Efficacy of OP-1 in a Challenging Multilevel Fusion Model**

· (a – Stryker Biotech)

Multiple level lumbar fusions are common for various diagnoses. Most of the preclinical and clinical studies using BMPs have evaluated single-level fusion. The purpose of this study was to evaluate the efficacy of Osteogenic Protein-1 (OP-1) in multiple level fusion when compared to autograft and carrier alone.

Eighteen sheep underwent bilateral posterolateral intertransverse process spine fusion from L5, 6, 7 to S1 using a Wiltse-type approach. The facets and midline structures were not disturbed. Six sheep were treated with OP-1 and its carrier, six with autograft, and six with the carrier alone. The animals healed for six months with unrestricted activity, were euthanized, and the spines harvested en-bloc from L4 to the sacrum. Six normal sheep spines were harvested from nonoperative control animals. The specimens were immediately analyzed for evidence of fusion by palpation. Radiographic analysis and biomechanical testing were also performed. All spines were tested in torsion, flexion/extension, and lateral bending modes. Stiffness, neutral angle, and maximum angle values from the experimental specimens were normalized to nonoperative control specimens. A two-way ANOVA and multiple comparison procedures were used to determine difference in stiffness, neutral angle, and maximum angle for treatment groups and fusion level.

All the animals survived the surgery with no neurological injuries or infections. Manual palpation testing for the amount of bone formation and presence of fusion showed none of the specimens fused all three levels or fused at the L7-S1 level. The L6-7 level fused more often than the L5-6 level in the OP-1 and autograft groups. Radiographic analysis of each level using the Lenke grading system showed the OP-1 group with 4(A), 4(B), 1(C), and 9(D) fusions and the autograft group with 2(A), 5(B), 7(C), and 4(D) fusions. The carrier group had 18(D) fusions. No difference was found between the OP-1 and autograft groups’ fusion rates based on radiographic grading (p=0.757). The OP-1 and autograft groups had significantly greater overall stiffness, lower overall maximum angle, and lower overall neutral angle when compared to the carrier and control groups (p<0.05). Fusion scores were significantly greater for the OP-1 and autograft groups compared to the carrier and control groups (p<0.05). There was no significant difference in any of the biomechanical parameters between the OP-1 and autograft groups (p<0.05).

No model prior to this exists that tests the efficacy of BMPs in as challenging an environment. Extrapolation of single-level preclinical and clinical studies with BMPs for use in multilevel fusion requires careful review.

A high rate of nonunion is seen with this multiple level fusion to the sacrum using autograft or OP-1. The biological enhancement with OP-1 is not able to overcome this mechanically rigorous model.

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

· If noted, the author indicates something of value received. The codes are identified as: a-research or institutional support; b-miscellaneous funding; c-royalties; d-stock options.