Recombinant human BMP-7 effectively prevents non-union in both young and old rats.
The purpose of this study was to evaluate the influence of age on the effectiveness of rhBMP-7 treatment in a fracture with severe periosteal damage that is known to result in non-union formation. Closed stabilized femur fractures were produced in 3-month-old and 18-month-old rats. The fracture site was exposed and 2 mm of the periosteum cauterized circumferentially to impair normal fracture healing. The cauterized fracture site was immediately treated with either 100 microg rhBMP-7 (BMP-7 group), or with 25 microL of vehicle alone (control group). Fracture healing was evaluated with radiographs taken at 3 and 6 weeks. Animals were sacrificed at 3 and 6 weeks and specimens subjected to biomechanical and histological evaluation. In both age groups, none of the control animals healed throughout the 6 weeks experimental duration. All of the rhBMP-7-treated 3-month-old animals were radiographically healed at 3 weeks. In comparison, only 56% (9/16) of the rhBMP-7-treated 18-month-old animals were radiographically healed at 3 weeks. At 6 weeks, however, all of the 18-month-old rhBMP-7-treated animals had healed. Histology revealed slower healing in the 18-month-old animals. Treatment with rhBMP-7 significantly increased all of the biomechanical properties in both age groups. In the 3-month-old animals the mechanical strength approached that of the intact femur at 3 weeks, while in the 18-month-old animals this did not occur until 6 weeks. In conclusion, rhBMP-7 can effectively stimulate fracture repair in both young (3-month-old) and old (18-month-old) rats. However, the effect of rhBMP-7 on the rate of fracture healing is greater in young rats compared to old rats.
Hak
David J
DJ
Department of Orthopaedic Surgery and Center for Tissue Regeneration and Repair, University of California, Davis, Sacramento, California 95817, USA. david.hak@ucdmc.ucdavis.edu
Makino
Takeshi
T
Niikura
Takahiro
T
Hazelwood
Scott J
SJ
Curtiss
Shane
S
Reddi
A Hari
AH
D000375:Aging / Q000502:physiology*; D000818:Animals; D001696:Biomechanical Phenomena; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D005264:Femoral Fractures / Q000000981:diagnostic imaging / Q000473:pathology; D017102:Fracture Healing / Q000187:drug effects*; D050723:Fractures, Bone / Q000000981:diagnostic imaging / Q000473:pathology*; D006801:Humans; D011859:Radiography; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
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