The Use of rhBMP-2 in Cervical Fusion: A Systematic Review

The Use of rhBMP-2 in Cervical Fusion: A Systematic Review | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The Use of rhBMP-2 in Cervical Fusion: A Systematic Review Jamie Lee, Jonathan P. Japa, Linus Lee, Kevin Yoon, Mark Ehioghae, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8780018/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Context: Recombinant human bone morphogenetic protein-2 (rhBMP-2) is used off-label in anterior and posterior cervical spine fusion (ACF and PCF) as an alternative to autologous or allogenic grafts, enhancing fusion potential. However, concerns regarding complications such as neck swelling and dysphagia have been raised. Purpose Therefore, this study aims to assess complication profiles of rhBMP-2 in cervical fusions, comparing anterior and posterior approaches and examining the impact of dosage, patient-specific risk factors, and preventive strategies. Study Design: Systematic review Methods We conducted a systematic literature search in June 2025 in accordance with PRISMA guidelines. PubMed and Embase were queried with keywords involving rhBMP-2 and cervical fusion. Eligible studies included clinical studies reporting outcomes of anterior or posterior cervical fusion with rhBMP-2. Data on fusion rates, complications, and their relevant factors were extracted and analyzed. Results Thirty-four studies, 26 ACF and 8 PCF, met our inclusion criteria. Fusion rates with rhBMP-2 were consistently high, ranging from 81.8–100% in ACF and 82.4–100% in PCF. Comparative data generally demonstrated superior fusion rates with rhBMP-2 compared to controls, with some evidence of accelerated fusion times. However, use of rhBMP-2 was also associated with more severe cases of cervical swelling and dysphagia in ACF. rhBMP-2 groups in PCF generally did not demonstrate significantly higher incidence of complications compared to control groups. Conclusions Our systematic review suggests that rhBMP-2 successfully augments cervical fusion; however, it also increases the risk of certain complications, particularly in anterior cervical surgery. Dosing, specific levels fused, number of levels fused, and patient-specific factors all significantly influence the risk of complications. Importantly, prophylactic measures, such as containment, drain placement, and local steroid administration, show potential in reducing the severity of adverse outcomes. Ultimately, careful patient selection and complication prevention strategies may enable rhBMP-2 to provide its intended benefits while minimizing risks. recombinant human Bone Morphogenetic Proteins Cervical vertebrae Spinal fusion Intervertebral disc Figures Figure 1 INTRODUCTION Cervical fusion is indicated for various conditions, including trauma, tumors, deformities, and degenerative disorders, which can result in myelopathy or radiculopathy [ 1 , 2 ]. Cervical fusion is categorized by approach, including anterior and posterior methods. A Recent Pearl Diver database study reported over 50,000 anterior cervical discectomies and fusions (ACDFs) and over 16,000 posterior cervical fusions (PCFs) were performed in the United States in 2022 [ 3 ]. Currently, ACDF remains the most commonly performed cervical spine surgery, while PCF is becoming increasingly popular [ 3 ]. The introduction of INFUSE® in 2002 offered a recombinant human bone morphogenetic protein-2 (rhBMP-2)-based alternative to Iliac crest bone graft (ICBG) [ 4 ]. Early clinical studies of lumbar fusion using rhBMP-2 revealed fusion rates that were comparable to or often higher than those achieved with autologous bone grafts [ 5 ]. rhBMP-2 is hypothesized to exert its osteoinductive and chondrogenic effects by promoting the differentiation of mesenchymal stem cells into osteoblasts and chondrocytes, thereby facilitating effective bony growth and fusion [ 6 ]. However, other studies on the use of rhBMP-2 in ACFs have reported elevated complication rates, including cervical swelling, dysphagia, and dyspnea [ 7 , 8 ]. A proposed mechanism involves excess rhBMP-2 diffusing out of the target site and into the surrounding environment, causing inflammation and ectopic bone formation [ 6 ]. In response to the concerning findings, the FDA issued a black-box warning for rhBMP-2 for cervical spine surgery in 2008 [ 9 ]. Subsequent concerns about rhBMP-2 in the cervical spine has limited its use for most, but not all, surgeons, as many continued to use it off-label. In a recent survey of orthopedic and neurosurgeons, both U.S. and non-U.S.-based, revealed that 13% of surgeons still utilized rhBMP-2 in multilevel ACDFs [ 10 ]. This notable use of rhBMP-2 in the cervical spine highlights the need for reassessment. Therefore, this systematic review aims to assess complications associated with rhBMP-2 in anterior and posterior cervical fusions and to examine the impact of dosage, patient-specific risk factors, and preventive strategies. METHODS Search Strategy A systematic review was conducted in accordance with PRISMA guidelines. Databases PubMed and Embase were used for our search. Within each database, block searches were conducted using keywords and Boolean operators. Key words included: “bone morphogenetic protein 2,” “recombinant bone morphogenetic protein 2,” “BMP2,” “BMP-2”. “rhBMP2,” “cervical spine,” “cervical spine surgery,” “complication,” “efficacy,” and “outcomes.” Inclusion and Exclusion Criteria Studies that used rhBMP-2 in cervical fusion and reported clinical outcomes and complications were included in the analysis. Non-human studies, case reports, review articles, and non-English articles were excluded. Finally, articles reporting fewer than 20 patients and those reporting pediatric patients were excluded. Study selection and screening Two reviewers independently screened titles and abstracts. Full texts were retrieved for potentially eligible articles. Disagreements were resolved by discussion; if consensus was not reached, a third reviewer was consulted. The selection process is summarized in a PRISMA flow diagram (Fig. 1 ). Data extraction From each study, we collected: study design; sample size, BMP-2 dosage; details of the BMP-2 delivery method; comparator group if present; reported clinical outcomes, including fusion rates and postoperative complications. Risk of bias assessment We applied the Robins-I V2 tool in order to assess risk of bias (Table 1). In summary, the primary source of bias was the absence of a comparator group in the case series and the selection of patients receiving BMP-2 in comparative studies. However, all studies reported primary outcomes related to BMP-2 use in cervical surgery. RESULTS Anterior Cervical Fusion Case Studies A total of 16 case series [ 8 , 11 – 25 ], encompassing 1,240 patients, met our inclusion criteria (Table 2 ). Table 1 Risk of Bias Assessment using Robins-I V2 Author, Year Domain 1: Confounding Domain 2: Classification of Interventions Domain 3: Selection of Participants Domain 4: Deviations from Intended Interventions Domain 5: Missing Data Domain 6: Measurement of Outcomes Domain 7: Selection of the Reported Result Overall Risk of Bias Lanman et al., 2004 Serious Moderate Low Moderate Serious Moderate Serious Serious Boakye et al., 2005 Serious Moderate Low Moderate Moderate Moderate Moderate Serious Shields et al., 2006 Serious Moderate Moderate Moderate Moderate Moderate Moderate Serious Tumialan et al., 2008 Serious Moderate Low Moderate Moderate Serious Moderate Serious Vaidya et al., 2008 Serious Moderate Low Moderate Moderate Moderate Moderate Serious Klimo et al., 2009 Serious Moderate Low Moderate Moderate Moderate Moderate Serious Shen et al., 2010 Serious Moderate Moderate Moderate Moderate Moderate Moderate Serious Stachniak et al., 2011 Serious Low Moderate Moderate Moderate Moderate Moderate Serious Sethi et al., 2011 Serious Low Moderate Moderate Moderate Moderate Serious Serious Khajavi et al., 2014 Serious Moderate Low Moderate Moderate Moderate Moderate Serious Kukreja et al., 2015 Serious Moderate Low Moderate Moderate Serious Moderate Serious Pourtaheri et al., 2015 Serious Moderate Low Moderate Low Moderate Moderate Serious Maza et al., 2019 Serious Low Low Moderate Moderate Moderate Moderate Serious Wang et al., 2020 Serious Low Moderate Moderate Moderate Moderate Moderate Serious Mendenhall et al., 2021 Serious Low Low Moderate Low Serious Moderate Serious Medina et al., 2024 Serious Low Low Moderate Moderate Moderate Moderate Serious Smucker et al., 2006 Moderate Low Low Low Moderate Moderate Moderate Moderate Vaidya et al., 2007 Moderate Low Moderate Moderate Moderate Moderate Moderate Moderate Lu et al., 2013 Moderate Low Moderate Moderate Moderate Moderate Moderate Moderate Frenkel et al., 2013 Moderate Low Moderate Moderate Moderate Moderate Moderate Moderate Tan et al., 2015 Moderate Low Low Low Moderate Moderate Moderate Moderate Lovasik et al., 2017 Moderate Low Moderate Moderate Serious Moderate Moderate Serious Riederman et al., 2017 Moderate Low Moderate Moderate Moderate Serious Moderate Serious Burkus et al., 2017 Moderate Moderate Low Moderate Moderate Low Moderate Moderate Bellamy et al., 2022 Moderate Low Moderate Moderate Moderate Moderate Moderate Moderate Chen et al., 2025 Low Low Low Moderate Moderate Moderate Moderate Moderate Hamilton et al., 2011 Serious Low Moderate Moderate Moderate Moderate Moderate Serious Hodges et al., 2012 Serious Low Serious Moderate Moderate Moderate Moderate Serious Hood et al., 2012 Serious Low Serious Moderate Moderate Moderate Moderate Serious Ishida et al., 2019 Serious Low Moderate Moderate Serious Moderate Moderate Serious Crawford et al., 2009 Moderate Low Low Moderate Moderate Moderate Moderate Moderate Yan et al., 2014 Moderate Low Low Moderate Moderate Moderate Moderate Moderate Takahashi et al., 2017 Moderate Low Moderate Low Moderate Low Moderate Moderate Iyer et al., 2018 Moderate Low Moderate Moderate Moderate Moderate Moderate Moderate Fusion and Pseudoarthrosis Analysis of 14 studies reporting fusion rates revealed high rates, ranging from 81.8% to 100%. Seven studies reported 100% fusion rates, either by 9 months [ 16 , 25 ] or by 12 months [ 12 , 13 , 22 , 24 ]. Uniquely, Lanman et al. reported 100% fusion as early as 3 months [ 11 ]. Four studies reported pseudoarthrosis rates, ranging from 1% to 18.2% [ 14 , 15 , 19 , 20 ]. The highest pseudoarthrosis rates reported were by Kilmo et al. (18.2%) and Shen et al. (10.2%) [ 14 , 15 ]. Klimo et al. investigated the use of rhBMP-2 in 22 ACDF patients, with 4 developing pseudoarthrosis. Shen et al. evaluated rhBMP-2 in multi-level (≥ 3 level) ACFs and reported pseudoarthrosis in 48% (13/127) patients, with 8 of those patients requiring revision surgery. Notably, nearly half (44.9%) of the patients included in this study had a prior ACDF with adjacent segment degeneration and/or pseudoarthrosis, likely explaining the higher observed pseudoarthrosis rate observed by the authors. Complications Dysphagia Thirteen case series reported the incidence of dysphagia, ranging from 2.13% to 13.2% [ 8 , 11 – 14 , 21 – 24 ]. Tumialan et al. reported 14 patients with dysphagia in their series of 200 single and multi-level ACDFs. Five patients had severe dysphagia, and four of these patients ultimately required a percutaneous endoscopic gastrostomy tube [ 13 ]. Only one of these four patients remained on a PEG tube chronically due to a history of ALS. Kukreja et al. reported a dysphagia rate of 13.2% in ACF, with 11 patients classified as “substantial,” with one requiring a PEG tube and an extended hospital stay. Nine of these patients had spontaneous resolution of their dysphagia, and the other two patients had resolution with intravenous dexamethasone followed by oral methylprednisone [ 19 ]. Cervical/Neck Swelling Six case series reported cervical swelling [ 16 , 17 , 19 – 21 , 23 ]. Stachniak et al., Sethi et al., and Pourtaheri et al. all reported radiographic measurements of cervical swelling in their similarly sized series of ~ 30 ACDF patients. Stachniak et al. reported their peak at two weeks (21.8 ± 5.0 mm)[ 16 ] and no patients required additional intervention. Sethi et al. noted a peak at one week at the C3 level (15.7 ± 7.8 mm) [ 17 ]. One patient was taken back to the operating room for suspected wound infection, but was noted to have diffuse prevertebral swelling, and resolved without additional intervention [ 17 ]. Pourtaheri et al. observed their mean peak at two weeks of 9.6 mm. However, all patients were asymptomatic. Notably, these authors used the lowest dose of rhBMP-2 out of all 6 studies discussed here, of ~ 0.3mg/level [ 20 ]. The remaining studies noted patient-reported cervical swelling, which ranged from 6% to 8.6%, all of which resolved spontaneously or with medical management. Other complications Endplate resorption was observed to be 100% by Vaidaya et al. and Pourtaheri et al. [ 20 , 25 ]. Conversely, Klimo et al reported endplate resorption in 80% (28/35) of operated levels, resulting in PEEK cage subsidence [ 14 ]. Vaidya et al. reported subsidence in 13/32 levels (40.5%) in their 23 ACDF patients [ 25 ]. Pourtaheri et al. identified 4 (10.8%) cases of subsidence. None of the authors reported that patients were symptomatic as a result of their end plate resorption or subsidence [ 20 ]. Three studies reported on hematoma or seroma as postoperative complications [ 8 , 13 , 23 ]. Shields et al. reported the highest hematoma rate at 9.9% (15/151) in their 151 ACF patients; eight of the 15 required surgical evacuation [ 8 ]. Conversely, Tumialan et al. and Mendenhall et al. reported much lower rates of postoperative hematoma or seroma (2% and 2.5% respectively); however, almost all of their patients required surgical evacuation. Three studies noted radiographic signs of heterotopic ossification [ 12 , 14 , 20 ]. Boakye et al. reported that three (12.5%) of their patients developed asymptomatic heterotopic bone formation [ 12 ], while Pourtaheri et al. found seven (19.5%) of their patients with hypertrophic ossification posterior to the graft [ 20 ]. Klimo et al. reported heterotopic bone formation in 26 of the 38 operated levels (68%) [ 14 ]. Anterior Cervical Fusion Comparative Studies A total of 10 comparative studies on rhBMP-2 use were analyzed for anterior cervical fusion, with a total of 1,371 rhBMP-2 patients compared to 1,721 control patients (Table 3 ) [ 7 , 26 – 34 ]. Table 2 Characteristics of included anterior cervical fusion case series studies. Author No. of patients Surgery and Delivery Method Containment measures rhBM2P dosage mg/level Peri/post-operative Steroid Drain use Fusion Rates % (rhBMP2/control) Complication Rates (rhBMP2/control) Lanman et al. 2004 20 1, 2, 3-level ACDF CORNERSTONE-SR™ Epidural space Sealed with Tisseel thrombin glue NR NR NR 100% (20/20) Severe dysphagia : 1 (5%) Boakye et al. 2005 24 1, 2, 3-level ACDF PEEK Interbody space NR Initially 2.1 Adjusted: 1.05 PERI : 10 mg dexamethasone Soft-tissue drain for 24–48 hours in multi-level procedures 100% (22/22) Heterotopic bone formation: 3 (12.5%) Transient dysphagia: 2 (8.3%) Shields et al. 2006 151 1, 2, 3-level ACDF 1, 2, 3, 4-level ACVF HYDROSORB 228 or CORNERSTONE PYRAMESH 228 Additional rhBMP2 placed lateral and anterior to the graft within disc space NR Up to 2.1 Higher amounts in ACVF pts NR Drain placed in 35 (25.4%) of 138 ACDF patients 8 (61.5%) of 13 ACVF patients NR Total complication: 35 (23.2%) Hematoma: 15 (9.9%) Dysphagia, respiratory difficulty, cervical swelling: 13 (8.6%) • Prolonged hospital stay: 5 (3.3%) • Readmission: 8 (5.3%) Tumialan et al. 2008 200 1, 2, 3, 4-level ACDF PEEK Placed within the cage Avoided irrigation 2.1 (n = 24) 1.05 (n = 93) 0.7 (n = 83) PERI : 10 mg dexamethasone in non-diabetic pts Drains placed in ~ 50% of single-level cases 100% of multilevel cases 100% (193/193) Total complication: 14 (7%) Dysphagia: 14 (7%) • Mild: 6 (3%) • Moderate: 3 (1.5%) • Severe: 5 (2.5%) Hematoma: 2 (1%) Seroma: 2 (1%) Vaidya et al. 2008 23 Single and multilevel ACDF PEEK Placed within the cage or graft NR About 1.0 NR NR 100% (23/23) End plate resorption: 23 (100%) Subsidence: 13 of 32 ACDF levels (40.5%) Klimo et al. 2009 22 38 levels 1, 2, 3-level ACDF PEEK Placed within the cage Floseal injected lateral to grafts if persistent leaking was present 2.1 (n = 12 levels) 1.4 (n = 21 levels) 1.1 (n = 5 levels) NR No drains used 89% (34/38 levels) Pseudorathrosis: 4 levels (11.8%) Heterotopic bone formation with ossification into canal: 26 levels (68%) End-plate resorption: 28 of 35 levels (80%) Shen et al. 2010 127 3 or more -level ACCF Some ACDF Structural allograft PEEK or Titanium mesh w/wo local autograft bone Placed within the cage Decreased amount of rhBMP2 used NR 1.33 (3-level) 2.0 (4-level) 1.6 (5-level) PERI : 10 mg dexamethasone POST : If patients had swallowing difficulty, additional dose of dexamethasone NR 89.8% (114/127) Dysphagia: Most patients Neck swelling: Most patients Pseudoarthrosis: 13 (10.2%) Stachniak et al. 2011 30 2 or 3-level ACDF PEEK Placed within the cage Avoided irrigation 0.6 POST : Dexamethasone taper NR 100% (30/30) Cervical swelling: 28 (93%) Dysphagia : • Choking on food: (19%) • Choking on drinks: (4.8%) • Food sticking: (47.6%) Sethi et al. 2011 34 Single and multilevel ACF with Decompression PEEK or allograft spacer NR 1.0 NR NR 100% (23/23)for PEEK cage 81.8% (9/11)for Allograft spacer End plate resorption: 34 (100%) Cage migration: Mostly in pts who received PEEK Cervical swelling: 34 (100%) Khajavi et al. 2014 72 2, 3, 4-level ACDF CORNERSTONE Allograft or ICBG Placed within graft Decreased amount of rhBMP2 used NR 0.7 (n = 29) 0.5 (n = 43) NR NR 98.6% (169/72) Total complication: 8 (11%) Dysphagia: 38 (53%) at 2 wks, 4 (5%) at last follow-up Readmission for severe dysphagia: 2 (3%) Seroma evacuation: 1 (1.4%) Return to OR for nonunion: 1 (1.4%) Kukreja et al. 2015 197 2, 3, 4-level ACDF and/or ACCF PEEK or PEEK prevail Placed within the cage Demineralized bone matrix putty placed from top and bottom over centrally located INFUSE within PEEK cage Avoided irrigation 0.7 PERI : 10 mg dexamethasone POST : 4 mg oral dexamethasone taper NR 99% (195/197) Dysphagia: 26 (13.2%) • Severe dysphagia w/ PEG tube: 1 (0.5%) Cervical swelling: 17 (8.7%) Readmission for neck swelling/dysphagia: 2 (1%) Pseudoarthrosis: 2 (1%) Pourtaheri et al. 2015 37 3-level ACDF w/wo single-level Cervical Corpectomy Corticocancellous allograft Placed within the graft Fibrin sealant 0.26–0.35 PERI : Methylprednisolone IV POST : All pts placed on IV tapered dose of methylprednisolone Cervical drains placed in all cases 97.3% (36/37) Dysphagia: 12 (50%) at 2 wks, 4 (11%) at last follow-up • Mild: 8 (21.6%) • Moderate: 3 (8.1%) • Severe: 1 (2.7%) Pseudoarthrosis: 1 (2.7%) Hypertrophic ossification: 7 (19%) Subsidence: 4 (10.8%) Maza et al. 2019 47 1, 2, 3, 4-level ACDF Allograft or PEEK Placed within graft or cage at center Bone wax used to prevent leakage with PEEK 0.525 POST : Pts given IV steroids during hospital stay and prescribed methylprednisolone to take home 15-Fr Blake drain NR Dysphagia: 1 (2.1%) Mild cervical swelling: 1 (2.1%) Wang et al. 2020 32 1, 2, 3, 4-level ACDF Cage E.coli -derived BMP2 administered with bTCP NR 0.45–0.75 NR NR 100% (32/32) Dysphagia: 1 (3.1%) Mendenhall et al. 2021 198 1, 2, 3, 4-level ACF Noncontained vs contained spacers Placed within spacers NR 0.50 +/- 0.09 NR NR 96–100% Dysphagia: 22 (11%) Cervical swelling: 11 (6%) Hematoma: 3 (1.5%) Seroma: 2 (1%) Pseudoarthrosis: 2 (1%) Medina et al. 2024 26 Single and multilevel ACC w/wo PCF Titanium cage Tricalcium phosphate graft covering both ends Tricalcium phosphate graft over and under the cage 0.7 PERI : 12 mg of dexamethasone POST : IV antibiotics for 6 weeks NR 100% (26/26) Total complication: 4 (15%) Dysphagia: 2 (7.5%) Transient tetraparesis: 1 (3.8%) Fusion Seven studies reported fusion rates, and all but one demonstrated significantly higher fusion rates in the rhBMP2 group compared to the control group [ 27 – 30 , 32 , 34 ]. In the one exception observed by Vaidya et al., the rhBMP-2 group still achieved a greater fusion rate (100%), than the control group (95.8%) at 12 months. Two studies, Tan et al. and Chen et al., compared PEEK and allograft with rhBMP2 to ICBG in ACDF patients found a significant difference in fusion rates of 87.7% vs. 74.0% ( p < 0.036 ) and 83% vs. 74% ( p < 0.05 ), respectively [ 29 , 34 ]. The latter study reported that both patient groups achieved 100% solid fusion by 12 months [ 34 ]. The former study, Tan et al., also reported that the ICBG with rhBMP-2 and local autograft group had significantly faster fusion times compared to the ICBG control group ( p < 0.013 ) with an average fusion time of 82.6 days [ 29 ]. Complications Dysphagia Eight studies reported dysphagia rates, with four reporting statistically significant greater incidence of dysphagia in the rh-BMP2 group compared to control groups [ 26 – 28 , 30 – 34 ]. Two studies implemented a SWAL-QOL-based scoring system for dysphagia [ 27 , 33 ]. Bellamy et al. used a 70-point scoring system where a higher score equated to less severe symptoms [ 33 ]. After adjusting for the baseline, they found that the rhBMP-2 group had a score of 59.5, which was significantly lower than the control group with a score of 63.2 ( p = 0.002 ), though the authors admit that it remained unclear whether this difference was clinically relevant [ 33 ]. Vaidya et al. created their own scale based on discomfort and inability to swallow and found significantly higher dysphagia rates (65%) in the rhBMP-2 group compared to 22% in the control group at 6 weeks ( p < 0.0189 ) [ 26 ]. However, at the 2-year follow-up, it was found that both groups had mild persistent dysphagia at rates of 20% and 22% [ 26 ]. Riederman et al. reported dysphagia rates of 25.5% for the investigational group and 15% for the control group ( p < 0.01 ) [ 31 ], while Burkus et al. found dysphagia rates of 16.4% and 7.3% ( p < 0.001 ) [ 32 ]. Lu et al. found that the rhBMP-2 group (dysphagia score = 0.76) had a significantly greater dysphagia severity compared to the control group (dysphagia score = 0.596) following two-level ACDF after stratifying for the number of levels fused ( p < 0.005 ) [ 27 ]. Cervical swelling A total of 5 studies reported instances or measurements of cervical swelling [ 7 , 26 , 28 , 32 , 34 ]. Smucker et al. found that 27.5% of those treated with rhBMP-2 showed cervical swelling as opposed to 3.6% treated without by an average of 4.2 postoperative days ( p < 0.0001 ) [ 7 ]. Burkus et al. reported a much lower incidence of cervical swelling at rates of 3.6% for the rhBMP-2 group and 0.8% for the control, which were not statistically significant [ 32 ]. Vaidya et al. reported that the cervical swelling at the C3 level was significantly higher in the rhBMP-2 group at 6 weeks (8.0 ± 3.1 mm vs. 5.9 ± 3.1 mm, p = 0.03) [ 26 ]. Chen et al. also reported on C3 level swelling measurements, but found no significant difference between the two groups in measurements (10.7 ± 1.3 mm vs. 9.0 ± 1.2 mm, p > 0.05. Posterior Cervical Surgery Case Studies A total of four case series involving rhBMP-2 use in posterior cervical fusion were analyzed, encompassing 203 patients (Table 4 ) [ 35 – 38 ]. Table 4 Characteristics of included anterior cervical fusion comparative series studies. Significant findings have been bolded. Paper No. of patients rhBMP2/control Surgery and Delivery Method rhBMP2 | Control Containment measures rhBM2P dosage mg/level Peri/post-operative Steroid Drain use Fusion Rates % (rhBMP2/control) Complication Rates (rhBMP2/control) Smucker et al. 2006 69 / 165 Single and multilevel ACDF NR NR NR NR NR Swelling Complications: 19 (27.5%) / 6 (3.6%) • Severe dysphagia: 5 (7.2%) / 2 (1.2%) • Severe dysphagia: 5 (7.2%) / 2 (1.2%) • Return to clinic or EMR: 3 (4.3%) / 1 (0.6%) • Incision + drainage: 3 (4.3%) / 0 • Visible neck swelling: 2 (2.9%) / 0 • Readmissions: 2 (2.9%) / 0 • Outpatient ENT consult: 2 (2.9%) / 0 • Reintubation: 2 (2.9%) / 0 • PEG placement: 1 (1.4%) / 2 (1.2%) • Tracheostomy: 1 (1.4%)) / 1 (0.6%) • Delay in extubation: 0 / 1 (0.6%) Allograft/ autograft/ PEEK Allograft/ autograft Vaidya et al. 2007 22 / 24 1, 2, 3, -level ACDF NR 1.0 NR ⅛ -inch Hemovac drain 100% / 95.8% Endplate resorption: 22 (100%) / 0 Cervical swelling: 22 (100%) / 24 (100%) • C3 swelling: Significantly greater in rhBMP2 group Dysphagia: 17/20 (85%) / 10/18 (56%) Hoarseness: 13 (60%) / 15 (62%) PEEK [Allograft interbody spacers/ Allograft spacers] + DBM Lu et al. 2013 100 / 50 Multilevel ACDF Avoided irrigation 2.1 (n = 10) 1.05 (n = 48) 0.7 (n = 42) PERI: 10 mg dexamethasone NR 100% / 84% Dysphagia: (40%) / (44%) • Readmission: 3 (3%) / 0 • PEG placement: 4 (4%) / 0 Short-term Complication: 13 (13%) / 4 (8%) Hematoma: 2 (2%) / (0%) Seroma: 2 (2%) / (0%) CSF leakage: 1 (1%) / (0%) Recurrent laryngeal nerve palsy: 3 (3%) / 0 Aspiration pneumonia: 1 (1%) / 0 Transient C5 nerve root palsy: 1 (1%) / 1 (2%) PEEK Mechanical structural allograft spacer with local bone shaving Frenkel et al. 2013 22 / 23 2 or more level -ACDF NR 2.1 (n = 5) 1.4 (n = 3) 0.5–1.1 (n = 5) < 0.5 (n = 9) Mean of 1.0 mg NR NR 100% / 83% Dysphagia: 4 (18.2%) / 2 (8.7%) Total complication: 9 (22.7%) / 4 (17.4%) Tracheal swelling/ Reintubation: 0 / 1 (4.2%) Cervical swelling: 1 (4.5%) / 0 Fibular allografts Fibular allograft with vertebral autograft Tan et al. 2015 73 / 73 2-level ACDF Antibiotics given NR 0.9 NR Deep and superficial drains for 48 hours 87.7% / 74.0% Total complication : (21.6%) / (17.8%) Deep wound infection: 4 (5.48%) / 2 (2.74%) Prolonged wound drainage: 4 (5.48%) / 3 (4.11%) Cardiac infection: 2 (2.7%) / 1 (1.4%) GI infection: 2 (2.7%) / 3 (4.1%) UTI: 3 (4.1%) / 1 (1.4%) DVT: 1 (1.4%) / 1 (1.4%) Iliac crest site deep infection: 1 (1.4%) / 1 (1.4%) ICBG with local autograft ICBG Lovasik et al. 2017 84 / 107 Single and multilevel ACDF NR 0.5 NR NR 98.6% / 85.3% Clinically significant dysphagia: 11 (13.1%) / 14 (13%) Dysphagia: 17 (20.2%) / 18 (16.8%) Subsequent spine surgery: 2 (2.4%) / 4 (3.7%) PEEK or Allograft bTCP bone graft with PEEK or Allograft with morselized autologous and blood aspirate Riederman et al. 2017 200 / 200 1, 2, 3, 4-level ACDFs All wounds irrigated with antibiotic solution NR 0.7 NR Penrose drain NR Dysphagia: 51 (25.5%) / 30 (15%) Post-op steroid use: 21 (10.5%) / 12 (6%) Dysphonia: 5 (2.5%) / 9 (4.5%) Hematoma: 1 (0.5%) / 0 Freeze-dried allograft Cornerstone bone ICBG Burkus et al. 2017 224 / 486 Single-level ACDFs PEEK or allograft Placed within cage NR 0.6 (n = 240) 1.05 (n = 4) PERI: Corticosteroids used at discretion NR 99.4% / 87.2% Dysphagia: (16.7%) / (7.5%) Serious complications: (34.6%) / (34.7%) • Intervertebral disk protrusion: (7.0%) / (7.1%) Cervical swelling: (3.6%) / (0.8%) PEEK Cortical ring allograft spacers Bellamy et al. 2022 39 / 75 Single or 2-level ACDF Allograft Placed within graft NR 0.5 PERI: 10 mg dexamethasone POST: Oral taper steroid on discharge Hemovac or Jackson-Pratt suction drain NR Baseline-adjusted SWAL-QOL (Lower is more severe) • SWAL-QOL Scores: 59.5 / 63.2 Allograft Allograft Chen et al. 2025 538 / 518 Single or 2-level ACDF Local auto osteophyte or ICBG NR 0.5 PERI: Methylprednisolone POST: Methylprednisolone NR 83% / 74% at 3 mo 100% / 100% at 1 year Dysphagia: 54 (10%) / 47 (9%) • Mild: 47 (8.7%) / 42 (8.1%) • Moderate: 5 (0.9%) / 4 (0.8%) • Severe: 2 (0.4%) / 1 (0.2%) Subsidence: 48 (8.9%) / 66 (13%) PEEK and local autoosteophyte ICBG Fusion and Pseudoarthrosis Two studies reported 100% fusion by 24 months postoperatively [ 35 , 37 ]. Hamilton et al. observed 53 patients who had undergone occipitocervical, cervical, or cervicothoracic posterior cervical fusions (PCFs) with morselized autograft or allograft with rhBMP-2 and achieved 100% fusion by 24 months [ 35 ]. Similarly, the series by Hood et al. evaluated C1-C2 PCFs demonstrated 100% fusion by 24 months in all patients who achieved sufficient follow-up (50/52) [ 37 ]. Additionally, these authors observed signs of fusion as early as two months [ 37 ]. The remaining two studies reported fusion rates greater than 90%. Two series, by Hodges et al. and Ishida et al., reported pseudoarthrosis rates of 10.3% (3/29) in patients who underwent single and multilevel PCF, and 5.7% (4/69) in patients who underwent C1-C2 PCFs, respectively [ 36 , 38 ]. Complications The PCF case studies showed great variability in the types of complications observed [ 35 – 38 ]. Hamilton et al. reported two complications: one a superficial wound infection and the other an adjacent-level degeneration [ 35 ]. In the largest series, Ishida et al. reported a 10% reoperation rate due to seven cases of instrumentation failure, two cases of adjacent segment disease, and 2 cases of dysphagia and dyspnea [ 38 ]. Posterior Cervical Fusion Comparative Studies A total of four comparative studies on rhBMP-2 use in PCF were analyzed [ 39 – 42 ]. There were a total of 313 rhBMP-2 patients and 2,422 control patients. Notably, the majority of the patients (89%) from these studies came from a database study by Takahashi et al. (Table 5 ). Table 4 Characteristics of included posterior cervical fusion case series studies. Paper No. of patients rhBMP2/control Surgery and Delivery Method rhBM2P dosage mg/level Peri/post-operative Measures Drain use Fusion Rates % (rhBMP2/control) Complication Rates (rhBMP2/control) Hamilton et al. 2011 53 Occipitocervical, cervical, or cervicothoracic PCF Morselized autograft/allograft Mean : 1.8 Range : 1.1–2.9 NR Two ⅛ -inch Hemovac drains 100% (53/53) Total complication: 2 (3.8%) Superficial wound infection: 1 (1.9%) Adjacent-level degeneration: 1 (1.9%) Hodges et al. 2012 29 Single and multilevel PCF with Decompression Morselized autograft/allograft or hydroxyapatite:TCP ceramic matrix Mean : 2.1 Range : NR NR NR 89.7% (26/29) Pseudoarthrosis: 3 (10.3%) Hood et al. 2014 52 C1-C2 PCF With IC allograft (n = 24) Nonstructural corticocancellous allograft with local autograft (n = 28) Mean : 4.5 Range : 2.2–12 NR NR 100% (50/50) Postoperative tachycardia: 1 (1.9%) Shock and respiratory failure: 1 (1.9%) Hospital-acquired pneumonia: 1 (1.9%) DVT: 1 (1.9%) Ishida et al. 2019 69 C1-C2 PCF Hydroxyapatite and local autograft chips and/or morselized allograft Mean : 2.5 ± 0.9 Range : 0.8–6.0 NR NR 94.3% (65/69) Instrumentation failure: 7 (10.1%) Reoperation: 7 (10.1%) Pseudoarthrosis: 4 (5.7%) Dysphagia/dyspnea: 2 (2.8%) Phonation difficulty: 1 (1.5%) Intraoperative dural tear: 1 (1.5%) Table 5. Characteristics of included posterior cervical fusion comparative studies. Significant findings have been bolded. Paper No. of patients rhBMP2/control Surgery and Delivery Method rhBMP2 | Control rhBM2P dosage mg/level Peri/post-operative Steroid Drain use Fusion Rates % (rhBMP2/control) Complication Rates (rhBMP2/control) Crawford et al. 2009 41 / 36 Single and multilevel PCF Mean : 3.6 Range : 1.05–6.0 Large kit (n = 19) Small kit (n = 22) Abx preoperatively until all drains removed Deep and superficial drains NR Wound complications: 6 (14.6%) / 1 (2.8%) Harvest site deep infection: 0 / 1 (2.8%) Postoperative tachycardia: 0 / 1 (2.8%) Postoperative anemia: 0 / 1 (2.8%) Postoperative nausea, headaches: 0 / 1 (2.8%) Local autograft ICBG Yan et al. 2014 68 / 66 C1-C2 PCF NR Abx preoperatively until all drains removed Deep drain 82.4% / 78.4% Wound complication: 6 (8.8%) / 2 (3.0%) Intraoperative dural tear: 1 (1.5%) / 1 (1.5%) GI infection: 2 (2.9%) / 4 (6.1%) Cardiac infection: 1 (1.5%) / 3 (4.5%) UTI: 1 (1.5%) / 3 (4.5%) DVT: 1 (1.5%) / 3 (4.5%) ICBG with local autograft ICBG Takahashi et al. 2017 Upper: 73 / 279 Lower: 78 / 1994 Upper (O-C2) and Lower (C3-C7) PCF NR NR NR NR Total complications Upper: 7 (9.6%) / 34 (12%) Lower: 42 (11%) / 276 (14%) Wound complication Upper: 1 (1.4%) / 5 (1.8%) Lower: 23 (6.1%) / 75 (3.8%) Neck complication Upper: 0 / 2 (0.7%) Lower: 2 (0.5%) / 15 (0.8%) Other complications Upper: 7 (9.6%) / 31 (11%) Lower: 37 (9.8%) / 263 (13%) With rhBMP-2 Without rhBMP-2 Iyer et al. 2018 53 / 47 Posterior cervical surgery Mean : 1.49 Range : 0.13–8.57 NR NR NR Neurological complication: 12 (27.9%) / 18 (34.6%) Operative complication: 11 (25.6%) / 11 (21.2%) Cardiopulmonary complication: 9 (20.9%) / 8 (15.4%) Dysphagia: 8 (18.6%) / 3 (5.8%) Infection: 8 (18.6%) / 7 (13.5%) Radiographic complication: 5 (11.6%) / 3 (5.8%) Instrumentation complication: 3 (7.0%) / 1 (1.8%) Outcomes: Fusion and Pseudoarthrosis Only one out of the four comparative studies reported fusion rates. Yan et al. compared C1-C2 PCF outcomes between ICBG groups treated with or without rhBMP-2 [ 40 ]. The rhBMP-2 group demonstrated superior fusion rate compared to controls (82.4% vs. 78.4%) however, this difference was not statistically significant (p=.782). Complications Three out of four studies reported wound complication rates with rhBMP-2 use, ranging from 1.4% to 14.6% [ 39 – 41 ]. Crawford et al. analyzed single and multilevel PCF patients treated with rhBMP-2 and local autograft or ICBG and observed wound complication rates in 6 (13.6%) patients and 1 patient (2.8%), respectively, with no significant difference [ 39 ]. Yan et al. similarly reported no significant difference between wound complication rates of patients undergoing C1-C2 ICBG PCF with rhBMP-2 and local autograft versus without it (8.8% vs. 3.0%) [ 40 ]. Interestingly, Takahashi et al. reported complication incidence in patients who underwent upper (occipital - C2) or lower (C3 - C7) level PCF. They found a significant difference in lower cervical fusion wound complication rates amongst patients treated with rhBMP-2 (6.1%) and without it (3.8%) ( p = 0.037 ). DISCUSSION Anterior Cervical Fusion Fusion rates were high among all ACF studies in this review, with fusion rates ranging from 80–100% [ 27 – 30 , 32 , 34 ]. All seven competitive studies reported higher fusion rates compared to controls, and all but one achieved statistical significance. Despite concerns about complications, rhBMP-2 consistently demonstrated strong osteoinductive capacity in cervical fusion. A recent meta-analysis by Ibrahim et al. analyzed 20 studies with 5,828 patients who underwent ACDF with or without rhBMP-2 and found that its use was associated with significantly higher fusion rates (98.9% vs. 93.6%) but also with an increased risk of dysphagia (24.7% vs. 8.1%) [ 43 ]. They concluded that the benefit of fusion outweighs the risk of dysphagia in older patients undergoing fusion at fewer than two cervical levels [ 43 ]. Further risk-benefit analyses of rhBMP-2 are needed to help define the threshold at which patients at risk for pseudoarthrosis may most appropriately receive rhBMP-2. Complications The most commonly reported complications of ACF in this review were dysphagia, cervical swelling, pseudoarthrosis, heterotopic bone formation, endplate resorption, hematoma/seroma, and subsidence. These findings are consistent with previous literature. Robertson and Ashley, in their series of 2,579 ACDFs performed by a single surgeon between 1998 and 2017, identified dysphagia (7%) and hematoma (0.9%) amongst the most frequent adverse events [ 44 ]. Similarly, Yee et al., in a review of 240 prospective and retrospective studies, reported adjacent segment disease, dysphagia, C5 palsy, graft or hardware failure, pseudoarthrosis, recurrent laryngeal nerve palsy, infection, and hematoma as the most prevalent complications [ 45 ]. Dysphagia In this review, reported dysphagia rates with rhBMP-2 ranged from 2.13% to 65%, with the highest incidence being reported in comparative studies. A prior review of ACDF studies also identified widely ranging postoperative dysphagia, from 1.7% to 67% [ 46 ]. This wide variability likely reflects differences in assessment methodology. Reported measures from this review included SWAL-QOL point systems, the Bazaz grading scale, patient questionnaires, and study-specific severity grading methods. Because each system defines severity differently, literature reports remain inconsistent. Notably, two comparative studies found no significant difference in dysphagia incidence between rhBMP-2 and controls [ 27 , 34 ], though one reported greater dysphagia severity in the rhBMP-2 group [ 27 ]. Cervical Swelling Cervical swelling with rhBMP-2 in this review ranged from 2.13–8.6% in case series and 3.6–27.5% in comparative studies. Similar variability is reported in the literature, with excessive neck swelling occurring in 11.3% of ACDF cases in one review of PubMed, Embase, and Cochrane databases [ 47 ], and soft tissue swelling/hematoma reported at 1.7% in ACDF literature from 1989–2019 [ 48 ]. All comparative studies showed numerically higher rates and greater swelling in the rhBMP-2 group, with two achieving statistical significance. A meta-analysis of 27 studies reported a 1.43-fold increased risk of cervical swelling complications with rhBMP-2 [ 49 ]. Independent of rhBMP-2 use, anterior cervical procedures require retraction of the esophageal, tracheal, and pharyngeal tissues, predisposing to inflammation and prevertebral swelling [ 43 ]. rhBMP-2 may further potentiate inflammation and swelling through its pro-inflammatory and angiogenic properties. In a rat arthrodesis model, Hsu et al. demonstrated increased circulating pro-inflammatory cytokines (TNF-ɑ, MIP-1ɑ, IL-1β) following rhBMP-2 implantation [ 46 ]. This inflammatory cascade, combined with angiogenesis, may prolong tissue swelling and exacerbate postoperative dysphagia compared to a control environment without rhBMP-2. Posterior Cervical Fusion Fusion rates with rhBMP-2 in this review ranged from 82.4% to 100%. The only comparative study of PCF reported a higher fusion rate in the rhBMP-2 group than in controls (p=.782) [ 40 ]. Despite fusion rate differences not achieving statistical significance, the time to fusion was faster in the rhBMP-2 group by 11 days [ 40 ]. While statistically significant, this is unlikely to be clinically significant. More studies are needed to identify whether rhBMP-2 may confer a time-to-fusion benefit in PCF. Complications The most common complications of posterior cervical surgery identified in this review were systemic complications (tachycardia, infection, DVT), wound complications, pseudoarthrosis, intraoperative dural tears, and instrumentation failure. These findings align with prior reviews, such as that by Badiee et al., who reported wound infection, incidental durotomy, and pseudoarthrosis as the most frequent short- and long-term complications [ 50 ]. Higher rates of pseudoarthrosis and durotomy in their study were attributed to mechanical stress from longer fusion constructs, revision surgery, and patient comorbidities, including obesity, smoking, diabetes, rheumatoid arthritis, older age, and chronic steroid use [ 50 ]. Notably, PCF is often performed in older patients with multilevel disease and preexisting comorbidities, which inherently increases their complication risk [ 50 ]. Wound complications Wound complications in the reviewed studies encompassed infection, hemorrhage, hematoma, and wound disruption. Across all studies reporting wound complications, incidence was consistently higher in rhBMP-2 cohorts [ 39 – 42 ]. However, Takahashi et al. was the only study to demonstrate a statistically significant difference in their C3–C7 PCF cohort [ 41 ]. The higher incidence of wound complications has been attributed to the rhBMP-2-induced inflammation, as well as surgical invasiveness in PCF [ 39 ]. Posterior approaches require larger incisions and extensive dissection through subcutaneous tissue to access the paraspinal muscles and cervical spine, which likely contributes to the higher rate of wound-related complications [ 51 ]. rhBMP-2 Dosage and Complications Several studies have demonstrated a dose-dependent relationship between rhBMP-2 and complication rates in cervical fusion. A meta-analysis by Wen et al. stratified their rhBMP-2 dosages by low ( 1.1 mg/level). The included studies with low doses did not report complication rates, but the complication rates increased from the middle (15.26%) to high (24.14%) doses. However, the authors did not report whether this difference was statistically significant [ 52 ]. Frenkel et al., however, identified a significant correlation (Pearson correlation 0.753, p < 0.01) between dosage and complications [ 28 ]. Conversely, Tumialan et al. found no reduction in complications when the dose was reduced from 2.1 mg/level to 0.7 mg/level [ 13 ]. However, the authors admit that several confounders, including repeated operations and multi-level cases, limited their ability to argue against the dose-dependent relationship that other authors have found. Additional cohort data corroborate the dose-dependent relationship between rhBMP-2 and complications, with higher per-level dosing significantly predicting deep infection and pseudoarthrosis [ 53 , 54 ]. In the context of PCF, there is no consensus on the optimal rhBMP-2 dosage. Hamilton et al. reported favorable results with an average dose of 1.8 mg/level [ 35 ], whereas Crawford et al., using 3.6 mg/level, observed a markedly higher wound complication rate (14.6% vs. 1.9%) [ 39 ]. These findings suggest that higher doses may cause leakage of rhBMP-2 into surrounding tissues, potentiating inflammation and impairing wound healing. Recent practice patterns within this review indicate a shift toward lower dosing, 0.2–0.6 mg/level for anterior cervical fusions and 1.49–2.5 mg/level for posterior fusions, as a strategy to balance efficacy and safety. Minimizing Complications Recent studies reflect a growing emphasis on prophylactic measures to mitigate rhBMP-2–related complications. Pourtaheri et al. and Maza et al. reported use of fibrin sealant and bone wax, respectively, to contain rhBMP-2 within the graft or cage [ 11 , 21 ]. Several authors also described avoiding irrigation of the surgical site after rhBMP-2 placement to reduce spread into adjacent soft tissues [ 13 , 16 , 19 , 27 ]. In anterior cervical surgery, perioperative and postoperative steroid use, along with soft-tissue drains, were frequently employed to decrease inflammation. Notably, a randomized controlled trial by Edwards et al. found that local depomedrol administration after ACDF with low-dose rhBMP-2 significantly reduced both dysphagia incidence and severity compared to controls at one, two, three, and four weeks postoperatively (p < 0.5) [ 55 ]. Limitations This review is subject to several limitations. Firstly, the heterogeneity across the included studies, in terms of dosing strategies, follow-up duration, and outcome reporting, precluded a formal meta-analysis and limits direct comparability. The measurement of complications, particularly dysphagia and swelling, was inconsistently applied across studies. Secondly, the included studies and published data are subject to bias, as many of the included articles were case series lacking control groups. Future research can prioritize standardized definitions and reporting of complications, as well as the optimization of delivery and containment techniques, to establish evidence-based protocols for dosing tailored to the number of operated surgical levels, patient-specific risk factors, and surgical approach. Conclusion rhBMP-2 in cervical fusion is associated with consistently high fusion rates and, in many studies, accelerated fusion compared to traditional bone grafts. However, these benefits come at the cost of increased complications, particularly in anterior cervical fusions, where dysphagia and cervical swelling were the most prevalent. In posterior cervical fusions, rhBMP-2 use was not observed to be associated with significantly higher complication rates, except for wound complications. Emerging strategies, including lower dosing, use of sealants or glue, avoidance of irrigation, and prophylactic steroid use, may reduce adverse outcomes by confining rhBMP-2 to the intended fusion site and decreasing inflammation. Due to ongoing safety concerns, rhBMP-2 should be reserved for select cervical spine patients at risk of pseudoarthrosis, where benefits outweigh potential risks, especially in anterior cervical fusions. Declarations Competing Interests Addisu Mesfin, following conflict of interest: Grants from Nuvasive, OREF grant, Depuy speaking fees, Globus consulting. The remaining co-authors have nothing to disclose. Author Contribution Authors AM and JPJ contributed to curation and supervision of the study. Authors JL, JPJ, LL, ME, and KY completed data collection/analysis and manuscript formulation. Authors JL, JPJ, AP, AA, JH, and SB supported editing and submission of the study. All authors reviewed and approved the final manuscript. 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Clin Spine Surgery: Spine Publication 30(9):E1321–E1332 Bellamy JT, Dilbone E, Schell A, Premkumar A, Geddes B, Leckie S et al (2022) Prospective comparison of dysphagia following anterior cervical discectomy and fusion (ACDF) with and without rhBMP-2. Spine J 22(2):256–264 Chen T, Wu X, Li X, Shi J, Zhu Y, Zhou H et al (2025) A Randomized Controlled Trial Evaluating Efficacy and Complications of Low-Dose rhBMP-2 for Anterior Cervical Diskectomy and Fusion. Neurosurgery [Internet]. Apr 23 [cited 2025 June 19]; Available from: https://journals.lww.com/ 10.1227/neu.0000000000003461 Hamilton DK, Smith JS, Reames DL, Williams BJ, Chernavvsky DR, Shaffrey CI, Safety (2011 July) Efficacy, and Dosing of Recombinant Human Bone Morphogenetic Protein-2 for Posterior Cervical and Cervicothoracic Instrumented Fusion With a Minimum 2-Year Follow-up. Neurosurgery 69(1):103–111 Hodges SD, Eck JC, Newton D Retrospective Study of Posterior Cervical Fusions With rhBMP-2. Orthopedics [Internet]. 2012 June [cited 2025 July 15];35(6). Available from: https://journals.healio.com/doi/ 10.3928/01477447-20120525-30 Hood B, Hamilton DK, Smith JS, Dididze M, Shaffrey C, Levi AD (2014) The Use of Allograft and Recombinant Human Bone Morphogenetic Protein for Instrumented Atlantoaxial Fusions. World Neurosurg 82(6):1369–1373 Ishida W, Ramhmdani S, Xia Y, Kosztowski TA, Xu R, Choi J et al (2019) Use of Recombinant Human Bone Morphogenetic Protein-2 at the C1-C2 Lateral Articulation without Posterior Structural Bone Graft in Posterior Atlantoaxial Fusion in Adult Patients. World Neurosurg 123:e69–76 Crawford CH, Carreon LY, McGinnis MD, Campbell MJ, Glassman SD (2009 June) Perioperative Complications of Recombinant Human Bone Morphogenetic Protein-2 on an Absorbable Collagen Sponge Versus Iliac Crest Bone Graft for Posterior Cervical Arthrodesis: Spine. 34(13):1390–1394 Yan L, Chang Z, He B, Liu T, Wang X, Guo H et al (2014) Efficacy of rhBMP-2 versus iliac crest bone graft for posterior C1-C2 fusion in patients older than 60 years. Orthopedics 37(1):e51–57 Takahashi S, Buser Z, Cohen JR, Roe A, Myhre SL, Meisel HJ et al (2017) Complications Related to the Recombinant Human Bone Morphogenetic Protein 2 Use in Posterior Cervical Fusion. Clin Spine Surgery: Spine Publication 30(9):E1269–E1273 Iyer S, Kim HJ, Bao H, Smith JS, Gupta M, Albert TJ et al (2018 Sept) The Posterior Use of BMP-2 in Cervical Deformity Surgery Does Not Result in Increased Early Complications: A Prospective Multicenter Study. Global Spine J 8(6):622–628 Tsalimas G, Evangelopoulos DS, Benetos IS, Pneumaticos S (2022 July) Dysphagia as a Postoperative Complication of Anterior Cervical Discectomy and Fusion. Cureus 14(7):e26888 Robertson SC, Ashley MR (2023) Complications of Anterior Cervical Discectomy and Fusion. Acta Neurochir Suppl 130:169–178 Ibrahim S, Michalopoulos GD, Flanigan P, Johnson SE, Katsos K, Sebastian AS et al (2024) Bone morphogenetic protein in subaxial cervical arthrodesis: a meta-analysis of 5828 patients. J Neurosurg Spine 41(2):174–187 Hsu HP, Zanella JM, Peckham SM, Spector M (2006) Comparing ectopic bone growth induced by rhBMP-2 on an absorbable collagen sponge in rat and rabbit models. J Orthop Res 24(8):1660–1669 Tavanaei R, Ansari A, Hatami A, Heidari MJ, Dehghani M, Hajiloo A et al (2025) Postoperative complications of anterior cervical discectomy and fusion: A comprehensive systematic review and meta-analysis. N Am Spine Soc J 21:100596 Epstein NE (2019) A Review of Complication Rates for Anterior Cervical Diskectomy and Fusion (ACDF). Surg Neurol Int 10:100 Martin CT, Holton K, Broida SE, Hickmann AK, Bakker C, Lender PA et al (2024) Comparative Complications Associated With BMP Use In Patients Undergoing ACDF for Degenerative Spinal Conditions: Systematic Review and Meta-Analysis. Global Spine J 14(2suppl):94S–109S Badiee RK, Mayer R, Pennicooke B, Chou D, Mummaneni PV, Tan LA (2020) Complications following posterior cervical decompression and fusion: a review of incidence, risk factors, and prevention strategies. J Spine Surg 6(1):323–333 Abel F, Tan ET, Lin Y, Chazen JL, Lebl DR, Sneag DB (2025) MRI after Cervical Spine Decompression and Fusion Surgery: Technical Considerations, Expected Findings, and Complications. Radiology 314(2):e232961 Wen YD, Jiang WM, Yang HL, Shi JH (2020 Sept) Exploratory meta-analysis on dose-related efficacy and complications of rhBMP-2 in anterior cervical discectomy and fusion: 1,539,021 cases from 2003 to 2017 studies. J Orthop Translation 24:166–174 Lytle EJ, Slavnic D, Tong D, Bahoura M, Govila L, Gonda R et al (2019) Minimally Effective Dose of Bone Morphogenetic Protein in Minimally Invasive Lumbar Interbody Fusions: Six Hundred Ninety Patients in a Dose-Finding Longitudinal Cohort Study. Spine (Phila Pa 1976). 15(14):989–995 De Stefano FA, Elarjani T, Burks JD, Burks SS, Levi AD (2021) Dose Adjustment Associated Complications of Bone Morphogenetic Protein: A Longitudinal Assessment. World Neurosurg 156:e64–71 Edwards CC, Dean C, Edwards CC, Phillips D, Blight A (2016) Can Dysphagia Following Anterior Cervical Fusions With rhBMP-2 Be Reduced With Local Depomedrol Application? A Prospective, Randomized, Placebo-Controlled, Double-Blind Trial. SPINE 41(7):555–562 Additional Declarations Competing interest reported. Addisu Mesfin, following conflict of interest: Grants from Nuvasive, OREF grant, Depuy speaking fees, Globus consulting. The remaining co-authors have nothing to disclose. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8780018","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":590490677,"identity":"a8b80a76-f77c-4dfb-b230-57d3ebf340be","order_by":0,"name":"Jamie Lee","email":"","orcid":"","institution":"Georgetown University","correspondingAuthor":false,"prefix":"","firstName":"Jamie","middleName":"","lastName":"Lee","suffix":""},{"id":590490680,"identity":"c04e37cd-fa25-4bbe-938c-b298e761f580","order_by":1,"name":"Jonathan P. Japa","email":"","orcid":"","institution":"MedStar Washington Hospital Center","correspondingAuthor":false,"prefix":"","firstName":"Jonathan","middleName":"P.","lastName":"Japa","suffix":""},{"id":590490682,"identity":"d567d8d6-9527-4016-a4b3-7d2bb9d56599","order_by":2,"name":"Linus Lee","email":"","orcid":"","institution":"Georgetown University Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Linus","middleName":"","lastName":"Lee","suffix":""},{"id":590490683,"identity":"4770439a-570e-4d75-9c69-72468d9bee17","order_by":3,"name":"Kevin Yoon","email":"","orcid":"","institution":"MedStar Washington Hospital Center","correspondingAuthor":false,"prefix":"","firstName":"Kevin","middleName":"","lastName":"Yoon","suffix":""},{"id":590490684,"identity":"b7358741-ae49-4872-97c7-ac6d2a4add85","order_by":4,"name":"Mark Ehioghae","email":"","orcid":"","institution":"MedStar Washington Hospital Center","correspondingAuthor":false,"prefix":"","firstName":"Mark","middleName":"","lastName":"Ehioghae","suffix":""},{"id":590490685,"identity":"bf38b6b5-0140-4995-aff3-4dcecff5949d","order_by":5,"name":"Aaron Phung","email":"","orcid":"","institution":"Georgetown University","correspondingAuthor":false,"prefix":"","firstName":"Aaron","middleName":"","lastName":"Phung","suffix":""},{"id":590490686,"identity":"e9fc0c43-868e-4691-8085-3e57a0d75727","order_by":6,"name":"Ala Alshomali","email":"","orcid":"","institution":"Georgetown University","correspondingAuthor":false,"prefix":"","firstName":"Ala","middleName":"","lastName":"Alshomali","suffix":""},{"id":590490687,"identity":"c7f771c0-f214-467b-97aa-7d29b62e75b4","order_by":7,"name":"Justin Hyde","email":"","orcid":"","institution":"Georgetown University","correspondingAuthor":false,"prefix":"","firstName":"Justin","middleName":"","lastName":"Hyde","suffix":""},{"id":590490688,"identity":"71badd4c-23c5-4c7b-b274-3d8cf0c52231","order_by":8,"name":"Sean Bae","email":"","orcid":"","institution":"Georgetown University","correspondingAuthor":false,"prefix":"","firstName":"Sean","middleName":"","lastName":"Bae","suffix":""},{"id":590490689,"identity":"1acf0b28-c0d6-4398-b005-3f9e8767c803","order_by":9,"name":"Addisu Mesfin","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxklEQVRIiWNgGAWjYLCCCgMGORB94AHRWs4YMBiDtSQQr4WBIbEBxCBKC/+0w4c/HCi4kz4/7PBDoC12croNBLRI3E5Lkzhg8Cx34+00A6CWZGOzA4SsuZ1jxvzB4HDuxtkJIC0HErcR0iJ/O//zhwMGh9MNZ6d/IE6Lwe0cBqDDDifIS+cQaYvh7TQzkBbDDdI5BQcSDIjwi9zt5McfDvw5LC8/O33zhw8VdnKEvQ93IVilAbHKQUC+gRTVo2AUjIJRMKIAAEq0S/6EmBB1AAAAAElFTkSuQmCC","orcid":"","institution":"MedStar Washington Hospital Center","correspondingAuthor":true,"prefix":"","firstName":"Addisu","middleName":"","lastName":"Mesfin","suffix":""}],"badges":[],"createdAt":"2026-02-03 21:53:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8780018/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8780018/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":102621288,"identity":"d5b6eb37-ed31-45f8-bd36-eaab8bc12be4","added_by":"auto","created_at":"2026-02-13 16:50:18","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":545011,"visible":true,"origin":"","legend":"\u003cp\u003ePRISMA Diagram.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8780018/v1/980aacdd018e6c1d7aba13d6.jpeg"},{"id":104404482,"identity":"d9449ca7-be0b-48e0-8467-cd3ba11088b6","added_by":"auto","created_at":"2026-03-11 12:20:22","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4099643,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8780018/v1/6327cab3-55f2-4c54-a7f0-51237a1b1143.pdf"}],"financialInterests":"Competing interest reported. Addisu Mesfin, following conflict of interest: Grants from Nuvasive, OREF grant, Depuy speaking fees, Globus consulting. The remaining co-authors have nothing to disclose.","formattedTitle":"The Use of rhBMP-2 in Cervical Fusion: A Systematic Review","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eCervical fusion is indicated for various conditions, including trauma, tumors, deformities, and degenerative disorders, which can result in myelopathy or radiculopathy [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Cervical fusion is categorized by approach, including anterior and posterior methods. A Recent Pearl Diver database study reported over 50,000 anterior cervical discectomies and fusions (ACDFs) and over 16,000 posterior cervical fusions (PCFs) were performed in the United States in 2022 [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Currently, ACDF remains the most commonly performed cervical spine surgery, while PCF is becoming increasingly popular [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe introduction of INFUSE\u0026reg; in 2002 offered a recombinant human bone morphogenetic protein-2 (rhBMP-2)-based alternative to Iliac crest bone graft (ICBG) [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Early clinical studies of lumbar fusion using rhBMP-2 revealed fusion rates that were comparable to or often higher than those achieved with autologous bone grafts [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. rhBMP-2 is hypothesized to exert its osteoinductive and chondrogenic effects by promoting the differentiation of mesenchymal stem cells into osteoblasts and chondrocytes, thereby facilitating effective bony growth and fusion [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHowever, other studies on the use of rhBMP-2 in ACFs have reported elevated complication rates, including cervical swelling, dysphagia, and dyspnea [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. A proposed mechanism involves excess rhBMP-2 diffusing out of the target site and into the surrounding environment, causing inflammation and ectopic bone formation [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In response to the concerning findings, the FDA issued a black-box warning for rhBMP-2 for cervical spine surgery in 2008 [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSubsequent concerns about rhBMP-2 in the cervical spine has limited its use for most, but not all, surgeons, as many continued to use it off-label. In a recent survey of orthopedic and neurosurgeons, both U.S. and non-U.S.-based, revealed that 13% of surgeons still utilized rhBMP-2 in multilevel ACDFs [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. This notable use of rhBMP-2 in the cervical spine highlights the need for reassessment. Therefore, this systematic review aims to assess complications associated with rhBMP-2 in anterior and posterior cervical fusions and to examine the impact of dosage, patient-specific risk factors, and preventive strategies.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eSearch Strategy\u003c/h2\u003e \u003cp\u003e A systematic review was conducted in accordance with PRISMA guidelines. Databases PubMed and Embase were used for our search. Within each database, block searches were conducted using keywords and Boolean operators. Key words included: \u0026ldquo;bone morphogenetic protein 2,\u0026rdquo; \u0026ldquo;recombinant bone morphogenetic protein 2,\u0026rdquo; \u0026ldquo;BMP2,\u0026rdquo; \u0026ldquo;BMP-2\u0026rdquo;. \u0026ldquo;rhBMP2,\u0026rdquo; \u0026ldquo;cervical spine,\u0026rdquo; \u0026ldquo;cervical spine surgery,\u0026rdquo; \u0026ldquo;complication,\u0026rdquo; \u0026ldquo;efficacy,\u0026rdquo; and \u0026ldquo;outcomes.\u0026rdquo;\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eInclusion and Exclusion Criteria\u003c/h3\u003e\n\u003cp\u003eStudies that used rhBMP-2 in cervical fusion and reported clinical outcomes and complications were included in the analysis. Non-human studies, case reports, review articles, and non-English articles were excluded. Finally, articles reporting fewer than 20 patients and those reporting pediatric patients were excluded.\u003c/p\u003e\n\u003ch3\u003eStudy selection and screening\u003c/h3\u003e\n\u003cp\u003eTwo reviewers independently screened titles and abstracts. Full texts were retrieved for potentially eligible articles. Disagreements were resolved by discussion; if consensus was not reached, a third reviewer was consulted. The selection process is summarized in a PRISMA flow diagram (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eData extraction\u003c/h3\u003e\n\u003cp\u003eFrom each study, we collected: study design; sample size, BMP-2 dosage; details of the BMP-2 delivery method; comparator group if present; reported clinical outcomes, including fusion rates and postoperative complications.\u003c/p\u003e\n\u003ch3\u003eRisk of bias assessment\u003c/h3\u003e\n\u003cp\u003eWe applied the Robins-I V2 tool in order to assess risk of bias (Table\u0026nbsp;1). In summary, the primary source of bias was the absence of a comparator group in the case series and the selection of patients receiving BMP-2 in comparative studies. However, all studies reported primary outcomes related to BMP-2 use in cervical surgery.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\n\u003ch2\u003eAnterior Cervical Fusion Case Studies\u003c/h2\u003e\n\u003cp\u003eA total of 16 case series [\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e], encompassing 1,240 patients, met our inclusion criteria (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab1\" style=\"width: 1046.34px;\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable\u0026nbsp;1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eRisk of Bias Assessment using Robins-I V2\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 88px;\" align=\"left\"\u003e\n\u003cp\u003eAuthor, Year\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 93px;\" align=\"left\"\u003e\n\u003cp\u003eDomain 1: Confounding\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\" align=\"left\"\u003e\n\u003cp\u003eDomain 2: Classification of Interventions\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 114px;\" align=\"left\"\u003e\n\u003cp\u003eDomain 3: Selection of Participants\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 153px;\" align=\"left\"\u003e\n\u003cp\u003eDomain 4: Deviations from Intended Interventions\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 82px;\" align=\"left\"\u003e\n\u003cp\u003eDomain 5: Missing Data\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 127px;\" align=\"left\"\u003e\n\u003cp\u003eDomain 6: Measurement of Outcomes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 124px;\" align=\"left\"\u003e\n\u003cp\u003eDomain 7: Selection of the Reported Result\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 72px;\" align=\"left\"\u003e\n\u003cp\u003eOverall Risk of Bias\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 88px;\" align=\"left\"\u003e\n\u003cp\u003eLanman et al., 2004\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 93px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 114px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 153px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 82px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 127px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 124px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 72px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 88px;\" align=\"left\"\u003e\n\u003cp\u003eBoakye et al., 2005\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 93px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 114px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 153px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 82px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 127px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 124px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 72px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 88px;\" align=\"left\"\u003e\n\u003cp\u003eShields et al., 2006\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 93px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 114px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 153px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 82px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 127px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 124px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 72px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 88px;\" align=\"left\"\u003e\n\u003cp\u003eTumialan et al., 2008\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 93px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 114px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 153px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 82px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 127px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 124px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 72px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 88px;\" align=\"left\"\u003e\n\u003cp\u003eVaidya et al., 2008\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 93px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 114px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 153px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 82px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 127px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 124px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 72px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 88px;\" align=\"left\"\u003e\n\u003cp\u003eKlimo et al., 2009\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 93px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 114px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 153px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 82px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 127px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 124px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 72px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 88px;\" align=\"left\"\u003e\n\u003cp\u003eShen et al., 2010\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 93px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 114px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 153px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 82px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 127px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 124px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 72px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 88px;\" align=\"left\"\u003e\n\u003cp\u003eStachniak et al., 2011\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 93px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 114px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 153px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 82px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 127px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 124px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 72px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 88px;\" align=\"left\"\u003e\n\u003cp\u003eSethi et al., 2011\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 93px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 114px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 153px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 82px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 127px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 124px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 72px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 88px;\" align=\"left\"\u003e\n\u003cp\u003eKhajavi et al., 2014\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 93px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 114px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 153px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 82px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 127px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 124px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 72px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 88px;\" align=\"left\"\u003e\n\u003cp\u003eKukreja et al., 2015\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 93px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 114px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 153px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 82px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 127px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 124px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 72px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 88px;\" align=\"left\"\u003e\n\u003cp\u003ePourtaheri et al., 2015\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 93px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 114px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 153px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 82px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 127px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 124px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 72px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 88px;\" align=\"left\"\u003e\n\u003cp\u003eMaza et al., 2019\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 93px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 114px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 153px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 82px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 127px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 124px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 72px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 88px;\" align=\"left\"\u003e\n\u003cp\u003eWang et al., 2020\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 93px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 114px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 153px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 82px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 127px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 124px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 72px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 88px;\" align=\"left\"\u003e\n\u003cp\u003eMendenhall et al., 2021\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 93px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 114px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 153px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 82px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 127px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 124px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 72px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 88px;\" align=\"left\"\u003e\n\u003cp\u003eMedina et al., 2024\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 93px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 114px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 153px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 82px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 127px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 124px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 72px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 88px;\" align=\"left\"\u003e\n\u003cp\u003eSmucker et al., 2006\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 93px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 114px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 153px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 82px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 127px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 124px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 72px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 88px;\" align=\"left\"\u003e\n\u003cp\u003eVaidya et al., 2007\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 93px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 114px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 153px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 82px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 127px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 124px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 72px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 88px;\" align=\"left\"\u003e\n\u003cp\u003eLu et al., 2013\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 93px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 114px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 153px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 82px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 127px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 124px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 72px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 88px;\" align=\"left\"\u003e\n\u003cp\u003eFrenkel et al., 2013\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 93px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 114px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 153px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 82px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 127px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 124px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 72px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 88px;\" align=\"left\"\u003e\n\u003cp\u003eTan et al., 2015\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 93px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 114px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 153px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 82px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 127px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 124px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 72px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 88px;\" align=\"left\"\u003e\n\u003cp\u003eLovasik et al., 2017\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 93px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 114px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 153px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 82px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 127px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 124px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 72px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 88px;\" align=\"left\"\u003e\n\u003cp\u003eRiederman et al., 2017\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 93px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 114px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 153px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 82px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 127px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 124px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 72px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 88px;\" align=\"left\"\u003e\n\u003cp\u003eBurkus et al., 2017\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 93px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 114px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 153px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 82px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 127px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 124px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 72px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 88px;\" align=\"left\"\u003e\n\u003cp\u003eBellamy et al., 2022\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 93px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 114px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 153px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 82px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 127px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 124px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 72px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 88px;\" align=\"left\"\u003e\n\u003cp\u003eChen et al., 2025\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 93px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 114px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 153px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 82px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 127px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 124px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 72px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 88px;\" align=\"left\"\u003e\n\u003cp\u003eHamilton et al., 2011\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 93px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 114px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 153px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 82px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 127px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 124px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 72px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 88px;\" align=\"left\"\u003e\n\u003cp\u003eHodges et al., 2012\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 93px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 114px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 153px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 82px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 127px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 124px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 72px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 88px;\" align=\"left\"\u003e\n\u003cp\u003eHood et al., 2012\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 93px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 114px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 153px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 82px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 127px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 124px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 72px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 88px;\" align=\"left\"\u003e\n\u003cp\u003eIshida et al., 2019\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 93px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 114px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 153px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 82px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 127px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 124px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 72px;\" align=\"left\"\u003e\n\u003cp\u003eSerious\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 88px;\" align=\"left\"\u003e\n\u003cp\u003eCrawford et al., 2009\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 93px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 114px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 153px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 82px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 127px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 124px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 72px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 88px;\" align=\"left\"\u003e\n\u003cp\u003eYan et al., 2014\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 93px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 114px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 153px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 82px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 127px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 124px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 72px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 88px;\" align=\"left\"\u003e\n\u003cp\u003eTakahashi et al., 2017\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 93px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 114px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 153px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 82px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 127px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 124px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 72px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 88px;\" align=\"left\"\u003e\n\u003cp\u003eIyer et al., 2018\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 93px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 132px;\" align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 114px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 153px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 82px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 127px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 124px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 72px;\" align=\"left\"\u003e\n\u003cp\u003eModerate\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003ch3\u003eFusion and Pseudoarthrosis\u003c/h3\u003e\n\u003cp\u003eAnalysis of 14 studies reporting fusion rates revealed high rates, ranging from 81.8% to 100%. Seven studies reported 100% fusion rates, either by 9 months [\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e] or by 12 months [\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e]. Uniquely, Lanman et al. reported 100% fusion as early as 3 months [\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eFour studies reported pseudoarthrosis rates, ranging from 1% to 18.2% [\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e]. The highest pseudoarthrosis rates reported were by Kilmo et al. (18.2%) and Shen et al. (10.2%) [\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e]. Klimo et al. investigated the use of rhBMP-2 in 22 ACDF patients, with 4 developing pseudoarthrosis. Shen et al. evaluated rhBMP-2 in multi-level (\u0026ge;\u0026thinsp;3 level) ACFs and reported pseudoarthrosis in 48% (13/127) patients, with 8 of those patients requiring revision surgery. Notably, nearly half (44.9%) of the patients included in this study had a prior ACDF with adjacent segment degeneration and/or pseudoarthrosis, likely explaining the higher observed pseudoarthrosis rate observed by the authors.\u003c/p\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n\u003ch2\u003eComplications\u003c/h2\u003e\n\u003cdiv id=\"Sec12\" class=\"Section3\"\u003e\n\u003ch2\u003eDysphagia\u003c/h2\u003e\n\u003cp\u003eThirteen case series reported the incidence of dysphagia, ranging from 2.13% to 13.2% [\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e]. Tumialan et al. reported 14 patients with dysphagia in their series of 200 single and multi-level ACDFs. Five patients had severe dysphagia, and four of these patients ultimately required a percutaneous endoscopic gastrostomy tube [\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e]. Only one of these four patients remained on a PEG tube chronically due to a history of ALS. Kukreja et al. reported a dysphagia rate of 13.2% in ACF, with 11 patients classified as \u0026ldquo;substantial,\u0026rdquo; with one requiring a PEG tube and an extended hospital stay. Nine of these patients had spontaneous resolution of their dysphagia, and the other two patients had resolution with intravenous dexamethasone followed by oral methylprednisone [\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\n\u003ch2\u003eCervical/Neck Swelling\u003c/h2\u003e\n\u003cp\u003eSix case series reported cervical swelling [\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e]. Stachniak et al., Sethi et al., and Pourtaheri et al. all reported radiographic measurements of cervical swelling in their similarly sized series of ~\u0026thinsp;30 ACDF patients. Stachniak et al. reported their peak at two weeks (21.8\u0026thinsp;\u0026plusmn;\u0026thinsp;5.0 mm)[\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e] and no patients required additional intervention. Sethi et al. noted a peak at one week at the C3 level (15.7\u0026thinsp;\u0026plusmn;\u0026thinsp;7.8 mm) [\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e]. One patient was taken back to the operating room for suspected wound infection, but was noted to have diffuse prevertebral swelling, and resolved without additional intervention [\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e]. Pourtaheri et al. observed their mean peak at two weeks of 9.6 mm. However, all patients were asymptomatic. Notably, these authors used the lowest dose of rhBMP-2 out of all 6 studies discussed here, of ~\u0026thinsp;0.3mg/level [\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e]. The remaining studies noted patient-reported cervical swelling, which ranged from 6% to 8.6%, all of which resolved spontaneously or with medical management.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\n\u003ch2\u003eOther complications\u003c/h2\u003e\n\u003cp\u003eEndplate resorption was observed to be 100% by Vaidaya et al. and Pourtaheri et al. [\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e]. Conversely, Klimo et al reported endplate resorption in 80% (28/35) of operated levels, resulting in PEEK cage subsidence [\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e]. Vaidya et al. reported subsidence in 13/32 levels (40.5%) in their 23 ACDF patients [\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e]. Pourtaheri et al. identified 4 (10.8%) cases of subsidence. None of the authors reported that patients were symptomatic as a result of their end plate resorption or subsidence [\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eThree studies reported on hematoma or seroma as postoperative complications [\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e]. Shields et al. reported the highest hematoma rate at 9.9% (15/151) in their 151 ACF patients; eight of the 15 required surgical evacuation [\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e]. Conversely, Tumialan et al. and Mendenhall et al. reported much lower rates of postoperative hematoma or seroma (2% and 2.5% respectively); however, almost all of their patients required surgical evacuation.\u003c/p\u003e\n\u003cp\u003eThree studies noted radiographic signs of heterotopic ossification [\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e]. Boakye et al. reported that three (12.5%) of their patients developed asymptomatic heterotopic bone formation [\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e], while Pourtaheri et al. found seven (19.5%) of their patients with hypertrophic ossification posterior to the graft [\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e]. Klimo et al. reported heterotopic bone formation in 26 of the 38 operated levels (68%) [\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\n\u003ch2\u003eAnterior Cervical Fusion Comparative Studies\u003c/h2\u003e\n\u003cp\u003eA total of 10 comparative studies on rhBMP-2 use were analyzed for anterior cervical fusion, with a total of 1,371 rhBMP-2 patients compared to 1,721 control patients (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e) [\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e34\u003c/span\u003e].\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable\u0026nbsp;2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003e\u003cstrong\u003eCharacteristics of included anterior cervical fusion case series studies.\u003c/strong\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eAuthor\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eNo. of patients\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSurgery and Delivery Method\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eContainment measures\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003erhBM2P dosage mg/level\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ePeri/post-operative Steroid\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eDrain use\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eFusion Rates % (rhBMP2/control)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eComplication Rates (rhBMP2/control)\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLanman et al. 2004\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e20\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e1, 2, 3-level ACDF\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCORNERSTONE-SR\u0026trade;\u003c/p\u003e\n\u003cp\u003eEpidural space\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSealed with Tisseel thrombin glue\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e100% (20/20)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eSevere dysphagia\u003c/strong\u003e: \u003cstrong\u003e1 (5%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBoakye et al. 2005\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e24\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e1, 2, 3-level ACDF\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePEEK\u003c/p\u003e\n\u003cp\u003eInterbody space\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eInitially 2.1\u003c/p\u003e\n\u003cp\u003eAdjusted: 1.05\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003ePERI\u003c/strong\u003e: 10 mg dexamethasone\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSoft-tissue drain for 24\u0026ndash;48 hours in multi-level procedures\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e100% (22/22)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eHeterotopic bone formation: 3 (12.5%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTransient dysphagia: 2 (8.3%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eShields et al. 2006\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e151\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e1, 2, 3-level ACDF\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e1, 2, 3, 4-level ACVF\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHYDROSORB 228 or CORNERSTONE PYRAMESH 228\u003c/p\u003e\n\u003cp\u003eAdditional rhBMP2 placed lateral and anterior to the graft within disc space\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUp to 2.1\u003c/p\u003e\n\u003cp\u003eHigher amounts in ACVF pts\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDrain placed in\u003c/p\u003e\n\u003cp\u003e35 (25.4%) of 138 ACDF patients\u003c/p\u003e\n\u003cp\u003e8 (61.5%) of 13 ACVF patients\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eTotal complication:\u0026nbsp; 35 (23.2%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHematoma: 15 (9.9%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDysphagia, respiratory difficulty, cervical swelling: 13 (8.6%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026bull; Prolonged hospital stay: 5 (3.3%)\u003c/p\u003e\n\u003cp\u003e\u0026bull; Readmission: 8 (5.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTumialan et al. 2008\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e200\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e1, 2, 3, 4-level ACDF\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePEEK\u003c/p\u003e\n\u003cp\u003ePlaced within the cage\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAvoided irrigation\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.1 (n\u0026thinsp;=\u0026thinsp;24)\u003c/p\u003e\n\u003cp\u003e1.05 (n\u0026thinsp;=\u0026thinsp;93)\u003c/p\u003e\n\u003cp\u003e0.7 (n\u0026thinsp;=\u0026thinsp;83)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003ePERI\u003c/strong\u003e: 10 mg dexamethasone in non-diabetic pts\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDrains placed in\u003c/p\u003e\n\u003cp\u003e~\u0026thinsp;50% of single-level cases\u003c/p\u003e\n\u003cp\u003e100% of multilevel cases\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e100% (193/193)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eTotal complication: 14 (7%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDysphagia: 14 (7%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026bull; Mild: 6 (3%)\u003c/p\u003e\n\u003cp\u003e\u0026bull; Moderate: 3 (1.5%)\u003c/p\u003e\n\u003cp\u003e\u0026bull; Severe: 5 (2.5%)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHematoma: 2 (1%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSeroma: 2 (1%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eVaidya et al. 2008\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e23\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eSingle and multilevel ACDF\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePEEK\u003c/p\u003e\n\u003cp\u003ePlaced within the cage or graft\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAbout 1.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e100% (23/23)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eEnd plate resorption: 23 (100%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSubsidence: 13 of 32 ACDF levels (40.5%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eKlimo et al. 2009\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e22\u003c/p\u003e\n\u003cp\u003e38 levels\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e1, 2, 3-level ACDF\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePEEK\u003c/p\u003e\n\u003cp\u003ePlaced within the cage\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFloseal injected lateral to grafts if persistent leaking was present\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.1 (n\u0026thinsp;=\u0026thinsp;12 levels)\u003c/p\u003e\n\u003cp\u003e1.4 (n\u0026thinsp;=\u0026thinsp;21 levels)\u003c/p\u003e\n\u003cp\u003e1.1 (n\u0026thinsp;=\u0026thinsp;5 levels)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eNR\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo drains used\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e89% (34/38 levels)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003ePseudorathrosis: 4 levels (11.8%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHeterotopic bone formation with ossification into canal: 26 levels (68%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEnd-plate resorption: 28 of 35 levels (80%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eShen et al. 2010\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e127\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e3 or more -level ACCF\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSome ACDF\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStructural allograft\u003c/p\u003e\n\u003cp\u003ePEEK or Titanium mesh w/wo local autograft bone\u003c/p\u003e\n\u003cp\u003ePlaced within the cage Decreased amount of rhBMP2 used\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.33 (3-level)\u003c/p\u003e\n\u003cp\u003e2.0 (4-level)\u003c/p\u003e\n\u003cp\u003e1.6 (5-level)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003ePERI\u003c/strong\u003e: 10 mg dexamethasone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePOST\u003c/strong\u003e: If patients had swallowing difficulty, additional dose of dexamethasone\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e89.8% (114/127)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eDysphagia: Most patients\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNeck swelling: Most patients\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePseudoarthrosis: 13 (10.2%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eStachniak et al. 2011\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e30\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e2 or 3-level ACDF\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePEEK\u003c/p\u003e\n\u003cp\u003ePlaced within the cage\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAvoided irrigation\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003ePOST\u003c/strong\u003e: Dexamethasone taper\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e100% (30/30)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eCervical swelling: 28 (93%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDysphagia\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003e\u0026bull; Choking on food: (19%)\u003c/p\u003e\n\u003cp\u003e\u0026bull; Choking on drinks: (4.8%)\u003c/p\u003e\n\u003cp\u003e\u0026bull; Food sticking: (47.6%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSethi et al. 2011\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e34\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eSingle and multilevel ACF with Decompression\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePEEK or allograft spacer\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e100% (23/23)for PEEK cage\u003c/p\u003e\n\u003cp\u003e81.8% (9/11)for Allograft spacer\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eEnd plate resorption: 34 (100%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCage migration: Mostly in pts who received PEEK\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCervical swelling: 34 (100%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eKhajavi et al. 2014\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e72\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e2, 3, 4-level ACDF\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCORNERSTONE\u003c/p\u003e\n\u003cp\u003eAllograft or ICBG\u003c/p\u003e\n\u003cp\u003ePlaced within graft\u003c/p\u003e\n\u003cp\u003eDecreased amount of rhBMP2 used\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.7 (n\u0026thinsp;=\u0026thinsp;29)\u003c/p\u003e\n\u003cp\u003e0.5 (n\u0026thinsp;=\u0026thinsp;43)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e98.6% (169/72)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eTotal complication: 8 (11%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDysphagia: 38 (53%) at 2 wks, 4 (5%) at last follow-up\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eReadmission for severe dysphagia: 2 (3%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSeroma evacuation: 1 (1.4%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eReturn to OR for nonunion: 1 (1.4%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eKukreja et al. 2015\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e197\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e2, 3, 4-level ACDF and/or ACCF\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePEEK or PEEK prevail\u003c/p\u003e\n\u003cp\u003ePlaced within the cage\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDemineralized bone matrix\u0026nbsp; putty placed from top and bottom over centrally located INFUSE within PEEK cage\u003c/p\u003e\n\u003cp\u003eAvoided irrigation\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003ePERI\u003c/strong\u003e: 10 mg dexamethasone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePOST\u003c/strong\u003e: 4 mg oral dexamethasone taper\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e99% (195/197)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eDysphagia: 26 (13.2%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026bull; \u003cstrong\u003eSevere dysphagia w/\u0026nbsp; PEG tube: 1 (0.5%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCervical swelling: 17 (8.7%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eReadmission for neck swelling/dysphagia: 2 (1%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePseudoarthrosis: 2 (1%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePourtaheri et al. 2015\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e37\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e3-level ACDF w/wo single-level Cervical Corpectomy\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCorticocancellous allograft\u003c/p\u003e\n\u003cp\u003ePlaced within the graft\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFibrin sealant\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.26\u0026ndash;0.35\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003ePERI\u003c/strong\u003e: Methylprednisolone IV\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePOST\u003c/strong\u003e: All pts placed on IV tapered dose of methylprednisolone\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCervical drains placed in all cases\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e97.3% (36/37)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eDysphagia: 12 (50%) at 2 wks, 4 (11%) at last follow-up\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026bull; Mild: 8 (21.6%)\u003c/p\u003e\n\u003cp\u003e\u0026bull; Moderate: 3 (8.1%)\u003c/p\u003e\n\u003cp\u003e\u0026bull; Severe: 1 (2.7%)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePseudoarthrosis: 1 (2.7%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHypertrophic ossification: 7 (19%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSubsidence: 4 (10.8%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMaza et al. 2019\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e47\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e1, 2, 3, 4-level ACDF\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAllograft or PEEK\u003c/p\u003e\n\u003cp\u003ePlaced within graft or cage at center\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBone wax used to prevent leakage with PEEK\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.525\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003ePOST\u003c/strong\u003e: Pts given IV steroids during hospital stay and prescribed methylprednisolone to take home\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15-Fr Blake drain\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eDysphagia: 1 (2.1%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMild cervical swelling: 1 (2.1%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWang et al. 2020\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e32\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e1, 2, 3, 4-level ACDF\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCage\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eE.coli\u003c/em\u003e-derived BMP2 administered with bTCP\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.45\u0026ndash;0.75\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e100% (32/32)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eDysphagia: 1 (3.1%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMendenhall et al. 2021\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e198\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e1, 2, 3, 4-level ACF\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNoncontained vs contained spacers\u003c/p\u003e\n\u003cp\u003ePlaced within spacers\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.50 +/- 0.09\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e96\u0026ndash;100%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eDysphagia: 22 (11%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCervical swelling: 11 (6%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHematoma: 3 (1.5%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSeroma: 2 (1%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePseudoarthrosis: 2 (1%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMedina et al. 2024\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e26\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eSingle and multilevel ACC w/wo PCF\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTitanium cage\u003c/p\u003e\n\u003cp\u003eTricalcium phosphate graft covering both ends\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTricalcium phosphate graft over and under the cage\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003ePERI\u003c/strong\u003e: 12 mg of dexamethasone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePOST\u003c/strong\u003e: IV antibiotics for 6 weeks\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e100% (26/26)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eTotal complication: 4 (15%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDysphagia: 2 (7.5%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTransient tetraparesis: 1 (3.8%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\n\u003ch2\u003eFusion\u003c/h2\u003e\n\u003cp\u003eSeven studies reported fusion rates, and all but one demonstrated significantly higher fusion rates in the rhBMP2 group compared to the control group [\u003cspan class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e34\u003c/span\u003e]. In the one exception observed by Vaidya et al., the rhBMP-2 group still achieved a greater fusion rate (100%), than the control group (95.8%) at 12 months.\u003c/p\u003e\n\u003cp\u003eTwo studies, Tan et al. and Chen et al., compared PEEK and allograft with rhBMP2 to ICBG in\u003c/p\u003e\n\u003cp\u003eACDF patients found a significant difference in fusion rates of 87.7% vs. 74.0% (\u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.036\u003c/em\u003e) and 83% vs. 74% (\u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/em\u003e), respectively [\u003cspan class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e34\u003c/span\u003e]. The latter study reported that both patient groups achieved 100% solid fusion by 12 months [\u003cspan class=\"CitationRef\"\u003e34\u003c/span\u003e]. The former study, Tan et al., also reported that the ICBG with rhBMP-2 and local autograft group had significantly faster fusion times compared to the ICBG control group (\u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.013\u003c/em\u003e) with an average fusion time of 82.6 days [\u003cspan class=\"CitationRef\"\u003e29\u003c/span\u003e].\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\n\u003ch2\u003eComplications\u003c/h2\u003e\n\u003cdiv id=\"Sec18\" class=\"Section3\"\u003e\n\u003ch2\u003eDysphagia\u003c/h2\u003e\n\u003cp\u003eEight studies reported dysphagia rates, with four reporting statistically significant greater incidence of dysphagia in the rh-BMP2 group compared to control groups [\u003cspan class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e34\u003c/span\u003e]. Two studies implemented a SWAL-QOL-based scoring system for dysphagia [\u003cspan class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e33\u003c/span\u003e]. Bellamy et al. used a 70-point scoring system where a higher score equated to less severe symptoms [\u003cspan class=\"CitationRef\"\u003e33\u003c/span\u003e]. After adjusting for the baseline, they found that the rhBMP-2 group had a score of 59.5, which was significantly lower than the control group with a score of 63.2 (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.002\u003c/em\u003e), though the authors admit that it remained unclear whether this difference was clinically relevant [\u003cspan class=\"CitationRef\"\u003e33\u003c/span\u003e]. Vaidya et al. created their own scale based on discomfort and inability to swallow and found significantly higher dysphagia rates (65%) in the rhBMP-2 group compared to 22% in the control group at 6 weeks (\u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.0189\u003c/em\u003e) [\u003cspan class=\"CitationRef\"\u003e26\u003c/span\u003e]. However, at the 2-year follow-up, it was found that both groups had mild persistent dysphagia at rates of 20% and 22% [\u003cspan class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eRiederman et al. reported dysphagia rates of 25.5% for the investigational group and 15% for the control group (\u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.01\u003c/em\u003e) [\u003cspan class=\"CitationRef\"\u003e31\u003c/span\u003e], while Burkus et al. found dysphagia rates of 16.4% and 7.3% (\u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/em\u003e) [\u003cspan class=\"CitationRef\"\u003e32\u003c/span\u003e]. Lu et al. found that the rhBMP-2 group (dysphagia score\u0026thinsp;=\u0026thinsp;0.76) had a significantly greater dysphagia severity compared to the control group (dysphagia score\u0026thinsp;=\u0026thinsp;0.596) following two-level ACDF after stratifying for the number of levels fused (\u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.005\u003c/em\u003e) [\u003cspan class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec19\" class=\"Section2\"\u003e\n\u003ch2\u003eCervical swelling\u003c/h2\u003e\n\u003cp\u003eA total of 5 studies reported instances or measurements of cervical swelling [\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e34\u003c/span\u003e]. Smucker et al. found that 27.5% of those treated with rhBMP-2 showed cervical swelling as opposed to 3.6% treated without by an average of 4.2 postoperative days (\u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.0001\u003c/em\u003e) [\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e]. Burkus et al. reported a much lower incidence of cervical swelling at rates of 3.6% for the rhBMP-2 group and 0.8% for the control, which were not statistically significant [\u003cspan class=\"CitationRef\"\u003e32\u003c/span\u003e]. Vaidya et al. reported that the cervical swelling at the C3 level was significantly higher in the rhBMP-2 group at 6 weeks (8.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1 mm vs. 5.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1 mm, \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.03)\u003c/em\u003e [\u003cspan class=\"CitationRef\"\u003e26\u003c/span\u003e]. Chen et al. also reported on C3 level swelling measurements, but found no significant difference between the two groups in measurements (10.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3 mm vs. 9.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2 mm, \u003cem\u003ep\u0026thinsp;\u0026gt;\u0026thinsp;0.05.\u003c/em\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec20\" class=\"Section2\"\u003e\n\u003ch2\u003ePosterior Cervical Surgery Case Studies\u003c/h2\u003e\n\u003cp\u003eA total of four case series involving rhBMP-2 use in posterior cervical fusion were analyzed, encompassing 203 patients (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e) [\u003cspan class=\"CitationRef\"\u003e35\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e38\u003c/span\u003e].\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003e\u003cstrong\u003eCharacteristics of included anterior cervical fusion comparative series studies.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSignificant findings have been bolded. \u003c/strong\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ePaper\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eNo. of patients rhBMP2/control\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eSurgery and Delivery Method\u003c/p\u003e\n\u003cp\u003erhBMP2 | Control\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eContainment measures\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003erhBM2P dosage mg/level\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ePeri/post-operative Steroid\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eDrain use\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eFusion Rates % (rhBMP2/control)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eComplication Rates (rhBMP2/control)\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eSmucker et al. 2006\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e69 / 165\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eSingle and multilevel ACDF\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eSwelling Complications: 19 (27.5%) / 6 (3.6%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026bull; Severe dysphagia: 5 (7.2%) / 2 (1.2%)\u003c/p\u003e\n\u003cp\u003e\u0026bull; Severe dysphagia: 5 (7.2%) / 2 (1.2%)\u003c/p\u003e\n\u003cp\u003e\u0026bull; Return to clinic or EMR: 3 (4.3%) / 1 (0.6%)\u003c/p\u003e\n\u003cp\u003e\u0026bull; Incision\u0026thinsp;+\u0026thinsp;drainage: 3 (4.3%) / 0\u003c/p\u003e\n\u003cp\u003e\u0026bull; Visible neck swelling: 2 (2.9%) / 0\u003c/p\u003e\n\u003cp\u003e\u0026bull; Readmissions: 2 (2.9%) / 0\u003c/p\u003e\n\u003cp\u003e\u0026bull; Outpatient ENT consult: 2 (2.9%) / 0\u003c/p\u003e\n\u003cp\u003e\u0026bull; Reintubation: 2 (2.9%) / 0\u003c/p\u003e\n\u003cp\u003e\u0026bull; PEG placement: 1 (1.4%) / 2 (1.2%)\u003c/p\u003e\n\u003cp\u003e\u0026bull; Tracheostomy: 1 (1.4%)) / 1 (0.6%)\u003c/p\u003e\n\u003cp\u003e\u0026bull; Delay in extubation: 0 / 1 (0.6%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAllograft/ autograft/ PEEK\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAllograft/ autograft\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eVaidya et al. 2007\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e22 / 24\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e1, 2, 3, -level ACDF\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eNR\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e1.0\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eNR\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e⅛ -inch Hemovac drain\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e100% / 95.8%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eEndplate resorption: 22 (100%) / 0\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCervical swelling: 22 (100%) / 24 (100%)\u003c/p\u003e\n\u003cp\u003e\u0026bull; \u003cstrong\u003eC3 swelling: Significantly greater in rhBMP2 group\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDysphagia: 17/20 (85%) / 10/18 (56%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHoarseness: 13 (60%) / 15 (62%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePEEK\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e[Allograft interbody spacers/ Allograft spacers]\u0026thinsp;+\u0026thinsp;DBM\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eLu et al. 2013\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e100 / 50\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eMultilevel ACDF\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eAvoided irrigation\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e2.1 (n\u0026thinsp;=\u0026thinsp;10)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e1.05 (n\u0026thinsp;=\u0026thinsp;48)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e0.7 (n\u0026thinsp;=\u0026thinsp;42)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003ePERI: 10 mg dexamethasone\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eNR\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e100% / 84%\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eDysphagia: (40%) / (44%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026bull; \u003cstrong\u003eReadmission: 3 (3%) / 0\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026bull; \u003cstrong\u003ePEG placement: 4 (4%) / 0\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eShort-term Complication: 13 (13%) / 4 (8%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHematoma: 2 (2%) / (0%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSeroma: 2 (2%) / (0%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCSF leakage: 1 (1%) / (0%)\u003c/p\u003e\n\u003cp\u003eRecurrent laryngeal nerve palsy: 3 (3%) / 0\u003c/p\u003e\n\u003cp\u003eAspiration pneumonia: 1 (1%) / 0\u003c/p\u003e\n\u003cp\u003eTransient C5 nerve root palsy: 1 (1%) / 1 (2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePEEK\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMechanical structural allograft spacer with local bone shaving\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eFrenkel et al. 2013\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e22 / 23\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e2 or more level -ACDF\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eNR\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e2.1 (n\u0026thinsp;=\u0026thinsp;5)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e1.4 (n\u0026thinsp;=\u0026thinsp;3)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e0.5\u0026ndash;1.1 (n\u0026thinsp;=\u0026thinsp;5)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.5 (n\u0026thinsp;=\u0026thinsp;9)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMean of 1.0 mg\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eNR\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eNR\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e100% / 83%\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eDysphagia: 4 (18.2%) / 2 (8.7%)\u003c/p\u003e\n\u003cp\u003eTotal complication: 9 (22.7%) / 4 (17.4%)\u003c/p\u003e\n\u003cp\u003eTracheal swelling/ Reintubation: 0 / 1 (4.2%)\u003c/p\u003e\n\u003cp\u003eCervical swelling: 1 (4.5%) / 0\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFibular allografts\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFibular allograft with vertebral autograft\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eTan et al. 2015\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e73 / 73\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e2-level ACDF\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAntibiotics given\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eNR\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.9\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eNR\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eDeep and superficial drains for 48 hours\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e87.7% / 74.0%\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eTotal complication\u003c/strong\u003e: \u003cstrong\u003e(21.6%) / (17.8%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDeep wound infection: 4 (5.48%) / 2 (2.74%)\u003c/p\u003e\n\u003cp\u003eProlonged wound drainage: 4 (5.48%) / 3 (4.11%)\u003c/p\u003e\n\u003cp\u003eCardiac infection: 2 (2.7%) / 1 (1.4%)\u003c/p\u003e\n\u003cp\u003eGI infection: 2 (2.7%) / 3 (4.1%)\u003c/p\u003e\n\u003cp\u003eUTI: 3 (4.1%) / 1 (1.4%)\u003c/p\u003e\n\u003cp\u003eDVT: 1 (1.4%) / 1 (1.4%)\u003c/p\u003e\n\u003cp\u003eIliac crest site deep infection: 1 (1.4%) / 1 (1.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eICBG with local autograft\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eICBG\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eLovasik et al. 2017\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e84 / 107\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eSingle and multilevel ACDF\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eNR\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.5\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eNR\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eNR\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e98.6% / 85.3%\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eClinically significant dysphagia:\u0026nbsp; 11 (13.1%) / 14 (13%)\u003c/p\u003e\n\u003cp\u003eDysphagia: 17 (20.2%) / 18 (16.8%)\u003c/p\u003e\n\u003cp\u003eSubsequent spine surgery: 2 (2.4%) / 4 (3.7%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePEEK or Allograft\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ebTCP bone graft with PEEK or Allograft with morselized autologous and blood aspirate\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eRiederman et al. 2017\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e200 / 200\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e1, 2, 3, 4-level ACDFs\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll wounds irrigated with antibiotic solution\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eNR\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.7\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eNR\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003ePenrose drain\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eDysphagia: 51 (25.5%) / 30 (15%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePost-op steroid use: 21 (10.5%) / 12 (6%)\u003c/p\u003e\n\u003cp\u003eDysphonia: 5 (2.5%) / 9 (4.5%)\u003c/p\u003e\n\u003cp\u003eHematoma: 1 (0.5%) / 0\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFreeze-dried allograft Cornerstone bone\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eICBG\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eBurkus et al. 2017\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e224 / 486\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eSingle-level ACDFs\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePEEK or allograft\u003c/p\u003e\n\u003cp\u003ePlaced within cage\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eNR\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.6 (n\u0026thinsp;=\u0026thinsp;240)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e1.05 (n\u0026thinsp;=\u0026thinsp;4)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003ePERI: Corticosteroids used at discretion\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eNR\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e99.4% / 87.2%\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eDysphagia: (16.7%) / (7.5%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSerious complications: (34.6%) / (34.7%)\u003c/p\u003e\n\u003cp\u003e\u0026bull; Intervertebral disk protrusion: (7.0%) / (7.1%)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCervical swelling: (3.6%) / (0.8%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePEEK\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCortical ring allograft spacers\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eBellamy et al. 2022\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e39 / 75\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eSingle or 2-level ACDF\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAllograft\u003c/p\u003e\n\u003cp\u003ePlaced within graft\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eNR\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.5\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003ePERI: 10 mg dexamethasone\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePOST: Oral taper steroid on discharge\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eHemovac or Jackson-Pratt suction drain\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eBaseline-adjusted SWAL-QOL (Lower is more severe)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026bull; \u003cstrong\u003eSWAL-QOL Scores: 59.5 / 63.2\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAllograft\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAllograft\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eChen et al. 2025\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e538 / 518\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eSingle or 2-level ACDF\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLocal auto osteophyte or ICBG\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eNR\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.5\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003ePERI: Methylprednisolone\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePOST: Methylprednisolone\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eNR\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e83% / 74% at 3 mo\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e100% / 100% at 1 year\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eDysphagia: 54 (10%) / 47 (9%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026bull; Mild: 47 (8.7%) / 42 (8.1%)\u003c/p\u003e\n\u003cp\u003e\u0026bull; Moderate: 5 (0.9%) / 4 (0.8%)\u003c/p\u003e\n\u003cp\u003e\u0026bull; Severe: 2 (0.4%) / 1 (0.2%)\u003c/p\u003e\n\u003cp\u003eSubsidence: 48 (8.9%) / 66 (13%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePEEK and local autoosteophyte\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eICBG\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec21\" class=\"Section2\"\u003e\n\u003ch2\u003eFusion and Pseudoarthrosis\u003c/h2\u003e\n\u003cp\u003eTwo studies reported 100% fusion by 24 months postoperatively [\u003cspan class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e37\u003c/span\u003e]. Hamilton et al. observed 53 patients who had undergone occipitocervical, cervical, or cervicothoracic posterior cervical fusions (PCFs) with morselized autograft or allograft with rhBMP-2 and achieved 100% fusion by 24 months [\u003cspan class=\"CitationRef\"\u003e35\u003c/span\u003e]. Similarly, the series by Hood et al. evaluated C1-C2 PCFs demonstrated 100% fusion by 24 months in all patients who achieved sufficient follow-up (50/52) [\u003cspan class=\"CitationRef\"\u003e37\u003c/span\u003e]. Additionally, these authors observed signs of fusion as early as two months [\u003cspan class=\"CitationRef\"\u003e37\u003c/span\u003e]. The remaining two studies reported fusion rates greater than 90%.\u003c/p\u003e\n\u003cp\u003eTwo series, by Hodges et al. and Ishida et al., reported pseudoarthrosis rates of 10.3% (3/29) in patients who underwent single and multilevel PCF, and 5.7% (4/69) in patients who underwent C1-C2 PCFs, respectively [\u003cspan class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e38\u003c/span\u003e].\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec22\" class=\"Section2\"\u003e\n\u003ch2\u003eComplications\u003c/h2\u003e\n\u003cp\u003eThe PCF case studies showed great variability in the types of complications observed [\u003cspan class=\"CitationRef\"\u003e35\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e38\u003c/span\u003e]. Hamilton et al. reported two complications: one a superficial wound infection and the other an adjacent-level degeneration [\u003cspan class=\"CitationRef\"\u003e35\u003c/span\u003e]. In the largest series, Ishida et al. reported a 10% reoperation rate due to seven cases of instrumentation failure, two cases of adjacent segment disease, and 2 cases of dysphagia and dyspnea [\u003cspan class=\"CitationRef\"\u003e38\u003c/span\u003e].\u003c/p\u003e\n\u003cdiv id=\"Sec23\" class=\"Section3\"\u003e\n\u003ch2\u003ePosterior Cervical Fusion Comparative Studies\u003c/h2\u003e\n\u003cp\u003eA total of four comparative studies on rhBMP-2 use in PCF were analyzed [\u003cspan class=\"CitationRef\"\u003e39\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e42\u003c/span\u003e]. There were a total of 313 rhBMP-2 patients and 2,422 control patients. Notably, the majority of the patients (89%) from these studies came from a database study by Takahashi et al. (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab4\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable\u0026nbsp;4\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003e\u003cstrong\u003eCharacteristics of included posterior cervical fusion case series studies.\u003c/strong\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ePaper\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eNo. of patients rhBMP2/control\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSurgery and Delivery Method\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003erhBM2P dosage mg/level\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ePeri/post-operative Measures\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eDrain use\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eFusion Rates % (rhBMP2/control)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eComplication Rates (rhBMP2/control)\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHamilton et al. 2011\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e53\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eOccipitocervical, cervical, or cervicothoracic PCF\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMorselized autograft/allograft\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eMean\u003c/strong\u003e: 1.8\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRange\u003c/strong\u003e: 1.1\u0026ndash;2.9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTwo ⅛ -inch Hemovac drains\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e100% (53/53)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTotal complication: 2 (3.8%)\u003c/p\u003e\n\u003cp\u003eSuperficial wound infection: 1 (1.9%)\u003c/p\u003e\n\u003cp\u003eAdjacent-level degeneration: 1 (1.9%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHodges et al. 2012\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e29\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eSingle and multilevel PCF with Decompression\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMorselized autograft/allograft or hydroxyapatite:TCP ceramic matrix\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eMean\u003c/strong\u003e: 2.1\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRange\u003c/strong\u003e: NR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e89.7% (26/29)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePseudoarthrosis: 3 (10.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHood et al. 2014\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e52\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eC1-C2 PCF\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWith IC allograft (n\u0026thinsp;=\u0026thinsp;24)\u003c/p\u003e\n\u003cp\u003eNonstructural corticocancellous allograft with local autograft (n\u0026thinsp;=\u0026thinsp;28)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eMean\u003c/strong\u003e: 4.5\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRange\u003c/strong\u003e: 2.2\u0026ndash;12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e100% (50/50)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePostoperative tachycardia: 1 (1.9%)\u003c/p\u003e\n\u003cp\u003eShock and respiratory failure: 1 (1.9%)\u003c/p\u003e\n\u003cp\u003eHospital-acquired pneumonia: 1 (1.9%)\u003c/p\u003e\n\u003cp\u003eDVT: 1 (1.9%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIshida et al. 2019\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e69\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eC1-C2 PCF\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHydroxyapatite and local autograft chips and/or morselized allograft\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eMean\u003c/strong\u003e: 2.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRange\u003c/strong\u003e: 0.8\u0026ndash;6.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e94.3% (65/69)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eInstrumentation failure: 7 (10.1%)\u003c/p\u003e\n\u003cp\u003eReoperation: 7 (10.1%)\u003c/p\u003e\n\u003cp\u003ePseudoarthrosis: 4 (5.7%)\u003c/p\u003e\n\u003cp\u003eDysphagia/dyspnea: 2 (2.8%)\u003c/p\u003e\n\u003cp\u003ePhonation difficulty: 1 (1.5%)\u003c/p\u003e\n\u003cp\u003eIntraoperative dural tear: 1 (1.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003cstrong\u003eTable 5. Characteristics of included posterior cervical fusion comparative studies. \u003c/strong\u003e\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003eSignificant findings have been bolded.\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Taba\" border=\"1\"\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ePaper\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eNo. of patients rhBMP2/control\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eSurgery and Delivery Method\u003c/p\u003e\n\u003cp\u003erhBMP2 | Control\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003erhBM2P dosage mg/level\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ePeri/post-operative Steroid\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eDrain use\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eFusion Rates % (rhBMP2/control)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eComplication Rates (rhBMP2/control)\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eCrawford et al. 2009\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e41 / 36\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eSingle and multilevel PCF\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eMean\u003c/strong\u003e: 3.6\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRange\u003c/strong\u003e: 1.05\u0026ndash;6.0\u003c/p\u003e\n\u003cp\u003eLarge kit (n\u0026thinsp;=\u0026thinsp;19)\u003c/p\u003e\n\u003cp\u003eSmall kit (n\u0026thinsp;=\u0026thinsp;22)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eAbx preoperatively until all drains removed\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eDeep and superficial drains\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eWound complications: 6 (14.6%) / 1 (2.8%)\u003c/p\u003e\n\u003cp\u003eHarvest site deep infection: 0 / 1 (2.8%)\u003c/p\u003e\n\u003cp\u003ePostoperative tachycardia: 0 / 1 (2.8%)\u003c/p\u003e\n\u003cp\u003ePostoperative anemia: 0 / 1 (2.8%)\u003c/p\u003e\n\u003cp\u003ePostoperative nausea, headaches: 0 / 1 (2.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLocal autograft\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eICBG\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eYan et al. 2014\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e68 / 66\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eC1-C2 PCF\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eAbx preoperatively until all drains removed\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eDeep drain\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e82.4% / 78.4%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eWound complication: 6 (8.8%) / 2 (3.0%)\u003c/p\u003e\n\u003cp\u003eIntraoperative dural tear: 1 (1.5%) / 1 (1.5%)\u003c/p\u003e\n\u003cp\u003eGI infection: 2 (2.9%) / 4 (6.1%)\u003c/p\u003e\n\u003cp\u003eCardiac infection: 1 (1.5%) / 3 (4.5%)\u003c/p\u003e\n\u003cp\u003eUTI: 1 (1.5%) / 3 (4.5%)\u003c/p\u003e\n\u003cp\u003eDVT: 1 (1.5%) / 3 (4.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eICBG with local autograft\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eICBG\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eTakahashi et al. 2017\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eUpper: 73 / 279\u003c/p\u003e\n\u003cp\u003eLower: 78 / 1994\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eUpper (O-C2) and Lower (C3-C7) PCF\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eTotal complications\u003c/p\u003e\n\u003cp\u003eUpper: 7 (9.6%) / 34 (12%)\u003c/p\u003e\n\u003cp\u003eLower: 42 (11%) / 276 (14%)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWound complication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUpper: 1 (1.4%) / 5 (1.8%)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLower: 23 (6.1%) / 75 (3.8%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNeck complication\u003c/p\u003e\n\u003cp\u003eUpper: 0 / 2 (0.7%)\u003c/p\u003e\n\u003cp\u003eLower: 2 (0.5%) / 15 (0.8%)\u003c/p\u003e\n\u003cp\u003eOther complications\u003c/p\u003e\n\u003cp\u003eUpper: 7 (9.6%) / 31 (11%)\u003c/p\u003e\n\u003cp\u003eLower: 37 (9.8%) / 263 (13%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWith rhBMP-2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWithout rhBMP-2\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIyer et al. 2018\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e53 / 47\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003ePosterior cervical surgery\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eMean\u003c/strong\u003e: 1.49\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRange\u003c/strong\u003e: 0.13\u0026ndash;8.57\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNeurological complication: 12 (27.9%) / 18 (34.6%)\u003c/p\u003e\n\u003cp\u003eOperative complication: 11 (25.6%) / 11 (21.2%)\u003c/p\u003e\n\u003cp\u003eCardiopulmonary complication: 9 (20.9%) / 8 (15.4%)\u003c/p\u003e\n\u003cp\u003eDysphagia: 8 (18.6%) / 3 (5.8%)\u003c/p\u003e\n\u003cp\u003eInfection: 8 (18.6%) / 7 (13.5%)\u003c/p\u003e\n\u003cp\u003eRadiographic complication: 5 (11.6%) / 3 (5.8%)\u003c/p\u003e\n\u003cp\u003eInstrumentation complication: 3 (7.0%) / 1 (1.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec24\" class=\"Section2\"\u003e\n\u003ch2\u003eOutcomes: Fusion and Pseudoarthrosis\u003c/h2\u003e\n\u003cp\u003eOnly one out of the four comparative studies reported fusion rates. Yan et al. compared C1-C2 PCF outcomes between ICBG groups treated with or without rhBMP-2 [\u003cspan class=\"CitationRef\"\u003e40\u003c/span\u003e]. The rhBMP-2 group demonstrated superior fusion rate compared to controls (82.4% vs. 78.4%) however, this difference was not statistically significant (p=.782).\u003c/p\u003e\n\u003cdiv id=\"Sec25\" class=\"Section3\"\u003e\n\u003ch2\u003eComplications\u003c/h2\u003e\n\u003cp\u003eThree out of four studies reported wound complication rates with rhBMP-2 use, ranging from 1.4% to 14.6% [\u003cspan class=\"CitationRef\"\u003e39\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e41\u003c/span\u003e]. Crawford et al. analyzed single and multilevel PCF patients treated with rhBMP-2 and local autograft or ICBG and observed wound complication rates in 6 (13.6%) patients and 1 patient (2.8%), respectively, with no significant difference [\u003cspan class=\"CitationRef\"\u003e39\u003c/span\u003e]. Yan et al. similarly reported no significant difference between wound complication rates of patients undergoing C1-C2 ICBG PCF with rhBMP-2 and local autograft versus without it (8.8% vs. 3.0%) [\u003cspan class=\"CitationRef\"\u003e40\u003c/span\u003e]. Interestingly, Takahashi et al. reported complication incidence in patients who underwent upper (occipital - C2) or lower (C3 - C7) level PCF. They found a significant difference in lower cervical fusion wound complication rates amongst patients treated with rhBMP-2 (6.1%) and without it (3.8%) (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.037\u003c/em\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cdiv id=\"Sec27\" class=\"Section2\"\u003e \u003ch2\u003eAnterior Cervical Fusion\u003c/h2\u003e \u003cp\u003eFusion rates were high among all ACF studies in this review, with fusion rates ranging from 80\u0026ndash;100% [\u003cspan additionalcitationids=\"CR28 CR29\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. All seven competitive studies reported higher fusion rates compared to controls, and all but one achieved statistical significance. Despite concerns about complications, rhBMP-2 consistently demonstrated strong osteoinductive capacity in cervical fusion.\u003c/p\u003e \u003cp\u003eA recent meta-analysis by Ibrahim et al. analyzed 20 studies with 5,828 patients who underwent ACDF with or without rhBMP-2 and found that its use was associated with significantly higher fusion rates (98.9% vs. 93.6%) but also with an increased risk of dysphagia (24.7% vs. 8.1%) [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. They concluded that the benefit of fusion outweighs the risk of dysphagia in older patients undergoing fusion at fewer than two cervical levels [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. Further risk-benefit analyses of rhBMP-2 are needed to help define the threshold at which patients at risk for pseudoarthrosis may most appropriately receive rhBMP-2.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec28\" class=\"Section2\"\u003e \u003ch2\u003eComplications\u003c/h2\u003e \u003cp\u003eThe most commonly reported complications of ACF in this review were dysphagia, cervical swelling, pseudoarthrosis, heterotopic bone formation, endplate resorption, hematoma/seroma, and subsidence. These findings are consistent with previous literature. Robertson and Ashley, in their series of 2,579 ACDFs performed by a single surgeon between 1998 and 2017, identified dysphagia (7%) and hematoma (0.9%) amongst the most frequent adverse events [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. Similarly, Yee et al., in a review of 240 prospective and retrospective studies, reported adjacent segment disease, dysphagia, C5 palsy, graft or hardware failure, pseudoarthrosis, recurrent laryngeal nerve palsy, infection, and hematoma as the most prevalent complications [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec29\" class=\"Section2\"\u003e \u003ch2\u003eDysphagia\u003c/h2\u003e \u003cp\u003eIn this review, reported dysphagia rates with rhBMP-2 ranged from 2.13% to 65%, with the highest incidence being reported in comparative studies. A prior review of ACDF studies also identified widely ranging postoperative dysphagia, from 1.7% to 67% [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]. This wide variability likely reflects differences in assessment methodology. Reported measures from this review included SWAL-QOL point systems, the Bazaz grading scale, patient questionnaires, and study-specific severity grading methods. Because each system defines severity differently, literature reports remain inconsistent. Notably, two comparative studies found no significant difference in dysphagia incidence between rhBMP-2 and controls [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e], though one reported greater dysphagia severity in the rhBMP-2 group [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eCervical Swelling\u003c/h3\u003e\n\u003cp\u003eCervical swelling with rhBMP-2 in this review ranged from 2.13\u0026ndash;8.6% in case series and 3.6\u0026ndash;27.5% in comparative studies. Similar variability is reported in the literature, with excessive neck swelling occurring in 11.3% of ACDF cases in one review of PubMed, Embase, and Cochrane databases [\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e], and soft tissue swelling/hematoma reported at 1.7% in ACDF literature from 1989\u0026ndash;2019 [\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e]. All comparative studies showed numerically higher rates and greater swelling in the rhBMP-2 group, with two achieving statistical significance. A meta-analysis of 27 studies reported a 1.43-fold increased risk of cervical swelling complications with rhBMP-2 [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIndependent of rhBMP-2 use, anterior cervical procedures require retraction of the esophageal, tracheal, and pharyngeal tissues, predisposing to inflammation and prevertebral swelling [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. rhBMP-2 may further potentiate inflammation and swelling through its pro-inflammatory and angiogenic properties. In a rat arthrodesis model, Hsu et al. demonstrated increased circulating pro-inflammatory cytokines (TNF-ɑ, MIP-1ɑ, IL-1β) following rhBMP-2 implantation [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]. This inflammatory cascade, combined with angiogenesis, may prolong tissue swelling and exacerbate postoperative dysphagia compared to a control environment without rhBMP-2.\u003c/p\u003e \u003cdiv id=\"Sec31\" class=\"Section2\"\u003e \u003ch2\u003ePosterior Cervical Fusion\u003c/h2\u003e \u003cp\u003e Fusion rates with rhBMP-2 in this review ranged from 82.4% to 100%. The only comparative study of PCF reported a higher fusion rate in the rhBMP-2 group than in controls (p=.782) [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. Despite fusion rate differences not achieving statistical significance, the time to fusion was faster in the rhBMP-2 group by 11 days [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. While statistically significant, this is unlikely to be clinically significant. More studies are needed to identify whether rhBMP-2 may confer a time-to-fusion benefit in PCF.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec32\" class=\"Section2\"\u003e \u003ch2\u003eComplications\u003c/h2\u003e \u003cp\u003eThe most common complications of posterior cervical surgery identified in this review were systemic complications (tachycardia, infection, DVT), wound complications, pseudoarthrosis, intraoperative dural tears, and instrumentation failure. These findings align with prior reviews, such as that by Badiee et al., who reported wound infection, incidental durotomy, and pseudoarthrosis as the most frequent short- and long-term complications [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]. Higher rates of pseudoarthrosis and durotomy in their study were attributed to mechanical stress from longer fusion constructs, revision surgery, and patient comorbidities, including obesity, smoking, diabetes, rheumatoid arthritis, older age, and chronic steroid use [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]. Notably, PCF is often performed in older patients with multilevel disease and preexisting comorbidities, which inherently increases their complication risk [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e].\u003c/p\u003e \u003cdiv id=\"Sec33\" class=\"Section3\"\u003e \u003ch2\u003eWound complications\u003c/h2\u003e \u003cp\u003eWound complications in the reviewed studies encompassed infection, hemorrhage, hematoma, and wound disruption. Across all studies reporting wound complications, incidence was consistently higher in rhBMP-2 cohorts [\u003cspan additionalcitationids=\"CR40 CR41\" citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. However, Takahashi et al. was the only study to demonstrate a statistically significant difference in their C3\u0026ndash;C7 PCF cohort [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. The higher incidence of wound complications has been attributed to the rhBMP-2-induced inflammation, as well as surgical invasiveness in PCF [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Posterior approaches require larger incisions and extensive dissection through subcutaneous tissue to access the paraspinal muscles and cervical spine, which likely contributes to the higher rate of wound-related complications [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec34\" class=\"Section3\"\u003e \u003ch2\u003erhBMP-2 Dosage and Complications\u003c/h2\u003e \u003cp\u003eSeveral studies have demonstrated a dose-dependent relationship between rhBMP-2 and complication rates in cervical fusion. A meta-analysis by Wen et al. stratified their rhBMP-2 dosages by low (\u0026lt;\u0026thinsp;0.7 mg/level), middle (0.7\u0026ndash;2.2 mg/level), and high (\u0026gt;\u0026thinsp;1.1 mg/level). The included studies with low doses did not report complication rates, but the complication rates increased from the middle (15.26%) to high (24.14%) doses. However, the authors did not report whether this difference was statistically significant [\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e]. Frenkel et al., however, identified a significant correlation (Pearson correlation 0.753, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) between dosage and complications [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Conversely, Tumialan et al. found no reduction in complications when the dose was reduced from 2.1 mg/level to 0.7 mg/level [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. However, the authors admit that several confounders, including repeated operations and multi-level cases, limited their ability to argue against the dose-dependent relationship that other authors have found. Additional cohort data corroborate the dose-dependent relationship between rhBMP-2 and complications, with higher per-level dosing significantly predicting deep infection and pseudoarthrosis [\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e, \u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn the context of PCF, there is no consensus on the optimal rhBMP-2 dosage. Hamilton et al. reported favorable results with an average dose of 1.8 mg/level [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e], whereas Crawford et al., using 3.6 mg/level, observed a markedly higher wound complication rate (14.6% vs. 1.9%) [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. These findings suggest that higher doses may cause leakage of rhBMP-2 into surrounding tissues, potentiating inflammation and impairing wound healing. Recent practice patterns within this review indicate a shift toward lower dosing, 0.2\u0026ndash;0.6 mg/level for anterior cervical fusions and 1.49\u0026ndash;2.5 mg/level for posterior fusions, as a strategy to balance efficacy and safety.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e\n\u003ch3\u003eMinimizing Complications\u003c/h3\u003e\n\u003cp\u003eRecent studies reflect a growing emphasis on prophylactic measures to mitigate rhBMP-2\u0026ndash;related complications. Pourtaheri et al. and Maza et al. reported use of fibrin sealant and bone wax, respectively, to contain rhBMP-2 within the graft or cage [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Several authors also described avoiding irrigation of the surgical site after rhBMP-2 placement to reduce spread into adjacent soft tissues [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. In anterior cervical surgery, perioperative and postoperative steroid use, along with soft-tissue drains, were frequently employed to decrease inflammation. Notably, a randomized controlled trial by Edwards et al. found that local depomedrol administration after ACDF with low-dose rhBMP-2 significantly reduced both dysphagia incidence and severity compared to controls at one, two, three, and four weeks postoperatively (p\u0026thinsp;\u0026lt;\u0026thinsp;0.5) [\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e].\u003c/p\u003e"},{"header":"Limitations","content":"\u003cp\u003eThis review is subject to several limitations. Firstly, the heterogeneity across the included studies, in terms of dosing strategies, follow-up duration, and outcome reporting, precluded a formal meta-analysis and limits direct comparability. The measurement of complications, particularly dysphagia and swelling, was inconsistently applied across studies. Secondly, the included studies and published data are subject to bias, as many of the included articles were case series lacking control groups. Future research can prioritize standardized definitions and reporting of complications, as well as the optimization of delivery and containment techniques, to establish evidence-based protocols for dosing tailored to the number of operated surgical levels, patient-specific risk factors, and surgical approach.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003erhBMP-2 in cervical fusion is associated with consistently high fusion rates and, in many studies, accelerated fusion compared to traditional bone grafts. However, these benefits come at the cost of increased complications, particularly in anterior cervical fusions, where dysphagia and cervical swelling were the most prevalent. In posterior cervical fusions, rhBMP-2 use was not observed to be associated with significantly higher complication rates, except for wound complications.\u003c/p\u003e \u003cp\u003eEmerging strategies, including lower dosing, use of sealants or glue, avoidance of irrigation, and prophylactic steroid use, may reduce adverse outcomes by confining rhBMP-2 to the intended fusion site and decreasing inflammation. Due to ongoing safety concerns, rhBMP-2 should be reserved for select cervical spine patients at risk of pseudoarthrosis, where benefits outweigh potential risks, especially in anterior cervical fusions.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003cp\u003eAddisu Mesfin, following conflict of interest: Grants from Nuvasive, OREF grant, Depuy speaking fees, Globus consulting. The remaining co-authors have nothing to disclose.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAuthors AM and JPJ contributed to curation and supervision of the study. Authors JL, JPJ, LL, ME, and KY completed data collection/analysis and manuscript formulation. Authors JL, JPJ, AP, AA, JH, and SB supported editing and submission of the study. All authors reviewed and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSong KJ, Choi BY (2014) Current concepts of anterior cervical discectomy and fusion: a review of literature. Asian Spine J 8(4):531\u0026ndash;539\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYoussef JA, Heiner AD, Montgomery JR, Tender GC, Lorio MP, Morreale JM et al (2019) Outcomes of posterior cervical fusion and decompression: a systematic review and meta-analysis. 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SPINE 41(7):555\u0026ndash;562\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"recombinant human Bone Morphogenetic Proteins, Cervical vertebrae, Spinal fusion, Intervertebral disc","lastPublishedDoi":"10.21203/rs.3.rs-8780018/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8780018/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground Context:\u003c/h2\u003e \u003cp\u003eRecombinant human bone morphogenetic protein-2 (rhBMP-2) is used off-label in anterior and posterior cervical spine fusion (ACF and PCF) as an alternative to autologous or allogenic grafts, enhancing fusion potential. However, concerns regarding complications such as neck swelling and dysphagia have been raised.\u003c/p\u003e\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eTherefore, this study aims to assess complication profiles of rhBMP-2 in cervical fusions, comparing anterior and posterior approaches and examining the impact of dosage, patient-specific risk factors, and preventive strategies.\u003c/p\u003e\u003ch2\u003eStudy Design:\u003c/h2\u003e \u003cp\u003eSystematic review\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003e We conducted a systematic literature search in June 2025 in accordance with PRISMA guidelines. PubMed and Embase were queried with keywords involving rhBMP-2 and cervical fusion. Eligible studies included clinical studies reporting outcomes of anterior or posterior cervical fusion with rhBMP-2. Data on fusion rates, complications, and their relevant factors were extracted and analyzed.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThirty-four studies, 26 ACF and 8 PCF, met our inclusion criteria. Fusion rates with rhBMP-2 were consistently high, ranging from 81.8\u0026ndash;100% in ACF and 82.4\u0026ndash;100% in PCF. Comparative data generally demonstrated superior fusion rates with rhBMP-2 compared to controls, with some evidence of accelerated fusion times. However, use of rhBMP-2 was also associated with more severe cases of cervical swelling and dysphagia in ACF. rhBMP-2 groups in PCF generally did not demonstrate significantly higher incidence of complications compared to control groups.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eOur systematic review suggests that rhBMP-2 successfully augments cervical fusion; however, it also increases the risk of certain complications, particularly in anterior cervical surgery. Dosing, specific levels fused, number of levels fused, and patient-specific factors all significantly influence the risk of complications. Importantly, prophylactic measures, such as containment, drain placement, and local steroid administration, show potential in reducing the severity of adverse outcomes. Ultimately, careful patient selection and complication prevention strategies may enable rhBMP-2 to provide its intended benefits while minimizing risks.\u003c/p\u003e","manuscriptTitle":"The Use of rhBMP-2 in Cervical Fusion: A Systematic Review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-13 16:50:09","doi":"10.21203/rs.3.rs-8780018/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e6a348b6-0fc4-4b03-bdf2-9f32efb61007","owner":[],"postedDate":"February 13th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-09T21:54:16+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-13 16:50:09","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8780018","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8780018","identity":"rs-8780018","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}