Prevention of atrophic nonunion development by recombinant human bone morphogenetic protein-7.
Severe periosteal and soft tissue disruption at the time of fracture may result in the formation of an atrophic nonunion. We have developed a reproducible atrophic nonunion in an animal model. The purpose of this study was to evaluate whether the immediate application of recombinant human BMP-7 to the fracture site could rescue the healing process in this nonunion model. A total of 56 three month old Fisher 344 rats were utilized. A 1.25 mm diameter K-wire was inserted into the femur in a retrograde fashion, and a mid-diaphyseal closed transverse fracture was created using a standard three point bending device. To create a nonunion, the fracture site was exposed and 2 mm of the periosteum was cauterized on each side of the fracture. The fracture site was immediately treated with either the application of rhBMP-7 50 microg in 25 microl of rat tail tendon collagen buffer (BMP-7 group), or with 25 microl of rat tail tendon collagen buffer only (Control group). Fracture healing was evaluated with serial radiographs every two weeks for an eight weeks period. Specimens at four and eight weeks were subjected to biomechanical and histological evaluation. None of the Control group healed throughout the eight weeks experimental duration. At four weeks 63% of the BMP-7 group had healed, and all had healed by six weeks. This investigation showed pronounced differences between the BMP-7 group and the Control group both histologically and biomechanically. In conclusion, we have demonstrated that the immediate application of BMP-7 may rescue the fracture healing process and prevent the development of nonunion following severe periosteal disruption.
Makino
Takeshi
T
Department of Orthopaedic Surgery and Center for Tissue Regeneration and Repair, University of California, Davis Sacramento, 95817, USA.
Hak
David J
DJ
Hazelwood
Scott J
SJ
Curtiss
Shane
S
Reddi
A Hari
AH
D000818:Animals; D001284:Atrophy; D001696:Biomechanical Phenomena; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D017102:Fracture Healing / Q000187:drug effects*; D050723:Fractures, Bone / Q000473:pathology*; D006801:Humans; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000627:therapeutic use; D016212:Transforming Growth Factor beta / Q000627:therapeutic use*
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