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Page 1: 121. In vivo BMP-7 enhancement of osteoporotic vertebral bodies in an ovine model

Proceedings of the NASS 19th Annual Meeting / The Spine Journal 4 (2004) 3S–119S62S

lesion. Neurosphere cells (100,000 cells in 0.1ml Phosphate buffered saline)were isolated from the hippocampus of a transgenic rat fetus expressinggreen fluorescent protein (GFP) and transplanted intravenously 24 hoursafter injury in 34 rats. In another 16 rats, contusion injury was carried outsame way and only 0.1ml PBS was injected. 1, 7, 21, 42, 56 days afterinjection, several rats from each group were sacrificed and spinal cordtissue was carefully removed for histological examination using the fluo-rescence microscope and double immunostaining for the anti-GFP antibod-ies and other neuronal or glial markers were performed. The antibodiesused was as follows: nestin, glial fibrillary acidic protein (GFAP), neuronalnullei (Neu-N), and anti GFP.RESULTS: In the intravenously injected group, a lot of cells, which emittedgreen fluorescence, were observed in the injured spinal cord lesion at oneday after injection by the fluorescence microscope. There were no suchcells in the control group and non-injured spinal cord. One day after intrave-nous injection, almost GFP-positive cells were co-labeled with nestin inthe transplanted group. The number of nestin-positive cells reduced dayby day, and no nestin-positive cells were observed at later than 42 days.At 56 days after injection, transplanted GFP-positive cells survived in thelesion, and there were 5% GFP/ NeuN co-labeled cells, 47% GFP/ GFAPco-labeled cells, 48% GFP/Gal-C co-labeled cells respectively.CONCLUSIONS: Our research indicated that the intravenously injectedneurosphere cells migrated to the injured lesion, and soon after transplanta-tion, the majority of injected cells were positive for nestin; this was usedas a marker of the undifferentiated neuronal cells such as neural stemcells. Therefore, intravenously injected neurosphere cells reached the lesionkeeping their undifferentiated potential. These cells survived at least for56 days, and differentiated into neurons, astrocytes and oligodendrocytes.Notably, results of this study suggested that the intravenous injection ofneurosphere cells is a promising method to deliver neurosphere cells tothe injured spinal cord lesion.DISCLOSURES: Device or drug: neural stem cell. Status: Investigational/Not approved.CONFLICT OF INTEREST: No Conflicts.

doi: 10.1016/j.spinee.2004.05.121

Saturday, October 30, 20044:30–5:15 PM

Concurrent Sessions 8A: Spinal Deformity

4:30122. Thirty-six years experience of cervical extension osteotomy inankylosing spondylitis techniques and outcomesEdward D. Simmons, MD1, Richard Distefano, MD2, Yinggang Zheng,MD1, Edward H. Simmons, MD1; 1University at Buffalo, Buffalo, NY,USA; 2Central New York Orthopaedic Center, Syracuse, NY, USA

BACKGROUND CONTEXT: Cervical osteotomy still remains the mostchallenging procedure in the correction of flexion deformity in ankylosingspondylitis. Some authors prefer using general anesthesia and prone positionfor their surgery, and some still use the conventional laminar resection areadescribed in the literature. Cervical osteotomy performed in the sittingposition and under local anesthesia has been practiced in our center for 36years and 131 patients have undergone this surgery.PURPOSE: This study will review our surgical techniques and clinicalresults.STUDY DESIGN/SETTING: Patient follow up was obtained by a combi-nation of retrospective chart review and telephone interview by two indepen-dent physicians.PATIENT SAMPLE: Cervical osteotomy has been performed by our twosenior authors in our center since the first case performed in 1967. Overthe past 36 years, the accumulation of 131 cases was classified into twophases: 114 cases of 1967–1994 (conventional group) by our senior authorand 17 cases of 1997–2003 (current group) by our first author.OUTCOME MEASURES: The flexion deformity was measured pre- andpost-operatively using chin-brow to vertical angle.METHODS: The average follow up time was 9.7 years for the conventionalgroup and 26 months for the current group. In both groups, the procedure

4:06121. In vivo BMP-7 enhancement of osteoporotic vertebral bodies inan ovine modelFrank Phillips1, Scott Sulpizio2, Karen Mohr3, A. Simon Turner4,Jennifer MacLeay5, Allen Pierce6, Carol Toth, PhD6, Donna Wheeler2;1Rush University / Rush- Presbyterian-St. Luke’s Medical Center,Chicago, IL, USA; 2Colorado State University, CO, USA; 3University atAlbany, SUNY, Albany, NY, USA; 4Colorado State University, Ft.Collins, CO, USA; 5University of Minnesota, St. Paul, MN, USA;6Stryker Biotech, Hopkinton, MA, USA

BACKGROUND CONTEXT: Prevention of osteoporotic vertebral com-pression fractures (VCFs) could help millions of at-risk individuals maintainpain-free independence and physical function. Current treatments for osteo-porosis comprise systemic therapies aimed at increasing bone mineral den-sity and reducing fracture risk. Although effective, these medications havea gradual time-dependent effect on fracture risk providing little protectionfrom fracture in the early period after initiation. Bone morphogenic proteins(BMPs) are characterized by their ability to rapidly induce local boneformation which may have therapeutic potential in the prevention of osteo-porotic VCFs.PURPOSE: To evaluate the feasibility of local BMP-7 treatment in enhanc-ing osteoporotic vertebral bone structure and function, thereby potentiallyreducing fracture risk.STUDY DESIGN/SETTING: We evaluated bone mass, biomechanicsand architecture of osteoporotic ovine vertebral bodies 6 months after invivo BMP-7(OP-1) treatment with various carriers.PATIENT SAMPLE: N/AOUTCOME MEASURES: The effects of OP-1 injections were measuredby BMD and histomorphometry.

METHODS: Sheep (n�24) underwent ovariectomy and were placed onlow cation relative to anion diet. These interventions reduce bone densityand induce skeletal fragility. After 6 months, sheep were assigned to treat-ments based on OP-1 dose (370 Yg or 0 Yg) and carrier (3 types) with 4animals/treatment group. Carriers A and B were PLGA biospheres withdifferent release kinetics (B allowing sustained BMP release); carrier Cwas carboxymethylcellulose. Sheep underwent intra-vertebral body injec-tions on 2 non-adjacent levels. Animals were euthanized 6 months followinginjections and BMD (DEXA), biomechanics (compression testing at 5mm/min to 20% strain) and histomorphometry were assessed. Two-wayANOVA was used to determine effects of OP-1 (N�0.05).RESULTS: An 81.9%, 333.2%, and 39.9 percent increase in stiffness wasseen for OP-1 treated vertebra with carriers A, B and C respectively.Histology showed injection sites to be void of marrow with varied degreesof boney healing. Histomorphometrically, OP-1 treated vertebra showedimproved bone architecture including percent bone (14% and 16% increasewith OP-1-Carrier A and Carrier B respectively). Similar trends were seenfor marrow and trabecular star volumes. Whole vertebral body BMD wasnot affected by any treatment.CONCLUSIONS: To our knowledge, this is the first report of local invivo BMP treatment of osteoporotic vertebra. Results suggest that OP-1treatment can improve the biomechanics and histomorphometry of osteopo-rotic vertebra. Controlled release microspheres appeared to be the moreeffective carrier for OP-1. Although this is a pilot study with low samplesize, the results suggest that BMP injections may provide a viable optionfor the prevention or treatment of osteoporotic vertebral fractures.DISCLOSURES: FDA device/drug: Osteogenic Protein-1. Status: Nodisclosures.CONFLICT OF INTEREST: Authors (AP, CT) Other: Employee ofStryker Biotech.

doi: 10.1016/j.spinee.2004.05.122

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