Trevor P Scott1, Kevin H Phan1, Haijun Tian1, Akinobu Suzuki1, Scott R Montgomery1, Jared S Johnson1, Elisa Atti2, Sotirios Tetratis2, Renata C Pereira3, Jeffrey C Wang4, Michael D Daubs5, Frank Stappenbeck6, Farhad Parhami7. 1. Department of Orthopedic Surgery, University of California-Los Angeles, 100 UCLA Plaza, Suite 755, Los Angeles, 90095, CA, USA. 2. School of Dentistry, University of California-Los Angeles, 714 Tiverton Ave., Los Angeles, 90095, CA, USA. 3. Department of Pediatric Nephrology, University of California-Los Angeles, 757 Westwood Plaza, Los Angeles, CA, 90095, USA. 4. Department of Orthopedic Surgery, University of Southern California, 1520 San Pablo Street, Suite 2000, Los Angeles, CA, 90033 USA; Department of Neurosurgery, University of Southern California, 1200 North State Street, Suite 3300 Los Angeles, CA, 90033, USA. 5. Department of Orthopedic Surgery, University of Nevada-Las Vegas, 1707 West Charleston Boulevard Las Vegas, NV, 89102, USA; Department of Neurosurgery, University of Nevada-Las Vegas, 1707 West Charleston Boulevard Las Vegas, NV, 89102, USA. 6. Division of Chemistry, MAX BioPharma, Inc., A2-237, 10833 Le Conte Ave., Los Angeles, CA 90095, USA. 7. Department of Medicine, David Geffen School of Medicine, University of California-Los Angeles, A2-237, 10833 Le Conte Ave., Los Angeles, CA 90095, USA. Electronic address: fparhami@mednet.ucla.edu.
Abstract
BACKGROUND CONTEXT: The nonunion rate after lumbar spinal fusion is as high as 25%. Recombinant human bone morphogenetic protein 2 (rhBMP2) has been used as a biological adjunct to promote bony fusion. However, recently there have been concerns about BMP2. Oxysterol 133 (Oxy133) has been shown to promote excellent fusion rates in rodent lumbar spine models and offers a potential alternative to rhBMP2. PURPOSE: The purpose of this study was to compare the fusion rate of rhBMP2 and Oxy133 in a randomized controlled trial using a posterolateral lumbar rabbit spinal fusion model. STUDY DESIGN: This was a randomized control animal study. METHODS: Twenty-four male adult white New Zealand rabbits (3-3.5 kg) underwent bilateral posterolateral lumbar spinal fusion at L4-L5. Rabbits were divided into four groups: control (A), 30-μg rhBMP2 (B), 20-mg Oxy133 (C), and 60-mg Oxy133 (D). At 4 weeks, fusion was evaluated by fluoroscopy, and at 8 weeks, the rabbits were sacrificed and fusion was evaluated radiographically, by manual palpation, and with microcomputed tomography. RESULTS: Fusion rates by radiographic analysis at 8 weeks were Group A, 40.0%; Group B, 91.7%; Group C, 91.7%; and Group D, 100%. Evaluation of fusion masses by manual palpation of excised spines after sacrifice showed the following fusion rates: Group A, 0%; Group B, 83.3%; Group C, 83.3%; and Group D, 90%. Microcomputed tomography scanning confirmed these findings. CONCLUSIONS: These findings in a rabbit model demonstrate that both 20- and 60-mg Oxy133 doses promote fusion that is equivalent to fusion induced by 30-μg rhBMP2 and significantly greater than the control group. The present findings confirm that Oxy133 is a promising candidate for therapeutic development as an alternative to rhBMP2 to promote spinal fusion.
BACKGROUND CONTEXT: The nonunion rate after lumbar spinal fusion is as high as 25%. Recombinant humanbone morphogenetic protein 2 (rhBMP2) has been used as a biological adjunct to promote bony fusion. However, recently there have been concerns about BMP2. Oxysterol 133 (Oxy133) has been shown to promote excellent fusion rates in rodent lumbar spine models and offers a potential alternative to rhBMP2. PURPOSE: The purpose of this study was to compare the fusion rate of rhBMP2 and Oxy133 in a randomized controlled trial using a posterolateral lumbar rabbit spinal fusion model. STUDY DESIGN: This was a randomized control animal study. METHODS: Twenty-four male adult white New Zealand rabbits (3-3.5 kg) underwent bilateral posterolateral lumbar spinal fusion at L4-L5. Rabbits were divided into four groups: control (A), 30-μg rhBMP2 (B), 20-mg Oxy133 (C), and 60-mg Oxy133 (D). At 4 weeks, fusion was evaluated by fluoroscopy, and at 8 weeks, the rabbits were sacrificed and fusion was evaluated radiographically, by manual palpation, and with microcomputed tomography. RESULTS: Fusion rates by radiographic analysis at 8 weeks were Group A, 40.0%; Group B, 91.7%; Group C, 91.7%; and Group D, 100%. Evaluation of fusion masses by manual palpation of excised spines after sacrifice showed the following fusion rates: Group A, 0%; Group B, 83.3%; Group C, 83.3%; and Group D, 90%. Microcomputed tomography scanning confirmed these findings. CONCLUSIONS: These findings in a rabbit model demonstrate that both 20- and 60-mg Oxy133 doses promote fusion that is equivalent to fusion induced by 30-μg rhBMP2 and significantly greater than the control group. The present findings confirm that Oxy133 is a promising candidate for therapeutic development as an alternative to rhBMP2 to promote spinal fusion.
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