Study Design. A therapeutic study compared the influence of osteogenic protein-1 to autograft and collagen carrier in multilevel sheep spine fusions.Objective. To evaluate the efficacy of osteogenic protein-1 compared to autograft and collagen carrier in achieving fusion in a challenging multilevel lumbar spine ovine model.Summary of Background Data. Bone morphogenetic proteins can successfully augment spinal fusion. To date, all the preclinical and clinical studies using bone morphogenetic proteins have evaluated single-level fusion. In practice, multiple level fusions are commonly required for various conditions, like spinal deformity.Methods. Eighteen sheep underwent three-level spine fusion. Six sheep were treated with osteogenic protein-1 and its carrier, autograft, or with the carrier alone. Specimens were analyzed for evidence of fusion by palpation, radiographic and histologic analysis, and biomechanical testing.Results. Manual palpation testing for the presence of fusion showed none of the specimens fused all three levels or fused at the lumbosacral junction. No statistically significant difference was found between the osteogenic protein-1 and autograft groups' fusion rates based on radiographic grading (P ϭ 0.65) or biomechanical testing. Histologic analysis showed no qualitative difference in bone morphology or cellularity of fusion masses when comparing the autograft and osteogenic protein-1 specimens.Conclusions. No model before this exists that tests the efficacy of bone morphogenic proteins in as challenging an environment. Extrapolation of single-level preclinical and clinical studies with bone morphogenic proteins for use in multilevel fusion requires careful review. Autograft and osteogenic protein-1 had similar rates of fusion. A high rate of nonunion is seen with this multiple level fusion to the sacrum using autograft or osteogenic protein-1. The biologic enhancement with osteogenic protein-1 is not able to overcome this mechanically rigorous Posterior spinal fusion is a commonly performed procedure for a variety of pathologies of the spine. Posterior approach is used for decompression of the neural elements and fusion with autograft and internal fixation. Nonunions and delayed unions still plague the method of posterior spinal fusion with overall rates as high as 40% and greater with multilevel fusions.1 Autograft has been used as the classic method for achieving posterolateral fusion. However, this method is associated with its own set of limitations. The amount of available autograft, its quality, pain at the donor site, infection, hemorrhage, nerve injury, and increased operative time contribute to the shortcomings of this standard.2-4 Much interest has been given to graft substitutes because of these problems. 5 Osteoinductive proteins, such as recombinant human bone morphogenetic protein-2 and -7 (rhBMP-2 and rhBMP-7, respectively), have improved the results of single-level fusions in animal models.2,5-7 Bone morphogenic protein-7 (BMP-7), also known as osteogenic protein-1 (OP-1; Str...

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