Effective doses of recombinant human bone morphogenetic protein-2 in experimental spinal fusion.

STUDY DESIGN

Nineteen dogs underwent L4-L5 intertransverse process fusions with either 58 micrograms, 115 micrograms, 230 micrograms, 460 micrograms, or 920 micrograms of recombinant human bone morphogenetic protein-2 carried by a polylactic acid polymer. A previous study (12 dogs) compared 2300 micrograms of recombinant human bone morphogenetic protein-2, autogenous iliac bone, and carrier alone in this model. All fusions subsequently were compared.

OBJECTIVES

To characterize the dose-response relationship of recombinant human bone morphogenetic protein-2 in a spinal fusion model.

SUMMARY OF BACKGROUND DATA

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.

METHODS

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.

RESULTS

As in the study using 2300 micrograms of recombinant human bone morphogenetic protein-2, implantation of 58-920 micrograms 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.

CONCLUSIONS

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.