Prospective randomized controlled animal model.
The purpose of this study is to determine whether the readministration of human recombinant bone morphogenetic protein-2 (rhBMP-2) induces an immune response and inhibits successful fusion in repeat posterolateral spinal surgery.
Little research has been performed on the effectiveness or immunoreactivity of rhBMP-2 (Infuse, Medtronic, Memphis, TN) in the context of its reuse in posterolateral fusion spinal surgery at adjacent levels.
A total of 34 New Zealand White rabbits underwent posterior intertransverse process fusion with the use of rhBMP-2 delivered on an absorbable collagen sponge (rhBMP-2/ACS). Two rabbits were killed early leaving 32 total rabbits. Serologic studies (Type I bovine collagen and rhBMP-2 antibodies) were obtained at 2-week intervals throughout the experiment. At 10 weeks, posteroanterior radiographs confirmed solid fusion masses in all rabbits. The 32 rabbits were randomly separated into 2 groups of 16, and each group underwent an adjacent level, bilateral intertransverse process fusion with either rhBMP-2/ACS or iliac crest.
There was no statistical difference in fusion rates with repeat use of rhBMP-2 (n = 15/16, 94%) or iliac crest (n = 11/16, 69%) (P = 0.17) at the adjacent level. Four rabbits (n = 4/32, 13%) developed rhBMP-2 antibodies. Of these 4 rabbits, 1 developed anti-rhBMP antibodies after the first exposure and 3 developed antibodies after the second surgery. Eight rabbits (n = 8/32, 25%) developed collagen antibodies with 7 rabbits developing antibodies after the first exposure and 1 rabbit developing antibodies after the second exposure. The development of antibodies did not effect fusion rates. No rabbit demonstrated evidence of a systemic or anaphylactic reaction to repeat exposure to rhBMP-2.
rhBMP-2 appears to be successful in promoting intertransverse fusions when used in both primary and repeat fusion environments. The infrequent development of antibodies to rhBMP-2 after re-exposure occurs without a predictable time course suggesting that host immunologic variation may play a role. This animal study would tend to support early clinical data emerging on the reuse of BMP-2 for lumbar fusion, suggesting an acceptable fusion rate without a high incidence of complications.
In a New Zealand White rabbit model, after initial posterolateral fusion with human recombinant bone morphogenetic protein-2 (rhBMP-2), repeat administration of rhBMP-2 for adjacent level fusion was highly successful. Of rabbits, 13% developed rhBMP-2 antibodies during the study; however, the development of antibodies did not effect fusion rates. No rabbit demonstrated evidence of a systemic or anaphylactic reaction to repeat exposure to rhBMP-2.
Department of Orthopedic Surgery, Rush University, Chicago, IL.
Address correspondence and reprint requests to Frank M. Phillips, MD, Rush University, 1653 W. Congress Parkway, Chicago, IL 60612; E-mail: firstname.lastname@example.org
Acknowledgment date: June 24, 2009. Revision date: October 19, 2009. Acceptance date: November 20, 2009.
The device(s)/drugs(s) that is/are the subject of this manuscript is/are not FDA-approved for this indication and is/are not commercially available in the United States.
Corporate/Industry funds were received in support of this work. Although one or more of the author(s) has/have received or will receive benefits for personal or professional use from a commercial party related directly or indirectly to the subject of this manuscript, benefits will be directed solely to a research fund, foundation, educational institution, or other non-profit organization which the author(s) has/have been associated.