Posterolateral Spinal Arthhrodesis using Osteogenic Protein-1: An In-Vivo Time-Course Study using a Canine Model*

BW Cunningham, MSc*†,
N Shimamoto, MD*,
JC Sefter DO†,
AE Dmitriev BS,
MA Catino MD†,
JD Cohen MD†,
IL Fedder MD†
and PC McAfee MD†
· (a – Stryker)
*Orthopaedic Biomechanics Laboratory, Union Memorial Hospital and
†St. Joseph Hospital, Scoliosis and Spine Center, Baltimore, Maryland, USA

INTRODUCTION:
Using a functional animal model, the current study was designed to investigate the time–course maturation process of lumbar posterolateral arthrodeses performed with Osteogenic Protein – 1 (rhOP–1) versus autograft. Success criteria were based on postmortem radiographical, biomechanical and histological analyses.

METHODS:
Thirty–six purpose–bred coonhounds were equally divided into four experimental groups based on post–operative time periods of four, eight, twelve and twenty–four weeks (9 animals/group). Following posterolateral surgical exposure of L3–L4 and L5–L6, one of three randomized treatments was performed at each level: 1) Autograft alone [4g] (n=6), 2) Autograft + rhOP–1 mix [50/50, 2g/2g] (n=6) or 3) rhOP–1 alone [2g] (n=6). The rhOP–1 Putty consisted of 3.5mg of rhOP–1 per gram of type 1 collagen / 200mg carboxymethylcellulose (CMC). Following the respective survival periods, operative level fusion status was assessed using radiography, biomechanical testing and undecalcified histopathologic analysis.

RESULTS:
All animals survived the operative procedures without intra– or peri–operative complications. Plain film radiographic analysis (Lenke Scale) of the four–week group indicated successful fusions in 0% autograft, 38% auto./rhOP–1 and 22% of the rhOP–1 alone treatments. By the eight–week time interval, these values increased to 22% autograft, 88% auto./rhOP–1 and 66% rhOP–1 alone. Similar trends were noted at twelve weeks with autograft at 27% and auto./rhOP–1 and rhOP–1 alone at 83% and 72%, respectively. Biomechanical testing of the four–week post–operative arthrodeses indicated no significant differences in peak range of motion (ROM) (p>0.05). By eight and twelve weeks, the auto./rhOP–1 and rhOP–1 alone groups indicated significantly lower flexion–extension and axial rotation ROM levels compared to the autograft alone treatments (p<0.05). Histopathologic review of the specimens indicated the fusion masses were well contained within the intended arthrodesis site, without adjacent level compromise or histopathologic response.

DISCUSSION AND CONCLUSIONS:
This serves as the first time–course study to document the comparative posterolateral fusion maturation rates between autograft and rhOP–1. The most noticeable radiographic and biomechanical transitions in rhOP–1 maturation occurred at the eight–week time period. Thee biomechanical data served to corroborate the radiographic findings as the rhOP–1 treatments consistently demonstrated lower range of motion levels compared the autograft group. The use of recombinant human Osteogenic Protein–1 appears to offer definitive advantages as a posterolateral bone graft substitute and expander.

*· 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, e–consultant. For full information, refer to page 3.
** 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).