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...

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Published in:Journal of orthopaedic research 2006-01, Vol.24 (1), p.11-20
Main Authors: Hak, David J., Makino, Takeshi, Niikura, Takahiro, Hazelwood, Scott J., Curtiss, Shane, Reddi, A. Hari
Format: Article
Language:English
Subjects:
aging
Aging - physiology
Animals
Biomechanical Phenomena
BMP
Bone Morphogenetic Protein 7
Bone Morphogenetic Proteins - pharmacology
Femoral Fractures - diagnostic imaging
Femoral Fractures - pathology
Fracture Healing - drug effects
fracture repair
Fractures, Bone - diagnostic imaging
Fractures, Bone - pathology
Humans
non-union
Radiography
Rats
Rats, Inbred F344
Recombinant Proteins - pharmacology
Transforming Growth Factor beta - pharmacology
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Summary: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 µg rhBMP‐7 (BMP‐7 group), or with 25 µL 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. © 2005 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
ISSN:0736-0266
1554-527X
DOI:10.1002/jor.20022