rhBMP-2 (ACS and CRM Formulations) Overcomes Pseudoarthrosis in a New Zealand White Rabbit Posterolateral Fusion Model

Background: Pseudarthrosis continues to be a problem with posterolateral lumbar fusions even using autograft, the current gold standard. Research continues to investigate the role of potential bone graft alternatives. Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been shown to be a potent osteoinductive factor.

Purpose: To use an established preclinical pseudoarthrosis repair model to evaluate the ability of two different formulations of rhBMP-2 to induce fusion versus controls.

Study design: Preclinical rabbit posterolateral lumbar pseudarthrosis repair model.

Methods: Seventy-two New Zealand white rabbits underwent posterolateral lumbar fusion with iliac crest autograft. Nicotine was continuously administered to all rabbits to induce pseudarthroses. At 5 weeks, the animals were surgically reexplored. Fused animals were excluded. Pseudarthrosis animals were re-decorticated and randomized to one of four bone graft materials: no additional graft, autograft, or one of two different formulations of rhBMP-2 (Medtronic); absorbable collagen sponge (ACS) or hydroxyapatite-tricalcium phosphate compression-resistant matrix (CRM). The ACS formulation (Infuse) contains 1.5 mL of 1.5 mg rhBMP-2 / mL per side. The CRM formulation (under development) contains 1.5 mL of 2.0 mg rhBMP-2 / mL per side. Nicotine pumps were exchanged. At 10 weeks, the rabbits were sacrificed and fusions were assessed with manual palpation and histology. Representative specimens were assessed with radiography or computed tomography.

Results: Four rabbits (5.5%) were lost to complications. Sixty-four (94%) had pseudarthroses on re-exploration and underwent repair. By manual palpation at 10 weeks, 1 of 16 (6.3%) pseudarthroses that received no graft fused, 5 of 17 (29.4%) pseudarthroses that received autograft fused, 31 of 31 (100%) pseudarthroses that received rhBMP-2 (with either ACS or CRM) fused. Plain radiographs, computed tomography, and histology further characterized the fusion masses.

Conclusions: Recombinant human bone morphogenetic protein-2 (in both carriers studied) was able to significantly increase fusion versus controls in this challenging preclinical posterolateral lumbar model.

** The FDA has not cleared a drug and/or medical device described in this presentation (i.e., the drug or medical device is being discussed in an (off-label use.)

Hibbs Award Nominee for Best Basic Science Paper