Abstract
Background Cervical ossification of the posterior longitudinal ligament (OPLL) frequently progresses despite decompression surgery, leading to recurrent myelopathy. This meta-analysis aims to quantify risk factors for OPLL progression, compare surgical strategies, and determine the pooled reoperation rate due to symptomatic progression.
Methods Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, 26 high-quality studies comprising 1929 patients were included. Standardized mean differences (SMDs) and odds ratios (ORs) with 95% confidence intervals were calculated to assess risk factors, and all of the analyses were done with a random-effects model. A network meta-analysis using a random-effects model was conducted to compare surgical approaches, utilizing laminoplasty (LP) as the reference node.
Results Significant demographic risk factors for OPLL progression included younger age (SMD: −0.68, P < 0.001) and higher body mass index (SMD: 0.43, P < 0.001). Radiographically, progression was strongly driven by longer preoperative OPLL (SMD: 0.42, P = 0.003), a lower preoperative cervical range of motion (SMD: −0.30, P = 0.039), and OPLL at the C3 level (OR: 7.04, P < 0.001). Mixed-type OPLL nearly tripled the progression risk (OR: 2.94, P < 0.001), whereas segmental-type was highly protective (OR: 0.13, P < 0.001).
The network meta-analysis demonstrated that motion-preserving posterior surgeries were associated with higher rates of OPLL progression. Compared with LP, anterior surgery provided the greatest reduction in progression risk (OR 0.28, P < 0.001), followed by laminectomy with fusion (OR 0.42, P < 0.001). Direct pairwise comparisons similarly confirmed that laminectomy with fusion significantly reduced the likelihood of progression compared with LP (OR 0.44, P = 0.002). Nonsurgical management was also associated with lower odds of progression; however, this finding should be interpreted with caution due to potential confounding by indication. Additionally, the pooled long-term reoperation rate due to neurological deterioration from OPLL progression was 6.1% (95% confidence interval 2.9%–10.2%) over a mean follow-up of 72.6 ± 63.7 months.
Conclusions OPLL progression is statistically predictable, driven by younger age, higher body mass index, reduced cervical range of motion, and mixed-type morphology. Because anterior and fusion procedures were associated with lower progression rates compared with LP, these approaches should be considered in high-risk patients; however, these findings should be interpreted with caution given the heterogeneity across included studies.
Clinical Relevance For patients with high-risk profiles (eg, mixed-type OPLL), fusion or anterior decompression should be strongly considered over LP. When laminoplasty is used in high-risk patients, they should be advised on the necessity of long-term surveillance.
Level of Evidence 3.
- ossification of the posterior longitudinal ligament (OPLL)
- cervical spine
- disease progression
- systematic review and meta-analysis
- cervical myelopathy
Introduction
Cervical ossification of the posterior longitudinal ligament (OPLL) is a progressive condition characterized by ectopic calcification within the posterior longitudinal ligament. This pathological ossification can narrow the spinal canal, leading to chronic compression of the spinal cord and resulting in progressive, debilitating neurological deficits, including myelopathy and radiculopathy.1
The clinical management of OPLL presents significant challenges owing to its inherently dynamic and often progressive nature.2 Even following successful surgical decompression, the ossified mass may continue to enlarge, potentially resulting in the recurrence of neurological symptoms and necessitating revision procedures.3 This progression compromises the long-term effectiveness of treatment and constitutes a substantial clinical concern. Therefore, it is of paramount importance to comprehend the factors that influence OPLL progression in order to optimize patient outcomes, inform surgical decision-making, and appropriately manage patient expectations.
Over recent decades, many studies have aimed to identify predictors of OPLL progression. Risk factors suggested include demographic aspects such as younger age and male gender, metabolic factors like increased body mass index (BMI), and specific radiological features, including the type of OPLL (eg, segmental, continuous, or mixed).4–6 Additionally, there is an ongoing debate about how the surgical approach affects progression. Some hypothesize that motion-preserving procedures like laminoplasty (LP) might promote a biomechanical environment that encourages further ossification, while fusion surgeries that restrict segmental motion could potentially halt disease progression.7,8 However, individual studies often yield conflicting results and are limited by small sample sizes, making it difficult to establish definitive clinical recommendations. A quantitative synthesis of the available evidence is therefore crucial to clarify these uncertainties.
This systematic review and meta-analysis aims to provide a comprehensive, evidence-based assessment of cervical OPLL progression by: (1) identifying and quantifying significant patient-related and radiological risk factors; (2) comparing the rates of OPLL progression following different surgical approaches, including LP and fusion procedures; and (3) determining the pooled long-term reoperation rate due to symptomatic progression. By consolidating the global literature, we seek to provide clinicians with high-level evidence to better inform risk stratification, surgical decision-making, and patient counseling.
Methods
Protocol and Registration
This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines.9 Our review is registered in PROSPERO under the registration number (the registration number omitted to keep the paper anonymous).
Search Strategy, Databases, Eligibility Criteria, and Selection Process
We performed a comprehensive search across the 4 main databases, including PubMed, Web of Science, Scopus, and Embase. The search strategy and eligibility criteria are summarized in Table 1. One author (S.B.) conducted the search and removed duplicate articles using the CADIMA tool.10 All screening was performed by 2 independent researchers using the CADIMA web tool, and any disagreements between researchers were resolved through discussion with the senior researcher.
Search strategy and eligibility criteria for the systematic review.
Extracted Outcomes and Data Collection Process
Two authors independently collected data for the analysis. We divided the patients into 2 groups for comparison: the progression group and the nonprogression group. We extracted demographic, radiological, and surgical factors to identify the risk factors for cervical OPLL progression.
When individual patient data were unavailable, standard methods were used to calculate summary statistics from reported group-level data. For repeated measures (paired) data where only summary statistics (mean ± SD) were available at baseline and follow-up, the mean change (delta) was calculated as the difference between group means, with the SD of the change estimated using the conservative formula assuming independence between time points:
This approach does not account for within-subject correlation and may overestimate the actual SD of change.
Risk of Bias Assessment Process and Sensitivity Analysis
Two authors independently assessed the quality of the selected studies using a standardized set of criteria. They used the Newcastle-Ottawa Scale11 to evaluate each study’s internal validity. When disagreements arose, a third reviewer was consulted to resolve the issues. Sensitivity analyses excluded studies with imputed data and removed outliers to assess the robustness of the results. Only studies with Newcastle-Ottawa Scale scores of 7 or above were included in the main analysis.
Handling of Overlapping Populations
To prevent double-counting, overlapping cohorts were compared by institutions, author lists, recruitment periods, and ethics approval identifiers. When 2 publications clearly represented the same cohort, the report was omitted. If multiple reports overlapped but differed in cohort size or data, the 1 with a larger sample size and broader variable coverage was retained. Data extraction was done variable-by-variable, using the larger cohort as the primary source and only extracting predictor-specific data from smaller reports when unavailable in the larger cohort, ensuring overlapping cohorts were never entered simultaneously into the same pooled analysis. Consequently, Kawaguchi (2018) was selected over Kawaguchi (2001), and Lee (2018) was included instead of Lee (2016) and Lee (2017) for surgical outcomes, as they provided the most comprehensive datasets.
Software and Statistical Methods
Software and Effect Size Measures
The meta-analysis was conducted using Comprehensive Meta-Analysis software, version 4.0; we used MetaAnalysisOnline12 for visualization of the Forest plot. Factors were analyzed only if reported in at least 3 studies. Effect sizes were assessed using a random-effects model due to high heterogeneity. The standardized mean difference (SMD) was used for continuous variables, with a 95% confidence interval (CI) calculated for each estimate. Statistical significance was assessed using P values, with a threshold of P < 0.05. When there were sufficient studies (at least 3) for different subgroups in each variable, we performed subgroup analysis. We also reported “mixed” analysis, which means that all subgroups were combined together.
Publication Bias Assessment
Publication bias was assessed using funnel plot analysis13 for factors with more than 3 studies. To minimize the impact of any detected publication bias, Trim and Fill corrections were applied to all relevant variables.14
Heterogeneity Assessment
The I 2 statistic was employed to evaluate heterogeneity,15 indicating the proportion of variability in observed effects due to true differences rather than sampling error. Statistical heterogeneity was classified based on I 2 values: 0% to 40% as unimportant, 30% to 60% as moderate, 50% to 90% as substantial, and 75% to 100% as considerable heterogeneity. Results with high heterogeneity (I 2 > 50%) were interpreted cautiously. An I 2 of zero signifies no observed heterogeneity. CIs (95%) were reported for each variable to assess heterogeneity.
Network Meta-Analysis
A network meta-analysis (NMA) was conducted to simultaneously compare the relative efficacy of multiple surgical and nonsurgical (NS) treatments regarding disease progression. LP was selected as the common reference node due to its high connectivity within the network. The treatment effect was measured using odds ratios (ORs) with 95% CIs. Because progression is an adverse event, an OR < 1.00 indicates a favorable outcome (lower odds of progression) compared with the reference treatment. A random-effects inverse-variance model was utilized for pooling the data. Studies reporting zero events in the reference arm (eg, Hirabayashi, 1981) were intentionally excluded from the final network model to prevent artificial variance inflation and skewing of estimates caused by standard continuity corrections. Statistical significance was defined as P < 0.05. All statistical analyses, including network estimations and ranking calculations, were performed using R statistical software (R Foundation for Statistical Computing, Vienna, Austria) utilizing the netmeta package.
Improving Language Quality
To ensure clarity, readability, and grammatical accuracy, the manuscript was reviewed using the automated grammar and style checker, Grammarly (Premium version, Grammarly Inc.). The software was employed to correct grammatical errors, improve sentence structure, and enhance the overall fluency of the text. All suggestions were manually reviewed by the authors to ensure that the original scientific meaning was preserved, and the final editorial decisions were made at the authors’ discretion.
Results
Study Selection
The process of searching and selecting literature is shown in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart (Figure 1). The initial search in PubMed, Scopus, Web of Science, and Embase resulted in 291 records. Citation searching added another 16 records. After removing 183 duplicates, 124 records remained for screening based on titles and abstracts, with 65 excluded. The full texts of the remaining 59 articles were obtained and evaluated for eligibility. After a detailed review, 33 articles were excluded due to reasons such as full-text duplication, being conference abstracts, or having data unsuitable for analysis. In the end, 26 studies met the criteria and were included in the systematic review and meta-analysis.2,16–39
Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 flow diagram illustrating the selection process for studies included in the systematic review.
Study Characteristics
This review included 26 mainly retrospective studies from 1971 to 2021, mostly from East Asia, especially Japan, with 1 from the USA. All studies were of high quality, scoring above 7, indicating low bias in patient selection, cohort comparability, and outcome assessment. It is important to note that the definition of what constituted OPLL progression was not uniform across all studies; various criteria were used, including specific thresholds for an increase in the length or thickness of the ossification, as detailed in the footnotes of Table 2.
Summary of the included studies reporting OPLL progression in the cervical spine.
Cumulatively, the included studies provided data on 1929 patients with cervical OPLL. The pooled mean age of the patient population was 59.3 years, and 1206 of the 1929 patients (62.5%) were men. A variety of management strategies were investigated across the included articles. The most frequently studied surgical intervention was LP, which was performed in 53.8% of the patients. Other common approaches included laminectomy with fusion (LF) (in 12.5%), anterior approaches (Ant; 5.55%), laminectomy without fusion (3.52%), and combined anterior-posterior approaches (0.62%). The follow-up periods varied considerably across the studies, ranging from approximately 24 months to 240 months.
Meta-Analysis of Risk Factors for OPLL Progression
The pooled analysis of risk factors for OPLL progression is summarized in Table 3. Regarding demographic and clinical factors: younger age (SMD: −0.68, P < 0.001) and higher BMI (SMD: 0.43, P < 0.001) were significantly correlated with an increased likelihood of progression. The male gender exhibited a trend toward a higher risk; however, this did not attain statistical significance (OR: 1.41, P = 0.057).
Summary of meta-analysis results investigating potential risk factors for the progression of OPLL.
Several radiographic features emerged as significant predictors. These included a lower preoperative cervical range of motion (ROM) (SMD: –0.30, P = 0.039), a longer preoperative OPLL (SMD: 0.42, P = 0.003), and OPLL at the C3 level (OR: 7.04, P < 0.001). The shape of the ossification was also a strong predictor. The mixed-type OPLL was linked to almost a 3-fold increase in the chance of progression (OR: 2.94, P < 0.001). In contrast, the segmental type significantly protected against progression (OR: 0.13, 95% CI [0.05, 0.36], P < 0.001).
Subgroup Analysis of OPLL Progression Risk Factors
To explore risk factors within specific populations, subgroup analyses were performed for asymptomatic patients and those who underwent LP (Table 4). In the asymptomatic cohort (which was mainly composed of natural history studies), younger age (SMD: –0.47, P = 0.001), mixed OPLL type (OR: 3.56, P < 0.001), and segmental OPLL type (OR: 0.14, P < 0.001) were significant risk factors for progression. The localized and continuous types were not significant factors. Among patients treated with LP, younger age (SMD: –0.73, P < 0.001) and greater preoperative OPLL length (SMD: 0.42, P = 0.003) were significant predictors of continued progression postsurgery. The segmental OPLL type was a very weak but significant protective factor in this group (OR: 0.02, P = 0.005).
Summary of the subgroup meta-analysis results for risk factors associated with the progression of OPLL in asymptomatic persons and laminoplasty patients.
Statistically significant differences in OPLL morphology distribution were observed between asymptomatic and LP cohorts. Segmental OPLL was significantly more prevalent among asymptomatic patients (P = 0.001), whereas mixed and localized types were significantly over-represented in LP cohorts (P = 0.014 and P = 0.013, respectively). No significant difference was observed for continuous OPLL (P = 0.24). These data demonstrate selective distribution for more extensive OPLL types in LP cohorts (mixed + continuous ≈ 70%), consistent with selection bias toward patients with multilevel or canal-occupying lesions.
NMA for the Impact of Surgical Approach on OPLL Progression
In the NMA, significant differences were observed among surgical and NS strategies for preventing OPLL progression. Using LP as the reference, anterior surgery was associated with a markedly lower risk of progression (OR = 0.28, 95% CI 0.15–0.52; P < 0.001), representing a 72% reduction in odds, and LF also demonstrated a significant protective effect (OR = 0.42, 95% CI 0.26–0.68; P < 0.001). NS management showed a significant trend toward reduced progression compared with LP (OR = 0.39, 95% CI 0.24–0.64; P < 0.001); however, the apparent protective effect of NS management is likely attributable to confounding by indication, whereby patients with less severe disease are preferentially managed conservatively. In contrast, laminectomy alone was associated with higher odds of progression, although this difference was not statistically significant (OR = 1.36, 95% CI 0.74–2.50; P = 0.32). SUCRA (Surface Under the Cumulative Ranking curve)-based ranking indicated that the anterior approach had the highest probability of being most effective (88%), followed by NS management (72%) and LF (65%). LP ranked lower (32%), while laminectomy alone had the lowest ranking (13%). The relatively high ranking of NS management likely reflects confounding by indication rather than a true treatment effect. This ranking indicates consistent superiority of anterior and fusion-based approaches in reducing OPLL progression.
Direct Comparison: LF vs LP
As previously mentioned, the rate of progression varies depending on different management protocols. However, subgroup analysis indicates that there are differences between the groups, though it does not specify the direction of these differences. Therefore, we conducted a direct, pairwise meta-analysis, which confirmed that LF is more effective than LP in preventing OPLL progression (Table 5). Patients in the LF group showed a significantly lower overall progression (SMD: –0.53, P = 0.024) and a slower rate of progression (SMD: –0.44, P = 0.007) compared with the LP group. As a result, the likelihood of any progression was significantly reduced with LF compared with LP (OR: 0.44, 95% CI [0.26, 0.75], P = 0.002).
Pairwise meta-analysis comparing LF vs LP for cervical OPLL progression outcomes.
Reoperation Rate Due to Neurological Worsening Caused by OPLL Progression
A key measure of long-term treatment success is the reoperation rate due to neurological deterioration from OPLL progression. Analyzing data from 6 studies with 441 patients, a meta-analysis (Figure 2) found a 6.1% reoperation rate (95% CI: 2.9%–10.2%) over a pooled follow-up duration of 72.6 ± 63.7 months. This means about 1 in 16 patients may need a second surgery due to OPLL growth. The analysis found moderate heterogeneity (I² = 54.4%, P = 0.052), indicating variable reoperation rates across studies, likely due to factors like follow-up duration, surgical techniques, baseline severity of OPLL, and clinical thresholds. Reoperation rates ranged from 1.3% to 14.3%, highlighting significant inter-study differences.
Forest plot of pooled reoperation rate due to symptomatic progression of cervical ossification of the posterior longitudinal ligament (OPLL). Forest plot illustrating the pooled proportion of reoperations performed due to neurological deterioration caused by progression of cervical OPLL. Each square represents the proportion reported by an individual study with its corresponding 95% confidence interval (CI), and the size of the square reflects the study weight in the random-effects model. The diamond represents the pooled estimate. Across 6 studies including 441 patients, the overall reoperation rate was 6.1% (95% CI: 2.9%–10.2%), with moderate heterogeneity among studies (I² = 54.4%, P = 0.052). The analysis summarizes the long-term risk of requiring revision surgery due to progressive OPLL.
Publication Bias and Sensitivity Analysis
Egger’s test evaluated publication bias. In the main risk factor analysis (Table 3), there was significant bias for segmental, localized, and continuous OPLL types (P < 0.05). A trim-and-fill correction was applied, which did not change the findings’ direction or significance. No other variables in the main or subgroup analyses showed significant publication bias.
To assess the robustness of our meta-analytic results, we performed a leave-one-out sensitivity analysis. This method involved sequentially removing each study and recalculating the combined effect size. The findings showed that removing any individual study did not substantially impact the overall estimates or alter the direction and significance of our main conclusions. This confirms the stability of our results.
Heterogeneity Assessment Results
Statistical heterogeneity across the included studies was quantified with the I² statistic. A significant degree of heterogeneity was identified among the different surgical approaches concerning OPLL progression rates (Q = 51.69, P < 0.001). Specifically, the LP cohort exhibited substantial heterogeneity (I² = 77.1%), and the LF group showed moderate heterogeneity (I² = 55.9%), while other approaches demonstrated low to no heterogeneity (Table 6). In the direct pairwise comparison between LF and LP, substantial heterogeneity was observed for progression speed (I² = 87.9%) and moderate heterogeneity for progression amount (I² = 62.3%), though it was low for the overall progression rate (I² = 6.1%; Table 5). The analysis of risk factors within subgroups also revealed notable variability; heterogeneity was substantial for several OPLL types within the LP patient group (I² ranging from 56.1% to 79.1%), which contrasted with the consistently low heterogeneity (I² < 29%) found for all risk factors in the asymptomatic patient subgroup (Table 4). Last, the pooled reoperation rate analysis demonstrated moderate heterogeneity across studies (I² = 54.4%). Given the moderate to substantial heterogeneity observed across several analyses, particularly within surgical subgroups, these findings should be interpreted with caution, and the pooled estimates should be considered as indicative trends rather than definitive effect sizes.
Network meta-analysis results comparing progression rate using LP as reference.
Discussion
Our review of 26 studies suggests several key findings: first, younger age and mixed-type OPLL are strong indicators of disease progression; second, motion-preserving surgeries like LP tend to have higher OPLL growth rates than fusion procedures; third, about 1 in 16 patients faces a long-term risk of reoperation due to OPLL progression.
Principal Risk Factors and Pathophysiological Insights
Our findings confirm that OPLL is a dynamic pathology influenced by various patient-specific factors. Younger age was consistently identified as a significant risk factor for progression (SMD: −0.68), a finding that holds true in both asymptomatic and postsurgical cohorts. This suggests that the biological mechanisms driving ossification are more active in younger individuals. This is further supported by the association with higher BMI (SMD: 0.43), which implicates systemic metabolic factors, such as chronic inflammation or metabolic syndrome, in creating a pro-osteogenic environment.8,38,40,41
Radiological morphology can help with risk stratification. Our analysis revealed that mixed-type OPLL confers a nearly 3-fold increased risk of progression (OR: 2.94), while segmental-type OPLL is strongly protective (OR: 0.13). This suggests that different OPLL morphologies may represent distinct pathobiological states. Segmental OPLL may reflect a more stable disease process, whereas the mixed type likely signifies a more aggressive, ongoing ossification.21,42 Also, our results indicated that the risk of OPLL progression increases with an increase in the length of preoperative OPLL (SMD: 0.42, P = 0.003). We can hypothesize that, as the segmental OPLL is confined to the vertebral body, it seems that dynamic cervical motion/microinstability has less effect on this type; however, the mixed type represents a more widespread abnormality, especially at disc levels, which may justify this increased risk of progression. As these morphologies are readily identifiable on preoperative imaging, they serve as a critical and practical tool for predicting the future behavior of the disease and guiding clinical management.
Role of Spinal Stability in Halting Progression
A central finding of this meta-analysis is the profound influence of surgical approach on postoperative OPLL growth. We observed a clear dichotomy: motion-preserving posterior surgeries are associated with high rates of progression, while motion-eliminating fusion procedures are protective. Our NMA demonstrates a clear hierarchy in treatment efficacy for preventing progression. Both the anterior approach and LF yielded a statistically significant reduction in progression compared with LP. Specifically, the anterior approach emerged as the most effective intervention in our network analysis, offering an 81% reduction in the odds of progression relative to LP. Conversely, laminectomy without fusion and NS management did not demonstrate a statistically significant difference from LP. These findings suggest that surgical approaches incorporating fusion or anterior decompression may offer superior long-term stabilization, thereby minimizing subsequent disease progression.
This conclusion is strongly reinforced by our direct pairwise meta-analysis, which showed that LF leads to a significantly smaller amount of total ossification growth and a slower progression speed compared with LP. Crucially, the odds of any progression occurring were more than halved after LF compared with LP (OR: 0.44). Taken together, these findings suggest a potential association between motion restriction and reduced OPLL progression; however, this interpretation should be made cautiously given the heterogeneity and potential confounding across studies. By achieving arthrodesis, fusion surgeries might lead to the arrest or stabilization of the pathological ossification process. Also, there are reports of OPLL resorption after successful cervical fusion.3,43
Our findings show that cervical ROM is notably lower in patients experiencing OPLL progression (SMD: −0.3, P = 0.39). This likely occurs because patients with OPLL inherently have microinstability and attempt to stabilize it through OPLL and decreased ROM. Consequently, segments with continuous ossification exhibit significantly reduced ROM compared with those without progression, suggesting that diminished ROM often indicates more advanced ossification.
In a study of patients with trauma treated with anterior cervical discectomy and fusion, reduced cervical lordosis and increased cervical sagittal vertical axis have been shown to increase OPLL progression. This study shows the impact of inappropriate force distribution on OPLL progression. However, due to the paucity of radiographic measurements in the included literature, we could not address the impact of alignment on OPLL progression. Future original studies in this topic should focus on reporting cervical alignment measures.5
Clinical Implications and Future Directions
Our pooled reoperation rate of 6.1% provides an acceptable metric for managing patient expectations. This quantifiable risk of requiring a second surgery due to symptomatic progression must be a key component of the shared decision-making process. It also underscores the necessity of continued long-term surveillance following the index procedure, particularly for patients with high-risk features or those who have undergone nonfusion surgery.
For a young, high-risk patient with a mixed-type OPLL, a nonfusion procedure like LP may provide adequate initial decompression but carries a high probability of future disease progression and potential neurological recurrence. Our data strongly suggest that a fusion-based procedure (anterior or posterior) should be the preferred intervention in such high-risk individuals to confer long-term stability and mitigate the risk of progression.
Limitations and Future Directions
This review’s main limitation is the heterogeneity seen in several key analyses, especially regarding progression rates after LP (I² = 77.1%). This variability is mainly due to the differing definitions of OPLL progression across the included studies, as shown in Table 2, as well as variations in surgical techniques and follow-up periods. Although a random-effects model was applied and sensitivity analyses demonstrated stable results, residual heterogeneity may limit the precision of pooled estimates. Therefore, the findings of this meta-analysis should be interpreted as reflecting general trends rather than definitive comparative effectiveness between treatment strategies. Additionally, the generalizability of our findings may be limited because most studies were conducted in East Asian populations, where OPLL epidemiology differs from that of other ethnic groups; however, it was not possible to perform subgroup analysis based on ethnicity. The predominance of retrospective studies further raises the possibility of bias. To advance the field, a standardized, quantitative definition of OPLL progression is urgently needed. Our findings in the NMA must be interpreted in the context of several limitations. Most importantly, inherent confounding factors within the included primary studies, such as variations in baseline disease severity, patient demographics, or OPLL type, may impact the validity of the NMA results. Because pooling data across heterogeneous studies can introduce selection bias, the apparent superiority of treatments like the anterior approach or LF should be interpreted with caution. Future research should focus on prospective controlled trials comparing modern fusion techniques with LP in high-risk patients to validate these findings and provide clearer surgical guidance.
Conclusion
This meta-analysis suggests that the progression of cervical OPLL follows identifiable patterns. Our results showed that specific risk factors significantly forecast progression, with younger age (SMD: −0.68) and mixed-type morphology (OR: 2.94) being potent predictors, while a segmental pattern is strongly protective (OR: 0.13). Our results also suggested that the choice of surgical intervention might be a critical determinant of the long-term radiographic outcome. Motion-preserving surgeries such as LP result in a higher rate of postoperative progression than the rate seen after fusion-based procedures such as LF or anterior approaches. This finding is further evidenced by direct comparisons showing that LF reduces the odds of progression by 56% relative to LP (OR: 0.44). With a pooled reoperation rate of 6.1% due to symptomatic progression of OPLL, this evidence provides a framework for clinicians to risk-stratify patients and guide surgical decision-making toward a more tailored management strategy.
Footnotes
Funding The authors received no financial support for the research, authorship, and/or publication of this article.
Declaration of Conflicting Interests The authors report no conflicts of interest in this work.
Ethics Approval The protocol for this systematic review was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO). The registration number is CRD420261323961.
- This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2026 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.
References
- 1.↵Head J , Rymarczuk G , Stricsek G , et al . Ossification of the posterior longitudinal ligament: surgical approaches and associated complications. Neurospine. 2019;16(3):517–529. 10.14245/ns.1938222.111
- 2.↵Katsumi K , Watanabe K , Izumi T , et al . Natural history of the ossification of cervical posterior longitudinal ligament: a three dimensional analysis. Int Orthop. 2018;42(4):835–842. 10.1007/s00264-017-3667-z
- 3.↵Matsunaga S , Sakou T . Ossification of the posterior longitudinal ligament of the cervical spine: etiology and natural history. Spine (Phila Pa 1976). 2012;37(5):E309–E314. 10.1097/BRS.0b013e318241ad33
- 4.↵Katsumi K , Hirai T , Yoshii T , et al . The impact of ossification spread on cervical spine function in patients with ossification of the posterior longitudinal ligament. Sci Rep. 2021;11(1):14337. 10.1038/s41598-021-93602-0
- 5.↵Koo J , Hwang S , Yoon SH , Shin HJ , Cho BK . Progression of ossification of posterior longitudinal ligament after anterior cervical discectomy and fusion in military patients exposed to minor trauma. Korean J Neurotrauma. 2022;18(2):254–267. 10.13004/kjnt.2022.18.e55
- 6.↵Vaziri S , Lockney DT , Dru AB , Polifka AJ , Fox WC , Hoh DJ . Does ossification of the posterior longitudinal ligament progress after fusion? Neurospine. 2019;16(3):483–491. 10.14245/ns.1938286.143
- 7.↵Furukawa K-I . Current topics in pharmacological research on bone metabolism: molecular basis of ectopic bone formation induced by mechanical stress. J Pharmacol Sci. 2006;100(3):201–204. 10.1254/jphs.fmj05004x4
- 8.↵Sugita D , Yayama T , Uchida K , et al . Indian hedgehog signaling promotes chondrocyte differentiation in enchondral ossification in human cervical ossification of the posterior longitudinal ligament. Spine (Phila Pa 1976). 2013;38(22):E1388–E1396. 10.1097/BRS.0b013e3182a40489
- 9.
- 10.↵Kohl C , McIntosh EJ , Unger S , et al . Online tools supporting the conduct and reporting of systematic reviews and systematic maps: a case study on CADIMA and review of existing tools. Environ Evid. 2018;7(1):8. 10.1186/s13750-018-0115-5
- 11.↵Stang A . Critical evaluation of the newcastle-ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25(9):603–605. 10.1007/s10654-010-9491-z
- 12.↵Fekete JT , Győrffy B . MetaAnalysisOnline.com: web-based tool for the rapid meta-analysis of clinical and epidemiological studies. J Med Internet Res. 2025;27:e64016. 10.2196/64016
- 13.↵Sterne JA , Egger M . Funnel plots for detecting bias in meta-analysis: guidelines on choice of axis. J Clin Epidemiol. 2001;54(10):1046–1055. 10.1016/s0895-4356(01)00377-8
- 14.↵Shi L , Lin L . The trim-and-fill method for publication bias: practical guidelines and recommendations based on a large database of meta-analyses. Medicine (Baltimore). 2019;98(23):e15987. 10.1097/MD.0000000000015987
- 15.↵Hemming K , Hughes JP , McKenzie JE , Forbes AB . Extending the i-squared statistic to describe treatment effect heterogeneity in cluster, multi-centre randomized trials and individual patient data meta-analysis. Stat Methods Med Res. 2021;30(2):376–395. 10.1177/0962280220948550
- 16.↵Hori T , Kawaguchi Y , Kimura T . How does the ossification area of the posterior longitudinal ligament progress after cervical laminoplasty? Spine (Phila Pa 1976). 2006;31(24):2807–2812. 10.1097/01.brs.0000245870.97231.65
- 17.↵Kawaguchi Y , Nakano M , Yasuda T , et al . Clinical impact of ossification of the posterior longitudinal ligament progression after cervical laminoplasty. Clin Spine Surg. 2019;32(3):E133–E139. 10.1097/BSD.0000000000000747
- 18.↵Lee D-H , Cho JH , Kim N-H , et al . Radiological risk factors for progression of ossification of posterior longitudinal ligament following laminoplasty. Spine J. 2018;18(7):1116–1121. 10.1016/j.spinee.2017.10.069
- 19.↵Kang MS , Kim KH , Park JY , et al . Progression of cervical ossification of posterior longitudinal ligament after laminoplasty or laminectomy with posterior fixation. Clin Spine Surg. 2019;32(9):363–368. 10.1097/BSD.0000000000000898
- 20.↵Lv C , Li J , Guo J , et al . Risk factor analysis and risk prediction model construction of ossification progression after postoperative cervical ossification of posterior longitudinal ligament. Spine. 2025;50(15):1025–1034. 10.1097/BRS.0000000000005286
- 21.↵Hisada Y , Endo T , Koike Y , et al . Distinct progression pattern of ossification of the posterior longitudinal ligament of the thoracic spine versus the cervical spine: a longitudinal whole-spine CT study. J Neurosurg Spine. 2022;37(2):175–182. 10.3171/2022.1.SPINE211010
- 22.↵Doi T , Sakamoto R , Horii C , et al . Risk factors for progression of ossification of the posterior longitudinal ligament in asymptomatic subjects. J Neurosurg Spine. 2020;33(3):316–322. 10.3171/2020.3.SPINE2082
- 23.↵Katsumi K , Watanabe K , Yamazaki A , et al . Predictive biomarkers of ossification progression and bone metabolism dynamics in patients with cervical ossification of the posterior longitudinal ligament. Eur Spine J. 2023;32(4):1282–1290. 10.1007/s00586-023-07565-z
- 24.↵Ruomu Q , Siyuan Q , Ben W , et al . Risk of ossification of posterior longitudinal ligament (OPLL) volume progression following laminoplasty. Spine J. 2025;25(12):2648–2655. 10.1016/j.spinee.2025.05.028
- 25.↵Shi H , Chen L , Zhu L , Jiang ZL , Wu XT . Instrumented fusion versus instrumented non-fusion following expansive open-door laminoplasty for multilevel cervical ossification of the posterior longitudinal ligament. Arch Orthop Trauma Surg. 2023;143(6):2919–2927. 10.1007/s00402-022-04498-y
- 26.↵Choi BW , Baek DH , Sheffler LC , Chang H . Analysis of progression of cervical OPLL using computerized tomography: typical sign of maturation of OPLL mass. J Neurosurg Spine Nov. 2015;23(5):539–543. 10.3171/2015.1.Spine131167
- 27.↵Matsuoka T , Yamaura I , Kurosa Y , Nakai O , Shindo S , Shinomiya K . Long-term results of the anterior floating method for cervical myelopathy caused by ossification of the posterior longitudinal ligament. Spine. 2001;26(3):241–248. 10.1097/00007632-200102010-00008
- 28.↵Takatsu T , Ishida Y , Suzuki K , Inoue H . Radiological study of cervical ossification of the posterior longitudinal ligament. J Spinal Disord. 1999;10(3):271. 10.1097/00002517-199906000-00019
- 29.↵Hirabayashi K , Miyakawa J , Satomi K , Maruyama T , Wakano K . Operative results and postoperative progression of ossification among patients with ossification of cervical posterior longitudinal ligament. Spine (Phila Pa 1976). 1981;6(4):354–364. 10.1097/00007632-198107000-00005
- 30.↵Kawaguchi Y , Kanamori M , Ishihara H , et al . Progression of ossification of the posterior longitudinal ligament following en bloc cervical laminoplasty. J Bone Joint Surg Am Dec. 2001;83(12):1798–1802. 10.2106/00004623-200112000-00005
- 31.↵Sakai K , Okawa A , Takahashi M , et al . Five-year follow-up evaluation of surgical treatment for cervical myelopathy caused by ossification of the posterior longitudinal ligament: a prospective comparative study of anterior decompression and fusion with floating method versus laminoplasty. Spine (Phila Pa 1976). 2012;37(5):367–376. 10.1097/BRS.0b013e31821f4a51
- 32.↵Lee CH , Jahng TA , Hyun SJ , Kim KJ , Kim HJ . Expansive laminoplasty versus laminectomy alone versus laminectomy and fusion for cervical ossification of the posterior longitudinal ligament: is there a difference in the clinical outcome and sagittal alignment? Clin Spine Surg. 2016;29(1):E9–E15. 10.1097/BSD.0000000000000058
- 33.↵Ota M , Furuya T , Maki S , et al . Addition of instrumented fusion after posterior decompression surgery suppresses thickening of ossification of the posterior longitudinal ligament of the cervical spine. Journal of Clinical Neuroscience. 2016;34:162–165. 10.1016/j.jocn.2016.06.013
- 34.↵Lee JJ , Shin DA , Yi S , et al . Effect of posterior instrumented fusion on three-dimensional volumetric growth of cervical ossification of the posterior longitudinal ligament: a multiple regression analysis. Spine J. 2018;18(10):1779–1786. 10.1016/j.spinee.2018.03.002
- 35.↵Sakaura H , Hosono N , Mukai Y , Iwasaki M , Yoshikawa H . Medium-term outcomes of C3–6 laminoplasty for cervical myelopathy: a prospective study with a minimum 5-year follow-up. Eur Spine J. 2011;20(6):928–933. 10.1007/s00586-011-1690-0
- 36.↵Katsumi K , Izumi T , Ito T , Hirano T , Watanabe K , Ohashi M . Posterior instrumented fusion suppresses the progression of ossification of the posterior longitudinal ligament: a comparison of laminoplasty with and without instrumented fusion by three-dimensional analysis. Eur Spine J. 2016;25(5):1634–1640. 10.1007/s00586-015-4328-9
- 37.↵Iwasaki M , Kawaguchi Y , Kimura T , Yonenobu K . Long-term results of expansive laminoplasty for ossification of the posterior longitudinal ligament of the cervical spine: more than 10 years follow up. J Neurosurg. 2002;96(2 Suppl):180–189.
- 38.↵Ogawa Y , Toyama Y , Chiba K , et al . Long-term results of expansive open-door laminoplasty for ossification of the posterior longitudinal ligament of the cervical spine. J Neurosurg Spine. 2004;1(2):168–174. 10.3171/spi.2004.1.2.0168
- 39.↵Chiba K , Yamamoto I , Hirabayashi H , et al . Multicenter study investigating the postoperative progression of ossification of the posterior longitudinal ligament in the cervical spine: a new computer-assisted measurement. J Neurosurg Spine. 2005;3(1):17–23. 10.3171/spi.2005.3.1.0017
- 40.↵Wu H , Ye C , Wang L , et al . Inflammation in ossification of the posterior longitudinal ligament of the cervical spine: monocytes and proinflammatory cytokines increased significantly. Clin Spine Surg. 2025;doi. 10.1097/BSD.0000000000001929
- 41.↵Tung NTC , He Z , Makino H , et al . Association of inflammation, ectopic bone formation, and sacroiliac joint variation in ossification of the posterior longitudinal ligament. J Clin Med. 2023;12(1):349. 10.3390/jcm12010349
- 42.↵Qin S , Qu R , Liu K , et al . Predicting postoperative progression of ossification of the posterior longitudinal ligament in the cervical spine using interpretable radiomics models. Neurospine. 2025;22(1):144–156. 10.14245/ns.2448846.423
- 43.↵Mehdi SK , Alentado VJ , Lee BS , Mroz TE , Benzel EC , Steinmetz MP . Comparison of clinical outcomes in decompression and fusion versus decompression only in patients with ossification of the posterior longitudinal ligament: a meta-analysis. Neurosurg Focus. 2016;40(6):E9. 10.3171/2016.3.FOCUS1630
