Systematic Review of Bioactive Glass Cages in Anterior Cervical Discectomy and Fusion

Abstract

Background

Anterior cervical discectomy and fusion (ACDF) is a standard procedure for cervical degenerative pathologies, typically using allograft or polyetheretherketone (PEEK) cages. Bioactive glass (BG) cages have emerged as a novel interbody option with osteoconductive and bioactive properties. This review aimed to compare clinical and radiological outcomes between BGC cages and traditional graft options (allograft or PEEK) in ACDF.

Methods

This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to compare BG and traditional techniques. PubMed and Google Scholar were queried for studies comparing BG and traditional methods. Studies that were non-English or focused on pediatric patients were excluded. Visual analog scale (VAS)-neck, VAS upper extremity (UE), Neck Disability Index (NDI), and computed tomography (CT) fusion rate were recorded. All meta-analyses were conducted using STATA 18.0, College Station, TX, USA.

Results

Our final review included 9 studies with 542 patients: 235 treated with BG and 307 with traditional methods (allograft or PEEK). There was no statistically significant difference between BG and control groups in improvement in neck pain (g = 0.00; 95% CI −0.19 to 0.18; P = 0.98) or UE pain (g = −0.15; 95% CI −0.42 to 0.11; P = 0.26). Similarly, there were no significant differences in postoperative neck VAS scores (g = 0.26; 95% CI −0.02 to 0.55; P = 0.07) or postoperative UE VAS scores (g = 0.05; 95% CI −0.22 to 0.31; P = 0.72). There was no significant difference between groups in NDI improvement (g = 0.12; 95% CI −0.30 to 0.54; P = 0.58) or postoperative NDI scores (g = 0.30; 95% CI −0.04 to 0.64; P = 0.08). Analysis showed that CT-confirmed fusion rates were comparable between groups, with no statistically significant difference observed (OR 1.12; 95% CI 0.72–1.76; P = 0.62).

Conclusion

All studies reported comparable clinical and radiological outcomes for BG compared with traditional methods for cages in ACDF. Outcomes, including VAS, NDI, CT fusion, and interspinous motion, were similar. Only 9 studies have been performed so far; thus, additional research is necessary to establish BG as a compelling alternative to traditional techniques.

Clinical Relevance

Bioactive glass cages demonstrate comparable clinical and radiographic outcomes to traditional cage materials in ACDF, suggesting they may be considered as an alternative graft option. However, the limited number of available studies and lack of high-level evidence constrain definitive clinical adoption.

Level of Evidence

3.

Introduction

Anterior cervical discectomy and fusion (ACDF) was first described by Cloward, Smith, and Robinson in 1958.^1,2 It is a standard procedure used to treat various pathologies caused by compression of the cervical spine or nerve root (Figure 1).³ Traditionally, an iliac crest autograft is used for interbody fusion. However, because of donor site morbidity, sometimes an autograft is not possible.⁴ As a result, this has led to a shift toward synthetic interbody grafts, as they have been shown to have higher rates of fusion and are more available for use.^5,6

Figure 1.

Spinal decompression: Anterior cervical discectomy and fusion (ACDF). On the left, the figure shows a diagram depicting cervical degenerative disc changes that are causing nerve spinal decompression due to herniation and stenosis of the intervertebral foramen. On the right, the figure depicts the outcome of ACDF surgery, highlighting hardware components and nerve decompression.

The most commonly used graft materials are polyetheretherketone (PEEK), allografts, and titanium.^7,8 However, there are unique drawbacks that can be attributed to these cage materials. While allografts have been shown to offer fusion success and clinical improvement comparable to those of autografts, there is potential for graft rejection, graft mechanical failure, and disease transmission.^9–11 On the other hand, the robust titanium cages may have a high incidence of subsidence compared with PEEK cages.⁶ PEEK may have lower rates of subsidence but typically requires an additional bone implant because it is unable to bond with bone.¹² Additionally, PEEK and titanium alloys lack osteoinductive or conductive properties.¹³ Due to these limitations, a novel cage material that provides structural integrity and is osteopromotive is needed.

In recent years, bioactive glass (BG) has emerged as a possible alternative to traditional cage materials.¹⁴ BG can stimulate the growth and osteogenic differentiation of human primary osteoblasts.¹⁵ As an osteogenic material, BG gradually resorbs through the controlled release of its constituent ions, maintaining bioactivity while offering temporary mechanical support.^16,17 It also provides additional benefits, including angiogenesis and antimicrobial properties.^18,19 Recent literature suggests that BG-autograft mixtures may confer similar rates of spinal fusion relative to standalone autograft without altering the risk of deep wound infection by promoting a proregenerative immune response.^20,21

There have been no prior systematic reviews performed on the use of BG in ACDF procedures. Prior reviews have focused broadly on cage material properties and BG effectiveness in spinal fusion surgery, without specifically evaluating the clinical performance of BG in ACDF.^20,22 Given the growing interest in biologically active interbody devices and the limited data on their role in ACDF, a targeted synthesis of the evidence is warranted. This systematic review aims to compare the effectiveness of BG with traditional methods, such as PEEK and allograft in ACDF. Primary outcomes include visual analog scale (VAS)-neck/upper extremity (UE) and Neck Disability Index (NDI) scores. Secondary outcomes include fusion rates and interspinous motion. We hypothesized that BG cages would provide similar outcomes as conventional materials for cages in ACDF.

Methods

Study Design

This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines to compare BG and traditional techniques.²³ The objective of the study was to compare the clinical effectiveness of BG and conventional interbody fusion materials in ACDF.

Search Strategy

A systematic search was conducted in PubMed and Google Scholar from 6 June to 13 June 2025 to identify relevant studies. The search strategy included the following terms: ACDF, BG, and interbody cage.

Inclusion Criteria

Studies were included if they met the following criteria: (1) population: adult patients undergoing ACDF; (2) intervention: use of BG or BG-ceramic (eg, BGS-7 and NOVOMAX) as an interbody spacer; (3) comparator: conventional interbody fusion materials such as PEEK cages or structural allograft; (4) outcomes: clinical outcomes including VAS for neck and UE pain, NDI, and computed tomography (CT)–assessed fusion rate; and (5) study design: randomized controlled trials (RCTs) or comparative cohort studies. Studies were excluded if they involved pediatric patients, were not published in English, or were noncomparative designs.

Literature Selection

Two independent reviewers screened all titles and abstracts for relevance. Full texts of potentially eligible studies were retrieved and reviewed in accordance with the inclusion and exclusion criteria. Disagreements were resolved by consensus or by consultation with a third reviewer. The study selection process was documented using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram Figure 2.

Figure 2.

Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram. ACDF, anterior cervical discectomy and fusion.

Risk of Bias Assessments

Study quality and risk of bias were evaluated using the Risk of Bias 2 tool for each included randomized study.²⁴ For nonrandomized studies, the Risk of Bias in Nonrandomized Studies of Interventions tool was employed.²⁵ Two reviewers independently performed all assessments, and discrepancies were resolved through discussion and consensus.

Meta-Analysis

A direct meta-analysis was performed for all recorded variables with sufficient data to compare both groups. Extracted data included study design, sample size, patient demographics, intervention and comparator details, clinical outcome measures (VAS-Neck, VAS-UE, and NDI), and radiographic outcomes (fusion rate via CT). All discrete variables were reported using odds ratios with 95% confidence intervals (CIs), while all continuous variables were reported as standardized mean differences (Hedges’ g) with 95% CIs. Every meta-analysis was conducted using random-effects models to account for variability between studies. The level of significance was set to P = 0.05. All statistical analyses were performed using STATA 18.0 BE-Basic Edition (StataCorp LLC, College Station, TX, USA).²⁶

Results

Study Characteristics

A total of 9 studies, comprising 2 RCTs, 2 prospective cohort studies, and 5 retrospective cohort studies, met the inclusion criteria, encompassing 542 patients who underwent ACDF (Table).^27–36 Among these, 235 patients were treated with BG interbody spacers, while 307 patients received traditional materials, including PEEK cages or structural allografts. Among the comparators, 7 studies used allograft, and 2 studies used PEEK cages. The follow-up duration varied across studies, ranging from 6 weeks to 89.2 months. Six out of the 9 studies had a follow-up period of 12 months, with 1 long-term prospective cohort study by Ryu et al reporting a mean follow-up of approximately 89.18 ± 5.44 months.³⁵ All studies were comparative in design and reported clinical and/or radiographic outcomes of interest.

Table.

Characteristics of studies investigating bioactive glass in patients undergoing ACDF.

Study	Year	Study Type	Sample Size		Comparator	Follow-up Duration
			Bioactive Glass	Allograft/PEEK
Park et al	2023	RCT	36	40	PEEK	12 mo
Liu et al	2023	RCT	22	18	Allograft	12 mo
Chung et al	2024	Retrospective cohort	33	44	Allograft	12 mo
Seung et al	2020	Prospective cohort	17	34	Allograft	24 mo
Ryu et al	2023	Prospective cohort	18	26	Allograft	89.18 ± 5.44 mo
Sehan Park et al	2020	Prospective cohort	26	37	Allograft	12 mo
Gi-Wuk Jang et al	2024	Retrospective cohort	54	27	Allograft	12 mo
Kim et al	2020	Retrospective cohort	36	35	Allograft	12 mo
Kwon et al	2024	Retrospective cohort	20	19	PEEK	6 wk

Abbreviations: ACDF, anterior cervical discectomy and fusion; PEEK, polyetheretherketone; RCT, randomized controlled trial.

Risk of Bias Assessment

Of the 9 included studies, 7 were observational designs (retrospective or prospective cohort), and 2 were RCTs. The Risk of Bias 2 tool was used to assess the risk of bias in RCTs, while the Risk of Bias in Nonrandomized Studies of Interventions tool was used for nonrandomized studies. The overall risk of bias varied, with most studies demonstrating moderate to high risk due to nonrandomized design and lack of blinding. The risk of bias summary is visually presented in Figures 3 and 4 using the robvis tool.

Figure 3.

Risk of bias assessment: Risk of Bias 2 tool.

Figure 4.

Risk of bias assessment: Risk of Bias in Nonrandomized Studies of Interventions.

VAS Score

Eight studies reported the VAS-neck score, and 6 studies reported the VAS-UE score. There was no statistically significant difference between the 2 groups in improvement in neck (g = 0.00; 95% CI −0.19 to 0.18; P = 0.98) and UE (g = −0.15; 95% CI −0.42 to 0.11; P = 0.26) VAS scores (Figures 5 and 6). There was moderate heterogeneity between studies for VAS UE improvement (I² = 39.09%) and low heterogeneity for VAS neck improvement (I² = 5.96%). Additionally, the postoperative neck (g = 0.26; 95% CI −0.02 to 0.55; P = 0.07) and UE (g = 0.05; 95% CI −0.22 to 0.31; P = 0.72) VAS scores showed no significant difference between the 2 groups (Figures 7 and 8). Postoperative neck VAS scores showed substantial heterogeneity between studies (I² = 60.79%), whereas postoperative UE VAS scores showed moderate heterogeneity (I² = 38.68%).

Figure 5.

Meta-analysis of postoperative visual analog scale (VAS) neck scores.

Figure 6.

Meta-analysis of postoperative visual analog scale (VAS) upper extremity (UE) scores.

Figure 7.

Meta-analysis of visual analog scale (VAS) neck improvement.

Figure 8.

Meta-analysis of visual analog scale (VAS) neck improvement.

NDI Score

Seven of the 9 studies reported NDI scores. There was no statistically significant difference between the 2 groups in improvement in NDI scores (g = 0.12; 95% CI −0.30 to 0.54; P = 0.58; Figure 9). Improvement in NDI scores showed considerable heterogeneity between studies (I² = 78.08%). The postoperative NDI scores (g = 0.30; 95% CI −0.04 to 0.64; P = 0.08) showed no significant difference between the 2 groups (Figure 10). Postoperative NDI scores showed substantial heterogeneity between studies (I² = 68.91%).

Figure 9.

Meta-analysis of postoperative Neck Disability Index (NDI) scores.

Figure 10.

Meta-analysis of Neck Disability Index (NDI) improvement.

Fusion Rates

Eight studies reported fusion rates. Meta-analysis showed that the odds of achieving CT-confirmed fusion were numerically higher in the BG group, but the difference was not statistically significant (OR 0.12; 95% CI −0.28 to 0.53; P = 0.55; Figure 11). CT fusion rates showed moderate heterogeneity between studies (I² = 46.96%).

Figure 11.

Meta-analysis of computed tomography (CT) fusion.

Discussion

ACDF has become the standard surgical approach for treating cervical spinal cord and nerve root compression. Although autografts have traditionally been used for interbody fusion, their associated donor site morbidity has led to an increased adoption of synthetic alternatives, such as PEEK, allograft, and titanium. However, these conventional materials each carry limitations such as poor osseointegration, subsidence, or immunological concerns, prompting interest in more biologically active options. This systematic review synthesized comparative studies evaluating the clinical and radiological outcomes of BG vs traditional cage materials in ACDF. We found that BG cages achieved similar improvements in VAS-neck, VAS-UE, and NDI scores compared with PEEK and allograft. Fusion rates and interspinous motion outcomes were also comparable between groups, with no statistically significant differences.

This review demonstrates that BG interbody spacers provide comparable improvements in neck pain, as measured by VAS-neck scores, to those of conventional materials. In posterior lumbar interbody fusion (PLIF), VAS-back showed no significant difference between patients who received a BG cage or a titanium cage.³⁷ Kwon et al also found similar fusion rates and clinical radiographic outcomes when comparing BG to PEEK cages in lumbar procedures.³⁸ These consistent results across cervical and lumbar procedures suggest that BG’s pain-relief benefit can be applied to different spinal regions or techniques. Our study contributes to the current literature by confirming the efficacy of BG in a focused ACDF population, thereby showing its potential to be beneficial in the anterior spinal column.

VAS-UE scores also showed similar improvement across groups. The lack of significant differences supports that BG does not compromise neural decompression efficacy or postoperative pain relief. Comparable findings have been reported in PLIF, where no intergroup differences were observed in VAS-leg pain scores between BG and conventional cages.^37,38 These consistent results across cervical and lumbar procedures reinforce the conclusion that BG provides effective neural decompression and symptom relief, regardless of spinal level or cage composition. Our study confirms that BG achieves clinical outcomes equivalent to standard materials without sacrificing analgesic or neurological benefits.

NDI outcomes were comparable between BG and traditional materials. In PLIF, studies comparing BG to conventional materials—such as titanium and PEEK cages—have demonstrated no significant differences in Oswestry Disability Index scores, suggesting equivalent functional outcomes.^37,38 These consistent outcomes across cervical and lumbar procedures suggest that BG supports similar improvements in patient function regardless of spinal region. Our study adds to this body of evidence by providing focused data on ACDF, further validating BG as a reliable alternative to traditional materials in terms of functional recovery.

Radiographic fusion remains a critical endpoint for evaluating interbody materials in ACDF. The studies included in this review reported CT-based fusion rates ranging from 75% to 97.8% for BG and from 70.4% to 100% for traditional materials, with no statistically significant difference (P > 0.05). While fusion was consistently achieved in both groups, there was no evidence that BG led to inferior or superior fusion outcomes. Cottrill et al conducted a systematic review that revealed preclinical data showing similar rates of fusion between BG and autograft groups.²⁰ Barrey et al supported this as they reported similar fusion rates (93%) using BG in posterior cervical and lumbar fusion to allograft.³⁹ Additionally, fusion rates of BG in PLIF were comparable to those of PEEK.³⁸ Our review builds on the literature by focusing on a specific spinal procedure, ACDF. Similar outcomes of BG in both anterior and posterior spinal fusions may show its versatility and potential as a standard interbody material across different surgical approaches.

This review has some limitations. The number of available studies examining BG in ACDF remains limited, and most have employed retrospective cohort designs with relatively small sample sizes. Variability in surgical technique, follow-up duration, and imaging protocols also introduces heterogeneity. Furthermore, the included studies used different types of BG, which may have variable performance characteristics. Despite these limitations, this study represents the first systematic review to compare BG cages in ACDF with traditional methods. Given these limitations, further RCTs with standardized outcome reporting are essential.

Conclusion

BG cages achieve similar clinical and radiological outcomes as traditional cage materials in ACDF. This suggests that BG spacers offer a viable alternative without compromising pain relief, neurological improvement, or fusion integrity. These findings support the broader incorporation of bioactive biomaterials in spinal fusion and warrant further investigation into their long-term efficacy and cost-effectiveness.