The osteoinductive capability of BMPs appears diminished in the setting of acute infection. We applied rhBMP-2 to a segmental defect in a rat femur and measured the expression of key bone formation genes in the presence of acute infection. Types I and II collagen, osteocalcin, and BMP Type II receptor mRNA expression were characterized in 72 Sprague-Dawley rats, which received either bovine collagen carrier with 200 μg rhBMP-2 plus Staphylococcus aureus, carrier with bacteria only, carrier with rhBMP-2 only, or carrier alone. Six animals from each group were euthanized at 1, 2, and 4 weeks. Total RNA was isolated and extracted, and mRNA was determined by real-time comparative quantitative PCR. Infected defects had little expression of collagen I and II and osteocalcin mRNAs, while BMP receptor II expression with infection was greater than carrier-only controls at Weeks 2 and 4. Notably, all four genes were upregulated in infected defects in the presence of rhBMP-2. Thus, in a clinical setting with a high risk of infection and nonunion, such as a compound fracture with bone loss, rhBMP-2 may increase the rate and extent of bone formation. Even if infection does occur, rhBMP-2 may allow a quicker overall recovery time.
Bibliographical noteFunding Information:
One or more of the authors have received funding from the Orthopaedic Trauma Association, Rosemont, IL (AHS), and Minneapolis Medical Research Foundation, Minneapolis, MN (LSK,WDL). Each author certifies that his or her institution has approved the animal protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.
Acknowledgments We thank Medtronic Sofamor Danek for supplying the rhBMP-2 and carrier, Anna Petryk for the use of her real-time PCR equipment, Erik Carlson for his expertise in quantitative PCR, and Ann Neumann for her assistance in technique development for sample analysis. We also thank the Orthopedic Trauma Association and the Midwest Orthopedic Research Foundation for their generous support of this investigation.