P92. Metal-on-Metal Lumbar Disc Arthroplasty - Two-year Minimum Follow-up

Proceedings of the NASS 22nd Annual Meeting / The Spine Journal 7 (2007) 1S–163S numerous biological processes and are known to induce new bone formation in both developing and mature skeletal systems. Osteogenic protein-1 (OP-1/BMP-7) is a well studied member of this family of growth factors and is now being used clinically in revision posterolateral spine fusions and long bone non unions.The cellular responses to BMPs are mediated by specific tetrameric receptor complexes, consisting of two Type I and two Type II receptors. The number of BMP ligands currently identified far exceeds the number of known receptors, suggesting that unique receptor combinations might mediate the specific signal of individual BMPs. PURPOSE: The purpose of this study was to identify specific receptors mediating BMP-7-induced osteoblast differentiation of primary human bone marrow derived mesenchymal stem cells (hMSC). These stem cells are considered a physiologically relevant model as they most likely mediate the effects of clinically administered BMPs in vivo. A thorough understanding of the mechanism through which BMP-7 activates target cells in vivo is critical to gaining a true appreciation of the potential of BMP-7 as a therapeutic agent. METHODS: hMSCs collected from human bone marrow were expanded in vitro and the expression of the six known BMP receptors (BMPR1A, BMPR1B, ACVR1A, BMPR2, BMPR2B and ACVR2B) was measured by quantitative PCR (QPCR). The activity of BMP-7, as determined by Id-1 gene expression, was measured in hMSCs following gene knockdown of each of the type I or type II receptors, alone or in combination. Potent receptor down regulation was achieved by RNA interference (RNAi) nucleofection in hMSCs. Studies were performed in multiple lots of hMSC, representing multiple donor pools. RESULTS: Measurement of receptor expression by QPCR revealed that ACVR1A and BMPR2 were the most abundantly expressed receptors in hMSC. BMPR1A and ACVR2A were expressed at relatively low levels, while BMPR1B and ACVR2B were not expressed at quantifiable levels in hMSC. Inhibition of any single receptor or combination of receptors did not affect the expression level of other receptors. SiRNA-mediated gene knockdown revealed that signaling through the type I receptors was nonredundant whereby roughly 80% of BMP-7 activity is elicited through ACVR1A and 20% through BMPR1A. Down regulation of BMPR1B did not affect BMP-7 induced Id-1 expression in these cells. Type II receptor gene knockdown showed that ACVR2A and BMPR2, but not ACVR2B mediate BMP-7 signaling in these cells. Redundancy was apparent in Type II receptor signaling, where BMPR2 and ACVR2A could compensate to some degree for the loss of the other. Specifically, expression of ACVR2A was sufficient for approximately 55% of BMP-7 signaling. In the absence of ACVR2A however, only 34% of BMP-7 activity was lost, suggesting that BMPR2 could partially compensate for the loss of ACVR2A. A similar result was observed for BMPR2 where this receptor was sufficient for approximately 62% of BMP-7 signaling, but necessary for only 48%. CONCLUSIONS: These data suggest that BMP-7 utilizes receptor complexes containing homodimers of ACVR1A or BMPR1A, complexed with BMPR2 or ACVR2A. Future studies will be aimed at further clarifying the mechanism through which BMP-7 and other BMPs transmit their signaling messages in human MSCs. FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs. doi: 10.1016/j.spinee.2007.07.298

P92. Metal-on-Metal Lumbar Disc Arthroplasty - Two-year Minimum Follow-up George Miz, MD1, Charles Theofilos, MD2; 1Oak Lawn, IL, USA; 2FL, USA BACKGROUND CONTEXT: In recent years, there has been renewed interest in disc arthroplasty as an alternative to fusion. The optimum mechanical design and choice of materials remains to be determined. The FlexiCore (Stryker Spine, Allendale, NJ) disc arthroplasty incorporates a stationary center of rotation with a metal-on-metal articulation. It is currently being evaluated in an IDE clinical trial.

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PURPOSE: To compare the safety and effectiveness of the FlexiCoreÒ Intervertebral Disc to circumferential spinal fusion surgery in the treatment of discogenic pain unresponsive to conservative treatment associated with degenerative disc disease (DDD) at a single level in the lumbosacral spine (L1-S1). STUDY DESIGN/SETTING: Data was collected from two study centers for patients enrolled in a multi-center, randomized, prospective IDE clinical trial comparing FlexiCore arthroplasty with anterior/posterior spinal fusion. PATIENT SAMPLE: At two study centers, 53 consecutive patients were randomized 2:1; arthroplasty vs. fusion. All 53 of the patients have a minimum of two years of follow-up. Surgical indications were one level symptomatic degenerative disc disease confirmed clinically and radiographically, unresponsive to adequate conservative management. OUTCOME MEASURES: Outcomes measures included pre- and postoperative Oswestry Disability Scale scores, Visual Analog Scale scores, return to work data, radiographic evaluation, peri-operative morbidity and complications. METHODS: Patients were compared with respect to pre- and post-operative ODS, VAS and return to work data as well as operative time, blood loss and incidence of complications. Data collection is pre-operatively and at 6 weeks, 3 months, 6 months, 1 year and 2 years post-operatively and annually thereafter. RESULTS: 35 patients were randomized to the arthroplasty group and 18 patients to the fusion group. Mean patient age in the arthroplasty group was 40.8 years and in the fusion group was 42.1. Operating time was a mean of 115 minutes in the arthroplasty group and 199 minutes in the fusion group. The mean estimated blood loss was 182 ml in the arthroplasty group and 284 ml in the fusion group. The incidence of complications and adverse events was similar to those previously reported for disc arthroplasty and circumferential fusion. At two year follow-up, the back pain VAS score improved by 61% from a pre-operative mean of 86.4 to a post-operative mean of 33.3 in the arthroplasty group and by 42% from a pre-operative mean of 83.9 to a post-operative mean of 35.1 in the fusion group. The ODI score improved by 49% from a pre-operative mean of 56.8 to a post-operative mean of 28.8 in the arthroplasty group and by 39.5% from a pre-operative mean of 64.8 to a post-operative mean of 39.2 in the fusion group. CONCLUSIONS: At two year minimum follow-up, both the arthroplasty and fusion patients from these two study centers exhibited clinically significant improvement in pain and function in this prospective randomized study. This data suggests that metal-on-metal lumbar disc arthroplasty is a viable alternative to interbody fusion for the treatment of disabling low back pain from single level degenerative disc disease. These findings need to be confirmed with longer follow-up and these results may not indicative of the overall study results. The results of the multi-center study are not yet available. FDA DEVICE/DRUG STATUS: FlexiCore Intervertebral Disc: Investigational/ Not approved. doi: 10.1016/j.spinee.2007.07.299

P93. Parameters Which Predict a Good Outcome When Deciding to Fuse to L3 in Double Major Idiopathic Scoliosis David Gurd, MD1, Sundeep Agrawal, BS2, Daniel Sucato, MD1; 1Dallas, TX, USA; 2TX, USA BACKGROUND CONTEXT: Factors determining fusion to L3 or L4 for a successful outcome when performing a posterior spinal fusion and instrumentation (PSFI) for double major adolescent idiopathic scoliosis (AIS) have not been fully defined. PURPOSE: To determine which factors predict good outcome when fusing to L3 when performing a posterior spinal fusion and instrumentation for double major scoliosis. STUDY DESIGN/SETTING: Retrospective cohort study. PATIENT SAMPLE: 41 patients who underwent a posterior spinal fusion and instrumentation for double major adolescent idiopathic scoliosis. OUTCOME MEASURES: Radiographic parameters relative to L3.