those of the control group on 2-weeks and 4-weeks. There was a significant decreasing in staining intenstiy of all both two groups on 8 weeks of consolidation period, but significant differences of immunostaining was not seen in two groups.
CONCLUSIONS
A single injection of rhBMP-7 at the time of osteotomy may stimulate the rate of regenerate ossification and increase callus maturation during distraction osteogenesis. In addition, it may shorten the distraction osteogenesis procedure and decrease the prevalence of complications associated with mandibular distraction osteogenesis.