INTRODUCTION
Adult spinal deformity (ASD) [1] consists of a heterogeneous spectrum of abnormalities of the lumbar or thoracolumbar spine throughout adulthood that contribute to pain, weakness, and impaired health-related quality of life. It affects 15%–20% of adults, with higher prevalence in elderly population [1]. Long-segment fusion corrective surgery can provide significant improvements in disability, quality of life, and pain in ASD patients [2]. Nevertheless, with stronger spinal fixation techniques, there is a greater risk of proximal junctional kyphosis (PJK) after surgery, especially in osteoporotic spines [3]. PJK is defined as the sagittal cobb angle subtended by the lower endplate of the uppermost instrumented vertebrae (UIV) to the upper endplate of 2 vertebrae proximal is ≥ 10° and at least 10° larger than the preoperative measurement [4]. PJK with fracture, vertebral subluxation or screws dislodgement is defined as proximal junctional failure (PJF). As PJF may result in more serious morbidities, such as back pain and neurologic deficits, it consequently requires a revision surgery [5]. Therefore, it is crucial to introduce preventive strategies to minimize the incidence of postoperative PJK and PJF.
Several prophylactic strategies [6] have been proposed to prevent PJK and PJF after spinal deformity correction surgery, such as vertebral cement augmentation (VCA), multilevel stabilization screws, tricortical screw and ligament augmentation [7]. Among these, VCA is gaining sustained interest given its successful application in osteoporotic vertebral compression fracture [8]. VCA has seen significant growth since the 1980s, proving advantages in managing osteoporotic compression fractures, pathological fractures, trauma, and spinal deformities [8,9]. Hart et al. [10] conducted the first cohort study on the use of VCA in ASD surgery to prevent PJK. Thereafter, an increasing number of centers and regions have recognized the application of VCA in spinal deformity corrective surgery [10-16]. Like osteoporotic fractures, osteoporosis is commonly present in ASD patients. In upper thoracic-to-pelvis spinal reconstruction for ASD, lower Hounsfield units at the UIV and UIV+1 were independently associated with PJK and PJF [17]. Pedicle screws with VCA have been shown to significantly improve the fixation strength in a severely osteoporotic spine [18]. Although VCA provides advantages in enhancing pullout strength of pedicle screws, surgeons may also be concerned about the related complications, such as bone cement leakage and pulmonary embolism [19].
Despite positive effects in osteoporotic fractures in the thoracic or lumbar spine [20,21], the use of VCA in spinal deformity surgery still lacks consensus. Several studies have reported the application of VCA in ASD corrective surgery [10-16], but showed contradictory conclusions about the effectiveness of VCA. This may stem from differences in the definition of PJK and PJF, insufficient sample sizes, and variations in patient selection and so on. Despite its clinical potential, complications like cement leakage and pulmonary embolism related to VCA are scarcely reported, its pooled prevalence and clinical consequence are poorly described [22]. Therefore, we performed this meta-analysis to systematically review and synthesize evidence in the literature on the effectiveness and safety of VCA in deformity correction surgery.
MATERIALS AND METHODS
1. Search Strategy
This systematic review and meta-analysis were conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines [23]. We systematically searched for the relevant articles in PubMed, Web of Science, and the Cochrane Library databases published up to December 30th, 2024. The following keywords were used in the search: “spinal fusion,” “Vertebroplasty,” “bone cement,” “proximal junctional kyphosis,” and “proximal junctional failure” and so on. The details of the search strategy are shown in Supplementary Material 1.
2. Study Selection
To fully elaborate the risk factors, we performed a comprehensive analysis of the included study with reported variables for PJK like age, bone density, and severity of deformity. Specifically, we applied the following inclusion criteria for the selection of articles: (1) surgical method: posterior spinal fusion surgery; (2) intervention in the experimental group: bone cement augmentation; (3) intervention in the control group: no cement augmentation; (4) primary outcomes: the incidence of postoperative PJK, PJF, and revision surgery for proximal junctional complications; (5) other complications: leakage of cement and cement pulmonary embolus; (6) study design: cohort studies and randomized controlled studies.
The exclusion criteria were as follows: (1) case reports, reviews, letters, meeting abstracts and comments; (2) single-armed studies without control group; (3) case-control studies; (4) biomechanical studies, finite element analyses and animal studies; (5) not published in English; (6) no report on study outcomes; (7) not spinal deformity corrective surgery.
3. Data Extraction
After discarding the duplicate studies, 2 reviewers (DL and XS) independently evaluated the potentially eligible studies. The articles were screened for eligibility based on a review of the title and abstract, and disagreements were resolved through consensus. After screening, the full texts of the eligible articles were read independently by the 2 reviewers, and the eligibility of each article was reassessed. Subsequently, the data, including the patient and study characteristics (first author, publication year, study type, number of patients, age, sex, indication, follow-up time, and T score), surgical details (UIV and levels instrumented) and outcome data (incidence of PJK, PJF, and revision and secondary outcomes), were extracted.
4. Quality Assessment
For cohort studies, the Newcastle-Ottawa scale (NOS) was used for the quality assessment [24]. The quality of each study was graded as low (0–3), moderate (4–6), or high (7–9). All divergences were resolved by consensus.
5. Statistical Analysis
The Review Manager (RevMan 5.4, Cochrane Collaboration, Oxford, UK) was used for the statistical analysis of the pooled data. To synthesize the data, both fixed-effects and random-effects models were considered. The choice of model was based on the level of heterogeneity among the included studies, as assessed by the I² statistic and Cochran Q test. If I² was below 50% and the Q test was not significant (p> 0.10), indicating low heterogeneity, a fixed-effects model was used. Conversely, if I² exceeded 50% or the Q test was significant (p≤ 0.10), suggesting substantial heterogeneity, a random-effects model was applied. To analyze the incidence of PJK, PJF, and reoperation, we analyzed the risk ratio (RR). Furthermore, 95% confidence intervals (CIs) were used in the analysis. A p-value < 0.05 was considered statistically significant.
6. Publication Bias
The publication bias was assessed by funnel plots generated by Review Manager (RevMan 5.4). And the symmetry of funnel plots was quantitatively assessed with Harbord test [25], performed by StatView ver. 18.0 (SAS Institute Inc., Cary, NC, USA).
RESULTS
1. Description of Studies
In total, 513 articles were searched, and 89 duplicate articles were removed (Fig. 1). After screening for eligibility, based on a review of the title and abstract, 27 articles were identified for full-text reading. After a detailed assessment, 20 articles were excluded, because of irrelevant intervention or no primary outcomes reported. Accordingly, 7 studies remained and were finally included in our meta-analysis.
2. Study Characteristics
The 7 eligible studies were all retrospective cohort studies, including 333 cases in the VCA group and 827 cases in the control group (Table 1). All the patients underwent correction surgery for ASD. Cement augmentation at the UIV and UIV+1 was applied in all cases from experimental groups included in the studies reviewed. And proximal tethering techniques were not used in any of the included cases. There were no significant differences in sex (p= 0.94) or follow-up time (p= 0.43) between the 2 groups (Fig. 2). However, patients in the VCA group had significantly older age (mean difference [MD]= 4.38; 95% CI, 0.94–7.82; p= 0.01) and lower T score (MD= -0.70; 95% CI, -1.04 to -0.35; p< 0.01).
4. Quality Evaluation
The quality of the included studies was evaluated using the NOS, as shown in Table 3. Total NOS scores ranged from 3 to 9, reflecting variability in study design and methodological rigor. Two studies were classified as high-quality studies (7–9), demonstrating strong representativeness, comparability, and outcome assessment, indicating robust methodological quality. Three studies were considered moderate-quality studies (5–6), with notable limitations in areas such as cohort comparability and follow-up duration. Two studies were rated as low-quality studies (3–4), primarily due to inadequate cohort comparability and insufficient follow-up. These findings highlight the diversity in study quality, which may impact the robustness and generalizability of the meta-analysis results, with lower-quality studies potentially introducing bias into the pooled effect estimations.
5. Proximal Junction Complications and Revision Rates
PJK was recorded in 4 studies comprising 642 patients (Table 4). The incidence of PJK was 23% lower in the VCA group compared to the control group, but there was no statistically significant difference (RR, 0.77; 95% CI, 0.39–1.50; p = 0.44) (Fig. 4). Obvious heterogeneity was found for the incidence of PJK (χ2= 20.73, p< 0.01; I²= 86%). Six studies comprising 789 patients recorded incidences of PJF, with meta-analysis showing significantly lower rates of PJF in patients who underwent VCA compared to control group (RR, 0.64; 95% CI, 0.43–0.96; p= 0.03). Low between-study heterogeneity was found for the PJF rates (χ2= 7.85, p = 0.16; I² = 36%). Rates of revision surgery were comparable between patients in VCA group or no not VCA, with meta-analysis of 7 included studies (1,160 patients) reflecting a RR of 0.29 (95% CI, 0.16–0.51; p < 0.01). Studies analyzing rates of revision surgery were homogenous (χ2= 4.66, p= 0.59; I²= 0%).
6. Sensitivity Analysis
To assess the robustness of our findings and the potential influence of lower-quality studies, we conducted a sensitivity analysis by excluding 2 studies with lower NOS scores (Supplementary Fig. 1). After recalculating the pooled effects, the results for PJK (RR, 0.60; 95% CI, 0.21–1.71; p= 0.34) and revision rates (RR, 0.27; 95% CI, 0.14–0.52; p < 0.001) were consistent with the original findings. However, the pooled effect for PJF changed from statistically significant (RR, 0.64; 95% CI, 0.43–0.96; p= 0.03) to nonsignificant (RR, 0.72; 95% CI, 0.46–1.12; p= 0.14), suggesting that the inclusion of lower-quality studies might have influenced the original finding for PJF. These results underscore the importance of study quality in meta-analytic conclusions, with higher-quality studies providing more reliable and generalizable evidence.
7. Secondary Outcomes
Three studies [12,15,16] reported preoperative and postoperative sagittal vertical axis and kyphosis or lordosis degrees (Table 5). As for overall complications, there was no significant difference between the 2 groups (p= 0.21) [11,13]. Five studies [10,11,13,15,16] reported no complications occurred related to VCA. One study [14] reported cement leakage occurred in 57 patients (48.3%) and radiographic pulmonary occurred in 5 patients (4.2%) in the VCA group.
8. Publication Bias
We performed Harbord tests for small-study effects to assess publication bias for PJK, PJF, and revision rates. For PJK, the Harbord test showed no significant small-study effects (β₁= 1.34, p= 0.799), and the funnel plot was symmetrical (Fig. 5A), indicating no publication bias. This suggests that the results for PJK are consistent across studies. For PJF, the test revealed significant small-study effects (β₁= -2.24, p= 0.020), suggesting that smaller studies may disproportionately affect the overall effect size. The funnel plot asymmetry (Fig. 5B) also indicates that smaller studies may report more extreme results for PJF. Caution is needed in interpreting the impact of VCA on PJF due to potential overestimation in smaller studies. For revision rates, no small-study effects were found (β₁ = -0.94, p = 0.325), and the funnel plot was symmetrical (Fig. 5C), confirming no significant publication bias.
DISCUSSION
To our knowledge, this is the first meta-analysis on the effectiveness and safety of VCA in ASD corrective surgery. The pooled effect showed that VCA at UIV and UIV+1 levels reduced the incidence of PJK, PJF, and revision. One study reported cement leakage and radiologic pulmonary embolism after VCA. The pooled effects in this meta-analysis supported VCA in reconstructive surgery for spinal deformities patients, especially in those with advanced age and osteoporosis.
PJK is characterized by a proximal junctional angle exceeding 10° and frequently occurs as a postoperative complication following reconstructive surgery of ASD. Our meta-analysis demonstrated a 23% reduction in the incidence of PJK in the VCA group compared to the control group, although the difference was not statistically significant (p= 0.44). It was comparable with the transverse process hooks technique and junctional tethers technique, which reduced PJK by 36% [26] and 24% [27] respectively. There are several potential reasons for this finding. First, the relatively small number of included studies may limit the statistical power to detect significant differences. Second, there was considerable heterogeneity among the included studies (χ2= 20.73, p < 0.01; I²= 86%), particularly with respect to the follow-up duration and the definition of PJK. Differences in how PJK was identified and measured across studies could have contributed to inconsistencies in the reported outcomes. These factors may have influenced the ability to detect a statistically significant effect of VCA on the incidence of PJK.
Various biomechanical studies support the use of VCA in preventing PJK. For constructs ending in the lower thoracic spine, PJK is predominantly caused by compression fractures or screw pullout [28]. Studies such as those by Leichtle et al. [29] and Evans et al. [30] show that cement augmentation significantly increases axial pullout strength and failure initiation force. These findings suggest that VCA enhances spinal stability, which is crucial for preventing complications like PJK. Particularly, cement augmentation of pedicle screws in osteoporotic spines can boost pullout strength by 80% to 1,031% [31,32]. While biomechanical evidence aligns with clinical observations, discrepancies in study designs, follow-up periods, and PJK definitions may explain the lack of significant statistical differences in some clinical studies. Further research with larger sample sizes and standardized outcome measures is necessary to better correlate biomechanical advantages with clinical outcomes in preventing PJK.
Given that PJK is a radiographic phenomenon, of clinical importance is to halt the progression of PJK and reduce the need of PJF and revisions. To advance research in this area, standardized definitions of PJK and PJF are urgently needed. Recently, Cetik et al. [33] proposed a novel classification of proximal junctional degeneration and failure, which divided PJD into 4 major types: single adjacent level collapse, multilevel symmetrical collapse, fractures and spondylolisthesis. Although these 4 types has different clinical courses, at the last follow-up, patients diagnosed with PJD all has high rates of revision surgery for neurologic deficit and symptoms of spinal stenosis, from 40% to 80% [33]. That is because PJD is progressive rather than stabilize over time. Pathological changes like fracture and disc space penetration by screws, may accelerate the degenerative process [33]. VCA is considered as a promising technique to reduce the incidence of PJK and to prevent it from developing into PJF [12,13]. In this meta-analysis, the incidence of PJF and revision in the VCA group was reduced by 36% and 71% respectively. Considering that there was no significant difference in surgical details between the VCA group and the control groups, VCA may play a protective role in preventing the progressive process of PJK. However, it is worth noting that the studies included in this review used varying definitions of PJK and PJF, which hinder direct comparisons and contribute to inconsistency in outcomes. To advance research in this area, standardized definitions of PJK and PJF are urgently needed, thereby enhancing comparability across studies and improving the reliability of future research findings. Besides, Bartolozzi et al. [11] provide insights into the long-term impact of VCA on PJD. Kaplan-Meier analyses presented in their study showed no significant differences in the development of PJK over time (p= 0.191), nor in rates of PJF (p= 0.247) or reoperation (p= 0.469) between patients with and without VCA. These findings suggest that VCA’s long-term impact on these outcomes remains uncertain. It underscores the need for further research with larger patient cohorts and extended follow-up periods to clarify the role of VCA in mitigating long-term risks.
Although radiographic outcomes are critical for evaluating the mechanical success of vertebral VCA, patient-centered outcomes, including pain relief, functional recovery, and quality of life, are equally important for assessing the overall impact of this intervention on patients’ well-being. Upon reviewing the included studies, we observed contrasting findings regarding the effect of VCA on pain relief and functional outcomes. Bartolozzi et al. [11] reported no significant difference in NPRS back pain scores between the VCA group and the control group. In contrast, Theologis et al. [16] found significant improvements in several patient-centered outcomes following surgery, including EuroQoL visual analogue scale (EQ-VAS), EuroQoL-5 dimensions utility index, Oswestry Disability Index, VAS back pain, and VAS leg pain scores in the VCA group. The divergent results underscore the necessity of incorporating patient-centered outcomes in future research to provide a more comprehensive evaluation of VCA’s effectiveness.
While VCA has demonstrated short-term benefits in terms of reducing complications such as PJF and improving screw fixation strength, its potential long-term effects on adjacent segment disease and overall spinal biomechanics remain largely unexplored. None of the included studies in our meta-analysis reported long-term effects on adjacent segment disease and overall spinal biomechanics. A biomechanical study by Nagaraja et al. [34] investigated the effect of vertebroplasty on spinal biomechanics, particularly in severely osteoporotic women. This study found that vertebroplasty altered spine biomechanics, resulting in increased compression on the adjacent vertebral body and intervertebral disc, potentially leading to the development of adjacent segment disease over time. While these findings are valuable, it is important to recognize that biomechanical studies often do not reflect the complexity of clinical settings. We recommend that future clinical trials focus on adjacent segment changes with extended follow-up periods, to provide more comprehensive data on the long-term outcomes of VCA.
Previous mate-analysis [35] has confirmed that age at surgery > 55 years, low bone mineral density and fusion to S1 were risk factors for PJK. Zhao et al. [36] also found that elderly women are more susceptible to osteoporosis, which may contribute to the higher incidence of PJK. In the current meta-analysis, 74% cases were female patients and there was no significant gender difference between the VCA and control groups. However, patients in the VCA group were significantly older and had lower T score as compared to the control group. Lower T score means more osteopenia or osteoporosis patients in the VCA group. This is because the eligible studies were all retrospective, patient selection bias could not be excluded. Indeed, surgeons prefers to use bone cement for patients with osteoporosis [9]. A biomechanical study showed that pull out strength of pedicle screw decreases with a decrease in bone density [37]. his may explain the increased PJK rates in osteoporosis patients [36]. Besides, in the current meta-analysis, 92% of patients have undergone pelvic fixation with no significant difference between the 2 groups. VCA is more likely used for patients with long fusion to the pelvis, in which situation the proximal region bears the most mechanical stress. Our results supported the use of VCA in the corrective surgery for ASD patients with these risk factors for developing PJK.
VCA in thoracolumbar fusion surgery includes prophylactic placement at the UIV and UIV+1, vertebroplasty of the adjacent vertebra, or strengthening pedicle screws in osteoporotic patients [9]. The incorporation of VCA introduced an additional step to the procedure, however, our findings demonstrated no significant escalation in operation duration or bleeding (Table 2). Although there was no significant difference of overall complication rates between the 2 groups in the current meta-analysis, it is necessary to take measures to minimize serious complications like pulmonary cement embolism [38]. Among the 7 eligible studies, Zygourakis et al. [14] reported 2 clinically silent pulmonary cement embolism and 1 patient requiring surgical decompression for cement leak into the spinal canal. Previous literature found that percutaneous vertebroplasty, thoracic vertebra, higher cement volume injected per level, more than 3 vertebrae treated per session, venous cement leakage were more likely to cause pulmonary cement embolism [39].
To reduce complications associated with VCA, several strategies have been proposed in the literature, including advanced imaging techniques, precise cement volume control, and postoperative monitoring protocols. For example, Hoppe et al. [40] demonstrated that sequential cement injections could effectively reduce the risk of cement leakage. By using small volumes of cement injected sequentially, further leakage paths can be blocked before additional cement is injected, thereby minimizing the risk of leakage and embolism. Laredo and Hamze [41] proposed a few surgical techniques to reduce VCA-related complications, such as beveled needle, pedicular route, bilateral transpedicular approach, visualization of the cement, and permanent fluoroscopic control. Besides, Prater et al. [42] found that pulmonary cement embolism could be prevented by inferior vena cava filter. Surgical technique is another key factor influencing complications like cement leakage in VCA. Although no clear statistical evidence exists, improper technique, nonstandard procedures, or inexperience can increase the risk of complications. Li et al. [43] found that unilateral perforation is a risk factor for leakage, likely due to a larger puncture angle and increased risk of pedicle damage. Given that, we emphasize the need for specialized training in VCA. Surgeons should undergo focused training to minimize risks associated with these techniques. We recommend developing certification programs or workshops to ensure proper technique and reduce complications.
Hart et al. [10] conducted a detailed analysis of the economic implications of VCA in patients with ASD. They found that 15.3% of patients who did not undergo VCA experienced PJF, while no patients in the VCA group experienced this complication. They estimated that the cost to prevent one case of PJF was $46,240 using VCA, while the average inpatient cost for revision instrumented fusion was $77,432. These results suggest that VCA could be a cost-effective intervention in elderly female patients undergoing extended lumbar fusions, as the expenditure for revision remarkably outweighs that of VCA technique.
In addition to VCA, there are various techniques for preventing PJK and PJF, such as junctional tethers, transverse process hooks, and ligament augmentation. Sursal et al. [44] reviewed 15 clinical studies on the use of proximal junctional tethers in ASD surgery and most studies suggest that use of ligamentous augmentation may be protective against the development of PJK or PJF. However, junctional tethers may cause soft tissue disruption due to tether placement. In the study by Viswanathan et al. [45], among 40 patients, 3 complications related to tethers were observed, including 2 with cerebrospinal fluid leakage and one instance of transient neurological deficit. Transverse process hooks as the UIV anchor provides a soft landing at the transitional segment of the long-segment fixation construct [46,47]. In the study by Erkilinc et al. [48], placement of transverse process hooks at the UIV level in posterior spinal fusion surgery for AIS patients was associated with decreased risk of PJK. However, results from Matsumura et al. [26] show that using transverse process hooks at UIV may not prevent PJK in ASD. In the study by Safaee et al. [49], authors analyzed cost-effectiveness of PJF prevention with ligament augmentation. They found that patients with ligament augmentation, compared with those without, had a higher cost of index surgery although ligament augmentation demonstrates a significant reduction in PJF and the need for revision surgery.
To translate the findings of this study into clinical practice, we propose a practical framework for implementing VCA. The framework, detailed in Fig. 6, includes 3 major components: patient selection, surgical decision-making, and postoperative care. This framework aims to standardize the application of VCA and provide clinicians with clear guidance to enhance procedural safety and efficacy.
This review has several limitations. First, all the eligible studies were retrospective in nature, which might impair the credibility and robustness of the meta-analysis due to inherent biases such as selection bias. Future research should prioritize well-designed multicenter or multinational studies that incorporate prospective designs and ensure rigorous control of baseline characteristics. Collaborative efforts across institutions and countries would be instrumental in achieving these goals and generating more generalizable and reliable findings for clinical practice.
Second, the included studies did not adequately match groups for baseline characteristics, including age and T score, which could contribute to confounding effects. Moreover, the current findings are based on limited populations, primarily within specific regions or healthcare systems. To ensure the generalizability of our conclusions, future studies should focus on external validation in diverse patient populations. Specifically, research should include patients from different ethnic backgrounds, healthcare systems, and surgical practices. Variability in genetic predisposition, access to healthcare, and surgical protocols across regions could influence outcomes, highlighting the need for such validation. These efforts would provide more robust evidence and enhance the applicability of our conclusions across various clinical settings.
Third, certain variables such as the type and dose of bone cement, the type of pedicle screws, and other technical details might influence the outcomes of VCA. However, due to the lack of detailed and consistent data across the included studies, these factors could not be systematically analyzed. Standardized reporting of procedural factors, such as the type and quantity of bone cement used and instrumentation details, is essential for pooled analyses that can more accurately assess the effectiveness of VCA. Future studies should aim to establish consensus on these procedural variables to improve study comparability and clinical implementation.
CONCLUSION
VCA at UIV and UIV+1 was effective in preventing PJK and PJF after correction surgery for ASD. Our results supported the use of VCA in reconstructive surgery for ASD, especially in patients with advanced age and osteoporosis. In the future, it is hoped that preventive measures for VCA-related complications will be developed to ensure optimal outcomes and minimize risks.
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