Date of Award

8-31-2009

Document Type

Thesis

Degree Name

Medical Doctor (MD)

First Advisor

Jonathan Grauer, MD

Second Advisor

Gary Friedlaender, MD

Third Advisor

Agnes Vignery

Abstract

Study Design: Posterolateral lumbar spine fusions in athymic rats. Objectives: To compare fusion rates of different production lots of demineralized bone matrix (DBM) to a dose response curve of rhBMP-2 in inactive DBM for posterolateral lumbar spinal fusion in an athymic rat model. Summary of Background Data: Demineralized bone matrix (DBM) preparations are available as bone graft supplements. Substantial variability in osteoinductive potential has been reported between different DBM products as well as between production lots of the same product. To date, no studies have correlated the osteoinductive indexing of a DBM product to in vivo performance in inducing spinal fusion. Methods: Single-level intertransverse process fusions were performed in 109 athymic nude rats. Fusion sites were prepared and implanted with no graft, iliac crest autograft, or 0.2 cc per bone graft alternative. Alternatives included: inactive BioSet DBM (0,0) or one of two production lots of BioSet DBM with different pre-implant osteoinductive activities: DBM Donor A(2,1 BioSet) and DBM Donor B(4,1 BioSet); and inactive 0,0 BioSet DBM plus 0.35 μg, 0.85 μg, 1.70 μg, or 10 μg of rhBMP-2. Animals were euthanized at 6 weeks post-operatively. Fusion masses were assessed by manual palpation, radiography, and histology. Results: At 6 weeks, manual palpation revealed a fusion rate with autograft of 25%, with 0,0 BioSet of 0%, with DBM Donor A of 17%, and with DBM Donor B of 36%. Radiographic and histologic analyses demonstrated statistically significant differences between fusion rates for DBM Donor A and Donor B. The dose response of rhBMP-2 with the 0,0 BioSet carrier had fusion rates of 45%, 91%, 90%, and 100%, respectively, the latter three significantly higher than autograft and both production lots of BioSet DBM (p<0.05). Conclusions: Differences between the ability of two variably osteoinductive BioSet DBM products to induce fusion in an athymic rat posterolateral lumbar spine fusion model were observed. The results of this preclinical animal study may compel the spine surgeon to more carefully evaluate the osteoinductive capacity of DBM products prior to their use in clinical scenarios.

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