Nineteen dogs underwent L4-L5 intertransverse process fusions with either 58 μg, 115 μg, 230 μg, 460 μg, or 920 μg of recombinant human bone morphogenetic protein-2 carried by a polylactic acid polymer. A previous study (12 dogs) compared 2300 μg of recombinant human bone morphogenetic protein-2, autogenous iliac bone, and carrier alone in this model. All fusions subsequently were compared.
To characterize the dose-response relationship of recombinant human bone morphogenetic protein-2 in a spinal fusion model.
Recombinant osteoinductive morphogens, such as recombinant human bone morphogenetic protein-2, are effective in vertebrate diaphyseal defect and spinal fusion models. It is hypothesized that the quality of spinal fusion produced with recombinant human bone morphogenetic protein-2, above a threshold dose, does not change with increasing amounts of inductive protein.
After decortication of the posterior elements, the designated implants were placed along the intertransverse process space bilaterally. The fusion sites were evaluated after 3 months by computed tomography imaging, high-resolution radiography, manual testing, mechanical testing, and histologic analysis.
As in the study using 2300 μg of recombinant human bone morphogenetic protein-2, implantation of 58–920 μg of recombinant human bone morphogenetic protein-2 successfully resulted in intertransverse process fusion in the dog by 3 months. This had not occurred in animals containing autograft or carrier alone. The cross-sectional area of the fusion mass and mechanical stiffness of the L4-L5 intersegment were not dose-dependent. Histologic findings varied but were not related to rhBMP-2 dose. Inflammatory reaction to the composite implant was proportional inversely to the volume of the fusion mass.
No mechanical, radiographic, or histologic differences in the quality of intertransverse process fusion resulted from a 40-fold variation in dose of recombinant human bone morphogenetic protein-2.
From the *Department of Orthopaedic Surgery and the UCLA Comprehensive Spine Center, UCLA School of Medicine, Los Angeles, California, and the †Department of Orthopaedic Surgery, The Medical College of Wisconsin, Milwaukee, Wisconsin.
Presented in part at the 30th Annual Meeting of the Scoliosis Research Society, Asheville, North Carolina, September 13–17, 1995; UCLA/ARC# 91–309–4.
Supported by research grant from Sofamor Danek USA, Memphis, Tennessee; rhBMP-2 provided by Genetics Institute, Andover, Massachusetts.
Acknowledgment date: October 4, 1995.
First revision date: December 19, 1995.
Acceptance date: March 27, 1996.
Device status categories: 7.
Address reprint requests to: Harvinder S. Sandhu, MD; UCLA School of Medicine; 200 UCLA Medical Plaza; Suite 140; Los Angeles, CA 90095–6902