|
1
|
Alavi SA, Imanian M, Alkaabi S, Al-Sabri G, Forouzanfar T, Helder M. A systematic review and meta-analysis on the use of regenerative graft materials for socket preservation in randomized clinical trials. Oral Surg Oral Med Oral Pathol Oral Radiol 2024; 138:702-718. [PMID: 39317600 DOI: 10.1016/j.oooo.2024.07.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Revised: 06/19/2024] [Accepted: 07/02/2024] [Indexed: 09/26/2024]
Abstract
OBJECTIVE To evaluate if regenerative materials with/without scaffold deployed in dental socket preservation led to reduced radiographic height and width bone resorption. STUDY DESIGN English-written human studies from January 2010 to December 2023 were selected from PubMed, EMBASE, MEDLINE, Cochrane CENTRAL, Google Scholar and manually searched journals. Six meta-analyses were conducted, addressing treatments with all blood-derived growth factor preparations as well as L-platelet-rich fibrin (L-PRF) separately, and recombinant human BMP-2 (rhBMP-2). An unpaired t-test on L-PRF and rhBMP-2 determined the clinically best preservation treatment. Cochrane risk of bias in all studies was analyzed. RESULTS Twenty-nine articles (1068 participants) were included. Meta-analyses on blood-derived preparations demonstrated nonsignificant alveolar width, but significant (p = .001) height preservation. L-PRF vs. natural healing demonstrated nonsignificant changes in both dimensions. RhBMP-2 caused highly significant reduced horizontal (p = .01) and vertical (p < .0008) bone resorptions. When comparing mean resorption rates, significant benefits of rhBMP-2 over L-PRF were observed for width but not height preservation (p < .0001 and p = .057, respectively). Six studies recorded low, 8 moderate, and 15 high net risks. CONCLUSIONS Regenerative materials appear beneficial for radiographic bone width and height preservation after tooth extraction. Although rhBMP-2 performed better in alveolar width preservation, L-PRF can be an autologous and cost-effective alternative.
Collapse
Affiliation(s)
- Seyed Abdolhojeh Alavi
- Department of Oral and Maxillofacial Surgery/Oral Pathology, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
| | - Mahsa Imanian
- Department of Oral and Maxillofacial Surgery, Leiden University Medical Centers, Universiteit Leiden, Leiden, Netherlands
| | - Salem Alkaabi
- Department of Oral and Maxillofacial Surgery, Fujairah Hospital, Emirates Health Services, United Arab Emirates, Department of Oral and Maxillofacial Surgery/Oral Pathology, Vrije Universiteit Amsterdam, Netherlands
| | - Ghamdan Al-Sabri
- Department of Oral and Maxillofacial Surgery/Oral Pathology, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
| | - Tim Forouzanfar
- Department of Oral and Maxillofacial Surgery, Leiden University Medical Centers, Universiteit Leiden, Leiden, Netherlands
| | - Marco Helder
- Department of Oral and Maxillofacial Surgery/Oral Pathology, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
| |
Collapse
|
|
2
|
Park S, Jeong YH, Ha BJ, Yoo BS, Kim SH, Lee CK, Yi S, Ha Y, Kim KN, Shin DA. Fusion rate of Escherichia coli-derived recombinant human bone morphogenetic protein-2 compared with local bone autograft in posterior lumbar interbody fusion for degenerative lumbar disorders. Spine J 2023; 23:1877-1885. [PMID: 37516282 DOI: 10.1016/j.spinee.2023.07.017] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 07/16/2023] [Accepted: 07/18/2023] [Indexed: 07/31/2023]
Abstract
BACKGROUND CONTEXT The use of recombinant human bone morphogenetic proteins-2 (rhBMP-2) for spinal fusion has been reported to be effective. However, most studies have focused on posterolateral and anterior lumbar interbody fusion, and few have investigated posterior lumbar interbody fusion (PLIF). PURPOSE This study aimed to determine the effectiveness and safety of the delivery of Escherichia coli-derived rhBMP-2 (E.BMP-2) with hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) poloxamer hydrogel composite carriers for PLIF. STUDY DESIGN A retrospective study. PATIENT SAMPLE Patients who underwent 1 to 3 levels of PLIF for lumbar degenerative disc disorders between 2015 and 2020 with a follow-up of ≥1 year were enrolled. In total, 254 patients (357 levels) were included in the analysis. The evaluation was performed at each segment level. In the E.BMP-2 group, 160 patients (221 levels) received autologous local bone with E.BMP-2 (maximum 0.5 mg/level), and in the control group, 94 patients (136 levels) received only local bone graft. OUTCOME MEASURES The primary outcome of this study was to compare the X-ray and CT fusion rates between the two groups. Secondary outcomes included analysis of the patients' clinical outcomes and postoperative complications on CT scans. METHODS Clinical evaluations were performed using a visual analog scale for back pain, the Oswestry Disability Index for disability, and physical and mental component summaries of the Short Form 36-Item Form Health Survey to assess functional effects and quality of life. The fusion was evaluated using radiography and CT. On radiography, solid fusion was defined when the difference between extension and flexion was less than 5°. On CT, solid fusion was defined when the upper and lower vertebral bodies were connected by the trabecular bone (bone bridge formation). In addition, complications such as osteolysis, cage subsidence, and screw loosening were investigated using CT. RESULTS All clinical results for low back pain, disability, and quality of life in both groups were excellent and showed statistically significant improvements compared with baseline (p<.0001). According to the X-ray evaluations, fusion was achieved in 92.31% (204/221) of the patients in the E.BMP-2 group and 82.35% (112/136) of the patients in the control group (p=.0041). According to the CT evaluations, the fusion rates were 93.21% (206/221) and 88.24% (120/136) in the E.BMP-2 and control groups (p=.1048), respectively. Except for screw loosening, which had a significantly higher incidence in the control group (p=.0014), the rates of most postoperative complications were not significantly different between the groups. CONCLUSIONS This study demonstrated that the adjunctive use of a low dose of E.BMP-2 with HA and β-TCP hydrogel can effectively promote bone fusion, making it a promising option for patients with limited autograft availability or compromised bone quality in PLIF.
Collapse
Affiliation(s)
- Sangman Park
- Department of Neurosurgery, Spine and Spinal Cord Institute, Severance Hospital, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea
| | - Yeong Ha Jeong
- Department of Neurosurgery, Spine and Spinal Cord Institute, Severance Hospital, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea
| | - Byeong Jin Ha
- Department of Neurosurgery, Spine and Spinal Cord Institute, Severance Hospital, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea
| | - Beom Seok Yoo
- Department of Neurosurgery, Spine and Spinal Cord Institute, Severance Hospital, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea
| | - Soo-Heon Kim
- Department of Neurosurgery, Spine and Spinal Cord Institute, Severance Hospital, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea
| | - Chang Kyu Lee
- Department of Neurosurgery, Spine and Spinal Cord Institute, Severance Hospital, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea
| | - Seong Yi
- Department of Neurosurgery, Spine and Spinal Cord Institute, Severance Hospital, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea
| | - Yoon Ha
- Department of Neurosurgery, Spine and Spinal Cord Institute, Severance Hospital, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea
| | - Keung Nyun Kim
- Department of Neurosurgery, Spine and Spinal Cord Institute, Severance Hospital, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea
| | - Dong Ah Shin
- Department of Neurosurgery, Spine and Spinal Cord Institute, Severance Hospital, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea.
| |
Collapse
|
|
3
|
Gianulis E, Wetzell B, Scheunemann D, Gazzolo P, Sohoni P, Moore MA, Chen J. Characterization of an advanced viable bone allograft with preserved native bone-forming cells. Cell Tissue Bank 2023; 24:417-434. [PMID: 36434165 PMCID: PMC10209280 DOI: 10.1007/s10561-022-10044-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Accepted: 10/11/2022] [Indexed: 11/26/2022]
Abstract
Bone grafts are widely used to successfully restore structure and function to patients with a broad range of musculoskeletal ailments and bone defects. Autogenous bone grafts are historically preferred because they theoretically contain the three essential components of bone healing (ie, osteoconductivity, osteoinductivity, and osteogenicity), but they have inherent limitations. Allograft bone derived from deceased human donors is one alternative that is also capable of providing both an osteoconductive scaffold and osteoinductive potential but, until recently, lacked the osteogenic component of bone healing. Relatively new, cellular bone allografts (CBAs) were designed to address this need by preserving viable cells. Although most commercially-available CBAs feature mesenchymal stem cells (MSCs), osteogenic differentiation is time-consuming and complex. A more advanced graft, a viable bone allograft (VBA), was thus developed to preserve lineage-committed bone-forming cells, which may be more suitable than MSCs to promote bone fusion. The purpose of this paper was to present the results of preclinical research characterizing VBA. Through a comprehensive series of in vitro and in vivo assays, the present results demonstrate that VBA in its final form is capable of providing all three essential bone remodeling properties and contains viable lineage-committed bone-forming cells, which do not elicit an immune response. The results are discussed in the context of clinical evidence published to date that further supports VBA as a potential alternative to autograft without the associated drawbacks.
Collapse
Affiliation(s)
- Elena Gianulis
- Global Scientific Affairs and Clinical Engagement, LifeNet Health®, 1864 Concert Dr., Virginia Beach, VA 23453 USA
| | - Bradley Wetzell
- Global Scientific Affairs and Clinical Engagement, LifeNet Health®, 1864 Concert Dr., Virginia Beach, VA 23453 USA
| | - Danielle Scheunemann
- Global Scientific Affairs and Clinical Engagement, LifeNet Health®, 1864 Concert Dr., Virginia Beach, VA 23453 USA
| | - Patrick Gazzolo
- Global Spine and General Orthopedics, LifeNet Health®, Virginia Beach, VA USA
| | - Payal Sohoni
- Global Trauma and CMF, LifeNet Health®, Virginia Beach, VA USA
| | - Mark A. Moore
- Global Scientific Affairs and Clinical Engagement, LifeNet Health®, 1864 Concert Dr., Virginia Beach, VA 23453 USA
| | - Jingsong Chen
- Institute of Regenerative Medicine, LifeNet Health®, Virginia Beach, VA USA
| |
Collapse
|
|
4
|
Patel HA, Wellington IJ, Lubonja K, Stelzer JW, Antonacci CL, Coskun E, Cote MP, Singh H, Mallozzi SS, Moss IL. Current Trends in Recombinant Human Bone Morphogenetic Protein 2 (rhBMP2) Usage for Spinal Fusion Surgery. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:medicina59050878. [PMID: 37241110 DOI: 10.3390/medicina59050878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Revised: 03/25/2023] [Accepted: 04/26/2023] [Indexed: 05/28/2023]
Abstract
(1) Background: Since first approved by the FDA, on-label and off-label usage of recombinant human bone morphogenetic protein 2 (rhBMP2) for spinal fusion surgeries has become widespread. While many studies have investigated the safety and efficacy of its use, as well as its economic impact, few have looked at the current trends in its on- and off-label use. The goal of this study is to evaluate the current trends of on- and off-label rhBMP2 use for spinal fusion surgery. (2) Methods: A deidentified survey was created and electronically distributed to members of two international spine societies. Surgeons were asked to report their demographic information, surgical experience, and current usage of rhBMP2. They were then presented with five spinal fusion procedures and asked to report if they use rhBMP2 for these indications in their current practice. Responses were stratified between rhBMP2 users vs. non-users and on-label vs. off-label use. Data were analyzed using chi-square with Fisher's exact test for categorical data. (3) Results: A total of 146 respondents completed the survey with a response rate of 20.5%. There was no difference in overall rhBMP2 usage based on specialty, experience, or number of cases per year. Fellowship-trained surgeons and those who practice in the United States were more likely to use rhBMP2. Surgeons who were trained in the Southeast and Midwest regions reported the highest usage rates. rhBMP2 use was more common among fellowship-trained and US surgeons for ALIFs; non-US surgeons for multilevel anterior cervical discectomy and fusions; and fellowship-trained and orthopedic spine surgeons for lateral lumbar interbody fusions. Non-US surgeons were more likely to use rhBMP2 for off-label indications compared to surgeons from the US. (4) Conclusions: While various demographics of surgeons report different rates of rhBMP2 use, off-label use remains relatively commonplace amongst practicing spine surgeons.
Collapse
Affiliation(s)
- Harshadkumar A Patel
- Westchester Medical Center, Department of Orthopaedic Surgery, Valhalla, NY 10595, USA
| | - Ian J Wellington
- Department of Orthopaedic Surgery, University of Connecticut, Farmington, CT 06108, USA
| | - Klair Lubonja
- Department of Orthopaedic Surgery, University of Connecticut, Farmington, CT 06108, USA
| | - John W Stelzer
- Department of Orthopaedic Surgery, University of Connecticut, Farmington, CT 06108, USA
| | | | - Ergin Coskun
- Department of Orthopaedic Surgery, University of Connecticut, Farmington, CT 06108, USA
| | - Mark P Cote
- Department of Orthopedic Surgery, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Hardeep Singh
- Department of Orthopaedic Surgery, University of Connecticut, Farmington, CT 06108, USA
| | - Scott S Mallozzi
- Department of Orthopaedic Surgery, University of Connecticut, Farmington, CT 06108, USA
| | - Isaac L Moss
- Department of Orthopaedic Surgery, University of Connecticut, Farmington, CT 06108, USA
| |
Collapse
|
|
5
|
Matsubara T, Yamada K, Kanazawa T, Sato K, Yokosuka K, Shiba N. Improved intervertebral bone union in ALIF rat model with porous hydroxyapatite/collagen combined with platelet-rich plasma. Spine J 2023; 23:325-335. [PMID: 36064089 DOI: 10.1016/j.spinee.2022.08.019] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Revised: 08/23/2022] [Accepted: 08/26/2022] [Indexed: 02/03/2023]
Abstract
BACKGROUND CONTEXT Platelet-rich plasma (PRP) can accelerate bone union in spinal fusion surgery with an autogenous bone graft. However, it is unclear whether bone union can be obtained by using artificial bone and PRP together in spinal interbody fusion surgery. PURPOSE This study aimed to determine whether interbody fusion can be achieved by transplanting porous hydroxyapatite/collagen(HAp/Col) which is an artificial bone material frequently used in spinal fusion surgery, together with PRP in the intervertebral disc space in rats. STUDY DESIGN AND SETTING A controlled laboratory study. METHODS A total of fourty 10-week old Sprague-Dawley rats were used in this study and assigned to three groups as follow: disc curettage only (control group, n=10), disc curettage + HAp/Col transplant (H group, n=10), and disc curettage + HAp/Col + PRP transplant (H+P group, n=10). The other 10 rats were sacrificed as blood donors for acquisition of PRP. Microcomputed tomography (μCT) examinations were performed to evaluate bone union, bone volume (BV), and bone mineral density (BMD) at 4, 8, and 12 weeks following surgery. Twelve weeks postoperatively, each group of three of L4-L5 spines was harvested to perform histological examination (hematoxylin & eosin stain) and the others were subjected to biomechanical testing (compression properties). RESULTS The platelet count in PRP was approximately 4.1 times greater than that in whole blood (260.6±26.2 × 104 mg/dL and 64.3±2.9 × 104 mg/dL in PRP and whole blood, respectively). All the L4-L5 lumbar discs were fused in the H+P group, whereas only one case was fused in the H group and none in the control group at 12 weeks after surgery. BV was significantly higher in the H+P group than in the H group or control groups (both p<.01), although BMD was not significantly different among the three groups. Upon histological analysis, mature bone formation was observed at the transplanted space in all cases in the H+P group, whereas fibrous tissue was observed at the location in the H and control groups. Regarding biomechanical properties, the ultimate load to failure was significantly higher in the H+P group than in the H group or control group (p=.021 and .013, respectively), although stiffness was not significantly different between the three groups. CONCLUSION The combination of porous HAp/Col and PRP at an appropriate concentration can promote bone union in the intervertebral disc space without using an autologous bone graft in the rat model. Bone tissue formation was histologically confirmed, and it was mechanically strong. CLINICAL SIGNIFICANCE This preclinical study showed that porous HAp/Col, when combined with PRP at an appropriate concentration, can induce bone union without autologous bone grafts. The results may eliminate the need for autologous bone collection for spinal fusion surgery in the future.
Collapse
Affiliation(s)
| | - Kei Yamada
- Department of Orthopedic Surgery, Kurume University, Fukuoka, Japan.
| | | | - Kimiaki Sato
- Department of Orthopedic Surgery, Kurume University, Fukuoka, Japan
| | - Kimiaki Yokosuka
- Department of Orthopedic Surgery, Kurume University, Fukuoka, Japan
| | - Naoto Shiba
- Department of Orthopedic Surgery, Kurume University, Fukuoka, Japan
| |
Collapse
|
|
6
|
Shah DS, Fisher MWA, Hurley RK, Bharmal H. Role of rhBMP-2 in Posterior Lumbar Fusion. Clin Spine Surg 2022; 35:229-232. [PMID: 34321391 DOI: 10.1097/bsd.0000000000001239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Accepted: 06/23/2021] [Indexed: 10/20/2022]
|
|
7
|
Im SK, Lee JH, Lee KY, Yoo SJ. Effectiveness and Feasibility of Injectable Escherichia coli-Derived Recombinant Human Bone Morphogenetic Protein-2 for Anterior Lumbar Interbody Fusion at the Lumbosacral Junction in Adult Spinal Deformity Surgery: A Clinical Pilot Study. Orthop Surg 2022; 14:1350-1358. [PMID: 35633034 PMCID: PMC9251273 DOI: 10.1111/os.13303] [Citation(s) in RCA: 3] [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: 02/07/2021] [Revised: 04/10/2022] [Accepted: 04/11/2022] [Indexed: 11/30/2022] Open
Abstract
Objective To explore the effectiveness and feasibility of injectable Escherichia coli‐derived recombinant human bone morphogenetic protein‐2 (injectable E‐rhBMP‐2, a combination of E. coli‐derived recombinant human bone morphogenic protein‐2 and a hydrogel type beta‐tricalcium phosphate carrier) as a bone substitute for anterior lumbar interbody fusion (ALIF) of the lumbosacral junction in adult spinal deformity (ASD) patients. Methods A prospective single‐institution therapeutic exploratory trial was conducted. Twenty patients (average age: 69.1 years; 19 female and one male; average fusion level: 7.95) diagnosed with ASD with sagittal imbalance who underwent surgical treatment including ALIF at the lumbosacral junction from December 2017 to January 2019 were evaluated. Injectable E‐rhBMP‐2 was prepared by dissolving 3 mg of E. coli‐derived recombinant human bone morphogenetic protein‐2 in 1.5 ml H2O and mixing in situ with 9 g hydrogel type beta‐tricalcium phosphate. This bone graft substitute was loaded onto a metal ALIF cage and L5–S1 ALIF was performed in routine manner. Then posterior column osteotomy with multilevel oblique lumbar interbody fusion or pedicle subtraction osteotomy with accessory rod technique was performed to restore sagittal balance. Patients were followed up for 12 months. CT‐based fusion rates were examined at 6 and 12 months after surgery. Also, clinical outcomes (Oswestry Disability Index [ODI], Visual Analog Scale [VAS] score of the back and leg) were evaluated at 6 and 12 months after surgery. All postoperative adverse events were evaluated for the association with injectable E.BMP‐2. Results Of the 20 patients, loss to follow‐up occurred with one patient at 6 months after surgery and one patient at 12 months after surgery, resulting in a total of 18 patients who were available for follow‐up. Six months after surgery, 68.4% patients achieved solid fusion. Twelve months after surgery, 100% fusion rate was achieved. Compared to baseline values, ODI scores improved to 45.8% and 63.7%, VAS (back) improved to 69.2% and 72.8%, and VAS (leg) improved to 49.2% and 64.8%, respectively, at 6 and 12 months after surgery (p < 0.001 for all). Ten cases of adverse events occurred. But no adverse events were associated with injectable E‐rhBMP‐2. Conclusion Injectable E‐rhBMP‐2 will be an effective bone graft substitute when achieving solid interbody fusion in the lumbosacral junction.
Collapse
Affiliation(s)
- Sang-Kyu Im
- Department of Orthopedic Surgery, Graduate School, College of Medicine, Kyung Hee University, Seoul, South Korea
| | - Jung-Hee Lee
- Department of Orthopedic Surgery, Graduate School, College of Medicine, Kyung Hee University, Seoul, South Korea
| | - Ki Young Lee
- Department of Orthopedic Surgery, Graduate School, College of Medicine, Kyung Hee University, Seoul, South Korea
| | - Seung-Jin Yoo
- Department of Radiology, College of Medicine, Hanyang University, Seoul, South Korea
| |
Collapse
|
|
8
|
Bari TJ, Hansen LV, Dahl B, Gehrchen M. Use of demineralized cortical fibers is associated with reduced risk of pseudarthrosis after pedicle subtraction osteotomy for adult spinal deformity. Spine Deform 2022; 10:657-667. [PMID: 34807398 DOI: 10.1007/s43390-021-00444-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 11/10/2021] [Indexed: 11/24/2022]
Abstract
PURPOSE To assess the effect of demineralized cortical fibers (DCF) on postoperative pseudarthrosis requiring revision surgery in patients undergoing pedicle subtraction osteotomy (PSO) for adult spinal deformity (ASD). METHODS The use of DCF was introduced across all procedures in 2017 and subsequent patients undergoing PSO surgery were prospectively and consecutively registered. Following sample-size estimation, a retrospective cohort was also registered undergoing the same procedure immediately prior to the implementation of DCF. The non-DCF group underwent surgery with ABG. Minimum follow-up was 2 years in both groups. The main outcome was postoperative pseudarthrosis, either CT-verified or verified intraoperatively during revision surgery due to rod breakage and assessed using Kaplan-Meier survival analyses. RESULTS A total of 48 patients were included in the DCF group and 76 in the non-DCF group. The DCF group had more frequently undergone previous spine surgery (60% vs 36%) and had shorter follow-up (32 ± 2 vs 40 ± 7 months). Pseudarthrosis occurred in 7 (15%) patients in the DCF group and 31 (41%) in the non-DCF group, corresponding to a relative risk increase of 2.6 (95%CI 1.3-2.4, P < 0.01). 1-KM survival analyses, taking time to event into account and thus the difference in follow-up, also showed increased pseudarthrosis in the non-DCF group (log-rank P = 0.022). Similarly, multivariate logistic regression adjusted for age, instrumented levels and sacral fusion was also with significantly increased odds of pseudarthrosis in the non-DCF group (OR: 4.3, 95%CI: 1.7-11.3, P < 0.01). CONCLUSION We found considerable and significant reductions in pseudarthrosis following PSO surgery with DCF compared to non-DCF. LEVEL OF EVIDENCE III.
Collapse
Affiliation(s)
- Tanvir Johanning Bari
- Spine Unit, Department of Orthopedic Surgery, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100, Copenhagen, Denmark.
| | - Lars Valentin Hansen
- Spine Unit, Department of Orthopedic Surgery, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100, Copenhagen, Denmark
| | - Benny Dahl
- Department of Orthopedics and Scoliosis Surgery, Texas Children's Hospital and Baylor College of Medicine, 6621 Fannin St, Houston, TX, 77030, USA
| | - Martin Gehrchen
- Spine Unit, Department of Orthopedic Surgery, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100, Copenhagen, Denmark
| |
Collapse
|
|
9
|
Wetzell B, McLean JB, Dorsch K, Moore MA. A 24-month retrospective update: follow-up hospitalization charges and readmissions in US lumbar fusion surgeries using a cellular bone allograft (CBA) versus recombinant human bone morphogenetic protein-2 (rhBMP-2). J Orthop Surg Res 2021; 16:680. [PMID: 34794470 PMCID: PMC8600873 DOI: 10.1186/s13018-021-02829-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Accepted: 11/03/2021] [Indexed: 08/30/2023] Open
Abstract
Background The objectives of this study were to build upon previously-reported 12-month findings by retrospectively comparing 24-month follow-up hospitalization charges and potentially-relevant readmissions in US lumbar fusion surgeries that employed either recombinant human bone morphogenetic protein-2 (rhBMP-2) or a cellular bone allograft comprised of viable lineage-committed bone cells (V-CBA) via a nationwide healthcare system database. Methods A total of 16,172 patients underwent lumbar fusion surgery using V-CBA or rhBMP-2 in the original study, of whom 3,792 patients (23.4%) were identified in the current study with all-cause readmissions during the 24-month follow-up period. Confounding baseline patient, procedure, and hospital characteristics found in the original study were used to adjust multivariate regression models comparing differences in 24-month follow-up hospitalization charges (in 2020 US dollars) and lengths of stay (LOS; in days) between the groups. Differences in potentially-relevant follow-up readmissions were also compared, and all analyses were repeated in the subset of patients who only received treatment at a single level of the spine. Results The adjusted cumulative mean 24-month follow-up hospitalization charges in the full cohort were significantly lower in the V-CBA group ($99,087) versus the rhBMP-2 group ($124,389; P < 0.0001), and this pattern remained in the single-level cohort (V-CBA = $104,906 vs rhBMP-2 = $125,311; P = 0.0006). There were no differences between groups in adjusted cumulative mean LOS in either cohort. Differences in the rates of follow-up readmissions aligned with baseline comorbidities originally reported for the initial procedure. Subsequent lumbar fusion rates were significantly lower for V-CBA patients in the full cohort (10.12% vs 12.00%; P = 0.0002) and similar between groups in the single-level cohort, in spite of V-CBA patients having significantly higher rates of baseline comorbidities that could negatively impact clinical outcomes, including bony fusion. Conclusions The results of this study suggest that use of V-CBA for lumbar fusion surgeries performed in the US is associated with substantially lower 24-month follow-up hospitalization charges versus rhBMP-2, with both exhibiting similar rates of subsequent lumbar fusion procedures and potentially-relevant readmissions.
Collapse
Affiliation(s)
- Bradley Wetzell
- Global Scientific Affairs and Clinical Engagement, LifeNet Health®, 1864 Concert Drive, Virginia Beach, VA, 23453, USA.
| | - Julie B McLean
- Global Scientific Affairs and Clinical Engagement, LifeNet Health®, 1864 Concert Drive, Virginia Beach, VA, 23453, USA
| | - Kimberly Dorsch
- Global Clinical Affairs, LifeNet Health®, Virginia Beach, VA, USA
| | - Mark A Moore
- Global Scientific Affairs and Clinical Engagement, LifeNet Health®, 1864 Concert Drive, Virginia Beach, VA, 23453, USA
| |
Collapse
|
|
10
|
Eleswarapu A, Rowan FA, Le H, Wick JB, Roberto RF, Javidan Y, Klineberg EO. Efficacy, Cost, and Complications of Demineralized Bone Matrix in Instrumented Lumbar Fusion: Comparison With rhBMP-2. Global Spine J 2021; 11:1223-1229. [PMID: 32748702 PMCID: PMC8453673 DOI: 10.1177/2192568220942501] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [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 cohort study. OBJECTIVES To evaluate demineralized bone matrix as an adjunct for instrumented lumbar spine fusion compared with recombinant human bone morphogenetic protein-2 (rhBMP-2). METHODS Clinical and radiographic review was performed of 43 patients with degenerative spine disease treated with posterolateral spinal fusion with or without posterior or transforaminal lumbar interbody fusion. Final analysis included sixteen patients treated with demineralized bone matrix (DBM; Accell Evo3, SeaSpine) compared with a retrospective matched group of 21 patients treated with rhBMP-2 (rhBMP-2, Infuse, Medtronic). All patients were followed for 24 months. Fusion was evaluated by computed tomography and/or x-ray. Clinical outcomes included visual analogue scale (VAS), Oswestry Disability Index (ODI), and Short Form 12 (SF-12). RESULTS Overall fusion rate, including posterolateral and/or interbody fusion, was 100% for both groups, though the fusion rates in the posterolateral space alone were 93.5% and 100% for the DBM and rhBMP-2 groups, respectively. Clinical outcomes were similar between groups, with the DBM group showing greater improvement in ODI. The rhBMP-2 group showed higher rates of radiographic complications with 7 of 21 patients (33.3%) demonstrating either adjacent level fusion or ectopic bone formation, compared with zero in the DBM group. Average biologic cost per level was $1522 for DBM and $3505 for rhBMP-2. CONCLUSIONS DBM and rhBMP-2 demonstrated similar radiographic and clinical outcomes in instrumented lumbar fusions. rhBMP-2 was associated with higher rates of radiographic complications and significantly higher costs.
Collapse
Affiliation(s)
| | | | - Hai Le
- University of California Davis, Sacramento, CA, USA
| | | | | | | | - Eric O. Klineberg
- University of California Davis, Sacramento, CA, USA,Eric O. Klineberg, Department of Orthopaedic Surgery, University of California, Davis, 4860 Y Street, Suite 3800, Sacramento, CA 95817, USA.
| |
Collapse
|
|
11
|
Gaihre B, Bharadwaz A, Unagolla JM, Jayasuriya AC. Evaluation of the optimal dosage of BMP-9 through the comparison of bone regeneration induced by BMP-9 versus BMP-2 using an injectable microparticle embedded thermosensitive polymeric carrier in a rat cranial defect model. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2021; 127:112252. [PMID: 34225891 PMCID: PMC8260961 DOI: 10.1016/j.msec.2021.112252] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Revised: 05/03/2021] [Accepted: 06/07/2021] [Indexed: 01/07/2023]
Abstract
Bone morphogenetic proteins (BMPs) are well known as enhancers and facilitators of osteogenesis during bone regeneration. The use of recombinant BMP-2 (rhBMP-2) in bone defect healing has drawbacks, which has driven the scouting for alternatives, such as recombinant BMP-9 (rhBMP-9), to provide comparable new bone formation. However, the dosage of rhBMP-9 is quintessential for the facilitation of adequate bone defect healing. Therefore, this study has been designed to evaluate the optimal dosage of BMP-9 by comparing the bone defect healing induced by rhBMP-9 over rhBMP-2. The chitosan (CS) microparticles (MPs), coated with BMPs, were embedded in a thermoresponsive methylcellulose (MC) and calcium alginate (Alg) based injectable delivery system containing a dosage of either 0.5 μg or 1.5 μg of the respective rhBMP per bone defect. A 5 mm critical-sized cranial defect rat model has been used in this study, and bone tissues were harvested at eight weeks post-surgery. The standard tools for comparing the new bone regeneration included micro computerized tomography (micro-CT) and histological analysis. A novel perspective of analyzing the new bone quality and crystallinity was employed by using Raman spectroscopy, along with its elastic modulus quantified through Atomic Force Microscopy (AFM). Results showed that the rhBMP-9 administered at a dosage of 1.5 μg per bone defect, using this delivery system, can adequately facilitate the bone void filling with ample new bone mineralization and crystallinity as compared to rhBMP-2, thus approving the hypothesis for a viable rhBMP-2 alternative.
Collapse
Affiliation(s)
- Bipin Gaihre
- Biomedical Engineering Program, Department of Bioengineering, College of Engineering, The University of Toledo, Toledo, OH 43607, USA
| | - Angshuman Bharadwaz
- Biomedical Engineering Program, Department of Bioengineering, College of Engineering, The University of Toledo, Toledo, OH 43607, USA
| | - Janitha M Unagolla
- Biomedical Engineering Program, Department of Bioengineering, College of Engineering, The University of Toledo, Toledo, OH 43607, USA
| | - Ambalangodage C Jayasuriya
- Biomedical Engineering Program, Department of Bioengineering, College of Engineering, The University of Toledo, Toledo, OH 43607, USA; Department of Orthopaedic Surgery, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH 43614, USA.
| |
Collapse
|
|
12
|
Shahrestani S, Ballatori AM, Chen X, Ton A, Wang JC, Buser Z. The Impact of Osteobiologic Subtype Selection on Perioperative Complications and Hospital-Reported Charges in Single- and Multi-Level Lumbar Spinal Fusion. Int J Spine Surg 2021; 15:654-662. [PMID: 34266932 DOI: 10.14444/8086] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
BACKGROUND Over the last several decades, various osteobiologics including allograft, synthetics, and growth factors have been used for lumbar spinal fusion surgery. However, the data on these osteobiologic products remain controversial with conflicting evidence in the literature. This study evaluates the influence of osteobiologic type selection on perioperative complications and hospital-reported charges in single-level and multilevel lumbar fusion. METHODS Using the 2016 and 2017 Nationwide Readmission Database, we conducted a retrospective cohort analysis of 125,143 patients who received lumbar fusion with either autologous tissue substitute, nonautologous tissue substitute, or synthetic substitute. This cohort was split into single-level and multilevel fusion procedures, and one-to-one age and sex propensity score matching was implemented. This resulted in cohorts each consisting of 1967 patients for single-level fusion, and cohorts each consisting of 1657 patients for multilevel fusion. Statistical analysis included one-way analysis of variance and Tukey multiple comparisons of means. RESULTS Autologous single-level fusion resulted in significantly more postoperative pain at 30-, 90-, and 180-day follow-up compared to fusion with nonautologous graft (P < .05). Multilevel fusion with autologous graft had higher rates of acute postsurgical anemia compared with synthetic (P = .021) and nonautologous (P = .016) alternatives, and less postsurgical infection when compared with nonautologous fusion (P = .0020). In addition, procedures using autologous osteobiologics were associated with significantly more neurological complications at 30 days (P = .049) and 90 days (P = .048) for multi-level fusion and at 30 days (P = .044) for single-level fusion compared with the nonautologous group. Lastly, for both cohorts, the total accrued inpatient hospital charges during admission for patients receiving nonautologous grafts were the most expensive and those for patients receiving autologous grafts were the least expensive. CONCLUSION Significant differences were found between the groups with respect to rates of complications, including infection, postoperative pain, and neurologic injury. Furthermore, the hospital-reported charges of each procedure varied significantly. As the field of biologics continues to expand, it is important to continually evaluate the safety, efficacy, and cost-effectiveness of these novel materials and techniques. LEVEL OF EVIDENCE 3 CLINICAL RELEVANCE: With increased utilization of osteobiologics and spinal fusion being a common procedure, longitudinal data on readmissions, and post-operative complications are critical in guiding evidence-based practice.
Collapse
Affiliation(s)
- Shane Shahrestani
- Department of Orthopaedic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California.,Department of Medical Engineering, California Institute of Technology, Pasadena, California
| | - Alexander M Ballatori
- Department of Orthopaedic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California
| | - Xiao Chen
- Department of Orthopaedic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California
| | - Andy Ton
- Department of Orthopaedic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California
| | - Jeffrey C Wang
- Department of Orthopaedic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California
| | - Zorica Buser
- Department of Orthopaedic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California
| |
Collapse
|
|
13
|
Wetzell B, McLean JB, Moore MA, Kondragunta V, Dorsch K. A large database study of hospitalization charges and follow-up re-admissions in US lumbar fusion surgeries using a cellular bone allograft (CBA) versus recombinant human bone morphogenetic protein-2 (rhBMP-2). J Orthop Surg Res 2020; 15:544. [PMID: 33213484 PMCID: PMC7678152 DOI: 10.1186/s13018-020-02078-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Accepted: 11/09/2020] [Indexed: 02/08/2023] Open
Abstract
Background The objective of this study was to retrospectively compare initial procedure and 12-month follow-up hospitalization charges and resource utilization (lengths of stay; LOS) for lumbar fusion surgeries using either recombinant human bone morphogenetic protein-2 (rhBMP-2) or a cellular bone allograft comprised of viable lineage-committed bone cells (V-CBA) via a large US healthcare system database. Potentially relevant re-admissions during the follow-up period were also assessed. Methods A total of 16,172 patients underwent lumbar fusion surgery using V-CBA or rhBMP-2, of whom 3503 (21.66%) patients had follow-up re-admission data. Initial patient, procedure, and hospital characteristics were assessed to determine confounding factors. Multivariate regression modeling compared differences in hospitalization charges (in 2018 US dollars) and LOS (in days) between the groups, as well as incidences of potentially relevant re-admissions during the 12-month follow-up period. Results The adjusted mean initial procedure and 12-month follow-up hospital charges were significantly lower in the V-CBA group versus the rhBMP-2 group ($109,061 and $108,315 versus $160,191 and $130,406, respectively; P < 0.0001 for both comparisons). This disparity remained in an ad hoc comparison of charges for initial single-level treatments only (V-CBA = $103,064, rhBMP-2 = $149,620; P < 0.0001). The adjusted mean initial LOS were significantly lower in the V-CBA group (3.77 days) versus the rhBMP-2 group (3.88 days; P < 0.0001), but significantly higher for the cumulative follow-up hospitalizations in the 12-month follow-up period (7.87 versus 7.46 days, respectively; P < 0.0001). Differences in rates of follow-up re-admissions aligned with comorbidities at the initial procedure. Subsequent lumbar fusion rates were comparable, but significantly lower for V-CBA patients who had undergone single-level treatments only, in spite of V-CBA patients having significantly higher rates of initial comorbidities that could negatively impact clinical outcomes. Conclusions The results of this study indicate that use of V-CBA for lumbar fusion surgeries performed in the US may result in substantially lower overall hospitalization charges versus rhBMP-2, with both exhibiting similar rates of 12-month re-admissions and subsequent lumbar fusion procedures.
Collapse
Affiliation(s)
- Bradley Wetzell
- Global Scientific Affairs and Clinical Engagement, LifeNet Health®, 1864 Concert Drive, Virginia Beach, VA, 23453, USA.
| | - Julie B McLean
- Global Scientific Affairs and Clinical Engagement, LifeNet Health®, 1864 Concert Drive, Virginia Beach, VA, 23453, USA
| | - Mark A Moore
- Global Scientific Affairs and Clinical Engagement, LifeNet Health®, 1864 Concert Drive, Virginia Beach, VA, 23453, USA
| | | | - Kimberly Dorsch
- Global Clinical Affairs, LifeNet Health®, Virginia Beach, VA, USA
| |
Collapse
|
|
14
|
Abstract
STUDY DESIGN Economic modeling of data from a multicenter, prospective registry. OBJECTIVE The aim of this study was to analyze the cost utility of recombinant human bone morphogenetic protein-2 (BMP) in adult spinal deformity (ASD) surgery. SUMMARY OF BACKGROUND DATA ASD surgery is expensive and presents risk of major complications. BMP is frequently used off-label to reduce the risk of pseudarthrosis. METHODS Of 522 ASD patients with fusion of five or more spinal levels, 367 (70%) had at least 2-year follow-up. Total direct cost was calculated by adding direct costs of the index surgery and any subsequent reoperations or readmissions. Cumulative quality-adjusted life years (QALYs) gained were calculated from the change in preoperative to final follow-up SF-6D health utility score. A decision-analysis model comparing BMP versus no-BMP was developed with pseudarthrosis as the primary outcome. Costs and benefits were discounted at 3%. Probabilistic sensitivity analysis was performed using mixed first-order and second-order Monte Carlo simulations. One-way sensitivity analyses were performed by varying cost, probability, and QALY estimates (Alpha = 0.05). RESULTS BMP was used in the index surgery for 267 patients (73%). The mean (±standard deviation) direct cost of BMP for the index surgery was $14,000 ± $6400. Forty patients (11%) underwent revision surgery for symptomatic pseudarthrosis (BMP group, 8.6%; no-BMP group, 17%; P = 0.022). The mean 2-year direct cost was significantly higher for patients with pseudarthrosis ($138,000 ± $17,000) than for patients without pseudarthrosis ($61,000 ± $25,000) (P < 0.001). Simulation analysis revealed that BMP was associated with positive incremental utility in 67% of patients and considered favorable at a willingness-to-pay threshold of $150,000/QALY in >52% of patients. CONCLUSION BMP use was associated with reduction in revisions for symptomatic pseudarthrosis in ASD surgery. Cost-utility analysis suggests that BMP use may be favored in ASD surgery; however, this determination requires further research. LEVEL OF EVIDENCE 2.
Collapse
|
|
15
|
Abstract
BACKGROUND As the frequency of adult deformity surgery (ADS) continues to increase, our understanding of techniques that enhance fusion must continue to evolve because pseudarthrosis can be a serious and costly event. PURPOSES/QUESTIONS We sought to conduct a review of the literature investigating techniques that can enhance outcomes of ADS. METHODS Two databases were searched for keywords such as "advances in spinal fusion," "new technology in adult spinal deformity," "interbody devices for adult spinal deformity," "adult spinal deformity rods," and "screw design in adult spinal deformity" to examine recent literature and trends in ADS. RESULTS We identified 45 articles for our review. Topics studied include the use of multiple rods, interbody fusion, distal fixation techniques, and bone morphogenetic protein or iliac crest bone graft. CONCLUSIONS Many recent innovations in treatments to enhance fusion in ADS have been studied, some more controversial than others. Further research into the efficacy of these techniques may increase fusion rates in ADS.
Collapse
|
|
16
|
Preoperative and Postoperative Spending Among Working-Age Adults Undergoing Posterior Spinal Fusion Surgery for Degenerative Disease. World Neurosurg 2020; 138:e930-e939. [PMID: 32251816 DOI: 10.1016/j.wneu.2020.03.143] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Accepted: 03/24/2020] [Indexed: 11/20/2022]
Abstract
OBJECTIVE To investigate the health care resource utilization and the associated 6 months preoperative and 6 months postoperative spending among patients undergoing posterior lumbar fusion. METHODS We retrospectively reviewed a private insurance claims database for patients who underwent single-level posterior spinal fusion from January 2011 to December 2015. Outpatient health services, prescription pain medications, and inpatient admissions were assessed. RESULTS Among 25,401 patients (mean age, 52 years; 58% female) in the final cohort, median spending during the period from 6 months before surgery to 6 months after surgery was $60,714 (interquartile range [IQR], $46,961-$79,892)/patient. Preoperative spending accounted for 7% ($121 million) of the total costs, and postoperative spending accounted for 8% ($135 million). Median preoperative spending was $3566 (IQR, $2144-$5857) per patient, with imaging accounting for the highest proportion (33%) of preoperative spending. In the 6 months period preceding surgery, 46% patients received injections and 47% received physical therapy. The median postoperative spending was $1954/patient (IQR, $735-$4416). Total postoperative spending was significantly higher among those not discharged home (median, $7525; IQR, $6779-$19,602) compared with those discharged home (median, $1617/patient; IQR, $648-$4033) and home with home care services (median, $2921; IQR, $1406-$5662) (P < 0.001). CONCLUSIONS Unplanned readmission after posterior spinal fusion was the highest contributor to postoperative spending and the second highest contributor to overall costs. Understanding factors that contribute to the costs in the preoperative and postoperative period in patients undergoing single-level posterior lumbar fusion for degenerative pathology is essential to identify targets for cost containment.
Collapse
|
|
17
|
Park SJ, Lee KH, Lee CS, Jung JY, Park JH, Kim GL, Kim KT. Instrumented surgical treatment for metastatic spinal tumors: is fusion necessary? J Neurosurg Spine 2020; 32:456-464. [PMID: 31756698 DOI: 10.3171/2019.8.spine19583] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Accepted: 08/21/2019] [Indexed: 11/06/2022]
Abstract
OBJECTIVE The goal of this study was to evaluate the radiographic and clinical results of instrumentation surgery without fusion for metastases to the spine. METHODS Between 2010 and 2017, patients with spinal tumors who underwent instrumentation without fusion surgery were consecutively evaluated. Preoperative and postoperative clinical data were evaluated. Data were inclusive for last follow-up and just prior to death if the patient died. Instrumentation-related complications included screw migration, screw or rod breakage, cage migration, and screw loosening. RESULTS Excluding patients who died within 6 months, a total of 136 patients (140 operations) were recruited. The average follow-up duration was 16.5 months (median 12.4 months). The pain visual analog scale score decreased from 6.4 to 2.5 (p < 0.001) and the Eastern Cooperative Oncology Group scale score improved (p < 0.001). There were only 3 cases (2.1%) of symptomatic instrumentation-related complications that resulted in revisions. There were 6 cases of nonsymptomatic complications. The most common complication was screw migration or pull-out (5 cases). There were 3 cases of screw or rod breakage and 1 case of cage migration. Two-thirds of the cases of instrumentation-related complications occurred after 6 months, with a mean postoperative period of 1 year. CONCLUSIONS The current study reported successful outcomes with very low complication rates after nonfusion surgery for patients with spinal metastases, even among those who survived for more than 6 months. More than half of the instrumentation-related complications were asymptomatic and did not require revision. The results suggest that nonfusion surgery might be sufficient for a majority of patients with spinal metastases.
Collapse
Affiliation(s)
- Se-Jun Park
- 1Department of Orthopedic Surgery, Spine Center, Samsung Medical Center, Sungkyunkwan University School of Medicine
| | - Keun-Ho Lee
- 2Department of Orthopedic Surgery, Kangdong Sacred Heart Hospital, Hallym University College of Medicine; and
| | - Chong-Suh Lee
- 1Department of Orthopedic Surgery, Spine Center, Samsung Medical Center, Sungkyunkwan University School of Medicine
| | - Joon Young Jung
- 2Department of Orthopedic Surgery, Kangdong Sacred Heart Hospital, Hallym University College of Medicine; and
| | - Jin Ho Park
- 2Department of Orthopedic Surgery, Kangdong Sacred Heart Hospital, Hallym University College of Medicine; and
| | - Gab-Lae Kim
- 2Department of Orthopedic Surgery, Kangdong Sacred Heart Hospital, Hallym University College of Medicine; and
| | - Ki-Tack Kim
- 3Department of Orthopedic Surgery, Kyung Hee University Hospital at Gangdong, Kyung Hee University, Seoul, Republic of Korea
| |
Collapse
|
|
18
|
Patient Perceptions of Iliac Crest Bone Grafting in Minimally Invasive Transforaminal Lumbar Interbody Fusion. Clin Spine Surg 2019; 32:430-434. [PMID: 31790370 DOI: 10.1097/bsd.0000000000000781] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
STUDY DESIGN Retrospective cohort. OBJECTIVE The objective of this study was to determine patients' perception of iliac crest bone graft (ICBG) harvesting and donor site pain following minimally invasive transforaminal lumbar interbody fusion (MIS TLIF). SUMMARY OF BACKGROUND DATA The incidence of donor site pain has been debated in the literature because of the varying techniques associated with its harvest. METHODS Patients undergoing primary, single-level MIS TLIF with ICBG were retrospectively identified. ICBG harvesting was performed using a percutaneous technique with a tubular retractor. A survey was administered to assess if patients could accurately describe which side of their iliac crest they believed was harvested, and if they were experiencing any pain perceived to be originating from the donor site. Patient characteristics were compared using χ analysis and independent t test. RESULTS In total, 82 patients were included. The majority of patients had the ICBG harvested from the left iliac crest (97.5%). Approximately half of the patients correctly identified the side of harvest (50.6%). 48.1% of patients reported they were not confident or had guessed on their response. Patients that reported pain from the ICBG were more likely to feel confident or somewhat confident in their harvest site identification (57.9% vs. 46.3%) but less likely to be correct (36.8% vs. 63.4%) than patients without pain. 22 patients (27.8%) correctly identified the side of harvest without guessing. Of these, 11 (13.9%) reported pain. CONCLUSIONS Approximately half of patients undergoing MIS TLIF with ICBG are able to correctly identify which side of their iliac crest was harvested. However, the majority of patients reporting pain were unable to correctly identify the side of harvest. This suggests that most patients are likely attributing other sources of pain to their ICBG. Therefore, rates of donor site pain may be over-reported in the current literature with contemporary harvesting techniques.
Collapse
|
|
19
|
Safaee MM, Dalle Ore CL, Zygourakis CC, Deviren V, Ames CP. Estimating a price point for cost-benefit of bone morphogenetic protein in pseudarthrosis prevention for adult spinal deformity surgery. J Neurosurg Spine 2019; 30:814-821. [PMID: 30849745 DOI: 10.3171/2018.12.spine18613] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2018] [Accepted: 12/17/2018] [Indexed: 11/06/2022]
Abstract
OBJECTIVE Bone morphogenetic protein (BMP) is associated with reduced rates of pseudarthrosis and has the potential to decrease the need for revision surgery. There are limited data evaluating the cost-benefit of BMP for pseudarthrosis-related prevention surgery in adult spinal deformity. METHODS The authors performed a single-center retrospective review of 200 consecutive patients with adult spinal deformity. Demographic data and costs of BMP, primary surgery, and revision surgery for pseudarthrosis were collected. Patients with less than 12 months of follow-up or with infection, tumor, or neuromuscular disease were excluded. RESULTS One hundred fifty-one patients (107 [71%] women) with a mean age of 65 years met the inclusion criteria. The mean number of levels fused was 10; BMP was used in 98 cases (65%), and the mean follow-up was 23 months. Fifteen patients (10%) underwent surgical revision for pseudarthrosis; BMP use was associated with an 11% absolute risk reduction in the rate of reoperation (17% vs 6%, p = 0.033), with a number needed to treat of 9.2. There were no significant differences in age, sex, upper instrumented vertebra, or number of levels fused in patients who received BMP. In a multivariate model including age, sex, number of levels fused, and the upper instrumented vertebra, only BMP (OR 0.250, 95% CI 0.078-0.797; p = 0.019) was associated with revision surgery for pseudarthrosis. The mean direct cost of primary surgery was $87,653 ± $19,879, and the mean direct cost of BMP was $10,444 ± $4607. The mean direct cost of revision surgery was $52,153 ± $26,985. The authors independently varied the efficacy of BMP, cost of BMP, and cost of reoperation by ± 50%; only reductions in the cost of BMP resulted in a cost savings per 100 patients. Using these data, the authors estimated a price point of $5663 in order for BMP to be cost-neutral. CONCLUSIONS Use of BMP was associated with a significant reduction in the rates of revision surgery for pseudarthrosis. At its current price, the direct in-hospital costs for BMP exceed the costs associated with revision surgery; however, this likely underestimates the true value of BMP when considering the savings associated with reductions in rehabilitation, therapy, medication, and additional outpatient costs.
Collapse
Affiliation(s)
| | | | - Corinna C Zygourakis
- 2Department of Neurological Surgery, Johns Hopkins University, Baltimore, Maryland
| | - Vedat Deviren
- 3Orthopedic Surgery, University of California, San Francisco, California; and
| | - Christopher P Ames
- Departments of1Neurological Surgery and
- 3Orthopedic Surgery, University of California, San Francisco, California; and
| |
Collapse
|
|
20
|
White KA, Olabisi RM. Spatiotemporal Control Strategies for Bone Formation through Tissue Engineering and Regenerative Medicine Approaches. Adv Healthc Mater 2019; 8:e1801044. [PMID: 30556328 DOI: 10.1002/adhm.201801044] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2018] [Revised: 11/06/2018] [Indexed: 02/06/2023]
Abstract
Global increases in life expectancy drive increasing demands for bone regeneration. The gold standard for surgical bone repair is autografting, which enjoys excellent clinical outcomes; however, it possesses significant drawbacks including donor site morbidity and limited availability. Although collagen sponges delivered with bone morphogenetic protein, type 2 (BMP2) are a common alternative or supplement, they do not efficiently retain BMP2, necessitating extremely high doses to elicit bone formation. Hence, reports of BMP2 complications are rising, including cancer promotion and ectopic bone formation, the latter inducing complications such as breathing difficulties and neurologic impairments. Thus, efforts to exert spatial control over bone formation are increasing. Several tissue engineering approaches have demonstrated the potential for targeted and controlled bone formation. These approaches include biomaterial scaffolds derived from synthetic sources, e.g., calcium phosphates or polymers; natural sources, e.g., bone or seashell; and immobilized biofactors, e.g., BMP2. Although BMP2 is the only protein clinically approved for use in a surgical device, there are several proteins, small molecules, and growth factors that show promise in tissue engineering applications. This review profiles the tissue engineering advances in achieving control over the location and onset of bone formation (spatiotemporal control) toward avoiding the complications associated with BMP2.
Collapse
Affiliation(s)
- Kristopher A. White
- Department of Chemical and Biochemical Engineering; Rutgers University; 98 Brett Road Piscataway NJ 08854 USA
| | - Ronke M. Olabisi
- Department of Biomedical Engineering; Rutgers University; 599 Taylor Road Piscataway NJ 08854 USA
| |
Collapse
|
|
21
|
Samra H, Abdulla S, Elias GJB, Murphy KJ. Why Do We Believe What We Believe? J Vasc Interv Radiol 2018; 29:1754-1755. [PMID: 30502879 DOI: 10.1016/j.jvir.2018.05.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2017] [Revised: 05/08/2018] [Accepted: 05/25/2018] [Indexed: 11/24/2022] Open
Affiliation(s)
- Humraaz Samra
- Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Sarah Abdulla
- Department of Neuroradiology, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada
| | - Gavin J B Elias
- Department of Neuroradiology, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada
| | - Kieran J Murphy
- Department of Neuroradiology, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
| |
Collapse
|
|
22
|
Iliac Crest Bone Graft for Minimally Invasive Transforaminal Lumbar Interbody Fusion: A Prospective Analysis of Inpatient Pain, Narcotics Consumption, and Costs. Spine (Phila Pa 1976) 2018; 43:1307-1312. [PMID: 29462060 DOI: 10.1097/brs.0000000000002599] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
STUDY DESIGN Retrospective Analysis OBJECTIVE.: The aim of this study was to determine whether an association between increased acute pain, postoperative time, and direct hospital costs exists between the use of iliac crest bone grafting (ICBG) and bone morphogenic protein (BMP)-2 following a primary, single-level minimally invasive transforaminal lumbar interbody fusion (MIS TLIF). SUMMARY OF BACKGROUND DATA ICBG has been associated with enhanced fusion rates. Concerns have been raised in regards to increased operative time and postoperative pain. The advantages of ICBG compared to other spinal fusion adjuncts have been debated. METHODS Prospective, consecutive analysis of patients undergoing primary, single-level MIS TLIF with ICBG was compared to a historical cohort of consecutive patients that received BMP-2. Operative characteristics were compared between groups using χ analysis or independent t test for categorical and continuous variables, respectively. Postoperative inpatient pain was measured using the Visual Analog Scale, and inpatient narcotics consumption was quantified as oral morphine equivalents. Outcomes were compared between groups using multivariate regression controlling for preoperative characteristics. RESULTS A total of 98 patients were included in this analysis, 49 in each cohort. No significant differences were noted between cohorts with exception to sex (Females: ICBG, 53.06% vs. BMP-2, 32.65%, P = 0.041). There was a significant increase in operative time (14.53 minutes, P = 0.006) and estimated blood loss (16.64 mL, P = 0.014) in the ICBG cohort. Narcotics consumption was similar between groups on postoperative days 0 and 1. ICBG was associated with decreased total direct costs ($19,315 vs. $21,645, P < 0.001) as compared to BMP-2. CONCLUSION Patients undergoing MIS TLIF with ICBG experienced increases in operative time and estimated blood loss that were not clinically significant. Furthermore, iliac crest harvesting did not result in an increase in acute pain or narcotics consumption. Further follow-up is necessary to determine the associated arthrodesis rates and long-term outcomes between each cohort. LEVEL OF EVIDENCE 3.
Collapse
|
|
23
|
Drakhshandeh D, Miller JA, Fabiano AJ. Instrumented Spinal Stabilization without Fusion for Spinal Metastatic Disease. World Neurosurg 2018; 111:e403-e409. [PMID: 29275052 PMCID: PMC6022282 DOI: 10.1016/j.wneu.2017.12.081] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2017] [Revised: 12/11/2017] [Accepted: 12/13/2017] [Indexed: 02/08/2023]
Abstract
OBJECTIVES Spinal stabilization surgery is an integral part of the treatment of spinal metastatic disease. Bony fusion is the hallmark of spinal stabilization in non-oncology patients. Spinal oncology patients are unlikely to achieve bony fusion because of their overall prognosis and concurrent therapies. Stabilization surgery without fusion may be a reasonable approach for these patients. Literature evaluating the effectiveness of this approach is limited. The object of this study was to investigate the rate of instrumentation failure in patients undergoing posterior spinal instrumented stabilization without fusion for spinal metastatic disease. METHODS Data from consecutive cases of spinal surgery at our institution during an 81-month period were reviewed. Demographics, clinical notes, and computed tomography findings were recorded and used to evaluate instrumentation failures. Patients who underwent separation surgery that included laminectomy and posterior spinal instrumentation without fusion for spinal metastatic disease and had follow-up computed tomography scans >3 months postoperatively were selected for the study. RESULTS Twenty-seven patients were included in the study. Mean age was 64.85 ± 6.53 years. Nine patients were women. A mean of 1.61 ± 0.96 laminectomy levels was performed. A mean of 8.26 ± 1.48 screws was inserted. The mean postoperative discharge date was 5.07 ± 1.47 days. Mean follow-up duration was 12.17 ± 11.73 months. None of the patients had a change in instrumentation position, pedicle screw pullout, change in spinal alignment, or progressive deformity. No patient required reoperation or instrumentation revision or replacement. CONCLUSIONS Our experience suggests that instrumented spinal stabilization without fusion is an acceptable approach for patients with spinal metastatic disease.
Collapse
Affiliation(s)
- Dori Drakhshandeh
- Department of Neurosurgery, Roswell Park Cancer Institute, Buffalo, New York, USA
| | - James A Miller
- Department of Neurosurgery, Roswell Park Cancer Institute, Buffalo, New York, USA; Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA
| | - Andrew J Fabiano
- Department of Neurosurgery, Roswell Park Cancer Institute, Buffalo, New York, USA; Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA.
| |
Collapse
|
|
24
|
Imagama S, Ando K, Kobayashi K, Ishikawa Y, Nakamura H, Hida T, Ito K, Tsushima M, Matsumoto A, Morozumi M, Tanaka S, Machino M, Ota K, Nakashima H, Takamatsu J, Matsushita T, Nishida Y, Ishiguro N, Matsuyama Y. Efficacy of Early Fusion With Local Bone Graft and Platelet-Rich Plasma in Lumbar Spinal Fusion Surgery Followed Over 10 Years. Global Spine J 2017; 7:749-755. [PMID: 29238638 PMCID: PMC5721988 DOI: 10.1177/2192568217696690] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
STUDY DESIGN Prospective clinical study. OBJECTIVE Many oral surgeons use platelet-rich plasma (PRP) for bone defects, but the efficacy of PRP for spinal arthrodesis remains uncertain. The objective was to compare the efficacy of autologous local bone graft and PRP with local bone graft alone for promotion of bony union in posterolateral lumbar fusion (PLF) surgery, with investigation of the safety of PRP over 10 years. METHODS A prospective study was conducted in 29 consecutive patients who underwent one-level PLF at L4/5 for degenerative lumbar disease. Local bone on the left (control) side and local bone with PRP on the right side were grafted. The fusion area and absorption of grafted bone at 58 regions were determined using computed tomography at 2 weeks and 3, 6, and 12 months after surgery. RESULTS Average bone fusion areas on the PRP side were significantly wider at 3 and 6 months after surgery (P < .05). Average absorption values were significantly lower on the PRP side than on the control side at 3 and 6 months after surgery (P < .05). The PRP/control ratio was significantly different at 3 and 6 months compared to that at 2 weeks (P < .005). No adverse events related to PRP occurred with good clinical outcome over 10 years follow-up. CONCLUSIONS Local application of PRP combined with autologous local bone graft has a positive impact on early fusion for lumbar arthrodesis with no adverse events over 10 years, and thus is a safe and low cost autologous option in spinal fusion.
Collapse
Affiliation(s)
- Shiro Imagama
- Nagoya University Graduate School of Medicine, Department of Orthopaedic Surgery, Nagoya, Aichi, Japan,Shiro Imagama, Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65, Tsurumai, Showa-ku, Nagoya, Aichi 466-8550, Japan.
| | - Kei Ando
- Nagoya University Graduate School of Medicine, Department of Orthopaedic Surgery, Nagoya, Aichi, Japan
| | - Kazuyoshi Kobayashi
- Nagoya University Graduate School of Medicine, Department of Orthopaedic Surgery, Nagoya, Aichi, Japan
| | - Yoshimoto Ishikawa
- Nagoya University Graduate School of Medicine, Department of Orthopaedic Surgery, Nagoya, Aichi, Japan
| | | | - Tetsuro Hida
- Nagoya University Graduate School of Medicine, Department of Orthopaedic Surgery, Nagoya, Aichi, Japan
| | - Kenyu Ito
- Nagoya University Graduate School of Medicine, Department of Orthopaedic Surgery, Nagoya, Aichi, Japan
| | - Mikito Tsushima
- Nagoya University Graduate School of Medicine, Department of Orthopaedic Surgery, Nagoya, Aichi, Japan
| | - Akiyuki Matsumoto
- Nagoya University Graduate School of Medicine, Department of Orthopaedic Surgery, Nagoya, Aichi, Japan
| | - Masayoshi Morozumi
- Nagoya University Graduate School of Medicine, Department of Orthopaedic Surgery, Nagoya, Aichi, Japan
| | - Satoshi Tanaka
- Nagoya University Graduate School of Medicine, Department of Orthopaedic Surgery, Nagoya, Aichi, Japan
| | - Masaaki Machino
- Nagoya University Graduate School of Medicine, Department of Orthopaedic Surgery, Nagoya, Aichi, Japan
| | - Kyotaro Ota
- Nagoya University Graduate School of Medicine, Department of Orthopaedic Surgery, Nagoya, Aichi, Japan
| | - Hiroaki Nakashima
- Nagoya University Graduate School of Medicine, Department of Orthopaedic Surgery, Nagoya, Aichi, Japan
| | - Junki Takamatsu
- Japan Red Cross Tokai-Hokuriku Block Blood Center, Seto, Aichi, Japan
| | - Tadashi Matsushita
- Nagoya University Hospital, Department of Transfusion Medicine, Nagoya, Aichi, Japan
| | - Yoshihiro Nishida
- Nagoya University Graduate School of Medicine, Department of Orthopaedic Surgery, Nagoya, Aichi, Japan
| | - Naoki Ishiguro
- Nagoya University Graduate School of Medicine, Department of Orthopaedic Surgery, Nagoya, Aichi, Japan
| | - Yukihiro Matsuyama
- Hamamatsu University School of Medicine, Department of Orthopaedic Surgery, Hamamatsu, Shizuoka, Japan
| |
Collapse
|
|
25
|
Complications Related to the Recombinant Human Bone Morphogenetic Protein 2 Use in Posterior Cervical Fusion. Clin Spine Surg 2017; 30:E1269-E1273. [PMID: 27632774 DOI: 10.1097/bsd.0000000000000443] [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: 11/26/2022]
Abstract
STUDY DESIGN A retrospective cohort study. OBJECTIVE To compare the complications between posterior cervical fusions with and without recombinant human bone morphogenetic protein 2 (rhBMP2). SUMMARY OF BACKGROUND DATA Use of rhBMP2 in anterior cervical spinal fusion procedures can lead to potential complications such as neck edema, resulting in airway complications or neurological compression. However, there are no data on the complications associated with the "off-label" use of rhBMP2 in upper and lower posterior cervical fusion approaches. MATERIALS AND METHODS Patients from the PearlDiver database who had a posterior cervical fusion between 2005 and 2011 were identified. We evaluated complications within 90 days after fusion and data was divided in 2 groups: (1) posterior cervical fusion including upper cervical spine O-C2 (upper group) and (2) posterior cervical fusion including lower cervical spine C3-C7 (lower group). Complications were divided into: any complication, neck-related complications, wound-related complications, and other complications. RESULTS Of the 352 patients in the upper group, 73 patients (20.7%) received rhBMP2, and 279 patients (79.3%) did not. Likewise, in the lower group of 2372 patients, 378 patients (15.9%) had surgery with rhBMP2 and 1994 patients (84.1%) without. In the upper group, complications were observed in 7 patients (9.6%) with and 34 patients (12%) without rhBMP2. In the lower group, complications were observed in 42 patients (11%) with and 276 patients (14%) without rhBMP2. Furthermore, in the lower group the wound-related complications were significantly higher in the rhBMP2 group (23 patients, 6.1%) compared with the non-rhBMP2 group (75 patients, 3.8%). CONCLUSIONS Our data showed that the use of rhBMP2 does not increase the risk of complications in upper cervical spine fusion procedures. However, in the lower cervical spine, rhBMP2 may elevate the risk of wound-related complications. Overall, there were no major complications associated with the use of rhBMP2 for posterior cervical fusion approaches. LEVEL OF EVIDENCE Level III.
Collapse
|
|
26
|
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: 32] [Impact Index Per Article: 4.0] [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.
Collapse
|
|
27
|
Tanaka M, Sato Y, Haniu H, Nomura H, Kobayashi S, Takanashi S, Okamoto M, Takizawa T, Aoki K, Usui Y, Oishi A, Kato H, Saito N. A three-dimensional block structure consisting exclusively of carbon nanotubes serving as bone regeneration scaffold and as bone defect filler. PLoS One 2017; 12:e0172601. [PMID: 28235026 PMCID: PMC5325283 DOI: 10.1371/journal.pone.0172601] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2016] [Accepted: 02/07/2017] [Indexed: 01/24/2023] Open
Abstract
Many recent studies have been conducted to assess the ability of composite materials containing carbon nanotubes (CNTs) with high bone affinity to serve as scaffolds in bone regenerative medicine. These studies have demonstrated that CNTs can effectively induce bone formation. However, no studies have investigated the usefulness of scaffolds consisting exclusively of CNTs in bone regenerative medicine. We built a three-dimensional block entity with maximized mechanical strength from multi-walled CNTs (MWCNT blocks) and evaluated their efficacy as scaffold material for bone repair. When MWCNT blocks containing recombinant human bone morphogenetic protein-2 (rhBMP-2) were implanted in mouse muscle, ectopic bone was formed in direct contact with the blocks. Their bone marrow densities were comparable to those of PET-reinforced collagen sheets with rhBMP-2. On day 1 and day 3, MC3T3-E1 preosteoblasts were attached to the scaffold surface of MWCNT blocks than that of PET-reinforced collagen sheets. They also showed a maximum compression strength comparable to that of cortical bone. Our MWCNT blocks are expected to serve as bone defect filler and scaffold material for bone regeneration.
Collapse
Affiliation(s)
- Manabu Tanaka
- Department of Orthopaedic Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, Japan
| | - Yoshinori Sato
- Graduate School of Environmental Studies, Tohoku University, Aoba 6-6-20, Aramaki, Aoba-ku, Sendai, Japan
| | - Hisao Haniu
- Department of Orthopaedic Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, Japan
- Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, Asahi 3-1-1, Matsumoto, Japan
| | - Hiroki Nomura
- Department of Orthopaedic Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, Japan
| | - Shinsuke Kobayashi
- Department of Orthopaedic Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, Japan
| | - Seiji Takanashi
- Department of Orthopaedic Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, Japan
| | - Masanori Okamoto
- Department of Orthopaedic Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, Japan
| | - Takashi Takizawa
- Department of Orthopaedic Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, Japan
| | - Kaoru Aoki
- Department of Applied Physical Therapy, Shinshu University School of Health Sciences, Asahi 3-1-1, Matsumoto, Japan
| | - Yuki Usui
- Aizawa Hospital Sports Medicine Center, Honjou 2-5-1, Matsumoto, Japan
| | - Ayumu Oishi
- Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, Asahi 3-1-1, Matsumoto, Japan
| | - Hiroyuki Kato
- Department of Orthopaedic Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, Japan
| | - Naoto Saito
- Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, Asahi 3-1-1, Matsumoto, Japan
| |
Collapse
|
|
28
|
Wilson RJ, Sulieman LM, VanHouten JP, Halpern JL, Schwartz HS, Devin CJ, Holt GE. Cost-utility of osteoarticular allograft versus endoprosthetic reconstruction for primary bone sarcoma of the knee: A markov analysis. J Surg Oncol 2017; 115:257-265. [PMID: 28105636 DOI: 10.1002/jso.24525] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2016] [Revised: 10/28/2016] [Accepted: 11/18/2016] [Indexed: 01/25/2023]
Abstract
BACKGROUND The most cost-effective reconstruction after resection of bone sarcoma is unknown. The goal of this study was to compare the cost effectiveness of osteoarticular allograft to endoprosthetic reconstruction of the proximal tibia or distal femur. METHODS A Markov model was used. Revision and complication rates were taken from existing studies. Costs were based on Medicare reimbursement rates and implant prices. Health-state utilities were derived from the Health Utilities Index 3 survey with additional assumptions. Incremental cost-effectiveness ratios (ICER) were used with less than $100 000 per quality-adjusted life year (QALY) considered cost-effective. Sensitivity analyses were performed for comparison over a range of costs, utilities, complication rates, and revisions rates. RESULTS Osteoarticular allografts, and a 30% price-discounted endoprosthesis were cost-effective with ICERs of $92.59 and $6 114.77. One-way sensitivity analysis revealed discounted endoprostheses were favored if allografts cost over $21 900 or endoprostheses cost less than $51 900. Allograft reconstruction was favored over discounted endoprosthetic reconstruction if the allograft complication rate was less than 1.3%. Allografts were more cost-effective than full-price endoprostheses. CONCLUSIONS Osteoarticular allografts and price-discounted endoprosthetic reconstructions are cost-effective. Sensitivity analysis, using plausible complication and revision rates, favored the use of discounted endoprostheses over allografts. Allografts are more cost-effective than full-price endoprostheses.
Collapse
Affiliation(s)
- Robert J Wilson
- Department of Orthopaedics and Rehabilitation, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Lina M Sulieman
- Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Jacob P VanHouten
- Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee.,Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Jennifer L Halpern
- Department of Orthopaedics and Rehabilitation, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Herbert S Schwartz
- Department of Orthopaedics and Rehabilitation, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Clinton J Devin
- Department of Orthopaedics and Rehabilitation, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Ginger E Holt
- Department of Orthopaedics and Rehabilitation, Vanderbilt University Medical Center, Nashville, Tennessee
| |
Collapse
|
|
29
|
Parker RM, Malham GM. Comparison of a calcium phosphate bone substitute with recombinant human bone morphogenetic protein-2: a prospective study of fusion rates, clinical outcomes and complications with 24-month follow-up. EUROPEAN SPINE JOURNAL : OFFICIAL PUBLICATION OF THE EUROPEAN SPINE SOCIETY, THE EUROPEAN SPINAL DEFORMITY SOCIETY, AND THE EUROPEAN SECTION OF THE CERVICAL SPINE RESEARCH SOCIETY 2016; 26:754-763. [PMID: 28028645 DOI: 10.1007/s00586-016-4927-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/21/2016] [Revised: 11/19/2016] [Accepted: 12/16/2016] [Indexed: 01/17/2023]
Abstract
PURPOSE Recombinant human bone morphogenetic protein-2 (rhBMP-2) generally provides high rates of clinical improvement and fusion. However, rhBMP-2 has been associated with adverse effects. Recently, a beta tricalcium phosphate (β-TCP) bone substitute has been developed. The aim of this study was to determine the fusion rates and clinical outcomes of patients treated with β-TCP compared to rhBMP-2. METHODS One hundred and thirty-five consecutive patients who underwent lateral lumbar interbody fusion with β-TCP (n = 25) or rhBMP-2 (n = 110) in the interbody cage were included in the study. The 25 β-TCP patients were a group of consecutive patients from numbers 46 to 70. Clinical outcomes included back and leg pain, Oswestry Disability Index (ODI), and SF-36 physical and mental component scores (PCS and MCS). CT scans were performed at 6, 12, 18, and 24 months until confirmation of solid interbody fusion, with no further scans performed once fusion was achieved. Targeted CT at the operative level(s) was performed to reduce radiation exposure. RESULTS At 24 months there was no significant difference between clinical outcomes of the β-TCP or rhBMP-2 patients, with improvements in back pain (46% and 49%; P = 0.98), leg pain (31 and 52%; P = 0.14), ODI (38 and 41%; P = 0.81), SF-36 PCS (37 and 38%; P = 0.87), and SF-36 MCS (8 and 8%; P = 0.93). The fusion rate was significantly higher for rhBMP-2 with 96% compared to 80% for β-TCP (P = 0.01). Separating patients into those with a standalone cage and those with supplemental posterior instrumentation, there was no significant difference between instrumented fusion rates of the β-TCP and rhBMP-2 patients at 6 (P = 0.44), 12 (P = 0.49), 18 (P = 0.31) or 24 (P = 0.14) months. For standalone patients there was a significant difference at 6 (P = 0.01), 12 (P = 0.008) and 18 months (P = 0.004) with higher fusion rates in the rhBMP-2 group; however, by 24 months this was not significant (P = 0.18). CONCLUSIONS Comparable clinical outcomes and complication rates suggest that β-TCP is a viable alternative to rhBMP-2. The difference in fusion rates for the standalone patients suggests that β-TCP may require supplemental posterior instrumentation to enhance fusion.
Collapse
Affiliation(s)
- Rhiannon M Parker
- Greg Malham Neurosurgeon, Suite 2, Level 1, 517 St. Kilda Road, Melbourne, VIC, 3004, Australia
| | - Gregory M Malham
- Greg Malham Neurosurgeon, Suite 2, Level 1, 517 St. Kilda Road, Melbourne, VIC, 3004, Australia. .,Neuroscience Institute, Epworth Hospital, Melbourne, VIC, 3121, Australia.
| |
Collapse
|
|
30
|
Poeran J, Opperer M, Rasul R, Mazumdar M, Girardi FP, Hughes AP, Memtsoudis SG, Vougioukas V. Change in Off-Label Use of Bone Morphogenetic Protein in Spine Surgery and Associations with Adverse Outcome. Global Spine J 2016; 6:650-659. [PMID: 27781184 PMCID: PMC5077709 DOI: 10.1055/s-0036-1571284] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2015] [Accepted: 11/24/2015] [Indexed: 01/17/2023] Open
Abstract
Study Design Retrospective cohort study. Objective The U.S. Food and Drug Administration issued a warning in 2008 against off-label bone morphogenetic protein (BMP-2) use. We aimed to determine (off-label) BMP-2 use in two periods and associations with complications. Methods We included 340,393 patients undergoing spinal fusions from the Premier Perspective database (2006 to 2012). BMP-2 use was determined from billing in 2006 to 2008 versus 2009 to 2012. Outcomes included revisions, length of hospital stay (LOHS), and cost of hospital stay (COH). Multilevel regressions measured associations between BMP-2 and outcomes; odds ratios (ORs) and 95% confidence intervals (CIs) are reported. Results BMP-2 use decreased from 18.7% in 2006 to 11.5% in 2012. Off-label use remains but is decreasing, particularly for cervical anterior (5.1 versus 2.0%) and cervical posterior procedures (15.3 versus 8.5%; both p < 0.01 comparing 2006 to 2008 with 2009 to 2012). BMP-2 remains associated with increased LOHS (median 2 versus 3 days; both periods) and COH (median $15,455 versus $27,881 in 2006 to 2008; $17,007 versus $30,331 in 2009 to 2012). Adjusted ORs for the association between BMP-2 and adverse outcomes were generally lower in 2009 to 2012 compared with 2006 to 2008. Most notably, we demonstrate lower ORs for revision after cervical fusions in 2009 to 2012 (OR 1.67, CI 1.01 to 2.78) compared with 2006 to 2008 (OR 2.43, CI 1.66 to 3.54). Conclusions Using a previously untapped data source, we show decreased (off-label) BMP-2 use in spinal fusions, particularly in cervical fusions. Although there was a tendency of decreased odds in 2009 to 2012, higher resource utilization and odds for complications remain in patients using BMP-2. A national registry or prospective observational studies will benefit the ongoing discussion.
Collapse
Affiliation(s)
- Jashvant Poeran
- Department of Population Health Science and Policy, Institute for Healthcare Delivery Science, Icahn School of Medicine at Mount Sinai, New York, New York, United States,Address for correspondence Jashvant Poeran, MD, PhD Department of Population Health Science and PolicyInstitute for Healthcare Delivery Science, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue (Box 1077), New York, NY 10029United States
| | - Mathias Opperer
- Department of Anesthesiology, Hospital for Special Surgery, New York, New York, United States
| | - Rehana Rasul
- Department of Population Health Science and Policy, Institute for Healthcare Delivery Science, Icahn School of Medicine at Mount Sinai, New York, New York, United States
| | - Madhu Mazumdar
- Department of Population Health Science and Policy, Institute for Healthcare Delivery Science, Icahn School of Medicine at Mount Sinai, New York, New York, United States
| | - Federico P. Girardi
- Department of Orthopedic Surgery, Hospital for Special Surgery, New York, New York, United States
| | - Alexander P. Hughes
- Department of Orthopedic Surgery, Hospital for Special Surgery, New York, New York, United States
| | - Stavros G. Memtsoudis
- Department of Anesthesiology, Hospital for Special Surgery, New York, New York, United States
| | - Vassilios Vougioukas
- Department of Neurosurgery, Albert Ludwig University of Freiburg, Freiburg, Germany
| |
Collapse
|
|
31
|
Guppy KH, Harris J, Chen J, Paxton EW, Bernbeck JA. Reoperation rates for symptomatic nonunions in posterior cervicothoracic fusions with and without bone morphogenetic protein in a cohort of 450 patients. J Neurosurg Spine 2016; 25:309-17. [DOI: 10.3171/2016.1.spine151330] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
OBJECTIVE
Fusions across the cervicothoracic junction have been challenging because of the large biomechanical forces exerted resulting in frequent reoperations for nonunions. The objective of this study was to investigate a retrospective cohort using chart review of posterior cervicothoracic spine fusions with and without bone morphogenetic protein (BMP) and to determine the reoperation rates for symptomatic nonunions in both groups.
METHODS
Between January 2009 and September 2013, posterior cervicothoracic spine fusion cases were identified from a large spine registry (Kaiser Permanente). Demographics, diagnoses, operative times, lengths of stay, and reoperations were extracted from the registry. Reoperations for symptomatic nonunions were adjudicated via chart review. Logistic regression was used to estimate odds ratios and 95% confidence intervals. Kaplan-Meier curves for the non-BMP and BMP groups were generated and compared using the log-rank test.
RESULTS
In this cohort there were 450 patients (32.7% with BMP) with a median follow-up of 1.4 years (interquartile range [IQR] 0.5–2.7 years). Kaplan-Meier curves showed no significant difference in reoperation rates for nonunions using the log-rank test (p = 0.088). In a subset of patients with more than 1 year of follow-up, 260 patients were identified (43.1% with BMP) with a median follow-up duration of 2.4 years (IQR 1.6–3.3 years). There was no statistically significant difference in the symptomatic operative nonunion rates for posterior cervicothoracic fusions with and without BMP (0.0% vs 2.7%, respectively; p = 0.137) for more than 1 year of follow-up.
CONCLUSIONS
This study presents the largest series of patients using BMP in posterior cervicothoracic spine fusions. Reoperation rates for symptomatic nonunions with more than 1 year of follow-up were 0% with BMP and 2.7% without BMP. No statistically significant difference in the reoperation rates for symptomatic nonunions with or without BMP was found.
Collapse
Affiliation(s)
- Kern H. Guppy
- 1Department of Neurosurgery, Kaiser Permanente Medical Group, Sacramento
| | - Jessica Harris
- 2Surgical Outcomes & Analysis Unit of Clinical Analysis, Kaiser Permanente, San Diego; and
| | - Jason Chen
- 2Surgical Outcomes & Analysis Unit of Clinical Analysis, Kaiser Permanente, San Diego; and
| | - Elizabeth W. Paxton
- 2Surgical Outcomes & Analysis Unit of Clinical Analysis, Kaiser Permanente, San Diego; and
| | - Johannes A. Bernbeck
- 3Department of Orthopaedics, Kaiser Permanente Southern California, Baldwin Park, California
| |
Collapse
|
|
32
|
Schmitt PJ, Kelleher JP, Ailon T, Heller JE, Kasliwal MK, Shaffrey CI, Smith JS. Long-Segment Fusion for Adult Spinal Deformity Correction Using Low-Dose Recombinant Human Bone Morphogenetic Protein-2. Neurosurgery 2016; 79:212-21. [DOI: 10.1227/neu.0000000000001194] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Abstract
BACKGROUND:
Although use of very high-dose recombinant human bone morphogenetic protein-2 (rhBMP-2) has been reported to markedly improve fusion rates in adult spinal deformity (ASD) surgery, most centers use much lower doses due to cost constraints. How effective these lower doses are for fusion enhancement remains unclear.
OBJECTIVE:
To assess fusion rates using relatively low-dose rhBMP-2 for ASD surgery.
METHODS:
This was a retrospective review of consecutive ASD patients that underwent thoracic to sacral fusion. Patients that achieved 2-year follow-up were analyzed. Impact of patient and surgical factors on fusion rate was assessed, and fusion rates were compared with historical cohorts.
RESULTS:
Of 219 patients, 172 (78.5%) achieved 2-year follow-up and were analyzed. Using an average rhBMP-2 dose of 3.1 mg/level (average total dose = 35.9 mg/case), the 2-year fusion rate was 73.8%. Cancellous allograft, local autograft, and very limited iliac crest bone graft (<20 mL, obtained during iliac bolt placement) were also used. On multivariate analysis, female sex was associated with a higher fusion rate, whereas age, comorbidity score, deformity type, and 3-column osteotomy were not. There were no complications directly attributable to rhBMP-2.
CONCLUSION:
Fusion rates for ASD using low-dose rhBMP-2 were comparable to those reported for iliac crest bone graft but lower than for high-dose rhBMP-2. Importantly, there were substantial differences between patients in the present series and those in the historical comparison groups that could not be fully adjusted for based on available data. Prospective evaluation of rhBMP-2 dosing for ASD surgery is warranted to define the most appropriate dose that balances benefits, risks, and costs.
Collapse
Affiliation(s)
- Paul J. Schmitt
- Department of Neurosurgery, University of Virginia Medical Center, Charlottesville, Virginia
| | - John P. Kelleher
- Department of Neurosurgery, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania
| | - Tamir Ailon
- Department of Neurosurgery, University of Virginia Medical Center, Charlottesville, Virginia
| | - Joshua E. Heller
- Department of Neurosurgery, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Manish K. Kasliwal
- Department of Neurosurgery, Rush University Medical Center, Chicago, Illinois
| | - Christopher I. Shaffrey
- Department of Neurosurgery, University of Virginia Medical Center, Charlottesville, Virginia
| | - Justin S. Smith
- Department of Neurosurgery, University of Virginia Medical Center, Charlottesville, Virginia
| |
Collapse
|
|
33
|
Recombinant Human Bone Morphogenetic Protein-2 in Posterolateral Spinal Fusion: What's the Right Dose? Asian Spine J 2016; 10:457-64. [PMID: 27340524 PMCID: PMC4917763 DOI: 10.4184/asj.2016.10.3.457] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2015] [Revised: 10/09/2015] [Accepted: 10/09/2015] [Indexed: 11/08/2022] Open
Abstract
STUDY DESIGN Single center retrospective cohort analysis. PURPOSE The goal was to evaluate the influence of varying amount of recombinant human bone morphogenetic protein 2 (rhBMP-2) per level on fusion rates and complications in posterolateral spinal fusions. OVERVIEW OF LITERATURE rhBMP-2 has been utilized for lumbar posterolateral fusions for many years. Initial rhBMP-2 recommendations were 20 mg/level of fusion. Dose and concentration per level in current studies vary from 4.2 to 40 mg and 1.5 to 2.0 mg/mL, respectively. Variable fusion and complication rates have been reported. METHODS Patients (n=1,610) undergoing instrumented lumbar spinal fusion (2003-2009) with utilization of rhBMP-2 were retrospectively evaluated. Patient demographics, body mass index (BMI), comorbidities, number of levels, associated interbody fusion, and types of bone void filler were analyzed. Fusions rates and nonunions were subdivided into number of levels and amount of rhBMP-2 used per level. RESULTS Patients (n=559) were evaluated with 58.5% females having an average age of 63 years, BMI of 31 kg/m(2). Number of levels fused ranged from 1 to 8. rhBMP-2 averaged 7.3 mg/level (range, 1.5-24 mg/level) based upon length of collagen sponge in relation to length of fusion levels. Patients with non-union formation had lower rhBMP-2 dose per level (p=0.016). A significant difference in non-union rate was found between patients undergoing fusion with <6 mg/level compared to those with >6 mg/level (9.1% vs. 2.4%, χ(2)=0.012). No significant differences were noted between 6-11.9 mg/level and ≥12 mg/level. No threshold was found for seroma formation or bone overgrowth. CONCLUSIONS Previous recommendation of 20 mg/level of rhBMP-2 is more than what is required for predictable fusion rates of 98%. No dose related increase of infection, seroma formation, and bone overgrowth has been found. In order to provide variable dosing and cost reduction, industry generated rhBMP-2 kit size should be optimized.
Collapse
|
|
34
|
The Cost Effectiveness of Polyetheretheketone (PEEK) Cages for Anterior Cervical Discectomy and Fusion. ACTA ACUST UNITED AC 2016; 28:E482-92. [PMID: 24662283 DOI: 10.1097/bsd.0b013e3182aa3676] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
STUDY DESIGN Cost-effectiveness analysis using a Markov model with inputs from published literature. OBJECTIVE To learn which graft or hardware option used in a single-level anterior cervical discectomy and fusion (ACDF) is most beneficial in terms of cost, quality of life, and overall cost effectiveness. Options studied were autograft, allograft, and polyetheretherketone (PEEK) cages for cervical fusion. SUMMARY OF BACKGROUND DATA ACDF is commonly used to treat cervical myelopathy and/or radiculopathy. No study has compared the cost effectiveness of autograft, allograft, and PEEK in 1-level ACDF. MATERIALS AND METHODS A literature review provided inputs into a Markov decision model to determine the most effective graft or hardware option for 1-level ACDF. Data regarding rate of complications, quality-adjusted life years (QALYs) gained, and cost for each procedure type was collected. The Markov model was first run in a base case, using all currently available data. The model was then tested using 1-way and 2-way sensitivity analyses to determine the validity of the model's conclusions if specific aspects of model were changed. This model was run for 10 years postoperatively. RESULTS The cost per QALY for each option in the base case analysis was $3328/QALY for PEEK, $2492/QALY for autograft, and $2492/QALY for allograft. All graft/hardware options are cost effective ways to improve outcomes for patients living with chronic neck pain. For graft/hardware options the most cost-effective option was allograft. The incremental cost-effectiveness ratio for PEEK compared with autograft or allograft was >$100,000/QALY. CONCLUSIONS Allograft is the most cost-effective graft/hardware option for ACDF. Compared with living with cervical myelopathy and/or radiculopathy, ACDF using any graft or hardware option is a cost-effective method of improving the quality of life of patients. PEEK is not a cost-effective option compared with allograft or autograft for use in ACDF.
Collapse
|
|
35
|
Guppy KH, Harris J, Chen J, Paxton EW, Alvarez J, Bernbeck J. Reoperation rates for symptomatic nonunions in posterior cervical (subaxial) fusions with and without bone morphogenetic protein in a cohort of 1158 patients. J Neurosurg Spine 2016; 24:556-64. [DOI: 10.3171/2015.7.spine15353] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
OBJECTIVE
Bone morphogenetic protein (BMP) was first approved in 2002 for use in single-level anterior lumbar fusions as an alternative to iliac crest grafts. Subsequent studies have concluded that BMP provides superior fusions rates and therefore reduces reoperations for nonunions. The purpose of this study was to determine the reoperation rates for symptomatic nonunions in posterior cervical (subaxial) spinal fusions with and without the use of BMP and to determine if the nonunion rates are statistically significantly different between the two groups.
METHODS
Between January 2009 and September 2013, the authors identified 1158 posterior cervical spinal fusion cases in the subaxial spine (C2–7) from a large spine registry (Kaiser Permanente). Patient characteristics, diagnoses, operative times, lengths of stay, and reoperations were extracted from the registry. Reoperations for symptomatic nonunions were adjudicated via chart review. Logistic regression was conducted to produce estimates of odds ratios (OR) and 95% confidence intervals (CIs). Kaplan-Meier curves for the non-BMP and BMP groups were generated and compared using the log-rank test.
RESULTS
In this cohort there were 1158 patients (19.3% with BMP) with a median follow up of 1.7 years (interquartile range [IQR] 0.7–2.9 years) and median duration to operative nonunion of 0.63 years (IQR 0.44–1.57 years). Kaplan-Meier curves showed no significant difference in reoperation rates for nonunions using the log-rank test (p = 0.179). In a subset of patients with more than 1 year of follow-up, 788 patients were identified (22.5% with BMP) with a median follow-up duration of 2.5 years (IQR 1.7–3.4 years) and a median time to operative nonunion of 0.73 years (IQR 0.44–1.57 years). There was no statistically significant difference in the symptomatic operative nonunion rates for posterior cervical (subaxial) fusions with BMP compared with non-BMP (1.1% vs 0.7%; crude OR 1.73, 95% CI 0.32–9.55, p = 0.527) for more than 1 year of follow-up.
CONCLUSIONS
This study presents the largest series of patients using BMP in posterior cervical (subaxial) spinal fusions. Reoperation rates for symptomatic nonunions with more than 1 year of follow-up were found to be 1.1% with BMP and 0.7% without BMP. There was no significant difference in the reoperation rates for symptomatic nonunions with or without BMP.
Collapse
Affiliation(s)
- Kern H. Guppy
- 1Department of Neurosurgery, Kaiser Permanente Medical Group, Sacramento
| | - Jessica Harris
- 2Surgical Outcomes & Analysis Unit of Clinical Analysis, Kaiser Permanente, San Diego; and
| | - Jason Chen
- 2Surgical Outcomes & Analysis Unit of Clinical Analysis, Kaiser Permanente, San Diego; and
| | - Elizabeth W. Paxton
- 2Surgical Outcomes & Analysis Unit of Clinical Analysis, Kaiser Permanente, San Diego; and
| | - Julie Alvarez
- 2Surgical Outcomes & Analysis Unit of Clinical Analysis, Kaiser Permanente, San Diego; and
| | - Johannes Bernbeck
- 3Department of Orthopaedics, Kaiser Permanente Southern California, Baldwin Park, California
| |
Collapse
|
|
36
|
Cost-Utility Analysis of 1- and 2-Level Dorsal Lumbar Fusions With and Without Recombinant Human Bone Morphogenic Protein-2 at 1-Year Follow-Up. Clin Spine Surg 2016; 29:E28-33. [PMID: 24870120 DOI: 10.1097/bsd.0000000000000079] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
STUDY DESIGN A retrospective 1-year cost-utility analysis. OBJECTIVE To determine the cost-effectiveness of using recombinant human bone morphogenic protein (rhBMP-2) in addition to autograft for 1- and 2-level lumbar fusions. SUMMARY OF BACKGROUND DATA rhBMP-2 has been studied extensively to identify its benefits, risks, patient outcomes, and costs relative to autograft [local bone or iliac crest bone graft (ICBG)]. This study seeks to analyze the cost-effectiveness of adding rhBMP-2 to autograft versus without rhBMP-2 in lumbar fusions. METHODS Thirty-three patients receiving rhBMP-2 in addition to either local bone autograft or ICBG (rhBMP-2 cohort) and 42 patients receiving only local bone autograft or ICBG (control cohort) for 1- or 2-level dorsal lumbar fusion were analyzed. This included posterolateral fusion, posterior lumbar interbody fusion, and transforaminal lumbar interbody fusion. One-year postoperative health outcomes were assessed based on Visual Analogue Scale, Pain Disability Questionnaire, Patient Health Questionnaire, and EuroQol-5 Dimensions questionnaires. Direct medical costs were estimated using Medicare national payment amounts and indirect costs were based on patient missed work days and patient income. Postoperative 1-year cost-utility ratios and the incremental cost-effectiveness ratio (ICER) were calculated to assess for cost-effectiveness using a threshold of $100,000/QALY gained. RESULTS The 1-year cost-utility ratio (total cost/ΔQALY) for the control cohort was significantly lower ($143,251/QALY gained) than that of the rhBMP-2 cohort ($272,414/QALY gained) (P<0.01). At 1-year follow-up, the control group dominated the ICER compared with the rhBMP-2 group. CONCLUSIONS Statistically significant and clinically relevant improvements (through minimum clinically important differences) were seen for both cohorts. In the ICER analysis, the control cohort dominated the rhBMP-2 group. Assuming durable per year gains in QALY, by 2 years fusion with autograft but without rhBMP-2 would be considered cost-effective ($71,625/QALY gained), whereas fusion with both autograft and rhBMP-2 would not be cost-effective ($136,207/QALY gained).
Collapse
|
|
37
|
Trends analysis of rhBMP utilization in single-level posterior lumbar fusion (PLF) in the United States. EUROPEAN SPINE JOURNAL : OFFICIAL PUBLICATION OF THE EUROPEAN SPINE SOCIETY, THE EUROPEAN SPINAL DEFORMITY SOCIETY, AND THE EUROPEAN SECTION OF THE CERVICAL SPINE RESEARCH SOCIETY 2015; 25:783-8. [PMID: 26003814 DOI: 10.1007/s00586-015-4032-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/17/2014] [Revised: 05/13/2015] [Accepted: 05/14/2015] [Indexed: 10/23/2022]
Abstract
PURPOSE A retrospective database review was carried out to evaluate the trends and demographics of rhBMP utilization in single-level posterior lumbar fusion (PLF) in the United States. METHODS Patients who underwent single-level PLF from 2005 to 2011 were identified by searching ICD-9 diagnosis and procedure codes in the PearlDiver Patient Records Database (PearlDiver Technologies, Fort Wayne, IN, USA), a national database of orthopaedic insurance records. The year of procedure, age, gender, and region of the United States were recorded for each patient. Results were reported for each variable as the incidence of procedures identified per 100,000 patients searched in the database. RESULTS Totally 5158 patients had single-level PLF in this study. The average rate of single-level PLF with rhBMP utilization maintained at a relatively stable level (19.1-23.5%) from 2005 to 2009, but sharply decreased to 6.8% in 2010 and 6.9% in 2011. The overall incidence of single-level PLF without rhBMP (1.37 cases per 100,000 patients) was more than five times of the incidence of single-level PLF with rhBMP (0.27 cases per 100,000 patients) (P < 0.01). The average rate of single-level PLF with rhBMP utilization is highest in Midwest (18.7%), followed by West (18.4%), South (16.4%) and Northeast (11.5%). The highest incidence of single-level PLF with rhBMP was observed in the group aged 70-74 years with an incidence of 0.33 per 100,000 patients. CONCLUSIONS The incidence of rhBMP utilization in single-level PLF increased from 2006 to 2009, but dropped to a low level in 2010 and 2011. The Northeast region had the lowest incidence of rhBMP utilization. The group aged 70-74 years trended to have the higher incidence of single-level PLF with rhBMP utilization.
Collapse
|
|
38
|
Loozen LD, van der Helm YJ, Öner FC, Dhert WJ, Kruyt MC, Alblas J. Bone Morphogenetic Protein-2 Nonviral Gene Therapy in a Goat Iliac Crest Model for Bone Formation. Tissue Eng Part A 2015; 21:1672-9. [DOI: 10.1089/ten.tea.2014.0593] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- Loek D. Loozen
- Department of Orthopaedics, University Medical Center Utrecht, Utrecht, The Netherlands
| | | | - F. Cumhur Öner
- Department of Orthopaedics, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Wouter J.A. Dhert
- Department of Orthopaedics, University Medical Center Utrecht, Utrecht, The Netherlands
- Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
| | - Moyo C. Kruyt
- Department of Orthopaedics, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Jacqueline Alblas
- Department of Orthopaedics, University Medical Center Utrecht, Utrecht, The Netherlands
| |
Collapse
|
|
39
|
Abstract
STUDY DESIGN Systematic review. OBJECTIVE To evaluate the cost-effectiveness of lumbar or cervical spinal arthrodesis using biological substitutes and extenders compared with iliac crest autograft for the treatment of degenerative spinal conditions. SUMMARY OF BACKGROUND DATA The cost-effectiveness of using bone graft substitutes and extenders for spinal fusion compared with using iliac crest autograft is not yet well established. METHODS A systematic search of PubMed/MEDLINE, the Cochrane Collaboration Library, EMBASE, the CRD (Centre for Reviews and Dissemination) database, and Tuft's CEA registry for literature published through December 2013 was performed to identify full formal economic analyses comparing the use of biological grafts with iliac crest bone graft in spinal fusion for thoracolumbar or cervical degenerative, deformity, and traumatic spinal conditions. Economic outcomes such as cost per improved outcome or cost per quality-adjusted life year were reported in the context of the model type, analytic perspective clinical comparisons, and sensitivity analyses employed. RESULTS The search strategy yielded 88 citations, and 6 full economic analyses ultimately met our inclusion criteria. For the comparison of recombinant human bone morphogenetic protein-2 to iliac crest bone graft in the lumbar spine, data from 4 cost-effectiveness studies and 1 cost-utility study provided discordant conclusions that varied with type of data used, cost-measurement methods, and study design. In the cervical spine, one study suggested that from a societal perspective, anterior cervical discectomy and fusion (ACDF) with allograft is similarly cost-effective as ACDF with autograft. CONCLUSION The results suggest that compared with use of iliac crest bone graft in lumbar spinal fusion, use of recombinant human bone morphogenetic protein is not cost-effective from a payer perspective with higher upfront costs, but it may be cost-effective from a societal perspective due to a decrease in lost productivity. The data in this study also suggest that from a societal perspective, ACDF with allograft is similarly cost-effective to ACDF with autograft. LEVEL OF EVIDENCE 3.
Collapse
|
|
40
|
Abstract
STUDY DESIGN A retrospective cohort study with medical record review. OBJECTIVE To determine if there is difference in the operative nonunion rates with and without the use of bone morphogenetic protein (BMP) after spinal fusions by analyzing data from an integrated health care system's spine registry. SUMMARY OF BACKGROUND DATA BMP was first approved in 2002 for use in single-level anterior lumbar fusions. Follow-up studies have advocated its use in reducing the need for reoperations for nonunions. Recent studies, however, have questioned these conclusions and the usefulness of BMP in spinal fusions has been highly debated. METHODS We identified 9425 spinal fusion cases between 2009 and 2011 from a spine registry in a large integrated health care organization. Patient characteristics, diagnosis, operative times, length of stay, and reoperations were extracted from the registry. Reoperations for nonunions were adjudicated via medical record review. Cox regression models were used to evaluate the risk of reoperation while adjusting for confounders. RESULTS In our cohort, there were 5456 BMP cases and 3969 non-BMP cases. The mean age was 60.4 years (standard deviation: 12.9 yr), with the majority being females (53%). The median follow-up time was 1.2 years (interquartile range: 0.6-2.0 yr). Reoperation rates for BMP versus non-BMP nonunions for all fusion cases with follow-up of 1 year or more (1.9% vs. 2.2%) and follow-up of 2 years or more (2.3% vs. 2.6%) were not statistically significantly different. Operative nonunion rates did not reach statistical significance for different spine regions and for different fused columns (anterior only, posterior only, or combined). After controlling for differences in patient characteristics, operative times, levels fused, and spinal regions, the risk of reoperation in the BMP versus non-BMP groups was 0.67 (95% CI: 0.42-1.06). CONCLUSION In this large cohort of spinal fusions at all spine regions involving all fused columns with and without BMP, we found no statistically significant difference in operative nonunion rates. LEVEL OF EVIDENCE 3.
Collapse
|
|
41
|
Louie PK, Hassanzadeh H, Singh K. Epidemiologic trends in the utilization, demographics, and cost of bone morphogenetic protein in spinal fusions. Curr Rev Musculoskelet Med 2014; 7:177-81. [PMID: 24903375 PMCID: PMC4596158 DOI: 10.1007/s12178-014-9222-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
Bone morphogenetic protein (BMP) utilization as an adjunct for spinal arthrodesis has gained considerable momentum among spine surgeons. Despite carrying Food and Drug Administration approval for only single level anterior lumbar interbody fusion from L4-S1, the majority of BMP administration is in "off label" settings. Over the last decade, BMP utilization has increased in all facets of spine surgery with the only exception being the anterior cervical spine, in which a downward trend resulted following the 2008 Food and Drug Administration warnings. The future application of BMP in spinal fusion, especially in anterior cervical fusions, will need to be further clarified in terms of efficacy, complications, and cost-effectiveness.
Collapse
Affiliation(s)
- Philip K. Louie
- Department of Orthopaedic Surgery, Midwest Orthopaedics at Rush, Rush University Medical Center, 1611 W Harrison St, Suite #300, Chicago, IL 60612 USA
| | - Hamid Hassanzadeh
- Department of Orthopaedic Surgery, Midwest Orthopaedics at Rush, Rush University Medical Center, 1611 W Harrison St, Suite #300, Chicago, IL 60612 USA
| | - Kern Singh
- Department of Orthopaedic Surgery, Midwest Orthopaedics at Rush, Rush University Medical Center, 1611 W Harrison St, Suite #300, Chicago, IL 60612 USA
| |
Collapse
|
|
42
|
Fox MG, Goldberg JM, Gaskin CM, Barr MS, Patrie JT, Shen FH, Alford B. MRI of transforaminal lumbar interbody fusion: imaging appearance with and without the use of human recombinant bone morphogenetic protein-2 (rhBMP-2). Skeletal Radiol 2014; 43:1247-55. [PMID: 24913556 DOI: 10.1007/s00256-014-1917-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2014] [Revised: 04/18/2014] [Accepted: 05/13/2014] [Indexed: 02/02/2023]
Abstract
PURPOSE To describe the vertebral endplate and intervertebral disc space MRI appearance following TLIF, with and without the use of rhBMP-2, and to determine if the appearance is concerning for discitis/osteomyelitis. MATERIALS AND METHODS After institutional review board approval, 116 TLIF assessments performed on 75 patients with rhBMP-2 were retrospectively and independently reviewed by five radiologists and compared to 73 TLIF assessments performed on 45 patients without rhBMP-2. MRIs were evaluated for endplate signal, disc space enhancement, disc space fluid, and abnormal paraspinal soft tissue. Endplate edema-like signal was reported when T1-weighted hypointensity, T2-weighted hyperintensity, and endplate enhancement were present. Subjective concern for discitis/osteomyelitis on MRI was graded on a five-point scale. Generalized estimating equation binomial regression model analysis was performed with findings correlated with rhBMP-2 use, TLIF level, graft type, and days between TLIF and MRI. RESULTS The rhBMP-2 group demonstrated endplate edema-like signal (OR 5.66; 95% CI [1.58, 20.24], p = 0.008) and disc space enhancement (OR 2.40; 95% CI [1.20, 4.80], p = 0.013) more often after adjusting for the TLIF level, graft type, and the number of days following TLIF. Both groups had a similar temporal distribution for endplate edema-like signal but disc space enhancement peaked earlier in the rhBMP-2 group. Disc space fluid was only present in the rhBMP-2 group. Neither group demonstrated abnormal paraspinal soft tissue and discitis/osteomyelitis was not considered likely in any patient. CONCLUSIONS Endplate edema-like signal and disc space enhancement were significantly more frequent and disc space enhancement developed more rapidly following TLIF when rhBMP-2 was utilized. The concern for discitis/osteomyelitis was similar and minimal in both groups.
Collapse
Affiliation(s)
- Michael G Fox
- Department of Radiology and Medical Imaging, University of Virginia, 1218 Lee Street, Box 800170, Charlottesville, VA, 22908, USA,
| | | | | | | | | | | | | |
Collapse
|
|
43
|
Han X, Zhang W, Gu J, Zhao H, Ni L, Han J, Zhou Y, Gu Y, Zhu X, Sun J, Hou X, Yang H, Dai J, Shi Q. Accelerated postero-lateral spinal fusion by collagen scaffolds modified with engineered collagen-binding human bone morphogenetic protein-2 in rats. PLoS One 2014; 9:e98480. [PMID: 24869484 PMCID: PMC4037187 DOI: 10.1371/journal.pone.0098480] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2013] [Accepted: 05/04/2014] [Indexed: 11/18/2022] Open
Abstract
Bone morphogenetic protein-2 (BMP-2) is a potent osteoinductive cytokine that plays a critical role in bone regeneration and repair. However, its distribution and side effects are major barriers to its success as therapeutic treatment. The improvement of therapy using collagen delivery matrices has been reported. To investigate a delivery system on postero-lateral spinal fusion, both engineered human BMP-2 with a collagen binding domain (CBD-BMP-2) and collagen scaffolds were developed and their combination was implanted into Sprague-Dawley (SD) rats to study Lumbar 4–5 (L4–L5) posterolateral spine fusion. We divided SD rats into three groups, the sham group (G1, n = 20), the collagen scaffold-treated group (G2, n = 20) and the BMP-2-loaded collagen scaffolds group (G3, n = 20). 16 weeks after surgery, the spines of the rats were evaluated by X-radiographs, high-resolution micro-computed tomography (micro-CT), manual palpation and hematoxylin and eosin (H&E) staining. The results showed that spine L4–L5 fusions occurred in G2(40%) and G3(100%) group, while results from the sham group were inconsistent. Moreover, G3 had better results than G2, including higher fusion efficiency (X score, G2 = 2.4±0.163, G3 = 3.0±0, p<0.05), higher bone mineral density (BMD, G2: 0.3337±0.0025g/cm3, G3: 0.4353±0.0234g/cm3. p<0.05) and more bone trabecular formation. The results demonstrated that with site-specific collagen binding domain, a dose of BMP-2 as low as 0.02mg CBD-BMP-2/cm3 collagen scaffold could enhance the posterolateral intertransverse process fusion in rats. It suggested that combination delivery could be an alternative in spine fusion with dramatically decreased side effects caused by high dose of BMP-2.
Collapse
Affiliation(s)
- Xinglong Han
- Orthopedic Department, the First Affiliated Hospital of Soochow University, Suzhou, P.R. China
| | - Wen Zhang
- Orthopedic Institute of Soochow University, Suzhou, P.R. China
| | - Jun Gu
- Orthopedic Department, the Second Affiliated Hospital of Soochow University, Suzhou, P.R. China
| | - Huan Zhao
- Orthopedic Department, the First Affiliated Hospital of Soochow University, Suzhou, P.R. China
| | - Li Ni
- Orthopedic Department, the First Affiliated Hospital of Soochow University, Suzhou, P.R. China
| | - Jiajun Han
- Orthopedic Department, the First Affiliated Hospital of Soochow University, Suzhou, P.R. China
| | - Yun Zhou
- Orthopedic Department, the First Affiliated Hospital of Soochow University, Suzhou, P.R. China
| | - Yannan Gu
- Orthopedic Department, the First Affiliated Hospital of Soochow University, Suzhou, P.R. China
| | - Xuesong Zhu
- Orthopedic Department, the First Affiliated Hospital of Soochow University, Suzhou, P.R. China
| | - Jie Sun
- Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, P.R. China
| | - Xianglin Hou
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, P.R. China
| | - Huilin Yang
- Orthopedic Department, the First Affiliated Hospital of Soochow University, Suzhou, P.R. China
| | - Jianwu Dai
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, P.R. China
- * E-mail: (QS); (JD)
| | - Qin Shi
- Orthopedic Department, the First Affiliated Hospital of Soochow University, Suzhou, P.R. China
- * E-mail: (QS); (JD)
| |
Collapse
|
|
44
|
Ching AC. How do we interpret national inpatient sample data about complications? Commentary on an article by Amit Jain, MD, et al.: "rhBMP Use in Cervical Spine Surgery: Associated Factors and In-hospital Complications". J Bone Joint Surg Am 2014; 96:e67. [PMID: 24740675 DOI: 10.2106/jbjs.n.00031] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
|
|
45
|
Complications with the use of bone morphogenetic protein 2 (BMP-2) in spine surgery. Spine J 2014; 14:552-9. [PMID: 24412416 DOI: 10.1016/j.spinee.2013.08.060] [Citation(s) in RCA: 322] [Impact Index Per Article: 29.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2012] [Revised: 07/16/2013] [Accepted: 08/23/2013] [Indexed: 02/03/2023]
Abstract
BACKGROUND CONTEXT Recombinant human bone morphogenetic protein 2 (rhBMP-2) is a very potent osteogenic growth factor that has been used successfully in various spine fusions, obviating the need for autologous iliac crest bone graft harvest and therefore avoiding the associated morbidities. PURPOSE In the past few years, a tremendous increase in rhBMP-2 usage was noted, and concerns regarding costs, benefits, and safety issues were raised by many. The goal of this work was to provide a comprehensive review of the adverse events and complications associated with use of rhBMP-2. STUDY DESIGN Literature review. METHODS This is a review of the current literature on the reported adverse events, complications, and concerns associated with rhBMP-2 use. RESULTS This article discusses the wide spectrum of adverse outcomes related to rhBMP-2 use in the lumbar and the cervical spine; retrograde ejaculation, antibodies formation, postoperative radiculitis, postoperative nerve root injury, ectopic bone formation, vertebral osteolysis/edema, dysphagia and neck swelling, hematoma formation, interbody graft lucency, and wound healing complications are reviewed. Cost-related concerns, dosage considerations, carrier types, and theoretical carcinogenesis concerns were also presented. CONCLUSIONS Despite the excellent spinal fusion rates promoted by this powerful molecule, the increasingly reported adverse outcomes associated with bone morphogenetic protein usage have created real concerns. This article will provide the reader with a good understanding of the reported complications associated with rhBMP-2 use and ultimately help recognize its safety spectrum and limits for better clinical application.
Collapse
|
|
46
|
Does recombinant human bone morphogenetic protein-2 use in adult spinal deformity increase complications and are complications associated with location of rhBMP-2 use? A prospective, multicenter study of 279 consecutive patients. Spine (Phila Pa 1976) 2014; 39:233-42. [PMID: 24477081 DOI: 10.1097/brs.0000000000000104] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
STUDY DESIGN Multicenter, prospective analysis of consecutive patients with adult spinal deformity (ASD). OBJECTIVE Evaluate complications associated with recombinant human bone morphogenetic protein-2 (rhBMP-2) use in ASD. SUMMARY OF BACKGROUND DATA Off-label rhBMP-2 use is common; however, underreporting of rhBMP-2 associated complications has been recently scrutinized. METHODS Patients with ASD consecutively enrolled into a prospective, multicenter database were evaluated for type and timing of acute perioperative complications. INCLUSION CRITERIA age 18 years and older, ASD, spinal arthrodesis of more than 4 levels, and 3 or more months of follow-up. Patients were divided into those receiving rhBMP-2 (BMP) or no rhBMP-2 (NOBMP). BMP divided into location of use: posterior (PBMP), interbody (IBMP), and interbody + posterior spine (I + PBMP). Correlations between acute perioperative complications and rhBMP-2 use including total dose, dose/level, and location of use were evaluated. RESULTS A total of 279 patients (mean age: 57 yr; mean spinal levels fused: 12.0; and mean follow-up: 28.8 mo) met inclusion criteria. BMP (n = 172; average posterior dose = 2.5 mg/level, average interbody dose = 5 mg/level) had similar age, smoking history, previous spine surgery, total spinal levels fused, estimated blood loss, and duration of hospital stay as NOBMP (n = 107; P > 0.05). BMP had greater Charlson Comorbidity Index (1.9 vs. 1.2), greater scoliosis (43° vs. 38°), longer operative time (488.2 vs. 414.6 min), more osteotomies per patient (4.0 vs. 1.6), and greater percentage of anteroposterior fusion (APSF; 20.9% vs. 8.4%) than NOBMP, respectively (P < 0.05). BMP had more total complications per patient (1.4 vs. 0.6) and more minor complications per patient (0.9 vs. 0.2) than NOBMP, respectively (P < 0.05). NOBMP had more complications requiring surgery per patient than BMP (0.3 vs. 0.2; P < 0.05). Major, neurological, wound, and infectious complications were similar for NOBMP, BMP, PBMP, IBMP, and I + PBMP (P > 0.05). Multivariate analysis demonstrated small to nonexistent correlations between rhBMP-2 use and complications. CONCLUSION RhBMP-2 use and location of rhBMP-2 use in ASD surgery, at reported doses, do not increase acute major, neurological, or wound complications. Research is needed for higher rhBMP-2 dosing and long-term follow-up. LEVEL OF EVIDENCE 2.
Collapse
|
|
47
|
Rodriguez I, Saxena G, Sell S, Bowlin G. Mineralization and Characterization of Composite Lyophilized Gelatin Sponges Intended for Early Bone Regeneration. Bioengineering (Basel) 2014; 1:62-84. [PMID: 28955017 DOI: 10.3390/bioengineering1010062] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2013] [Revised: 12/11/2013] [Accepted: 12/24/2013] [Indexed: 11/16/2022] Open
Abstract
The application of freeze-dried gelatin sponges as alternative bone grafting substitutes has many advantages, including the ability to swell, high porosity, tailorable degradation, and versatility to incorporate multiple components such as growth factors and nanofillers. The purpose of this study was to mineralize (M) and further characterize 1-Ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC) cross-linked gelatin sponges enhanced with preparations rich in growth factors, hydroxyapatite, and chitin whiskers (PHCE). Sponges were characterized for their swelling and in vitro mineralization potential, surface characteristics, protein release, mechanical properties, and MG-63 cell attachment and infiltration. All sponges swelled up to 50% of their original volume upon hydration. Scanning electron microscopy showed sparse mineral deposition for gelatin-M scaffolds while PHCE-M scaffolds exhibited more uniform mineral nucleation. Over 21 days, PHCE-M scaffolds cumulatively released significantly more (30%) of its initial protein content than all other scaffolds. PHCE-M scaffolds reported lower modulus values (1.3-1.6 MPa) when compared to gelatin control scaffolds (1.6-3.2 MPa). Increased cell attachment and infiltration was noticed on PHCE and PHCE-M scaffolds. The results of the study demonstrate the enhanced performance of PHCE and PHCE-M scaffolds to serve as bone healing scaffolds. Their potential to release incorporated factors, comparable composition/mechanical properties to tissues developed in the early stages of bone healing, and enhanced initial cellular response make them suitable for further studies evaluating more complex cellular interactions.
Collapse
Affiliation(s)
- Isaac Rodriguez
- Department of Biomedical Engineering, The University of Memphis and Joint University of Memphis-UTHSC-Memphis Biomedical Engineering Program, 119D Engineering Technology, Memphis, TN 38152, USA.
| | - Gunjan Saxena
- Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Grosvenor Hall, Athens, OH 45701, USA.
| | - Scott Sell
- Department of Biomedical Engineering, Parks College of Engineering, Aviation, and Technology, Saint Louis University, 3507 Lindell Blvd., St. Louis, MO 63103, USA.
| | - Gary Bowlin
- Department of Biomedical Engineering, The University of Memphis and Joint University of Memphis-UTHSC-Memphis Biomedical Engineering Program, 119D Engineering Technology, Memphis, TN 38152, USA.
| |
Collapse
|
|
48
|
Li AI, Hokugo A, Jarrahy R, Zuk PA. Human Adipose Tissue as a Source of Multipotent Stem Cells. STEM CELLS IN AESTHETIC PROCEDURES 2014:67-83. [DOI: 10.1007/978-3-642-45207-9_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
|
|
49
|
Dagostino PR, Whitmore RG, Smith GA, Maltenfort MG, Ratliff JK. Impact of bone morphogenetic proteins on frequency of revision surgery, use of autograft bone, and total hospital charges in surgery for lumbar degenerative disease: review of the Nationwide Inpatient Sample from 2002 to 2008. Spine J 2014; 14:20-30. [PMID: 23218827 DOI: 10.1016/j.spinee.2012.10.035] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2011] [Revised: 02/15/2012] [Accepted: 10/26/2012] [Indexed: 02/03/2023]
Abstract
BACKGROUND CONTEXT Bone morphogenetic proteins (BMPs) were developed with the goal of improving clinical outcomes through the promotion of bony healing and reducing morbidity from iliac crest bone graft harvest. PURPOSE To complete a population-based assessment of the impact of BMP on use of autograft, rates of operative treatment for lumbar pseudoarthrosis, and hospital charges. STUDY DESIGN Nationwide Inpatient Sample (NIS) retrospective cohort assessment of 46,452 patients from 2002 to 2008. PATIENT SAMPLE All patients who underwent lumbar arthrodesis procedures for degenerative spinal disease. OUTCOME MEASURES Use of BMP, revision surgery status as a percentage of total procedures, and autograft harvest in lumbar fusion procedures completed for degenerative diagnoses. METHODS Demographic and geographic/practice data, hospital charges, and length of stay of all NIS patients with thoracolumbar and lumbosacral procedure codes for degenerative spinal diagnoses were recorded. Codes for autograft harvest, use of BMP, and revision surgery were included in multivariable regression analysis. RESULTS The assessment found 46,452 patients from 2002 to 2008 undergoing thoracolumbar or lumbar arthrodesis procedures for degenerative disease. Assuming a representative sample, this cohort models more than 200,000 US patients. There was steady growth in lumbar spine fusion and in the use of BMP. The use of BMP increased from 2002 to 2008 (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.48-1.52). Revision procedures decreased over the study period (OR, 0.94; 95% CI, 0.91-0.96). The use of autograft decreased substantially after introduction of BMP but then returned to baseline levels; there was no net change in autograft use from 2002 to 2008. The use of BMP correlated with significant increases in hospital charges ($13,362.39; standard deviation ± 596.28, p<.00001). The use of BMP in degenerative thoracolumbar procedures potentially added more than $900 million to hospital charges from 2002 to 2008. CONCLUSIONS There was an overall decrease in rates of revision fusion procedures from 2002 to 2008. Introduction of BMP did not correlate with decrease in use of autograft bone harvest. Use of BMP correlated with substantial increase in hospital charges. The small decrease in revision surgeries recorded, combined with lack of significant change in autograft harvest rates, may question the financial justification for the use of BMP.
Collapse
Affiliation(s)
| | - Robert G Whitmore
- Department of Neurosurgery, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Gabriel A Smith
- Department of Neurosurgery, Temple University, Philadelphia, PA 19140, USA
| | - Mitchell G Maltenfort
- Department of Neurosurgery, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - John K Ratliff
- Department of Neurosurgery, Stanford University, 300 Pasteur Drive, Stanford, CA 94305, USA.
| |
Collapse
|
|
50
|
Comparison of TLIF with rhBMP-2 versus no TLIF and higher posterolateral rhBMP-2 dose at L5-S1 for long fusions to the sacrum with sacropelvic fixation in patients with primary adult deformity. Spine (Phila Pa 1976) 2013; 38:2264-71. [PMID: 24108280 DOI: 10.1097/brs.0000000000000045] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
STUDY DESIGN Comparvative case series. Data was prospectively entered and retrospectively analyzed. OBJECTIVE To evaluate the need for distal lumbar interbody fusion when sufficient recombinant human bone morphogenetic protein-2 (rhBMP-2) is used posterolaterally at L5-S1 in long spinal constructs for adult deformity via costs and radiographical and patient-reported outcome comparisons. SUMMARY OF BACKGROUND DATA Many authors and investigators have suggested that an interbody fusion is mandatory at L5-S1 with long fusion to the sacrum with sacropelvic fixation. Past studies have shown competitive fusion rates using rhBMP-2 versus iliac crest bone graft for long fusions. There are various advocates for anterior lumbar interbody fusion versus posterior lumbar interbody fusion versus transforaminal lumbar interbody fusion (TLIF). The optimal strategy remains elusive. METHODS Fifty-seven patients were studied at one institution. Thirty-one patients had no interbody fusion (NI group) with 20 mg of rhBMP-2 posterolaterally on 10 mL of carrier and 26 patients had TLIF at L5-S1 (TLIF group) with 6 mg of rhBMP-2 in the interbody space along with local bone graft and 6 mg of rhBMP-2 on carrier posterolaterally at L5-S1. Patients were followed for 24 to 87 months (mean follow-up, 3.92 yr). Demographics of the 2 groups were similar. RESULTS There were no detected nonunions at L5-S1 in either group. By our limited cost analysis, the expense of performing a TLIF at L5-S1 is higher than that of using extra rhBMP-2 posterolaterally at that segment. Improvement in outcomes scores, namely Scoliosis Research Society-22 and Oswestry Disability Index, were the same statistically in both groups. Blood loss was greater in the TLIF group than the NI group. There were no identified rhBMP-2 adverse events in either group. CONCLUSION Utilization of 20 mg of rhBMP-2 at L5-S1 has the potential to be less expensive than an interbody fusion in most patients having a primary long fusion for adult spinal deformity. The apparent fusion rates at L5-S1 were identical in both groups. Both strategies were successful in regard to improving patient outcomes and achieving apparent solid arthrodesis at the lumbosacral junction, which was the focus of this study. LEVEL OF EVIDENCE 2.
Collapse
|