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Cheers GM, Weimer LP, Neuerburg C, Arnholdt J, Gilbert F, Thorwächter C, Holzapfel BM, Mayer-Wagner S, Laubach M. Advances in implants and bone graft types for lumbar spinal fusion surgery. Biomater Sci 2024; 12:4875-4902. [PMID: 39190323 DOI: 10.1039/d4bm00848k] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/28/2024]
Abstract
The increasing prevalence of spinal disorders worldwide necessitates advanced treatments, particularly interbody fusion for severe cases that are unresponsive to non-surgical interventions. This procedure, especially 360° lumbar interbody fusion, employs an interbody cage, pedicle screw-and-rod instrumentation, and autologous bone graft (ABG) to enhance spinal stability and promote fusion. Despite significant advancements, a persistent 10% incidence of non-union continues to result in compromised patient outcomes and escalated healthcare costs. Innovations in lumbar stabilisation seek to mimic the properties of natural bone, with evolving implant materials like titanium (Ti) and polyetheretherketone (PEEK) and their composites offering new prospects. Additionally, biomimetic cages featuring precisely engineered porosities and interconnectivity have gained traction, as they enhance osteogenic differentiation, support osteogenesis, and alleviate stress-shielding. However, the limitations of ABG, such as harvesting morbidities and limited fusion capacity, have spurred the exploration of sophisticated solutions involving advanced bone graft substitutes. Currently, demineralised bone matrix and ceramics are in clinical use, forming the basis for future investigations into novel bone graft substitutes. Bioglass, a promising newcomer, is under investigation despite its observed rapid absorption and the potential for foreign body reactions in preclinical studies. Its clinical applicability remains under scrutiny, with ongoing research addressing challenges related to burst release and appropriate dosing. Conversely, the well-documented favourable osteogenic potential of growth factors remains encouraging, with current efforts focused on modulating their release dynamics to minimise complications. In this evidence-based narrative review, we provide a comprehensive overview of the evolving landscape of non-degradable spinal implants and bone graft substitutes, emphasising their applications in lumbar spinal fusion surgery. We highlight the necessity for continued research to improve clinical outcomes and enhance patient well-being.
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Affiliation(s)
- Giles Michael Cheers
- Department of Orthopaedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), LMU University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany.
| | - Lucas Philipp Weimer
- Department of Orthopaedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), LMU University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany.
| | - Carl Neuerburg
- Department of Orthopaedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), LMU University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany.
| | - Jörg Arnholdt
- Department of Orthopaedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), LMU University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany.
| | - Fabian Gilbert
- Department of Orthopaedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), LMU University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany.
| | - Christoph Thorwächter
- Department of Orthopaedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), LMU University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany.
| | - Boris Michael Holzapfel
- Department of Orthopaedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), LMU University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany.
| | - Susanne Mayer-Wagner
- Department of Orthopaedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), LMU University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany.
| | - Markus Laubach
- Department of Orthopaedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), LMU University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany.
- Australian Research Council (ARC) Training Centre for Multiscale 3D Imaging, Modelling and Manufacturing (M3D Innovation), Queensland University of Technology, Brisbane, QLD 4000, Australia
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Yoon J, Choi HY, Jo DJ. Comparison of Outcomes of Multi-Level Anterior, Oblique, Transforaminal Lumbar Interbody Fusion Surgery : Impact on Global Sagittal Alignment. J Korean Neurosurg Soc 2023; 66:33-43. [PMID: 35996945 PMCID: PMC9837492 DOI: 10.3340/jkns.2022.0112] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2022] [Revised: 07/12/2022] [Accepted: 08/19/2022] [Indexed: 01/25/2023] Open
Abstract
OBJECTIVE To compare the outcomes of anterior lumbar interbody fusion (ALIF), oblique lumbar interbody fusion (OLIF), and transforaminal lumbar interbody fusion (TLIF) in terms of global sagittal alignment. METHODS From January 2007 to December 2019, 141 adult patients who underwent multilevel interbody fusion for lumbar degenerative disorders were enrolled. Regarding the approach, patients were divided into the ALIF (n=23), OLIF (n=60), and TLIF (n=58) groups. Outcomes, including local radiographic parameters and global sagittal alignment, were then compared between the treatment groups. RESULTS Regarding local radiographic parameters, ALIF and OLIF were superior to TLIF in terms of the change in the anterior disc height (7.6±4.5 mm vs. 6.9±3.2 mm vs. 4.7±2.9 mm, p<0.001), disc angle (-10.0°±6.3° vs. -9.2°±5.2° vs. -5.1°±5.1°, p<0.001), and fused segment lordosis (-14.5°±11.3° vs. -13.8°±7.5° vs. -7.4°±9.1°, p<0.001). However, regarding global sagittal alignment, postoperative lumbar lordosis (-42.5°±9.6° vs. -44.4°±11.6° vs. -40.6°±12.3°, p=0.210), pelvic incidence-lumbar lordosis mismatch (7.9°±11.3° vs. 6.7°±11.6° vs. 11.5°±13.0°, p=0.089), and the sagittal vertical axis (24.3±28.5 mm vs. 24.5±34.0 mm vs. 25.2±36.6 mm, p=0.990) did not differ between the groups. CONCLUSION Although the anterior approaches were superior in terms of local radiographic parameters, TLIF achieved adequate global sagittal alignment, comparable to the anterior approaches.
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Affiliation(s)
- Jiwon Yoon
- Department of Neurosurgery, Kyung Hee University Hospital at Gangdong, Kyung Hee University College of Medicine, Seoul, Korea
| | - Ho Yong Choi
- Department of Neurosurgery, Kyung Hee University Hospital at Gangdong, Kyung Hee University College of Medicine, Seoul, Korea
| | - Dae Jean Jo
- Department of Neurosurgery, Kyung Hee University Hospital at Gangdong, Kyung Hee University College of Medicine, Seoul, Korea
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Surgical Outcomes and Fusion Rate Following Spinal Fusion in Patients with Chronic Kidney Disease: Impact of Kidney Function. World Neurosurg 2022; 168:e587-e594. [DOI: 10.1016/j.wneu.2022.09.068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Accepted: 09/15/2022] [Indexed: 11/20/2022]
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Cohen T, Kossover O, Peled E, Bick T, Hasanov L, Chun TT, Cool S, Lewinson D, Seliktar D. A combined cell and growth factor delivery for the repair of a critical size tibia defect using biodegradable hydrogel implants. J Tissue Eng Regen Med 2022; 16:380-395. [PMID: 35119200 PMCID: PMC9303443 DOI: 10.1002/term.3285] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Revised: 12/09/2021] [Accepted: 01/11/2022] [Indexed: 11/16/2022]
Abstract
The ability to repair critical‐sized long‐bone injuries using growth factor and cell delivery was investigated using hydrogel biomaterials. Physiological doses of the recombinant human bone morphogenic protein‐2 (rhBMP2) were delivered in a sustained manner from a biodegradable hydrogel containing peripheral human blood‐derived endothelial progenitor cells (hEPCs). The biodegradable implants made from polyethylene glycol (PEG) and denatured fibrinogen (PEG‐fibrinogen, PF) were loaded with 7.7 μg/ml of rhBMP2 and 2.5 × 106 cells/ml hEPCs. The safety and efficacy of the implant were tested in a rodent model of a critical‐size long‐bone defect. The hydrogel implants were formed ex‐situ and placed into defects in the tibia of athymic nude rats and analyzed for bone repair after 13 weeks following surgery. The hydrogels containing a combination of 7.7 μg/ml of rhBMP2 and 2.5 × 106 cells/ml hEPCs were compared to control hydrogels containing 7.7 μg/ml of rhBMP2 only, 2.5 × 106 cells/ml hEPCs only, or bare hydrogels. Assessments of bone repair include histological analysis, bone formation at the site of implantation using quantitative microCT, and assessment of implant degradation. New bone formation was detected in all treated animals, with the highest amounts found in the treatments that included animals that combined the PF implant with rhBMP2. Moreover, statistically significant increases in the tissue mineral density (TMD), trabecular number and trabecular thickness were observed in defects treated with rhBMP2 compared to non‐rhBMP2 defects. New bone formation was significantly higher in the hEPC‐treated defects compared to bare hydrogel defects, but there were no significant differences in new bone formation, trabecular number, trabecular thickness or TMD at 13 weeks when comparing the rhBMP2 + hEPCs‐treated defects to rhBMP2‐treated defects. The study concludes that the bone regeneration using hydrogel implants containing hEPCs are overshadowed by enhanced osteogenesis associated with sustained delivery of rhBMP2.
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Affiliation(s)
- Talia Cohen
- The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Olga Kossover
- Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, Israel
| | - Eli Peled
- The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.,Department of Orthopedic Surgery, Rambam Medical Center, Haifa, Israel
| | - Tova Bick
- The Institute of Research of Bone Healing, the Rambam Healthcare Campus, Haifa, Israel
| | - Lena Hasanov
- Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, Israel
| | - Tan Tuan Chun
- Glycotherapeutics Group, Institute of Molecular and Cell Biology, A*STAR, Singapore, Singapore
| | - Simon Cool
- Glycotherapeutics Group, Institute of Molecular and Cell Biology, A*STAR, Singapore, Singapore
| | - Dina Lewinson
- The Institute of Research of Bone Healing, the Rambam Healthcare Campus, Haifa, Israel
| | - Dror Seliktar
- Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, Israel
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Yaw Tee LY, Hunter S, Baker JF. BMP use in the surgical treatment of pyogenic spondylodiscitis: Is it safe? J Clin Neurosci 2021; 95:94-98. [PMID: 34929659 DOI: 10.1016/j.jocn.2021.11.018] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 10/09/2021] [Accepted: 11/21/2021] [Indexed: 11/17/2022]
Abstract
OBJECTIVE Use of BMP in the setting of infection remains controversial. We examined the safety and effectiveness of BMP in the surgical treatment of pyogenic spondylodiscitis and compared patients who have been treated with or without BMP during surgery. METHODS 57 patients who have undergone surgery for pyogenic spondylodiscitis after presenting to a tertiary Spine referral institution between 2011 and 2020 were included. 18 underwent surgery alone without BMP and 39 underwent surgery with BMP. Outcomes were compared between the two groups, including re-operations, infection recurrences, BMP- related complications and radiological fusion. RESULTS The cohort comprised 41 males (71.9%) with a mean age 63.7 +/- 13.3 years. Surgical indications include instability (n = 18), pain (n = 4), neurological deficit (n = 15) and sepsis or failure of non-operative management (n = 20). In the group who underwent surgery without BMP, there were two cases of re-operation for infection recurrence (11.1%) and three cases of cage subsidence; 80% achieved definitive and probable fusion. In the group who underwent surgery with BMP, there were three cases of re-operation for infection recurrence (7.7%), three cases of cage subsidence and one case of BMP- related radiculitis; 96.5% achieved definitive and probable fusion. CONCLUSIONS The use of BMP in the surgical treatment of pyogenic spondylodiscitis did not confer an increased risk of infection recurrence, revision surgery or radiculitis. BMP can be a useful and safe adjunct in surgical intervention for pyogenic spondylodiscitis.
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Affiliation(s)
- Lawrence Yoon Yaw Tee
- Department of Orthopaedic Surgery, Waikato Hospital, Pembroke Street, Hamilton New Zealand 3240, 5 Minchin Crescent, Saint Andrews 3200, New Zealand.
| | - Sarah Hunter
- Department of Orthopaedic Surgery, Waikato Hospital, Pembroke Street, Hamilton NZ3240, New Zealand.
| | - Joseph F Baker
- Department of Orthopaedic Surgery, Waikato Hospital, Pembroke Street, Hamilton NZ3240, New Zealand
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Berger MB, Bosh KB, Jacobs TW, Cohen DJ, Schwartz Z, Boyan BD. Growth factors produced by bone marrow stromal cells on nanoroughened titanium-aluminum-vanadium surfaces program distal MSCs into osteoblasts via BMP2 signaling. J Orthop Res 2021; 39:1908-1920. [PMID: 33002223 PMCID: PMC8012402 DOI: 10.1002/jor.24869] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2020] [Revised: 09/21/2020] [Accepted: 09/29/2020] [Indexed: 02/04/2023]
Abstract
Statement of Clinical Significance: There remains the need to develop materials and surfaces that can increase the rate of implant osseointegration. Though osteoanabolic agents, like bone morphogenetic protein (BMP), can provide signaling for osteogenesis, the appropriate design of implants can also produce an innate cellular response that may reduce or eliminate the need to use additional agents to stimulate bone formation. Studies show that titanium implant surfaces that mimic the physical properties of osteoclast resorption pits regulate cellular responses of bone marrow stromal cells (MSCs) by altering cell morphology, transcriptomes, and local factor production to increase their differentiation into osteoblasts without osteogenic media supplements required for differentiation of MSCs on tissue culture polystyrene (TCPS). The goal of this study was to determine how cells in contact with biomimetic implant surfaces regulate the microenvironment around these surfaces in vitro. Two different approaches were used. First, unidirectional signaling was assessed by treating human MSCs grown on TCPS with conditioned media from MSC cultures grown on Ti6Al4V biomimetic surfaces. In the second set of studies, bidirectional signaling was assessed by coculturing MSCs grown on mesh inserts that were placed into culture wells in which MSCs were grown on the biomimetic Ti6Al4V substrates. The results show that biomimetic Ti6Al4V surface properties induce MSCs to produce factors within 7 days of culture that stimulate MSCs not in contact with the surface to exhibit an osteoblast phenotype via endogenous BMP2 acting in a paracrine signaling manner.
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Affiliation(s)
- Michael B. Berger
- Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA, USA
| | - Kyla B. Bosh
- Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA, USA
| | - Thomas W. Jacobs
- Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA, USA
| | - D. Joshua Cohen
- Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA, USA
| | - Zvi Schwartz
- Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA, USA;,Department of Periodontology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
| | - Barbara D. Boyan
- Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA, USA;,Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Georgia Institute of Technology, Atlanta, GA, USA
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Son HJ, Choi SH, Lee MK, Kang CN. Efficacy and safety of Escherichia coli-derived recombinant human bone morphogenetic protein-2 in additional lumbar posterolateral fusion: minimum 1-year follow-up. Spine J 2021; 21:1340-1346. [PMID: 33848691 DOI: 10.1016/j.spinee.2021.04.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 03/26/2021] [Accepted: 04/06/2021] [Indexed: 02/03/2023]
Abstract
BACKGROUND CONTEXT Recombinant human bone morphogenetic protein-2 (BMP-2) is the growth factor with the most striking osteoinductive performance in orthopedic operations; it is also able to induce heterotopic bone formation. However, there has been little clinical research on Escherichia coli-derived BMP-2 (E.BMP-2). PURPOSE To confirm the efficacy and safety of E.BMP-2 with a hydroxyapatite carrier when applied to one-sided posterolateral fusion (PLF) in addition to lumbar interbody fusion (LIF), and to measure the lower dose of E.BMP-2 ever reported achieving solid fusion. STUDY DESIGN/SETTING Retrospective case-control study PATIENT SAMPLE: A total of 121 patients who received surgery for one or two levels of fusion for lumbar degenerative spinal stenosis or spondylolisthesis from January 2009 to December 2019 were included. OUTCOME MEASURES Clinical and functional outcomes were evaluated using preoperative and final follow-up visual analogue scales for back pain (VAS-BP) and leg pain (VAS-LP), and Korean Oswestry disability index (K-ODI) scores. Fusion rates were evaluated by computed tomography at six months and one year after surgery. In addition, a subgroup analysis of group E according to number of fusion levels was conducted, and the fusion rates in the one-level and two-level fusion groups were compared. METHODS LIF and additional one-sided PLF was performed in all patients. They received autogenous iliac bone grafts (Group C, n=69) or 1mg of E.BMP-2 (Group E, n=52). RESULTS There were no significant differences between preoperative and final VAS-BP, VAS-LP and K-ODI. The PLF rate was 79.7% for Group C and 82.7% for Group E at postoperative six months, and 94.2% for Group C and 100% for Group E at postoperative one year (p =.679, 0.134, respectively). The LIF rate was 71.0% in Group C and 71.2% in Group E at six months after surgery, and 97.1% in Group C and 100% in Group E at one year (p =.987, 0.506, respectively). In terms of numbers of fusion levels in Group E, PLF rates at six months (p =.486) and one year after surgery were similar in the two groups, as were LIF rates at six months (p =.822) and one year after surgery. There were no cases of malignancy or radiculopathy in Group E during one-year of follow-up. CONCLUSIONS One milligram of E.BMP-2 is a safe and effective osteoinductive material in short-level lumbar PLF surgery.
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Affiliation(s)
- Hee Jung Son
- Department of Orthopaedic Surgery, Hanyang University College of Medicine, Seoul, Republic of Korea
| | - Sung Hoon Choi
- Department of Orthopaedic Surgery, Hanyang University College of Medicine, Seoul, Republic of Korea
| | - Myoung Keun Lee
- Department of Orthopaedic Surgery, Hanyang University College of Medicine, Seoul, Republic of Korea
| | - Chang-Nam Kang
- Department of Orthopaedic Surgery, Hanyang University College of Medicine, Seoul, Republic of Korea.
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Hyun SJ, Yoon SH, Kim JH, Oh JK, Lee CH, Shin JJ, Kang J, Ha Y. A Prospective, Multi-Center, Double-Blind, Randomized Study to Evaluate the Efficacy and Safety of the Synthetic Bone Graft Material DBM Gel with rhBMP-2 versus DBM Gel Used during the TLIF Procedure in Patients with Lumbar Disc Disease. J Korean Neurosurg Soc 2021; 64:562-574. [PMID: 33906347 PMCID: PMC8273782 DOI: 10.3340/jkns.2020.0331] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Accepted: 01/27/2021] [Indexed: 11/27/2022] Open
Abstract
Objective This study is to evaluate the efficacy and safety of demineralized bone matrix (DBM) gel versus DBM gel with recombinant human bone morphogenetic protein-2 (rhBMP-2) used in transforaminal lumbar interbody fusion (TLIF).
Methods This study was designed as a prospective, multi-center, double-blind method, randomized study. All randomized subjects underwent TLIF with DBM gel with rhBMP-2 group (40 patients) as an experimental group or DBM gel group (36 patients) as a control group. Post-operative observations were performed at 12, 24, and 48 weeks. The spinal fusion rate on computed tomography scans and X-rays films, Visual analog scale pain scores, Oswestry disability index and SF-36 quality of life (QOL) scores were used for the efficacy evaluation. The incidence rate of adverse device effects (ADEs) and serious adverse device effects (SADEs) were used for safety evaluation.
Results The spinal fusion rate at 12 weeks for the DBM gel with rhBMP-2 group was higher with 73.68% compared to 58.82% for the DBM gel group. The 24 and 48 weeks were 72.22% and 82.86% for the DBM gel with rhBMP-2 group and 78.79% and 78.13%, respectively, for the DBM gel group. However, there were no significant differences between two groups in the spinal fusion rate at 12, 24, and 48 weeks post-treatment (p=0.1817, p=0.5272, p=0.6247). There was no significant difference between the two groups in the incidence rate of ADEs (p=0.3836). For ADEs in the experimental group, ‘Pyrexia’ (5.00%) was the most common ADE, followed by ‘Hypesthesia’, ‘Paresthesia’, ‘Transient peripheral paralysis’, ‘Spondylitis’ and ‘Insomnia’ (2.50%, respectively). ADEs reported in control group included ‘Pyrexia’, ‘Chest discomfort’, ‘Pain’, ‘Osteoarthritis’, ‘Nephropathy toxic’, ‘Neurogenic bladder’, ‘Liver function analyses’ and ‘Urticaria’ (2.86%, respectively). There was no significant difference between the two groups in the incidence rate of SADEs (p=0.6594). For SADE in the experimental group, ‘‘Pyrexia’ and ‘Spondylitis’ were 2.50%. SADE reported in the control group included 'Chest discomfort’, ‘Osteoarthritis’ and ‘Neurogenic bladder’. All SADEs described above were resolved after medical treatment.
Conclusion This study demonstrated that the spinal fusion rates of DBM gel group and DBM gel with rhBMP-2 group were not significantly different. But, this study provides knowledge regarding the earlier postoperative effect of rhBMP-2 containing DBM gel and also supports the idea that the longer term follow-up results are essential to confirm the safety and effectiveness.
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Affiliation(s)
- Seung-Jae Hyun
- Department of Neurosurgery, Spine Center, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Seung Hwan Yoon
- Department of Neurosurgery, Inha University College of Medicine, Incheon, Korea
| | - Joo Han Kim
- Department of Neurosurgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea
| | - Jae Keun Oh
- Department of Neurosurgery, Spine Center, Hallym University Sacred Heart Hospital, Anyang, Korea
| | - Chang-Hyun Lee
- Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Jun Jae Shin
- Department of Neurosurgery, Yongin Severance Hospital, Spine and Spinal Cord Institute, Yonsei University College of Medicine, Yongin, Korea
| | - Jiin Kang
- Department of Neurosurgery, Yongin Severance Hospital, Spine and Spinal Cord Institute, Yonsei University College of Medicine, Yongin, Korea
| | - Yoon Ha
- Department of Neurosurgery, Spine and Spinal Cord Institute, Yonsei University College of Medicine, Seoul, Korea
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Lytle EJ, Lawless MH, Paik G, Tong D, Soo TM. The minimally effective dose of bone morphogenetic protein in posterior lumbar interbody fusion: a systematic review and meta-analysis. Spine J 2020; 20:1286-1304. [PMID: 32339767 DOI: 10.1016/j.spinee.2020.04.012] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Revised: 04/14/2020] [Accepted: 04/16/2020] [Indexed: 02/03/2023]
Abstract
BACKGROUND CONTENT The risks and benefits of recombinant human bone morphogenetic protein-2 (BMP) in posterior lumbar interbody fusion (PLIF) and transforaminal lumbar interbody fusion (TLIF) have been widely reported. However, the BMP dose associated with such reports varied widely. Additionally, data on the location of BMP placement on complications and fusion are lacking. PURPOSE To determine the minimally effective dose (MED) of BMP which results in optimal fusion rates while minimizing complications; to determine the effects of the location of BMP placement has on fusion rates and complications. STUDY DESIGN Systematic review and meta-analysis. STUDY SAMPLE Adult patients undergoing PLIF/TLIF for degenerative indications. OUTCOME MEASURES Rates of radiculitis, fusion, osteolysis, heterotopic bone formation, and new cancer diagnosis. METHODS PubMed, Embase, and Cochrane Database were used to identify studies published between January 1, 2011 and April 30, 2019 reporting BMP usage in adult patients who underwent PLIF/TLIF degenerative indications. A qualitative and quantitative synthesis was performed to evaluate the MED of BMP and the effect of location of BMP placement on fusion and complications. Complications were defined as osteolysis, heterotopic bone growth, radiculitis, and rate of new cancer diagnosis. Complications and fusion outcomes were each pooled according to commercially available BMP doses. Additionally, complications and fusion outcomes were pooled according to 4 location groups (interbody cage only, interbody cage + posterolateral gutter [PLG], cage + interspace, and interspace + PLG). Heterogeneity was assessed with Q and I2 statistics. RESULTS Twenty-two articles, totaling 2,729 patients were included. Sixteen studies reported fusion and 15 reported complications. Among fusion studies, the mean BMP/level ranged from 1.28 to 12 mg/level. Among complication studies, the mean BMP/level ranged from 6.7 to 23.6 mg/level. The pooled overall fusion rate was 94.0% (91.4-95.8 confidence intervals). There was no significant difference in fusion and complication rates between different BMP doses. Thirteen studies included data on the location of BMP placement with 1,823 patients. At each BMP location, the fusion rate was not significantly different across the dose ranges (1.28-12 mg/level). We found the fusion rate to be marginally higher in the interspace + PLG group compared to the other groups. When BMP was placed in the interbody cage there was a mild increase in the rate of osteolysis compared to other placement locations. CONCLUSIONS Fusion and complication rates did not differ significantly between different doses of BMP with the lowest MED for fusion as low as 1.28 mg/level. The location of BMP placement does not significantly affect fusion or complication rates.
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Affiliation(s)
- Evan J Lytle
- Division of Neurosurgery, Ascension Providence Hospital, College of Human Medicine, Michigan State University, Southfield, 16001 West Nine Mile Rd, Southfield, MI 48075, USA
| | - Michael H Lawless
- Division of Neurosurgery, Ascension Providence Hospital, College of Human Medicine, Michigan State University, Southfield, 16001 West Nine Mile Rd, Southfield, MI 48075, USA.
| | - Gijong Paik
- Division of Neurosurgery, Ascension Providence Hospital, College of Human Medicine, Michigan State University, Southfield, 16001 West Nine Mile Rd, Southfield, MI 48075, USA
| | - Doris Tong
- Division of Neurosurgery, Ascension Providence Hospital, College of Human Medicine, Michigan State University, Southfield, 16001 West Nine Mile Rd, Southfield, MI 48075, USA
| | - Teck M Soo
- Division of Neurosurgery, Ascension Providence Hospital, College of Human Medicine, Michigan State University, Southfield, 16001 West Nine Mile Rd, Southfield, MI 48075, USA
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Liu S, Wang Y, Liang Z, Zhou M, Chen C. Comparative Clinical Effectiveness and Safety of Bone Morphogenetic Protein Versus Autologous Iliac Crest Bone Graft in Lumbar Fusion: A Meta-analysis and Systematic Review. Spine (Phila Pa 1976) 2020; 45:E729-E741. [PMID: 31923133 PMCID: PMC7282484 DOI: 10.1097/brs.0000000000003372] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Accepted: 11/20/2019] [Indexed: 02/01/2023]
Abstract
STUDY DESIGN This is a systematic literature review and meta-analysis. OBJECTIVE We aimed to evaluate the efficacy and safety of recombinant human bone morphogenetic protein (RhBMP) and autologous iliac crest bone graft (ICBG) in lumbar fusion. SUMMARY OF BACKGROUND DATA RhBMP has been emphasized in lumbar fusion due to high fusion success rate. However, ICBG remains the criterion standard graft approach for lumbar fusion. The safety and effectiveness of rhBMP are controversial. METHODS Prospective randomized controlled trials were searched from PubMed, EMBASE, and Cochrane Central Register of Controlled Trails by using Medical Subject Headings terms "bone morphogenetic protein,' "bone transplantation,' and "spinal fusion.' Two independent investigators screened eligible studies, assessed the bias of original articles, extracted data including fusion success, Oswestry disability index improvement, improved short form 36 questionnaire scores, adverse events and re-operation, and a subgroup analysis. The GRADE approach was used to grade quality of evidence. RESULTS Twenty randomized controlled trials (2185 patients) met the inclusion criteria. There were higher fusion success rate (odds ratio [OR] 3.79, 95% confidence interval [CI] 1.88-7.63, P = 0.0002), better improvement of Oswestry Disability Index (mean difference 1.54, 95% CI 0.18-2.89, P = 0.03), and lower re-operation rate (OR 0.59, 95% CI 0.43-0.80, P = 0.0007) in rhBMP group. Heterogeneity was obvious in fusion success rate (I = 58%); hence, a subgroup analysis, based on protein type (rhBMP-2 or rhBMP-7), was performed, which suggested that only rhBMP-2 was better than ICBG for lumbar fusion. There was no difference in the incidence of adverse events between rhBMP and ICBG (OR 0.91, 95% CI 0.70-1.18, P = 0.47). CONCLUSION In lumbar fusion, rhBMP-2 exhibited a higher fusion success rate and reduced the risk of re-operation. No difference in complication rate is between rhBMP (rhBMP-2 and rhBMP-7) and ICBG. We suggest rhBMP especially rhBMP-2 as an effective substitute for ICBG for lumbar fusion. LEVEL OF EVIDENCE 1.
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Affiliation(s)
- Shichao Liu
- Department of Neurosurgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
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Niu S, Anastasio AT, Faraj RR, Rhee JM. Evaluation of Heterotopic Ossification After Using Recombinant Human Bone Morphogenetic Protein-2 in Transforaminal Lumbar Interbody Fusion: A Computed Tomography Review of 996 Disc Levels. Global Spine J 2020; 10:280-285. [PMID: 32313793 PMCID: PMC7160810 DOI: 10.1177/2192568219846074] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
STUDY DESIGN Retrospective cohort study. OBJECTIVES Reported incidences and complications of heterotopic ossification (HO) after using recombinant human bone morphogenetic protein-2 (rhBMP-2) in transforaminal lumbar interbody fusion (TLIF) have been inconclusive. This study was designed to evaluate both incidences of radiologic and symptomatic HO in a large series of TLIFs using rhBMP-2. METHODS A total of 996 disc levels in 927 consecutive TLIF patients were retrospectively evaluated at 6-month postoperative follow-up in a single surgical practice. Subjects were separated into the BMP group and the control group. Operative reports, pre- and postoperative medical records were reviewed. Computed tomography (CT) scans were analyzed and graded independently for ossification at each disc level of TLIF. RESULTS A total of 933 disc levels were in the BMP group, and 63 were in the control group. Six-month fusion rate of interbody was 92.5% in the BMP group, which was significantly higher in contrast to 71.4% in the control group (P < .001). The incidence of radiologic HO in the BMP group was 13.5%, which was significantly higher than 1.6% in the control group (P = .006). After controlling for basic demographics and comorbidities, the presence of radiologic HO was significantly associated with the use of rhBMP-2 (P = .026). However, only one case in the BMP group (0.11%) developed a symptomatic HO (mild-medium left buttock pain, treated nonsurgically) involving left foramen of L5-S1. CONCLUSIONS rhBMP-2 can be safely used in TLIF with regard to HO. There was a low rate of radiologic HO and minimal symptomatic HO, with high fusion rates at 6 months postoperative.
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Affiliation(s)
- Shuo Niu
- Emory University School of Medicine, Atlanta, GA, USA
| | | | | | - John M. Rhee
- Emory University School of Medicine, Atlanta, GA, USA
- John M. Rhee, MD, Department of Orthopaedic Surgery,
Emory University School of Medicine, Emory Orthopaedics & Spine Center, Atlanta, GA
30329, USA.
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Konar M, Sahoo H. Tyrosine mediated conformational change in bone morphogenetic protein – 2: Biophysical implications of protein – phytoestrogen interaction. Int J Biol Macromol 2020; 150:727-736. [DOI: 10.1016/j.ijbiomac.2020.02.113] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2019] [Revised: 02/10/2020] [Accepted: 02/11/2020] [Indexed: 01/18/2023]
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Rosenberg M, Shilo D, Galperin L, Capucha T, Tarabieh K, Rachmiel A, Segal E. Bone Morphogenic Protein 2-Loaded Porous Silicon Carriers for Osteoinductive Implants. Pharmaceutics 2019; 11:E602. [PMID: 31726775 PMCID: PMC6920899 DOI: 10.3390/pharmaceutics11110602] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Revised: 11/07/2019] [Accepted: 11/08/2019] [Indexed: 12/19/2022] Open
Abstract
Bone morphogenetic proteins (BMPs) are probably the most important growth factors in bone formation and healing. However, the utilization of BMPs in clinical applications is mainly limited due to the protein poor solubility at physiological pH, rapid clearance and relatively short biological half-life. Herein, we develop degradable porous silicon (PSi)-based carriers for sustained delivery of BMP-2. Two different loading approaches are examined, physical adsorption and covalent conjugation, and their effect on the protein loading and release rate is thoroughly studied. The entrapment of the protein within the PSi nanostructures preserved its bioactivity for inducing osteogenic differentiation of rabbit bone marrow mesenchymal stems cells (BM-MSCs). BM-MSCs cultured with the BMP-2 loaded PSi carriers exhibit a relatively high alkaline phosphatase (ALP) activity. We also demonstrate that exposure of MSCs to empty PSi (no protein) carriers generates some extent of differentiation due to the ability of the carrier's degradation products to induce osteoblast differentiation. Finally, we demonstrate the integration of these promising BMP-2 carriers within a 3D-printed patient-specific implant, constructed of poly(caprolactone) (PCL), as a potential bone graft for critical size bone defects.
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Affiliation(s)
- Michal Rosenberg
- Department of Biotechnology and Food Engineering, Technion—Israel Institute of Technology, Haifa 3200003, Israel; (M.R.); (L.G.)
| | - Dekel Shilo
- Department of Oral and Maxillofacial Surgery, Rambam Health Care Campus, Haifa 3109601, Israel; (D.S.); (T.C.); (K.T.); (A.R.)
- Bruce Rappaport Faculty of Medicine, Technion—Israel Institute of Technology, Haifa 3109601, Israel
| | - Leonid Galperin
- Department of Biotechnology and Food Engineering, Technion—Israel Institute of Technology, Haifa 3200003, Israel; (M.R.); (L.G.)
| | - Tal Capucha
- Department of Oral and Maxillofacial Surgery, Rambam Health Care Campus, Haifa 3109601, Israel; (D.S.); (T.C.); (K.T.); (A.R.)
| | - Karim Tarabieh
- Department of Oral and Maxillofacial Surgery, Rambam Health Care Campus, Haifa 3109601, Israel; (D.S.); (T.C.); (K.T.); (A.R.)
| | - Adi Rachmiel
- Department of Oral and Maxillofacial Surgery, Rambam Health Care Campus, Haifa 3109601, Israel; (D.S.); (T.C.); (K.T.); (A.R.)
- Bruce Rappaport Faculty of Medicine, Technion—Israel Institute of Technology, Haifa 3109601, Israel
| | - Ester Segal
- Department of Biotechnology and Food Engineering, Technion—Israel Institute of Technology, Haifa 3200003, Israel; (M.R.); (L.G.)
- Russell Berrie Nanotechnology Institute, Technion—Israel Institute of Technology, Haifa 3200003, Israel
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Kossover O, Cohen N, Lewis JA, Berkovitch Y, Peled E, Seliktar D. Growth Factor Delivery for the Repair of a Critical Size Tibia Defect Using an Acellular, Biodegradable Polyethylene Glycol-Albumin Hydrogel Implant. ACS Biomater Sci Eng 2019; 6:100-111. [PMID: 33463206 DOI: 10.1021/acsbiomaterials.9b00672] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Growth factor delivery using acellular matrices presents a promising alternative to current treatment options for bone repair in critical-size injuries. However, supra-physiological doses of the factors can introduce safety concerns that must be alleviated, mainly by sustaining delivery of smaller doses using the matrix as a depot. We developed an acellular, biodegradable hydrogel implant composed of poly(ethylene glycol) (PEG) and denatured albumin to be used for sustained delivery of bone morphogenic protein-2 (BMP2). In this study, poly(ethylene glycol)-albumin (PEG-Alb) hydrogels were produced and loaded with 7.7 μg/mL of recombinant human BMP2 (rhBMP2) to be tested for safety and performance in a critical-size long-bone defect, using a rodent model. The hydrogels were formed ex situ in a 5 mm long cylindrical mold of 3 mm diameter, implanted into defects made in the tibia of Sprague-Dawley rats and compared to non-rhBMP2 control hydrogels at 13 weeks following surgery. The hydrogels were also compared to the more established PEG-fibrinogen (PEG-Fib) hydrogels we have tested previously. Comprehensive in vitro characterization as well as in vivo assessments that include: histological analyses, including safety parameters (i.e., local tolerance and toxicity), assessment of implant degradation, bone formation, as well as repair tissue density using quantitative microCT analysis were performed. The in vitro assessments demonstrated similarities between the mechanical and release properties of the PEG-Alb hydrogels to those of the PEG-Fib hydrogels. Safety analysis presented good local tolerance in the bone defects and no signs of toxicity. A significantly larger amount of bone was detected at 13 weeks in the rhBMP2-treated defects as compared to non-rhBMP2 defects. However, no significant differences were noted in bone formation at 13 weeks when comparing the PEG-Alb-treated defects to PEG-Fib-treated defects (with or without BMP2). The study concludes that hydrogel scaffolds made from PEG-Alb containing 7.7 μg/mL of rhBMP2 are effective in accelerating the bridging of boney defects in the tibia.
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Affiliation(s)
- Olga Kossover
- Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa 3200003, Israel
| | - Natalie Cohen
- The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 320003, Israel
| | - Jacob A Lewis
- Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa 3200003, Israel
| | - Yulia Berkovitch
- Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa 3200003, Israel
| | - Eli Peled
- The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 320003, Israel.,Department of Orthopedic Surgery, Rambam Medical Center, Haifa 3200000, Israel
| | - Dror Seliktar
- Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa 3200003, Israel
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Minimally Effective Dose of Bone Morphogenetic Protein in Minimally Invasive Lumbar Interbody Fusions: Six Hundred Ninety Patients in a Dose-Finding Longitudinal Cohort Study. Spine (Phila Pa 1976) 2019; 44:989-995. [PMID: 30817730 DOI: 10.1097/brs.0000000000002993] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
STUDY DESIGN Retrospective longitudinal cohort. OBJECTIVE We sought to demonstrate the minimally effective bone morphogenetic protein (BMP) dose to achieve fusion in minimally invasive transforaminal lumbar interbody fusions. SUMMARY OF BACKGROUND DATA Multiple studies have been conducted, which used a wide range of BMP doses for lumbar fusions highlighting associated risks and benefits. There is, however, a paucity in the literature in determining the minimally effective dose. METHODS Consecutive patients who underwent transforaminal lumbar interbody fusion from 2009 to 2014 were reviewed. Fusion was determined by a combination of computed tomography and dynamic x-ray by independent radiologists. We used backward stepwise multiple logistic regression with fusion as the dependent variable to determine whether BMP dose/level was a significant predictor for fusion. To determine the minimally effective dose of BMP/level, separate logistic regressions for different BMP dose ranges and sensitivity analyses were used. A P value ≤0.025 was considered significant. RESULTS There were 1102 interspaces among 690 patients. Average BMP dose was 1.28 mg/level. Overall fusion was 95.2% with a mean follow-up of 19 months. BMP dose/level was a significant predictor for fusion. Odds of fusion increased by 2.02 when BMP dose range was increased from (0.16-1 mg/level) to (1.0-2 mg/level), but fusion odds did not increase when BMP dose increased to more than 2 mg/level. CONCLUSION BMP dose/level was a significant predictor for fusion. There was a significant increase in odds of fusion when BMP dose increased from 0.16 to 1 mg/level to 1.0 to 2 mg/level. No benefit from increasing the dose more than 2 mg/level was found, suggesting 1.0 mg/level to be the minimally effective BMP dose. LEVEL OF EVIDENCE 3.
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Sebastian AS, Wanderman NR, Currier BL, Pichelmann MA, Treder VM, Fogelson JL, Clarke MJ, Nassr AN. Prospective Evaluation of Radiculitis following Bone Morphogenetic Protein-2 Use for Transforaminal Interbody Arthrodesis in Spine Surgery. Asian Spine J 2019; 13:544-555. [PMID: 30866616 PMCID: PMC6680045 DOI: 10.31616/asj.2018.0277] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2018] [Accepted: 12/13/2018] [Indexed: 11/30/2022] Open
Abstract
Study Design Prospective observational cohort study. Purpose This study aims to evaluate the safety and efficacy of bone morphogenetic protein-2 (BMP-2) in transforaminal lumbar interbody fusion (TLIF) with regard to postoperative radiculitis. Overview of Literature Bone morphogenetic protein (BMP) is being used increasingly as an alternative to iliac crest autograft in spinal arthrodesis. Recently, the use of BMP in TLIF has been examined, but concerns exist that the placement of BMP close to the nerve roots may cause postoperative radiculitis. Furthermore, prospective studies regarding the use of BMP in TLIF are lacking. Methods This prospective study included 77 patients. The use of BMP-2 was determined individually, and demographic and operative characteristics were recorded. Leg pain was assessed using the Visual Analog Scale (VAS) for pain and the Sciatica Bothersome Index (SBI) with several secondary outcome measures. The outcome data were collected at each follow-up visit. Results Among the 77 patients, 29 were administered with BMP. Postoperative leg pain significantly improved according to VAS leg and SBI scores for the entire cohort, and no clinically significant differences were observed between the BMP and control groups. The VAS back, Oswestry Disability Index, and Short-Form 36 scores also significantly improved. A significantly increased 6-month fusion rate was noted in the BMP group (82.8% vs. 55.3%), but no significant differences in fusion rate were observed at the 12- and 24-month follow-up. Heterotopic ossification was observed in seven patients: six patients and one patient in the BMP and control groups, respectively (20.7% vs. 2.1%). However, no clinical effect was observed. Conclusions In this prospective observational trial, the use of BMP in TLIF did not lead to significant postoperative radiculitis, as measured by VAS leg and SBI scores. Back pain and other functional outcome scores also improved, and no differences existed between the BMP and control groups. The careful use of BMP in TLIF appears to be both safe and effective.
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Affiliation(s)
| | | | | | | | - Vickie M Treder
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
| | | | | | - Ahmad N Nassr
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
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Minimally invasive transforaminal lumbar interbody fusion for dual-segment lower lumbar degenerative disease. Wideochir Inne Tech Maloinwazyjne 2018; 13:525-532. [PMID: 30524625 PMCID: PMC6280081 DOI: 10.5114/wiitm.2018.76151] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2018] [Accepted: 04/20/2018] [Indexed: 11/17/2022] Open
Abstract
Introduction Transforaminal lumbar interbody fusion (TLIF) has been widely used to treat degenerative lumbar diseases. The PIPELINE Access minimally invasive system allows reduction of the trauma to the patient during TLIF. Aim To present our preliminary experience with the minimally invasive TLIF (mTLIF) technique performed on the first 7 patients with dual-segment lower lumbar degenerative disease (DS-LLDD). Material and methods A retrospective analysis was performed on the first 7 patients with spondylolisthesis and foraminal stenosis operated upon between January 2011 and June 2013. All 7 patients underwent fusion at the L4-S1 level. Results The pedicle screws entered the spinal canal in 2 patients. No other intraoperative or postoperative complications occurred with the mTLIF technique. Improvement of the leading symptom in the early postoperative period (sciatica: 7/7, low back pain: 7/7) was achieved in all patients. The mean improvements in the visual analog scale scores for low back and leg pain were 5.1 and 5.7 points, respectively. The mean Oswestry Disability Index scores were 52% (range: 20–74%) before surgery and 27% (range: 10–48%) at the 3-month follow-up (mean improvement: 25%). The average hospital stay was reduced to 6 days. Conclusions Our initial experience suggests that the mTLIF technique is a viable method for treating DS-LLDD. Nevertheless, longer observations on larger groups of patients are needed to reliably evaluate the safety of the method and sustainability of the results.
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Sharmin F, O'Sullivan M, Malinowski S, Lieberman JR, Khan Y. Large scale segmental bone defect healing through the combined delivery of VEGF and BMP‐2 from biofunctionalized cortical allografts. J Biomed Mater Res B Appl Biomater 2018; 107:1002-1010. [DOI: 10.1002/jbm.b.34193] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2017] [Revised: 07/18/2017] [Accepted: 08/22/2017] [Indexed: 11/11/2022]
Affiliation(s)
- Farzana Sharmin
- Department of Materials Science and EngineeringUniversity of Connecticut Storrs Connecticut
- Institute for Regenerative EngineeringUConn Health Farmington Connecticut
| | | | - Seth Malinowski
- Department of Biomedical EngineeringUniversity of Connecticut Storrs Connecticut
| | - Jay R. Lieberman
- Department of Orthopedic SurgeryKeck School of Medicine of the University of Southern California California Los Angeles
| | - Yusuf Khan
- Department of Materials Science and EngineeringUniversity of Connecticut Storrs Connecticut
- Institute for Regenerative EngineeringUConn Health Farmington Connecticut
- Department of Orthopaedic SurgeryUConn Health Farmington Connecticut
- Department of Biomedical EngineeringUniversity of Connecticut Storrs Connecticut
- UConn Musculoskeletal Institute Farmington Connecticut
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Parajón A, Alimi M, Navarro-Ramirez R, Christos P, Torres-Campa JM, Moriguchi Y, Lang G, Härtl R. Minimally Invasive Transforaminal Lumbar Interbody Fusion: Meta-analysis of the Fusion Rates. What is the Optimal Graft Material? Neurosurgery 2018; 81:958-971. [PMID: 28419312 DOI: 10.1093/neuros/nyx141] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2015] [Accepted: 02/28/2017] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is an increasingly popular procedure with several potential advantages over traditional open TLIF. OBJECTIVE The current study aimed to compare fusion rates of different graft materials used in MIS-TLIF, via meta-analysis of the published literature. METHODS A Medline search was performed and a database was created including patient's type of graft, clinical outcome, fusion rate, fusion assessment modality, and duration of follow-up. Meta-analysis of the fusion rate was performed using StatsDirect software (StatsDirect Ltd, Cheshire, United Kingdom). RESULTS A total of 1533 patients from 40 series were included. Fusion rates were high, ranging from 91.8% to 99%. The imaging modalities used to assess fusion were computed tomography scans (30%) and X-rays (70%). Comparison of all recombinant human bone morphogenetic protein (rhBMP) series with all non-rhBMP series showed fusion rates of 96.6% and 92.5%, respectively. The lowest fusion rate was seen with isolated use of autologous local bone (91.8%). The highest fusion rate was observed with combination of autologous local bone with bone extender and rhBMP (99.1%). The highest fusion rate without the use of BMP was seen with autologous local bone + bone extender (93.1%). The reported complication rate ranged from 0% to 35.71%. Clinical improvement was observed in all studies. CONCLUSION Fusion rates are generally high with MIS-TLIF regardless of the graft material used. Given the potential complications of iliac bone harvesting and rhBMP, use of other bone graft options for MIS-TLIF is reasonable. The highest fusion rate without the use of rhBMP was seen with autologous local bone plus bone extender (93.1%).
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Affiliation(s)
- Avelino Parajón
- Department of Neurological Surgery, Weill Cornell Brain and Spine Center, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, New York
| | - Marjan Alimi
- Department of Neurological Surgery, Weill Cornell Brain and Spine Center, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, New York
| | - Rodrigo Navarro-Ramirez
- Department of Neurological Surgery, Weill Cornell Brain and Spine Center, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, New York
| | - Paul Christos
- Department of Statistics, Weill Cornell Medicine, New York, New York
| | - Jose M Torres-Campa
- Department of Neurological Surgery, Weill Cornell Brain and Spine Center, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, New York
| | - Yu Moriguchi
- Department of Neurological Surgery, Weill Cornell Brain and Spine Center, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, New York
| | - Gernot Lang
- Department of Neurological Surgery, Weill Cornell Brain and Spine Center, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, New York.,Department of Orthopedics and Trauma Surgery, Medical Center - Albert-Ludwigs-University of Freiburg, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Germany
| | - Roger Härtl
- Department of Neurological Surgery, Weill Cornell Brain and Spine Center, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, New York
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Hoppe S, Albers CE, Elfiky T, Deml MC, Milavec H, Bigdon SF, Benneker LM. First Results of a New Vacuum Plasma Sprayed (VPS) Titanium-Coated Carbon/PEEK Composite Cage for Lumbar Interbody Fusion. J Funct Biomater 2018. [PMID: 29538285 PMCID: PMC5872109 DOI: 10.3390/jfb9010023] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
The aim of this study was to assess the performance of a new vacuum plasma sprayed (VPS) titanium-coated carbon/polyetheretherketone (PEEK) cage under first use clinical conditions. Forty-two patients who underwent a one or two segment transforaminal lumbar interbody fusion (TLIF) procedure with a new Ca/PEEK composite cage between 2012 and 2016 were retrospectively identified by an electronic patient chart review. Fusion rates (using X-ray), patient’s satisfaction, and complications were followed up for two years. A total of 90.4% of the patients were pain-free and satisfied after a follow up (FU) period of 29.1 ± 9 (range 24–39) months. A mean increase of 3° in segmental lordosis in the early period (p = 0.002) returned to preoperative levels at final follow-ups. According to the Bridwell classification, the mean 24-month G1 fusion rate was calculated as 93.6% and the G2 as 6.4%. No radiolucency around the cage (G3) or clear pseudarthrosis could be seen (G4). In conclusion, biological properties of the inert, hydrophobic surface, which is the main disadvantage of PEEK, can be improved with VPS titanium coating, so that the carbon/PEEK composite cage, which has great advantages in respect of biomechanical properties, can be used safely in TLIF surgery. High fusion rates, good clinical outcome, and low implant-related complication rates without the need to use rhBMP or additional iliac bone graft can be achieved.
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Affiliation(s)
- Sven Hoppe
- Department of Orthopedic Surgery and Traumatology, Spine Unit, Inselspital, Bern University Hospital, Bern 3010, Switzerland.
| | - Christoph E Albers
- Department of Orthopedic Surgery and Traumatology, Spine Unit, Inselspital, Bern University Hospital, Bern 3010, Switzerland.
| | - Tarek Elfiky
- Spine Surgery Unit, El-Hadra University Hospital, Alexandria University, Alexandria 21561, Egypt.
| | - Moritz C Deml
- Department of Orthopedic Surgery and Traumatology, Spine Unit, Inselspital, Bern University Hospital, Bern 3010, Switzerland.
| | - Helena Milavec
- Department of Orthopedic Surgery and Traumatology, Spine Unit, Inselspital, Bern University Hospital, Bern 3010, Switzerland.
| | - Sebastian F Bigdon
- Department of Orthopedic Surgery and Traumatology, Spine Unit, Inselspital, Bern University Hospital, Bern 3010, Switzerland.
| | - Lorin M Benneker
- Department of Orthopedic Surgery and Traumatology, Spine Unit, Inselspital, Bern University Hospital, Bern 3010, Switzerland.
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Khan TR, Pearce KR, McAnany SJ, Peters CM, Gupta MC, Zebala LP. Comparison of transforaminal lumbar interbody fusion outcomes in patients receiving rhBMP-2 versus autograft. Spine J 2018; 18:439-446. [PMID: 28822825 DOI: 10.1016/j.spinee.2017.08.230] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2017] [Revised: 06/20/2017] [Accepted: 08/09/2017] [Indexed: 02/03/2023]
Abstract
BACKGROUND CONTEXT Recombinant human bone morphogenetic protein 2 (rhBMP-2) plays a pivotal role in complex spine surgery. Despite its limited approval, the off-label use of rhBMP-2 is prevalent, particularly in transforaminal lumbar interbody fusions (TLIFs). PURPOSE To determine the effectiveness and safety of rhBMP-2 use in TLIF procedures versus autograft. STUDY DESIGN Retrospective cohort study. PATIENT SAMPLE Patients older than 18 years undergoing spine surgery for lumbar degenerative spine disease at a single academic institution. OUTCOME MEASURES Clinical outcome was determined according to patient records. Radiographic outcome was determined according to plain X-rays and computed tomography (CT). METHODS A retrospective study from 1997 to 2014 was conducted on 191 adults undergoing anterior-posterior instrumented spinal fusion with TLIF at a single academic institution. Patient data were gathered from operative notes, follow-up clinic notes, and imaging studies to determine complications and fusion rates. One hundred eighty-seven patients fit the criteria, which included patients with a minimum of one TLIF, and had a minimum 2-year radiographic and clinical follow-up. Patients were further classified into a BMP group (n=83) or non-BMP group (n=104). Three logistic regression models were run using rhBMP-2 exposure as the independent variable. The respective outcome variables were TLIF-related complications (radiculitis, seroma, osteolysis, and ectopic bone), surgical complications, and all complications. RESULTS Bone morphogenetic protein (n=83) and non-BMP (n=104) groups had similar baseline demographics (sex, diabetes, pre-existing cancer). On average, the BMP and non-BMP groups were similarly aged (51.9 vs. 47.9 years, p>.05), but the BMP group had a shorter follow-up time (3.03 vs. 4.06 years; p<.001) and fewer smokers (8 vs. 21 patients; p<.048). The fusion rate for the BMP and non-BMP groups was 92.7% and 92.3%, respectively. The pseudoarthrosis rate was 7.5% (14 of 187 patients). Radiculitis was observed in seven patients in the BMP group (8.4%) and two patients in the non-BMP group (1.9%). Seroma was observed in two patients in the BMP group (2.4%) and none in the non-BMP group. No deep infections were observed in the BMP group, and in one patient in the non-BMP group (0.96%). Although patients exposed to BMP were at a significantlygreater risk of developing radiculitis and seroma (odds ratio [OR]=4.53, confidence interval [CI]=1.42-14.5), BMP exposure was not a significant predictor of surgical complications (OR=0.32, CI=0.10-1.00) or overall complications (OR=1.11, CI=0.53-2.34). The outcome of TLIF-related complications was too rare and the confidence interval too wide for practical significance of the first model. CONCLUSION Evidence supports the hypothesis that off-label use of rhBMP-2 in TLIF procedures is relatively effective for achieving bone fusion at rates similar to patients receiving autograft. Patients exhibited similar complication rates between the two groups, with the BMP group exhibiting slightly higher rates of radiculitis and seroma.
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Affiliation(s)
- Taleef R Khan
- Department of Orthopedics-Spine Surgery, Washington University in Saint Louis, Saint Louis, MO, USA
| | - Kalin R Pearce
- BJC Institute of Health, Washington University's Brown School of Social Work, 425 S. Euclid Ave, Suite 5505, St. Louis, MO 63110, USA
| | - Steven J McAnany
- Department of Orthopedics-Spine Surgery, Washington University in Saint Louis, Saint Louis, MO, USA
| | - Colleen M Peters
- Department of Orthopedics-Spine Surgery, Washington University in Saint Louis, Saint Louis, MO, USA
| | - Munish C Gupta
- Department of Orthopedics-Spine Surgery, Washington University in Saint Louis, Saint Louis, MO, USA
| | - Lukas P Zebala
- Department of Orthopedics-Spine Surgery, Washington University in Saint Louis, Saint Louis, MO, USA.
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Arzeno A, Wang T, Huddleston JI. Abundant heterotopic bone formation following use of rhBMP-2 in the treatment of acetabular bone defects during revision hip arthroplasty. Arthroplast Today 2018; 4:162-168. [PMID: 29896546 PMCID: PMC5994604 DOI: 10.1016/j.artd.2017.12.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2017] [Revised: 12/12/2017] [Accepted: 12/13/2017] [Indexed: 01/28/2023] Open
Abstract
Revision hip arthroplasty in the setting of periacetabular bone loss presents a significant challenge, as options for restoring bone loss are limited. Recombinant human bone morphogenetic protein-2 may offer a solution by promoting bone growth to restore bone stock before implant reimplantation. Here we present a case of a patient with a periprosthetic acetabulum fracture, resulting in pelvic discontinuity as the result of significant periacetabular bone loss. Using a staged approach, periacetabular bone stock was nearly entirely reconstituted using recombinant BMPs and allograft, which resulted in stable fixation, but with abundant heterotopic bone formation. Recombinant BMP-2 offers a useful tool for restoring bone stock in complex hip arthroplasty revision cases with periacetabular bone loss; however, caution must be used as overabundant bone growth as heterotopic ossification may result.
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Affiliation(s)
- Alexander Arzeno
- Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, CA, USA
| | - Tim Wang
- Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, CA, USA
| | - James I Huddleston
- Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, CA, USA
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Zhu X, Zhang H, Zhang X, Ning C, Wang Y. In vitro study on the osteogenesis enhancement effect of BMP-2 incorporated biomimetic apatite coating on titanium surfaces. Dent Mater J 2017; 36:677-685. [PMID: 28883298 DOI: 10.4012/dmj.2016-189] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
To fabricate a sustained-release delivery system of bone morphogenetic protein (BMP-2) on titanium surface, explore the effect of BMP-2 concentration on the loading/release behavior of BMP-2 and evaluate the cell compatibility of the system in vitro, pure titanium specimens were immersed into supersaturated calcium phosphate solutions (SCP) containing 4 different concentrations of BMP-2: 0, 50, 100, 200 and 400 ng/mL. Biomimetic calcium phosphate coating was formed on titanium surface and BMP-2 was incorporated into the coating through co-deposition. The release profile of BMP-2 suggested that BMP-2 were delivered sustainably up to 20 days. CCK-8 and ALP assay showed that 200 group and 400 ng/mL BMP-2 group have significant effect on promoting MC3T3-E1 cell proliferation and differentiation. The BMP-2 incorporated into the hybrid coating released in a sustained manner and significantly promoted the proliferation and differentiation of MC3T3-E1 on the titanium surface.
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Affiliation(s)
- Xiaojing Zhu
- Department of Prosthodontics, Guanghua School of Stomatology & Hospital of Stomatology, Guangdong Key Laboratory of Stomatology, Sun Yat-sen University
| | - Hui Zhang
- Department of Prosthodontics, Guanghua School of Stomatology & Hospital of Stomatology, Guangdong Key Laboratory of Stomatology, Sun Yat-sen University
| | - Xinchun Zhang
- Department of Prosthodontics, Guanghua School of Stomatology & Hospital of Stomatology, Guangdong Key Laboratory of Stomatology, Sun Yat-sen University
| | - Chengyun Ning
- School of Material Science and Engineering, South China University of Technology
| | - Yan Wang
- Department of Prosthodontics, Guanghua School of Stomatology & Hospital of Stomatology, Guangdong Key Laboratory of Stomatology, Sun Yat-sen University
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Abstract
STUDY DESIGN Retrospective database review. OBJECTIVE OF THE STUDY The objective of the study was to assess whether bone morphogenetic protein (BMP) decreases the risk of revision surgery in elderly patients treated with 3-7 level or 8 or greater level fusions. SUMMARY OF BACKGROUND DATA Revision spine surgery in the elderly is a complex undertaking, highlighting the importance of discovering methods to decrease the risk of repeat procedures. The role of BMP in modulating risk of future revision surgery is not well studied in the elderly. MATERIALS AND METHODS The PearlDiver database (2005-2012) was queried for elderly adult spinal deformity patients treated with a primary thoracolumbar posterolateral fusion of 3 or more levels. To compare how BMP modifies revision surgery rates in 3-7 level versus 8 level or greater fusions, 4 mutually exclusive cohorts were created and matched to one another: 1043 patients treated with 8 or greater level fusions with BMP; 1111 patients with 8 or greater level fusions without BMP; 2813 patients with 3-7 level fusions with BMP; and 4770 patients with 3-7 level fusions without BMP. Revision and complication rates were compared. Complications included seroma formation, heterotopic ossification, and postoperative neuritis within 90 days. RESULTS Patients treated with BMP during an 8 or greater level fusion were significantly less likely to require a revision surgery than matched controls (relative risk, 0.75, P=0.015). BMP use was not associated with a decreased risk of revision surgery in 3-7 level fusions (relative risk, 0.89, P=0.20). Patients treated with BMP during 3-7 level fusions were significantly less likely to develop any of the assessed complications (P=0.02). There were no other significant differences in pairwise comparisons of subcohorts of each of the fusion lengths. CONCLUSIONS BMP use decreases revision rates in elderly adult spinal deformity patients treated with 8 or greater level fusions, but not in those treated with 3-7 level fusions. LEVEL OF EVIDENCE Level III.
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Lykissas M, Gkiatas I. Use of recombinant human bone morphogenetic protein-2 in spine surgery. World J Orthop 2017; 8:531-535. [PMID: 28808623 PMCID: PMC5534401 DOI: 10.5312/wjo.v8.i7.531] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2016] [Revised: 02/05/2017] [Accepted: 04/20/2017] [Indexed: 02/06/2023] Open
Abstract
Bone morphogenetic proteins are osteoinductive factors which have gained popularity in orthopaedic surgery and especially in spine surgery. The use of recombinant human bone morphogenetic protein-2 has been officially approved by the United States Food and Drug Administration only for single level anterior lumbar interbody fusion, nevertheless it is widely used by many surgeons with off-label indications. Despite advantages in bone formation, its use still remains a controversial issue and several complications have been described by authors who oppose their wide use.
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Radiographic and Clinical Outcome of Silicate-substituted Calcium Phosphate (Si-CaP) Ceramic Bone Graft in Spinal Fusion Procedures. Clin Spine Surg 2017; 30:E845-E852. [PMID: 27623299 DOI: 10.1097/bsd.0000000000000432] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
STUDY DESIGN Retrospective cohort study. OBJECTIVE To evaluate the radiographic and clinical outcome of silicate-substituted calcium phosphate (Si-CaP), utilized as a graft substance in spinal fusion procedures. SUMMARY OF BACKGROUND DATA Specific properties of Si-CaP provide the graft with negative surface charge that can result in a positive effect on the osteoblast activity and neovascularization of the bone. METHODS This study included those patients who underwent spinal fusion procedures between 2007 and 2011 in which Si-CaP was used as the only bone graft substance. Fusion was evaluated on follow-up CT scans. Clinical outcome was assessed using Oswestry Disability Index, Neck Disability Index, and the visual analogue scale (VAS) for back, leg, neck, and arm pain. RESULTS A total of 234 patients (516 spinal fusion levels) were studied. Surgical procedures consisted of 57 transforaminal lumbar interbody fusion, 49 anterior cervical discectomy and fusion, 44 extreme lateral interbody fusion, 30 posterior cervical fusions, 19 thoracic fusion surgeries, 17 axial lumbar interbody fusions, 16 combined anterior and posterior cervical fusions, and 2 anterior lumbar interbody fusion. At a mean radiographic follow-up of 14.2±4.3 months, fusion was found to be present in 82.9% of patients and 86.8% of levels. The highest fusion rate was observed in the cervical region. At the latest clinical follow-up of 21.7±14.2 months, all clinical outcome parameters showed significant improvement. The Oswestry Disability Index improved from 45.6 to 13.3 points, Neck Disability Index from 40.6 to 29.3, VAS back from 6.1 to 3.5, VAS leg from 5.6 to 2.4, VAS neck from 4.7 to 2.7, and VAS arm from 4.1 to 1.7. Of 7 cases with secondary surgical procedure at the index level, the indication for surgery was nonunion in 3 patients. CONCLUSIONS Si-CaP is an effective bone graft substitute. At the latest follow-up, favorable radiographic and clinical outcome was observed in the majority of patients. LEVEL OF EVIDENCE Level-III.
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Neuroforaminal Bone Growth Following Minimally Invasive Transforaminal Lumbar Interbody Fusion With BMP: A Computed Tomographic Analysis. Clin Spine Surg 2017. [PMID: 28632565 DOI: 10.1097/bsd.0000000000000347] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
STUDY DESIGN Computed tomographic analysis. OBJECTIVE To identify radiographic patterns of symptomatic neuroforaminal bone growth (NFB) in patients who have undergone a single-level minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) augmented with bone morphogenetic proteins (BMP) utilizing computed tomography (CT). SUMMARY OF BACKGROUND DATA BMP induces osteoblast differentiation leading to new bone formation. The association of BMP utilization and heterotopic bone formation after an MIS-TLIF has been described. However, studies have been limited in their patient population and details regarding diagnosis and treatment of NFB. MATERIALS AND METHODS Postoperative CT scans of the symptomatic and asymptomatic patients were analyzed to identify patterns of heterotopic bone growth on axial and sagittal views. The area of bone growth at the disk level, lateral recess, adjacent foramen, and retrovertebral area were measured. Mann-Whitney U test was used to compare the areas of bone growth between cohorts. RESULTS Postoperative CT images between 18 symptomatic and 13 asymptomatic patients were compared. On axial views, the symptomatic patients demonstrated greater areas of bone growth at the disk level (164.0±92.4 vs. 77.0±104.9 mm), and lateral recess (69.6±70.5 and 5.9±12.5 mm) as well as in the total cross-sectional area (290.3±162.1 vs. 119.4±115.6 mm). On sagittal imaging, the mean bone growth at the subarticular level (148.7±185.1 vs. 35.8±37.4 mm) and the total cross-sectional area (298.4±324.4 vs. 85.8±76.3 mm) were greater in symptomatic patients (P<0.01). Amount of BMP utilized and operative levels were no different between cohorts. CONCLUSIONS The findings of the present study suggest that an anatomic association exists between recalcitrant postoperative radiculopathy and NFB following an MIS-TLIF with BMP. Increased total bone growth as measured on serial axial and sagittal sections was associated with postoperative radiculopathy. The association between radiculopathy and the extension of BMP-induced bone growth toward the traversing nerve root appeared the most significant.
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Zigdon-Giladi H, Elimelech R, Michaeli-Geller G, Rudich U, Machtei EE. Safety profile and long-term engraftment of human CD31 + blood progenitors in bone tissue engineering. Cytotherapy 2017; 19:895-908. [PMID: 28495397 DOI: 10.1016/j.jcyt.2017.03.079] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2016] [Revised: 03/23/2017] [Accepted: 03/24/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUND Endothelial progenitor cells (EPCs) participate in angiogenesis and induce favorable micro-environments for tissue regeneration. The efficacy of EPCs in regenerative medicine is extensively studied; however, their safety profile remains unknown. Therefore, our aims were to evaluate the safety profile of human peripheral blood-derived EPCs (hEPCs) and to assess the long-term efficacy of hEPCs in bone tissue engineering. METHODS hEPCs were isolated from peripheral blood, cultured and characterized. β tricalcium phosphate scaffold (βTCP, control) or 106 hEPCs loaded onto βTCP were transplanted in a nude rat calvaria model. New bone formation and blood vessel density were analyzed using histomorphometry and micro-computed tomography (CT). Safety of hEPCs using karyotype analysis, tumorigenecity and biodistribution to target organs was evaluated. RESULTS On the cellular level, hEPCs retained their karyotype during cell expansion (seven passages). Five months following local hEPC transplantation, on the tissue and organ level, no inflammatory reaction or dysplastic change was evident at the transplanted site or in distant organs. Direct engraftment was evident as CD31 human antigens were detected lining vessel walls in the transplanted site. In distant organs human antigens were absent, negating biodistribution. Bone area fraction and bone height were doubled by hEPC transplantation without affecting mineral density and bone architecture. Additionally, local transplantation of hEPCs increased blood vessel density by nine-fold. CONCLUSIONS Local transplantation of hEPCs showed a positive safety profile. Furthermore, enhanced angiogenesis and osteogenesis without mineral density change was found. These results bring us one step closer to first-in-human trials using hEPCs for bone regeneration.
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Affiliation(s)
- Hadar Zigdon-Giladi
- Department of Periodontology, School of Graduate Dentistry, Rambam Health Care Campus, Haifa, Israel; Research Institute for Bone Repair, Rambam Health Care Campus, Haifa, Israel; The Rappaport Family Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
| | - Rina Elimelech
- Department of Periodontology, School of Graduate Dentistry, Rambam Health Care Campus, Haifa, Israel; Research Institute for Bone Repair, Rambam Health Care Campus, Haifa, Israel
| | - Gal Michaeli-Geller
- Research Institute for Bone Repair, Rambam Health Care Campus, Haifa, Israel
| | - Utai Rudich
- Orthopedic Department, Rambam Health Care Campus, Haifa, Israel
| | - Eli E Machtei
- Department of Periodontology, School of Graduate Dentistry, Rambam Health Care Campus, Haifa, Israel; Research Institute for Bone Repair, Rambam Health Care Campus, Haifa, Israel; The Rappaport Family Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
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Hindoyan K, Tilan J, Buser Z, Cohen JR, Brodke DS, Youssef JA, Park JB, Yoon ST, Meisel HJ, Wang JC. A Retrospective Analysis of Complications Associated With Bone Morphogenetic Protein 2 in Anterior Lumbar Interbody Fusion. Global Spine J 2017; 7:148-153. [PMID: 28507884 PMCID: PMC5415156 DOI: 10.1177/2192568217694010] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
STUDY DESIGN Retrospective review. OBJECTIVE The aim of our study was to quantify the frequency of complications associated with recombinant human bone morphogenetic protein 2 (rhBMP-2) use in anterior lumbar interbody fusion (ALIF). METHODS The orthopedic subset of the Medicare database (PearlDiver) was queried for this retrospective cohort study using International Statistical Classification of Diseases 9 (ICD-9) and Current Procedure Terminology (CPT) codes for ALIF procedures with and without rhBMP-2 between 2005 and 2010. Frequencies of complications and reoperations were then identified within 1 year from the index procedure. Complications included reoperations, pulmonary embolus, deep vein thrombosis, myocardial infarction, nerve-related complications, incision and drainage procedures, wound, sepsis, pneumonia, urinary tract infections, respiratory, heterotopic ossification, retrograde ejaculation, radiculopathy, and other medical complications. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the statistical significance. RESULTS We identified a total of 41 865 patients who had an ALIF procedure. A total of 14 384 patients received rhBMP-2 while 27 481 did not. Overall, 6016 (41.8%) complications within 1 year from surgery were noted within the group who received rhBMP-2 and 12 950 (47.1%) complications within 1 year from surgery were recorded in those who did not receive rhBMP-2 (OR = 0.81, CI = 0.77-0.84). Overall, exposure to rhBMP-2 was associated with significantly decreased odds of complications with exception to reoperation rates (0.9% rhBMP-2 vs 1.0% no rhBMP-2; OR = 0.88, CI = 0.71-1.09) and radiculopathy (4.4% rhBMP-2 vs 4.3% no rhBMP-2; OR = 1.02, CI = 0.93-1.13). CONCLUSIONS The use of rhBMP-2 in patients undergoing ALIF procedure was associated with a significantly decreased rate of complications. Further studies are needed to elucidate a true incidence of complication.
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Affiliation(s)
| | - Justin Tilan
- University of Southern California, Los Angeles, CA, USA
| | - Zorica Buser
- University of Southern California, Los Angeles, CA, USA,Zorica Buser, Department of Orthopaedic Surgery, Keck School of Medicine, University of Southern California, Hoffman Medical Research Center HMR 710, 2011 Zonal Ave, Los Angeles, CA 90033, USA.
| | | | | | - Jim A. Youssef
- Durango Orthopedic Associates, P.C./Spine Colorado, Durango, CO, USA
| | - Jong-Beom Park
- Uijongbu St. Mary’s Hospital, The Catholic University of Korea, Uijongbu, Korea
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Nguyen V, Meyers CA, Yan N, Agarwal S, Levi B, James AW. BMP-2-induced bone formation and neural inflammation. J Orthop 2017; 14:252-256. [PMID: 28367006 DOI: 10.1016/j.jor.2017.03.003] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2016] [Accepted: 03/12/2017] [Indexed: 12/20/2022] Open
Abstract
Bone morphogenetic protein-2 (BMP-2), a potent osteoinductive cytokine from the transforming growth factor beta (TGF-β) family, is currently the most commonly used protein-based bone graft substitute. Although clinical use of BMP-2 has significantly increased in recent years, its prominence has also highlighted various adverse events, including induction of inflammation. This review will elucidate the relationship between BMP-2 and inflammation, with an emphasis on peripheral nerve inflammation and its sequelae. As well, we review the potential additive roles of nerve released factors with BMP2 in the context of bone formation.
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Affiliation(s)
- Vi Nguyen
- Department of Pathology, Johns Hopkins University, 21205, United States
| | - Carolyn A Meyers
- Department of Pathology, Johns Hopkins University, 21205, United States
| | - Noah Yan
- Department of Pathology, Johns Hopkins University, 21205, United States
| | - Shailesh Agarwal
- Department of Surgery, University of Michigan, 48109, United States
| | - Benjamin Levi
- Department of Surgery, University of Michigan, 48109, United States
| | - Aaron W James
- Department of Pathology, Johns Hopkins University, 21205, United States
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Litrico S, Langlais T, Pennes F, Gennari A, Paquis P. Lumbar interbody fusion with utilization of recombinant human bone morphogenetic protein: a retrospective real-life study about 277 patients. Neurosurg Rev 2017; 41:189-196. [DOI: 10.1007/s10143-017-0834-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2016] [Revised: 01/29/2017] [Accepted: 02/20/2017] [Indexed: 11/28/2022]
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Feasibility of Percutaneous Posterolateral Spinal Fusion With Recombinant Bone Morphogenetic Protein-2 (rhBMP-2): A Comparison With Standard Methods Using an Animal Model Study. Clin Spine Surg 2017; 30:E138-E147. [PMID: 28207623 DOI: 10.1097/bsd.0b013e3182aa6860] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND CONTEXT The clinical application of recombinant bone morphogenetic protein in spinal surgery has been shown to be safe and effective. However, its use in minimally invasive spine surgery has been limited to anterior interbody fusion procedures. To date, no study has evaluated the feasibility of percutaneous posterolateral fusion in the spine utilizing recombinant bone morphogenetic protein-2 (rhBMP-2). PURPOSE To evaluate the feasibility of percutaneous posterolateral fusion in the spine utilizing rhBMP-2. STUDY DESIGN Animal study. METHODS This is an animal research model involving 32 New Zealand white rabbits stratified into 4 study groups: control, autogenous iliac crest bone graft (ICBG), demineralized bone matrix (DBM), and rhBMP-2 groups, with 8 study subjects per group. The rhBMP-2 group was subdivided into the open technique (right side) and the percutaneous technique groups (left side). Fusion was graded at 6 weeks and 3 months after plain radiography, computed tomography, and clinical assessment with the following grading system: grade A, no bone formation; grade B, non-bridging bone formation; grade C, fusion; and grade D, fusion with ectopic bone formation. RESULTS No fusion was noted in the placebo and the DBM groups. However, in the DBM group, bone formation occurred in 37.5% of the subjects. The rhBMP-2 group had a higher fusion rate compared with the ICBG group at 6 weeks and 3 months. The fusion rate for the ICBG, the rhBMP-2 (open), and the rhBMP-2 (percutaneous) groups were 37.5%, 87.5%, and 50.0% at 6 weeks and 50.0%, 100.0%, and 62.5% at 3 months, respectively. Ectopic bone formation occurred in 12.5% of the cases in the rhBMP-2 (percutaneous) group and in 25.0% of the cases in the rhBMP-2 (open) group. CONCLUSIONS Usage of rhBMP-2 is feasible for percutaneous posterolateral fusion of the lumbar spine in this animal model. However, a more precise delivery system might improve the fusion rate when the percutaneous technique is used. A significant rate of ectopic bone formation occurred when rhBMP-2 was used.
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Kang DG, Hsu WK, Lehman RA. Complications Associated With Bone Morphogenetic Protein in the Lumbar Spine. Orthopedics 2017; 40:e229-e237. [PMID: 27992640 DOI: 10.3928/01477447-20161213-06] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2015] [Accepted: 05/24/2016] [Indexed: 02/03/2023]
Abstract
Complications associated with the use of recombinant human bone morphogenetic protein in the lumbar spine include retrograde ejaculation, ectopic bone formation, vertebral osteolysis and subsidence, postoperative radiculitis, and hematoma and seroma. These complications are controversial and remain widely debated. This article discusses the reported complications and possible implications for the practicing spine surgeon. Understanding the complications associated with the use of recombinant human bone morphogenetic protein and the associated controversies allows for informed decision making by both the patient and the surgeon. [Orthopedics. 2017; 40(2):e229-e237.].
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Xie L, Wu WJ, Liang Y. Comparison between Minimally Invasive Transforaminal Lumbar Interbody Fusion and Conventional Open Transforaminal Lumbar Interbody Fusion: An Updated Meta-analysis. Chin Med J (Engl) 2017; 129:1969-86. [PMID: 27503024 PMCID: PMC4989430 DOI: 10.4103/0366-6999.187847] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/04/2022] Open
Abstract
Background: The previous studies agree that minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) has better function outcomes, less blood loss, and shorter hospital stay, when compared to open-TLIF. However, there are no significance differences on operative time, complication, and reoperation rate between the two procedures. This could be from less relative literatures and lower grade evidence. The further meta-analysis is needed with more and higher grade evidences to compare the above two TLIF procedures. Methods: Prospective and retrospective studies that compared open-TLIF and MIS-TLIF were identified by searching the Medline, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang, and VIP database (the literature search comprised Medical Subject Heading terms and key words or Emtree term). The retrieval time ranged from the date when the database was founded to January 2015. Pooled risk ratios (RRs) and weighted mean differences (WMDs) with 95% confidence intervals were calculated for the clinical outcomes and perioperative data. Results: Twenty-four studies (n = 1967 patients) were included in this review (n = 951, open-TLIF, n = 1016, MIS-TLIF). MIS-TLIF was associated with a significant decrease in the visual analog score (VAS)-back pain score (WMD = −0.44; P = 0.001), Oswestry Disabilities Index (WMD = −1.57; P = 0.005), early ambulation (WMD = −1.77; P = 0.0001), less blood loss (WMD = −265.59; P < 0.00001), and a shorter hospital stay (WMD = −1.89; P < 0.0001). However, there were no significant differences in the fusion rate (RR = 0.99; P = 0.34), VAS-leg pain (WMD = −0.10; P = 0.26), complication rate (RR = 0.84; P = 0.35), operation time (WMD = −5.23; P = 0.82), or reoperation rate (RR = 0.73; P = 0.32). Conclusions: MIS-TLIF resulted in a similar fusion rate with better functional outcome, less blood loss, shorter ambulation, and hospital stay; furthermore, it did not increase the complication or reoperation rate based on the existing evidence.
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Affiliation(s)
- Lei Xie
- Department of Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025; Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese-Western Medicine, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Wen-Jian Wu
- Department of Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025; Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese-Western Medicine, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Yu Liang
- Department of Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025; Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese-Western Medicine, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
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Felbaum DR, Ryan JE, Stemer AB, Anaizi AN. Bilateral Subaxial Rotational Vertebral Artery Occlusion in a Setting of a Prior Cervical Construct. World Neurosurg 2017; 97:762.e5-762.e10. [DOI: 10.1016/j.wneu.2016.08.120] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2016] [Revised: 08/27/2016] [Accepted: 08/30/2016] [Indexed: 11/28/2022]
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Bae HW, Patel VV, Sardar ZM, Badura JM, Pradhan BB, Seim HB, Turner AS, Toth JM. Transient Local Bone Remodeling Effects of rhBMP-2 in an Ovine Interbody Spine Fusion Model. J Bone Joint Surg Am 2016; 98:2061-2070. [PMID: 28002369 DOI: 10.2106/jbjs.16.00345] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a powerful osteoinductive morphogen capable of stimulating the migration of mesenchymal stem cells (MSCs) to the site of implantation and inducing the proliferation and differentiation of these MSCs into osteoblasts. Vertebral end-plate and vertebral body resorption has been reported after interbody fusion with high doses of rhBMP-2. In this study, we investigated the effects of 2 rhBMP-2 doses on peri-implant bone resorption and bone remodeling at 7 time points in an end-plate-sparing ovine interbody fusion model. METHODS Twenty-one female sheep underwent an end-plate-sparing discectomy followed by interbody fusion at L2-L3 and L4-L5 using a custom polyetheretherketone (PEEK) interbody fusion device. The PEEK interbody device was filled with 1 of 2 different doses of rhBMP-2 on an absorbable collagen sponge (ACS): 0.13 mg (1×) or 0.90 mg (7×). Bone remodeling and interbody fusion were assessed via high-resolution radiography and histological analyses at 1, 2, 3, 4, 8, 12, and 20 weeks postoperatively. RESULTS Peri-implant bone resorption peaked between 3 and 8 weeks in both the 1× and the 7× rhBMP-2/ACS-dose group. Osteoclastic activity and corresponding peri-implant bone resorption was dose-dependent, with moderate-to-marked resorption at the 7×-dose level and less resorption at the 1×-dose level. Both dose (p < 0.0007) and time (p < 0.0025) affected bone resorption significantly. Transient bone-resorption areas were fully healed by 12 weeks. Osseous bridging was seen at all but 1 spinal level at 12 and at 20 weeks. CONCLUSIONS In the ovine end-plate-sparing interbody fusion model, rhBMP-2 dose-dependent osteoclastic resorption is a transient phenomenon that peaks at 4 weeks postoperatively. CLINICAL RELEVANCE Using the U.S. Food and Drug Administration (FDA)-approved rhBMP-2 concentration and matching the volume of rhBMP-2/ACS with the volume of desired bone formation within the interbody construct may limit the occurrence of transient bone resorption.
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Affiliation(s)
- Hyun W Bae
- 1Spine Center, Department of Surgery (H.W.B.), Cedars-Sinai Medical Center (Z.M.S.), Los Angeles, California 2Department of Orthopaedic and Spine Surgery, University of Colorado Health Sciences Center, Aurora, Colorado 3Medtronic Sofamor Danek, Inc., Memphis, Tennessee 4Risser Orthopaedic Group, Pasadena, California 5Department of Clinical Sciences, Colorado State University, Fort Collins, Colorado 6Department of Orthopaedic Surgery, The Medical College of Wisconsin, Milwaukee, Wisconsin
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Agarwal S, Cholok D, Loder S, Li J, Breuler C, Chung MT, Sung HH, Ranganathan K, Habbouche J, Drake J, Peterson J, Priest C, Li S, Mishina Y, Levi B. mTOR inhibition and BMP signaling act synergistically to reduce muscle fibrosis and improve myofiber regeneration. JCI Insight 2016; 1:e89805. [PMID: 27942591 DOI: 10.1172/jci.insight.89805] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Muscle trauma is highly morbid due to intramuscular scarring, or fibrosis, and muscle atrophy. Studies have shown that bone morphogenetic proteins (BMPs) reduce muscle atrophy. However, increased BMP signaling at muscle injury sites causes heterotopic ossification, as seen in patients with fibrodysplasia ossificans progressiva (FOP), or patients with surgically placed BMP implants for bone healing. We use a genetic mouse model of hyperactive BMP signaling to show the development of intramuscular fibrosis surrounding areas of ectopic bone following muscle injury. Rapamycin, which we have previously shown to eliminate ectopic ossification in this model, also eliminates fibrosis without reducing osteogenic differentiation, suggesting clinical value for patients with FOP and with BMP implants. Finally, we use reporter mice to show that BMP signaling is positively associated with myofiber cross-sectional area. These findings underscore an approach in which 2 therapeutics (rapamycin and BMP ligand) can offset each other, leading to an improved outcome.
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Affiliation(s)
- Shailesh Agarwal
- Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan, USA
| | - David Cholok
- Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan, USA
| | - Shawn Loder
- Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan, USA
| | - John Li
- Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan, USA
| | - Christopher Breuler
- Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan, USA
| | - Michael T Chung
- Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan, USA
| | - Hsiao Hsin Sung
- Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan, USA
| | - Kavitha Ranganathan
- Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan, USA
| | - Joe Habbouche
- Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan, USA
| | - James Drake
- Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan, USA
| | - Joshua Peterson
- Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan, USA
| | - Caitlin Priest
- Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan, USA
| | - Shuli Li
- Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan, USA
| | - Yuji Mishina
- School of Dentistry, University of Michigan, Ann Arbor, Michigan, USA
| | - Benjamin Levi
- Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan, USA
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Owens RK, Djurasovic M, Crawford CH, Glassman SD, Dimar JR, Carreon LY. Impact of Surgical Approach on Clinical Outcomes in the Treatment of Lumbar Pseudarthrosis. Global Spine J 2016; 6:786-791. [PMID: 27853663 PMCID: PMC5110356 DOI: 10.1055/s-0036-1582390] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2016] [Accepted: 02/25/2016] [Indexed: 11/06/2022] Open
Abstract
Study Design Retrospective comparative cohort. Objective Pseudarthrosis following fusion for degenerative lumbar spine pathologies remains a substantial problem. Current data shows that patients who develop a pseudarthrosis have suboptimal outcomes. This study evaluates if treatment of pseudarthrosis can be affected by surgical approach. Methods Medical records of 63 female and 65 male patients (mean age 50.37) who were treated for nonunion following lumbar fusion were reviewed. Sixty patients underwent posterolateral fusion (PSF), 18 underwent PSF with transforaminal interbody fusion (TLIF), 32 underwent anterior and posterior spinal fusion (AP), and 24 underwent anterior lumbar interbody fusion (ALIF). Results Significant differences between the treatment groups were observed in length of stay (p = 0.000), blood loss (p = 0.000), and operative time (p = 0.000). In the AP fusion group, minimal clinically important difference (MCID) was reached in 47% of patients for back pain, 28% for leg pain, and 28% for Oswestry Disability Index (ODI). PSF had the highest percentage of patients reaching MCID for Short Form-36 (SF-36) physical composite score at 25%. ALIF and TLIF subgroups reached MCID for ODI in 17% of patients. Linear regression analysis showed that type of surgical approach did not impact change in ODI scores. Conclusion Although not statistically significant, the AP fusion group reached MCID more frequently in all outcomes except SF-36 Physical Component Summary. All surgical approaches examined for treatment of lumbar pseudarthrosis resulted in only poor to modest improvement in ODI. This result further emphasizes the importance of achieving a solid fusion with the index surgery.
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Affiliation(s)
- R. Kirk Owens
- Norton Leatherman Spine Center, Louisville, Kentucky, United States
| | | | | | | | - John R. Dimar
- Norton Leatherman Spine Center, Louisville, Kentucky, United States
| | - Leah Y. Carreon
- Norton Leatherman Spine Center, Louisville, Kentucky, United States,Address for correspondence Leah Y. Carreon, MD, MSc Norton Leatherman Spine Center210 East Gray Street, Suite 900, Louisville, KY 40202United States
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Villavicencio AT, Burneikiene S. RhBMP-2-induced radiculitis in patients undergoing transforaminal lumbar interbody fusion: relationship to dose. Spine J 2016; 16:1208-1213. [PMID: 27343729 DOI: 10.1016/j.spinee.2016.06.007] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2015] [Revised: 05/02/2016] [Accepted: 06/21/2016] [Indexed: 02/03/2023]
Abstract
BACKGROUND CONTEXT Recombinant human bone morphogenetic protein-2 (rhBMP-2) remains the primary synthetic osteoinductive material used in spinal fusion surgery today. The early inflammation reaction to rhBMP-2 manifesting with radicular symptoms has been previously reported in patients undergoing transforaminal lumbar interbody fusion (TLIF). There is a disagreement with regard to the factors affecting its occurrence and whether such symptoms are dose dependent. PURPOSE The purpose of this analysis was to determine the incidence of rhBMP-2-induced radiculitis and its relationship to dose. STUDY DESIGN/SETTING A retrospective cohort analysis was performed of the prospectively collected data. PATIENT SAMPLE All consecutive patients (n=204) who underwent one- or two-level TLIF and instrumented posterolateral fusion with an off-label rhBMP-2 use were included in this analysis. OUTCOME MEASURES The patients who developed new radicular symptoms after initial improvement postoperatively and had sterile fluid collections indicative of inflammatory process, or in the absence of any structural abnormalities that would explain these symptoms on imaging studies, were deemed to have rhBMP-2-induced radiculitis. METHODS Magnetic resonance imaging (MRI) scans were obtained for all patients who developed postoperative radicular symptoms. Correlations between the total rhBMP-2 dose, dose per spinal level, and incidence of radiculitis were evaluated while controlling for age, sex, number of TLIF levels, and surgeon. RESULTS The incidence of postoperative radiculitis was 11.3% (23 out of 204). The average total rhBMP-2 dose was 4.9 mg (range=2.1-12) and the average dose per spinal level was 3.8 mg (range=1.05-12). Logistic regression analysis did not identify any significant correlations between the rhBMP-2 doses and the incidence of radiculitis (p=.6). CONCLUSION The incidence of rhBMP-2-induced radiculitis in patients undergoing TLIF is quite high, but there were no dose-related correlations found. The study, however, cannot rule out a possibility that a larger variation in bone morphogenetic protein (BMP) doses could still be a factor in the development of rhBMP-2-associated radiculitis.
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Affiliation(s)
- Alan T Villavicencio
- Boulder Neurosurgical Associates, 4743 Arapahoe Ave, Suite 202, Boulder, CO 80303, USA; Justin Parker Neurological Institute, 4743 Arapahoe Ave, Suite 202, Boulder, CO 80303, USA
| | - Sigita Burneikiene
- Boulder Neurosurgical Associates, 4743 Arapahoe Ave, Suite 202, Boulder, CO 80303, USA; Justin Parker Neurological Institute, 4743 Arapahoe Ave, Suite 202, Boulder, CO 80303, USA.
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Kadam A, Millhouse PW, Kepler CK, Radcliff KE, Fehlings MG, Janssen ME, Sasso RC, Benedict JJ, Vaccaro AR. Bone substitutes and expanders in Spine Surgery: A review of their fusion efficacies. Int J Spine Surg 2016; 10:33. [PMID: 27909654 DOI: 10.14444/3033] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
STUDY DESIGN A narrative review of literature. OBJECTIVE This manuscript intends to provide a review of clinically relevant bone substitutes and bone expanders for spinal surgery in terms of efficacy and associated clinical outcomes, as reported in contemporary spine literature. SUMMARY OF BACKGROUND DATA Ever since the introduction of allograft as a substitute for autologous bone in spinal surgery, a sea of literature has surfaced, evaluating both established and newly emerging fusion alternatives. An understanding of the available fusion options and an organized evidence-based approach to their use in spine surgery is essential for achieving optimal results. METHODS A Medline search of English language literature published through March 2016 discussing bone graft substitutes and fusion extenders was performed. All clinical studies reporting radiological and/or patient outcomes following the use of bone substitutes were reviewed under the broad categories of Allografts, Demineralized Bone Matrices (DBM), Ceramics, Bone Morphogenic proteins (BMPs), Autologous growth factors (AGFs), Stem cell products and Synthetic Peptides. These were further grouped depending on their application in lumbar and cervical spine surgeries, deformity correction or other miscellaneous procedures viz. trauma, infection or tumors; wherever data was forthcoming. Studies in animal populations and experimental in vitro studies were excluded. Primary endpoints were radiological fusion rates and successful clinical outcomes. RESULTS A total of 181 clinical studies were found suitable to be included in the review. More than a third of the published articles (62 studies, 34.25%) focused on BMP. Ceramics (40 studies) and Allografts (39 studies) were the other two highly published groups of bone substitutes. Highest radiographic fusion rates were observed with BMPs, followed by allograft and DBM. There were no significant differences in the reported clinical outcomes across all classes of bone substitutes. CONCLUSIONS There is a clear publication bias in the literature, mostly favoring BMP. Based on the available data, BMP is however associated with the highest radiographic fusion rate. Allograft is also very well corroborated in the literature. The use of DBM as a bone expander to augment autograft is supported, especially in the lumbar spine. Ceramics are also utilized as bone graft extenders and results are generally supportive, although limited. The use of autologous growth factors is not substantiated at this time. Cell matrix or stem cell-based products and the synthetic peptides have inadequate data. More comparative studies are needed to evaluate the efficacy of bone graft substitutes overall.
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Affiliation(s)
- Abhijeet Kadam
- Pennsylvania Hospital of the University of Pennsylvania Health System, Philadelphia, PA
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Khan NR, Foley KT. In Reply: Meta-analysis Does Not Support Lower Complication Rates in Minimally Invasive Transforaminal Lumbar Interbody Fusion. Neurosurgery 2016; 79:E549-51. [PMID: 27471978 DOI: 10.1227/neu.0000000000001372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Affiliation(s)
- Nickalus R Khan
- *Department of Neurosurgery, University of Tennessee Health Science Center, Memphis, Tennessee ‡Semmes-Murphey Neurologic & Spine Institute, Memphis, Tennessee
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Bhangoo SS. Letter: Meta-analysis Does Not Support Lower Complication Rates in Minimally Invasive Transforaminal Lumbar Interbody Fusion. Neurosurgery 2016; 79:E547-9. [PMID: 27471976 DOI: 10.1227/neu.0000000000001371] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
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Khan NR, Clark AJ, Lee SL, Venable GT, Rossi NB, Foley KT. Surgical Outcomes for Minimally Invasive vs Open Transforaminal Lumbar Interbody Fusion: An Updated Systematic Review and Meta-analysis. Neurosurgery 2016. [PMID: 26214320 DOI: 10.1227/neu.0000000000000913] [Citation(s) in RCA: 123] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Minimally invasive transforaminal lumbar interbody fusion (TLIF)-or MI-TLIF-has been increasing in prevalence compared with open TLIF (O-TLIF) procedures. The use of MI-TLIF is an evolving technique with conflicting reports in the literature about outcomes. OBJECTIVE To investigate the impact of MI-TLIF in comparison with O-TLIF for early and late outcomes by using the Visual Analog Scale for back pain (VAS-back) and the Oswestry Disability Index (ODI). Secondary end points include blood loss, operative time, radiation exposure, length of stay, fusion rates, and complications between the 2 procedures. METHODS During August 2014, a systematic literature search was performed identifying 987 articles. Of these, 30 met inclusion criteria. A random-effects meta-analysis was performed by using both pooled and subset analyses based on study type. RESULTS Our meta-analysis demonstrated that MI-TLIF reduced blood loss (P < .001), length of stay (P < .001), and complications (P = .001) but increased radiation exposure (P < .001). No differences were found in fusion rate (P = .61) and operative time (P = .34). A decrease in late VAS-back scores was demonstrated for MI TLIF (P < .001), but no differences were found in early VAS-back, early ODI, and late ODI. CONCLUSION MI-TLIF is associated with reduced blood loss, decreased length of stay, decreased complication rates, and increased radiation exposure. The rates of fusion and operative time are similar between MI-TLIF and O-TLIF. Differences in long-term outcomes in MI-TLIF vs O-TLIF are inconclusive and require more research, particularly in the form of large, multi-institutional prospective randomized controlled trials. ABBREVIATIONS CI, confidence intervalMCID, minimal clinically important differenceMI-TLIF, minimally invasive transforaminal lumbar interbody fusionODI, Oswestry Disability IndexO-TLIF, open transforaminal lumbar interbody fusionVAS, Visual Analog Scale.
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Affiliation(s)
- Nickalus R Khan
- *Department of Neurosurgery, University of Tennessee Health Sciences Center, Memphis, Tennessee; ‡Semmes-Murphey Neurologic & Spine Institute, Memphis, Tennessee; §Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; ‖College of Medicine, University of Tennessee Health Sciences Center, Memphis, Tennessee
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Bannwarth M, Kleiber JC, Marlier B, Eap C, Duntze J, Litre CF. Ectopic bone formation with joint impingement after posterior lumbar fusion with rhBMP-2. Orthop Traumatol Surg Res 2016; 102:255-6. [PMID: 26947733 DOI: 10.1016/j.otsr.2015.11.013] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2015] [Revised: 11/09/2015] [Accepted: 11/16/2015] [Indexed: 02/02/2023]
Abstract
Recombinant human bone morphogenetic protein-2 (rhBMP-2) was recently licensed for local administration during posterior lumbar fusion. In this indication, considerable uncertainty remains about the nature and mechanisms of the many adverse effects of rhBMP-2, such as ectopic bone formation. We report a case of ectopic bone formation with impingement on a facet joint and incapacitating low back pain after minimally invasive transforaminal L5-S1 interbody fusion with local application of rhBMP-2 (InductOs(®)). Revision surgery was eventually performed to alleviate the symptoms by removing the ectopic bone. Caution is in order regarding the use of rhBMP-2 during posterior lumbar fusion. Every effort should be made to minimise the risk of complications.
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Affiliation(s)
- M Bannwarth
- Neurosurgery department, Reims University Hospital, Reims, France.
| | - J C Kleiber
- Neurosurgery department, Reims University Hospital, Reims, France
| | - B Marlier
- Neurosurgery department, Reims University Hospital, Reims, France
| | - C Eap
- Neurosurgery department, Reims University Hospital, Reims, France
| | - J Duntze
- Neurosurgery department, Reims University Hospital, Reims, France
| | - C F Litre
- Neurosurgery department, Reims University Hospital, Reims, France
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Safety and efficacy of recombinant human bone morphogenetic protein 2 on cranial defect closure in the pediatric population. J Craniofac Surg 2015; 24:917-22. [PMID: 23714911 DOI: 10.1097/scs.0b013e318256657c] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Traditional reconstructive options for cranial defects include autogenous bone graft, bone substitutes, and synthetic materials. The established standard for repairing cranial defects is autogenous bone. However, young children do not have abundant donor sites for bone harvest, which leads to challenges in closing calvarial defects. Synthetic materials are not ideal alternatives because they require subsequent retrieval and are prone to infection. Their long-term effects on growth of the skull are also not well studied. Bone morphogenetic protein 2 (BMP-2), are shown to positively affect closure of cranial defects in animal models. We present a study comparing the efficacy and safety of closure of cranial defect with bone graft augmented with recombinant human BMP-2 (rhBMP-2) and compared with a series of patients treated with bone graft alone. METHODS This study is a retrospective multicenter evaluation of 36 patients spanning 5 years. Twenty-one patients undergoing cranial defect closure augmented with rhBMP-2 were compared with 15 patients who underwent cranial defect closure using cranial bone shavings alone. We measured preoperative and postoperative defect size on volumetric computed tomographic scan reconstructions to compare defect sizes. RESULTS The rhBMP-2 group had slightly increased proportional closure compared with the control group, 86% versus 76% (P < 0.018), respectively. Two patients in the rhBMP-2 group had postoperative fusion of a suture that was known to be patent at the time of cranial defect closure. No instances of brain edema, herniation, airway compromise, or other adverse effects directly attributable to rhBMP-2 were observed. CONCLUSIONS Bone morphogenetic protein 2 may increase the amplitude and uptake of cranial bone grafts in cranial defect closure. This study shows that defect sizes of up to 16 cm can be reliably closed using this technique. Postoperative fusion of uninvolved sutures in 2 patients indicates that rhBMP-2 may have unreported adverse effects; consideration of this finding should be weighed against the benefit of improved closure of calvarial defects.
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Villavicencio AT, Nelson EL, Rajpal S, Otalora F, Burneikiene S. Case Series of Anterior Intervertebral Graft Extrusions in Transforaminal Lumbar Interbody Fusion Surgeries. World Neurosurg 2015; 85:130-5. [PMID: 26341432 DOI: 10.1016/j.wneu.2015.08.047] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2015] [Revised: 08/07/2015] [Accepted: 08/08/2015] [Indexed: 02/08/2023]
Abstract
BACKGROUND According to the published reports, revision surgery is sometimes recommended even in patients with asymptomatic anterior lumbar intervertebral graft migrations. The main purpose of this chart review study was to report on the clinical course and outcomes of patients who had anterior intervertebral graft extrusions after transforaminal lumbar interbody fusion (TLIF). METHODS From July 2002 to July 2014, 1259 consecutive TLIF surgeries were performed. These were reviewed, and patients who had anterior intervertebral graft extrusions were identified. RESULTS The incidence of graft extrusion was 0.6% (7 of 1259 patients). There were 6 female patients and 1 male patient with an average age of 65.7 years (range, 44-80 years). All patients underwent TLIF with bilateral pedicle screw fixation, and 6 received recombinant human bone morphogenetic protein-2. Graft migrations were diagnosed between 5 days and 8 months postoperatively except for 2 cases in which migration occurred intraoperatively. The patients were closely followed for an average of 27.4 months (range, 12-43 months). All patients remained asymptomatic during the follow-up period and had solid fusion despite extrusions with an average time to fusion of 13 months (range, 10-18 months). No other adverse events occurred during the follow-up period. CONCLUSIONS The risks of additional and highly invasive revision surgery should be weighed against the potential short-term and long-term complications associated with graft extrusions or migrations. It was demonstrated that fusion may take longer but can be achieved, and close observation may be adequate for asymptomatic patients.
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Affiliation(s)
- Alan T Villavicencio
- Boulder Neurosurgical Associates, Boulder, Colorado, USA; Justin Parker Neurological Institute, Boulder, Colorado, USA
| | - E Lee Nelson
- Boulder Neurosurgical Associates, Boulder, Colorado, USA
| | - Sharad Rajpal
- Boulder Neurosurgical Associates, Boulder, Colorado, USA; Justin Parker Neurological Institute, Boulder, Colorado, USA
| | | | - Sigita Burneikiene
- Boulder Neurosurgical Associates, Boulder, Colorado, USA; Justin Parker Neurological Institute, Boulder, Colorado, USA.
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Bai J, Zhang W, Zhang X, Sun Y, Ding W, Shen Y. A Clinical Investigation of Contralateral Neurological Symptom after Transforaminal Lumbar Interbody Fusion (TLIF). Med Sci Monit 2015; 21:1831-8. [PMID: 26109143 PMCID: PMC4492481 DOI: 10.12659/msm.894159] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND The aim of this study was to analyze treatment outcomes and morbidity of contralateral neurological symptom in patients after TLIF surgery and to explore its possible causes. MATERIAL AND METHODS A retrospective study was conducted involving a total of 476 patients who underwent TILF from 2009 to 2012 in our hospital. These cases were divided into a symptomatic group (Group S) and a non-symptomatic group. The differences in contralateral foramen area and disc-height index(DHI) before and after surgery were compared between Group S and a random sample of 40 cases of non-symptomatic group patients (group N). In addition, according to whether the patient underwent second surgery, Group S patients were further divided into a transient neurologic symptoms group (Group T) and an operations exploration group (Group O). The time of symptom appearance, duration, and symptomatic severity (JOA VAS score) were compared between Group T and O. RESULTS Among the 476 patients, 18 had postoperative contralateral neurological symptoms; thus, the morbidity was 3.7815%. The indicators in Group S were lower than in Group N in the differences in contralateral foramen area and disc-height index(DHI) before and after surgery (p<0.05). Five patients (Group O) in Group S had second surgery because of invalid conservative treatment. The surgical exploration rate was 1.0504%. Compared with Group T, the symptoms of Group O patients appeared earlier, persisted longer, and were more serious (p<0.05). CONCLUSIONS Contralateral neurological symptom is a potential complication after TLIF, and its causes are diverse. Surgical explorations should be conducted early for those patients with the complication who present with obvious nerve damage.
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Affiliation(s)
- Jiayue Bai
- Department of The Third Hospital of Hebei Medical University, Key Biomechanical Laboratory of Orthopedics, Shijiazhuang, Hebei, China (mainland)
| | - Wei Zhang
- Department of The Third Hospital of Hebei Medical University, Key Biomechanical Laboratory of Orthopedics, Shijiazhuang, Hebei, China (mainland)
| | - Xin Zhang
- Department of The Third Hospital of Hebei Medical University, Key Biomechanical Laboratory of Orthopedics, Shijiazhuang, Hebei, China (mainland)
| | - Yapeng Sun
- Department of The Third Hospital of Hebei Medical University, Key Biomechanical Laboratory of Orthopedics, Shijiazhuang, Hebei, China (mainland)
| | - Wenyuan Ding
- Department of The Third Hospital of Hebei Medical University, Key Biomechanical Laboratory of Orthopedics, Shijiazhuang, Hebei, China (mainland)
| | - Yong Shen
- Department of The Third Hospital of Hebei Medical University, Key Biomechanical Laboratory of Orthopedics, Shijiazhuang, Hebei, China (mainland)
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The Fate of L5-S1 With Low-Dose BMP-2 and Pelvic Fixation, With or Without Interbody Fusion, in Adult Deformity Surgery. Spine (Phila Pa 1976) 2015; 40:E634-9. [PMID: 25768688 DOI: 10.1097/brs.0000000000000867] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
STUDY DESIGN Retrospective comparative case series. OBJECTIVE Evaluate L5-S1 fusion rates when lower dose of bone morphogenic protein-2 (BMP-2) (average 3.2 mg) and pelvic fixation were used, with or without interbody fusion. SUMMARY OF BACKGROUND DATA Pseudarthrosis at L5-S1 is one of the most common complications of long fusions to the sacrum in adult deformity surgery. Strategies for decreasing pseudarthrosis include interbody fusion, use of BMP-2 at the lumbosacral junction, and the use of sacropelvic fixation, individually or in combination. High-dose BMP-2 (20-40 mg) placed posterolaterally has shown comparable fusion rates with interbody fusion. METHODS Retrospective review of 61 consecutive patients with minimum 2-year follow-up at a single institution. All patients had an isolated posterior approach, 5 or more levels fused including L5-S1, use of pelvic fixation, and no prior L5-S1 procedures. The patients were divided in 2 groups for comparison on the basis of the use of an interbody cage/fusion at the L5-S1 level. Revision rates and implant-related complications were also reported. RESULTS The fusion rate at L5-S1 was 97% (59/61), with no difference between the interbody and no interbody fusion groups (97% vs. 96%, P = 1.0). There were no significant differences in the radiographical parameters or deformity correction between the groups. The mean amount of BMP-2 used in the interbody group was 4.1 mg (2-10), 2.5 mg (0-8) in the disc space, and 1.6 mg (0-4) in the interbody cage, whereas there was no difference in the amount of recombinant human bone morphogenic protein-2 placed posterolaterally between the 2 groups (interbody fusion = 1.6 vs. non-interbody fusion = 2.0 mg, P = 0.08) along with autograft and allograft. The overall revision rate for L5-S1 nonunion was 1.6%. CONCLUSION The use of low dose of BMP-2 at the L5-S1 level in combination with sacropelvic fixation achieved satisfactory fusion rates in adult deformity surgery. No additional benefit was encountered by adding an interbody cage. LEVEL OF EVIDENCE 4.
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Adverse Events With the Use of rhBMP-2 in Thoracolumbar and Lumbar Spine Fusions. ACTA ACUST UNITED AC 2015; 28:E277-83. [DOI: 10.1097/bsd.0b013e318287f2e2] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Villavicencio AT, Serxner BJ, Mason A, Nelson EL, Rajpal S, Faes N, Burneikiene S. Unilateral and Bilateral Pedicle Screw Fixation in Transforaminal Lumbar Interbody Fusion: Radiographic and Clinical Analysis. World Neurosurg 2015; 83:553-9. [DOI: 10.1016/j.wneu.2014.12.012] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2014] [Revised: 08/15/2014] [Accepted: 12/09/2014] [Indexed: 10/24/2022]
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