The effect of smoking on the radiological and functional outcomes of anterior cervical discectomy and fusion with anchored standalone cages

Introduction

Background

Anterior cervical discectomy and fusion using anchored standalone cages (ASC-ACDF) has gained increasing acceptance as a surgical technique for the management of degenerative cervical spine disorders. This technique relies on an integrated fixation component located on the interbody cage which is anchored onto the adjacent vertebrae. By avoiding traditional rigid anterior plating, these designs have advantages of a lower-profile construct, reduced risk of postoperative dysphagia (1) and shorter operative time (2).

ASC-ACDF has been described to have comparable outcomes (3) to traditional plate-and-screw techniques. Cadaveric studies have demonstrated comparable range of motion (ROM) restriction at instrumented levels between anchored standalone cages and rigid anterior plate with interbody spacers in single- (4,5) and double-level constructs (6), thereby concluding that both constructs have similar biomechanical stability. Similarly, clinical studies have found insignificant differences in Japanese Orthopaedic Association (JOA), Neck Disability Index (NDI) and Visual Analogue Scale (VAS) scores between anterior plating and anchored standalone cages (7).

Nonetheless, in vitro and finite element analyses can only provide short- to mid-term cage performances and cannot fully simulate the biological environment in vivo; meanwhile, clinical studies provides long-term outcomes, evaluates the in vivo performance of cages via radiological findings, and can also evaluate factors influencing mechanical performance (8). It is well known that patient-related factors, such as smoking, may significantly affect surgical outcomes.

Rationale and knowledge gap

Smoking is a well-established major risk factor for impaired bone healing. Nicotine inhibits cancellous bone graft revascularization (9), retards osteoblastic proliferation due to cytokine inhibition (10), ultimately compromising fusion. While smoking has been associated with significantly higher rates of pseudarthrosis in the lumbar spine (11,12), its impact in the cervical spine remains less clearly defined. Evidence in present literature is mixed, with some reporting lower fusion rates in ACDF in chronic smokers (13), whereas others demonstrated no significant difference in fusion rates between smokers and non-smokers (NS) using plate-and-screw constructs in two-level ACDF (14), with over 90% of patients per group achieving radiographic fusion (15). Similarly, published studies report conflicting results in subsidence in smokers post-ACDF with anterior plating—Igarashi et al. suggest no difference in mean subsidence between current smokers, former smokers and NS (16), while Pinter et al. identified smoking as an independent risk factor for interbody subsidence (17).

Objective

This study aims to evaluate the impact of smoking on the radiological and functional outcomes of patients undergoing single-level (SL) and double-level (DL) ASC-ACDF. The authors hypothesize that smoking is associated with increased subsidence after ASC-ACDF and poorer post-operative functional outcomes. Understanding this relationship may aid in patient counseling, optimize surgical decision-making, and guide perioperative smoking cessation strategies to improve overall outcomes. We present this article in accordance with the STROBE reporting checklist (available at https://jss.amegroups.com/article/view/10.21037/jss-25-126/rc).

Methods

Study design

This study is a retrospective review of electronic medical records of patients who underwent primary SL and DL ASC-ACDF at a single tertiary institution from 2015 to 2022. Inclusion criteria were patients aged between 40 to 90 years old with a diagnosis of cervical myelopathy, radiculopathy or myeloradiculopathy. Exclusion criteria were patients who had prior cervical spine surgery or a diagnosis of trauma, tumor or infection. Implants that were used for patients included in this study were anchored standalone interbody cages that were chiefly constructed of polyetheretherketone (PEEK) that were anchored to adjacent vertebrae either via anchoring fins (ROI-C^®, Zimmer Biomet, Austin, TX, USA), or by fastening screws (STALIFC^®, Centinel Spine, West Chester, PA, USA, or Zero-P^®, DePuy Synthes, Raynham, MA, USA). The cage graft material was either demineralized allogenic bone matrix putty or autologous bone graft. The decision on implant selection and graft was based on the surgeon’s preference and familiarity. The sizing of implants followed a standardised algorithm. Medio-lateral sizing was performed to allow the implant to sit from uncus to uncus while implant height and depth were estimated on lateral radiographs and the amount of interbody tension. Sizing was then a selection of the greatest value acceptable for these three parameters. Triple-level and above ASC-ACDF were excluded as at the time of this study, the ASC-ACDF implants lacked United States Food and Drug Administration (FDA) approval for fusion greater than 2 levels. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study’s protocol was reviewed and approved by the Singhealth Centralised Institutional Review Board (IRB No. 2023/2498). Individual consent for this analysis was waived due to the retrospective nature.

Patients were categorized into two groups based on a self-reported patient questionnaire: NS and current and ex-smokers (CES).

Data collection

Demographic and surgical data including age, gender, diagnosis, implant used and number of operated levels were collected.

Radiological data was collected at preoperative, immediately postoperative and at 1-year postoperative time points. The parameters measured included: total intervertebral height (TIH), defined as the distance between the midpoints of the superior endplate of the uppermost and inferior endplate of the lowermost instrumented vertebrae; postoperative subsidence rates, defined as a >2 mm reduction in TIH at 1-year follow-up; segmental sagittal Cobb’s angle (SCA), defined as the angle between the superior endplate of the uppermost and inferior endplate of the lowermost instrumented vertebrae; and fusion rates, determined by the presence of bridging trabecular bone across endplates on lateral radiographs (Figure 1). These measurements were done on the institution’s digital Picture Archiving and Communication System (PACS), VUE Motion (Carestream Health, Rochester, NY, USA). Changes in TIH (ΔTIH) and SCA (ΔSCA) were calculated for two intervals: from preoperative to immediate postoperative, and from immediate postoperative to 1-year postoperative.

Figure 1 Radiographs of anchored standalone cages for ACDF (ASC-ACDF) in-situ. (A) Radiographic measurement of TIH and segmental Cobb. (B) Radiographic image of fused segment showing bridging trabecular bone between endplates. (C) Radiographic image of unfused segment showing absence of bridging trabecular bone between endplates. ACDF, anterior cervical discectomy and fusion; TIH, total intervertebral height.

Functional parameters were analysed at preoperative, 6 months and 2 years postoperative time points. These included the JOA score, NDI, Visual Analogue Score for Neck Pain (VASNP) and Visual Analogue Score for Upper Limb Pain (VASLP). An independent third party, who was not involved in this study, performed the data extraction, and ensured that the data was anonymized prior to handing it to the study team in an electronic encrypted Excel spreadsheet for analysis.

Statistical analysis

Statistical analysis was performed with Microsoft Excel (v16.78; Microsoft Corp., Redmond, WA, USA), Chi-squared tests were performed for categorical variables: patient age and number of operated levels. Paired t-tests were performed to evaluate for significant differences in radiological and functional outcomes between CES and NS groups at each specified time points. A P value <0.05 was considered statistically significant for this study.

Results

A total of 71 patients were included in this study with 48 in the NS group and 23 in the CES group. The biodata of included patients are presented in Table 1.

Radiological outcomes

At 1-year follow-up, the CES group demonstrated a statistically greater loss of TIH (ΔTIH −2.4 mm) compared to NS (ΔTIH −1.7 mm) (P=0.04). Subsidence at 1-year follow up occurred in 60.9% of CES patients (n=14) versus 35.4% of NS patients (n=17) which was also statistically significant (P=0.042). No significant difference was found in ΔSCA [was −4.1° for CES and −3.8° for NS (P=0.78)], and fusion rates [91.3% for CES and 89.5% for NS (P=0.82)] at 1-year follow up between the two groups (Table 2).

Functional outcomes

JOA scores were similar across all time points for both groups. Both groups demonstrated statistically significant improvements for all four functional parameters (JOA, NDI, VASNP, VASLP) at 6 months and 2 years compared to the previous time points (P<0.05) (Tables 3,4 and Figures 2-5). CES patients exhibited higher scores for NDI, VASNP and VASLP at preoperative, 6-month and 2-year time points compared to NS, albeit with varying statistical significance (Table 5).

Figure 2 Functional outcome—JOA score. CES, current and ex-smokers; JOA, Japanese Orthopaedic Association; NS, non-smoker.

Figure 3 Functional outcome—NDI. CES, current and ex-smokers; NDI, Neck Disability Index; NS, non-smoker.

Figure 4 Functional outcome—VASNP. CES, current and ex-smokers; NS, non-smoker; VASNP, Visual Analogue Score for Neck Pain.

Figure 5 Functional outcome—VASLP. CES, current and ex-smokers; NS, non-smoker; VASLP, Visual Analogue Score for upper Limb Pain.

The rate of functional improvement, as defined as the change in score between two time points, was also evaluated. There was no statistically significant difference in the rate of improvement across all four functional parameters at all time intervals between CES and NS groups (Table 6).

Discussion

Key findings

This the first study that evaluates the difference in radiological and outcomes between smokers and NS in the use of anchored PEEK standalone cages. Despite the well-known increase in general morbidity following ACDF and its relationship to fusion status, there is no consensus on the effects of smoking on radiological and functional outcomes in ASC-ACDF. Among standalone cages, one study did not find any correlation between smoking and subsidence for titanium cages when used without anterior plating (18). Meanwhile, Bartels et al. had evaluated multiple factors in the use of cervical standalone carbon fibre cages, such as age, gender, preoperative cervical morphology, intraoperative distraction of vertebral bodies—he found that only smoking status was a predictive factor of subsidence, although not related to outcome or fusion rate (19).

This study demonstrates that at 1 year following ASC-ACDF, subsidence rates are nearly twice as high in smokers compared to NS, with a 0.7-mm greater mean TIH loss, which is 41% higher than NS. The findings of our study suggest that biomechanical limitations of ASC-ACDF may be exacerbated by the detrimental effects of smoking on bone quality and end-plate integrity. Chronic nicotine exposure is known to impair bony vasculature due to dysregulation of protein expression (20), affecting bony metabolism and endplate integrity (21). As standalone cages are fixed to the adjacent vertebrae via an internal fixation mechanism, the authors postulate that the lack of anterior plating support may cause more endplate stress distribution with subsequent endplate instability. In addition to poorer bone quality, which may compromise the anchorage of the cages, a standalone construct in smokers may pose a higher risk of collapse and migration under load.

Despite greater subsidence in the CES group, the loss of lordosis (as evidenced by ΔSCA) did not differ significantly compared to the NS group. This is consistent with Jin et al.’s finding that cage subsidence had minimal effect on loss of segmental lordosis in single segment ACDF surgeries, although its effect is more pronounced in multiple segment surgeries (22).

Fusion rates remained high and comparable between the two groups, congruent with the 90% fusion rates described in previous literature. The authors postulate that this could be due to the bone-implant complex subsiding into a stable configuration conducive for fusion. Subsidence could have resulted in recurrent cervical foraminal stenosis, accounting for the increased VASLP observed in the CES group at 2 years postoperatively.

The functional outcomes of smokers undergoing ACDF also remains controversial. While smoking has perennially been associated with poorer pre- and post-operative outcomes, a multicenter prospective study found no significant differences in NDI, SF-36 Physical Component Scores (PCS), and neck and arm pain scores between smokers and NS (23). Similarly, Mangan et al. described that smoking status was not an independent predictor of outcome scores (24).

For this present study, at the 2-year time point, NDI, VASNP and VASLP were noted to be more than twice as high in CES compared to NS group. The CES groups were also observed to have started off a higher value preoperatively, congruent with Chen et al., which found that patients with a history of smoking reporting a higher VAS score for neck and shoulder pain in comparison to NS (25). The rate of functional improvements was similar between CES and NS groups, akin to findings described by Mangan et al., who reported similar amounts of improvement in health-related quality of life outcomes measures between current smokers, former smokers, and NS after ACDF despite having a significantly different baseline score (24). This indicates that that smokers can improve to a similar degree compared to NS after ASC-ACDF, and thus should not be denied surgical treatment with ASC-ACDF for indicated conditions due to their smoking status. Nonetheless, these findings may guide pre-operative counselling.

JOA scores were found to be similar between CES and NS at all time periods suggesting that cord function and recovery after decompression is unaffected by smoking. Unlike the increase in VASLP from recurrent foraminal stenosis, subsidence does not cause a recurrent central canal stenosis.

Limitations

This study has a small sample size with an unmatched gender distribution. The gender disparity was due to a societal propensity for smokers to be male. However, studies have described a minimal impact of gender on fusion rates (26) and clinical outcomes after spine surgery (27). The small sample size precludes propensity matched studies and subgroup analysis between single and multilevel fusions.

The self-reported nature of smoking status lacked granularity in the number of cigarettes smoked, the duration of smoking history and/or the duration of cessation. As such, no dose-dependent information could be derived from within the smoking group. Nevertheless, including ex-smokers remains relevant. In a lumbar fusion cohort, Jazini et al. found that former smokers had baseline and 12-month postoperative PROMs intermediate between current and never-smokers (28). These findings indicated that smoking cessation was unable to fully mitigate the negative effects of smoking on baseline and postoperative PROMS in lumbar fusion. Similarly, Wang et al. reported that, in female patients undergoing anterior cervical fusion–non-fusion hybrid surgery, early fusion rates differed significantly in both current and former smokers compared with never-smoker (29). The ex-smoking group exhibited outcomes intermediate between current and never smokers. Beyond smoking, other forms of recreational tobacco use, such as vaping, were not taken into account for this present study.

Confounding factors that may influence functional outcomes after cervical fusion—such as female sex, postoperative cervical collar use, depression, compensation status (30-32), adjacent segment disease, or the development of new symptoms—were not accounted for. Similarly, potential confounders to fusion rates, including preoperative serum parathyroid hormone and HbA1c levels as identified by Inose et al. (33), were not collected. In addition, other clinical outcomes which may have impacted fusion rates and functional outcomes, such as perioperative complications (e.g., infection, wound dehiscence, reoperation rate, blood loss, and length of hospitalization), were not evaluated (Figure 6).

Figure 6 Directed acyclic graph—intermediate confounding factors between smoking and ACDF clinical outcomes. ACDF, anterior cervical discectomy and fusion; HbA1c, hemoglobin A1c; PTH, parathyroid hormone.

Three different systems were used among the included patients, in which the NS and CES groups were not matched. Multiple cadaveric studies have demonstrated that zero-profile interbody cages with 3 (5), 4 (34) or anchoring clips (35) have nonsignificant differences in postoperative ROM compared to anterior plating constructs; a review article by Huang et al. concluded that there the number of fastening screws integrated into the interbody device confers no appreciable difference in mechanical stability (8). However, the authors of this present study recognize that there have been no head-to-head comparative studies between these three implant systems at the time of writing. As such, individual implant choice with potential variations in biomechanical properties may have influenced the clinical and radiological outcomes in this study, and this warrants further biomechanical and clinical studies for validation.

Implications and actions needed

Although this study demonstrates a higher rate of radiological subsidence in smokers, functional outcomes still demonstrate substantial postoperative improvement. These findings suggest that smoking status alone should not be a disqualifying criterion for surgical intervention, especially in symptomatic patients who meet surgical indications. This underscores the importance of patient-centric care over blanket exclusions. As such, the findings of this study support the view that smokers should not be denied surgical treatment, or access to surgical treatment in terms of insurance coverage or subsides, on basis of smoking alone, although perioperative counselling and smoking cessation support should still be judiciously conducted. Further long-term clinical studies into this field of smoking and ASC-ACDF are recommended to deepen the understanding of the correlation between the two, and such findings may guide policies implementation in the future.

Conclusions

This study demonstrates that current and ex-smoking status may confer poorer radiological and functional outcomes compared to NS in patients undergoing ASC-ACDF. Higher rates of cage subsidence and greater loss of intervertebral height were observed, along with consistently lower pre- and postoperative patient-reported outcome measures (PROMs). Even so, the magnitude of functional improvement, overall fusion rates and lordosis correction were comparable in both smoking and non-smoking groups. Although this study’s findings suggest that smokers should not be excluded from receiving ASC-ACDF due to adequate improvement rates, smokers should still be counselled on suboptimal functional outcomes post-ASC-ACDF. Further studies are recommended to determine if plate-and-screw constructs are superior to ASC-ACDF in smokers, after accounting for their respective downsides.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jss.amegroups.com/article/view/10.21037/jss-25-126/rc

Data Sharing Statement: Available at https://jss.amegroups.com/article/view/10.21037/jss-25-126/dss

Peer Review File: Available at https://jss.amegroups.com/article/view/10.21037/jss-25-126/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jss.amegroups.com/article/view/10.21037/jss-25-126/coif). C.C.R.S. is a medical consultant for Highridge Medical which manufactures one of the standalone cage constructs used in this study. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the Singhealth Centralised Institutional Review Board (IRB No. 2023/2498). Individual consent for this analysis was waived due to the retrospective nature.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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