Acceleration of regenerate ossification during distraction osteogenesis with recombinant human bone morphogenetic protein-7.
BACKGROUND
Bone-lengthening can be accomplished by means of distraction osteogenesis. In the present study, we examined the effect of a single dose of recombinant human bone morphogenetic protein-7 (rhBMP-7) on the rate of new-bone formation during distraction osteogenesis in the rat.


METHODS
Fourteen Long-Evans rats were randomized into two groups of seven rats each. An external fixator was applied to the left femur, and a transverse osteotomy was performed. One group was treated with rhBMP-7 in an aqueous solvent, and the other group received the solvent alone and served as the control. rhBMP-7 was administered on the day of surgery by means of a single injection into the osteotomy gap. Distraction was started seven days after surgery at a rate of 0.25 mm every twelve hours. Distraction was continued for twenty days, resulting in a total of 10 mm of lengthening. The regenerate was monitored with use of radiographs and bone-mineral-density measurements at the conclusion of distraction and at two and four weeks after the cessation of distraction. The lengthened femora were harvested, and biomechanical studies were carried out to determine the stiffness and maximum torque to failure.


RESULTS
Radiographs showed accelerated regenerate ossification in the BMP-7 group, with a larger amount of new bone compared with the control group. The bone-mineral-density values were dramatically enhanced on Day 20 in the BMP-7 group (103.6 +/- 12.6 mg/cm (2) ) compared with the control group (26.2 +/- 15.1 mg/cm (2) ). These differences continued to be greater at two and four weeks after the cessation of distraction. Normalized values of stiffness (percent stiffness) reached 76.5% +/- 5.4% in the BMP-7 group, compared with 6.6% +/- 0.5% in the control group. The percent maximum torque at failure was 81.1% +/- 1.2% in the BMP-7 group, compared with 20.8% +/- 0.3% in the control group.


CONCLUSIONS
A single injection of rhBMP-7 at the time of osteotomy surgery stimulated the rate of regenerate ossification and increased bone-mineral density during distraction osteogenesis. The biomechanical properties of the newly formed bone were also increased by BMP-7 injection.
Mizumoto
Yoshihiko
Y
Moseley
Timothy
T
Drews
Michael
M
Cooper
Virgil N
VN
Reddi
A Hari
AH
D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000187:drug effects; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D016267:External Fixators; D005269:Femur / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D019857:Osteogenesis, Distraction; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta
C525819:BMP7 protein, human; C525821:Bmp7 protein, rat; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta