Potential Link between Ossification of Nuchal Ligament and the Risk of Cervical Ossification of Posterior Longitudinal Ligament: Evidence and Clinical Implication from a Meta-Analysis of 8429 Participants

Abstract

Objective: The aim of the present paper was to evaluate the strength and the magnitude of the association between ossification of the nuchal ligament (ONL) and the risk of cervical ossification of the posterior longitudinal ligament (COPLL) and to determine whether there is a direct association or whether COPLL is a consequence of shared risk factors.

Methods: Medline, Web of Science, Cochrane Library, and Embase databases were searched for studies evaluating the association of COPLL-ONL published before July 2020. Eligible studies were selected based on certain inclusion and exclusion criteria. Two investigators independently conducted the quality assessment and extracted the data, including study designs, countries, patients' age, gender, body mass index (BMI), and the risk of COPLL between individuals with and without ONL. A meta-analysis of homogenous data, a sensitivity analysis, a publication bias assessment, and a subgroup analysis were performed using Stata 12.0 software.

Results: A total of 10 cohort studies involving 8429 participants were incorporated into this analysis. Pooled results demonstrated a statistically significant association between the presence of ONL and the increased COPLL risk (odds ratio [OR] 3.84; 95% confidence interval [CI] 2.68-5.52, P < 0.001). Furthermore, subgroup analyses indicated that this association was independent of study design (6.36-fold in case-control studies vs 3.22-fold in cross-sectional studies), sex (6.33-fold in male-female ratio >2.5 vs 2.91-fold in male-female ratio <2.5), age (4.28-fold in age ≥55 years vs 3.45-fold in age <55 years), and BMI (3.88-fold in BMI ≥ 25 kg/m² vs 2.43-fold in BMI < 25 kg/m² ), which also indicated that obese, older male patients with ONL had a higher risk of OPLL. Moreover, combined two articles revealed that patients with larger-type ONL had a significantly higher risk of long-segment COPLL compared with controls (OR 1.86; 95% CI 1.41-2.47, P < 0.001).

Conclusion: This is the first meta-analysis to demonstrate a strong and steady association between ONL and higher risk of COPLL. This association was independent of sex, age, and BMI. Considering that ONL is generally asymptomatic and easily detectable on X-ray, our findings implied that ONL might serve as an early warning sign of the onset of COPLL and provide clinicians an opportunity for early detection and early intervention.

Keywords: Cervical; Meta-analysis; Ossification of the nuchal ligament; Ossification of the posterior longitudinal ligament; Risk.

Fig. 1

Classification of ossification of the nuchal ligament in cervical lateral radiographic images. (A) Round type. (B) Rod type. (C) Segmented type.

Fig. 2

Flow diagram of the study identification and selection process. ONL, ossification of the nuchal ligament.

Fig. 3

Funnel plot for testing the publication bias of the association between ossification of the nuchal ligament and the risk of cervical ossification of the posterior longitudinal ligament. Each point represents an individual study on the indicated association. The vertical line indicates the effect size. CI, confidence interval.

Fig. 4

Forest plot of included studies estimating the risk of cervical ossification of the posterior longitudinal ligament and ossification of the nuchal ligament. The diamond represents the pooled odds ratio (OR) and 95% confidence interval (CI).

Fig. 5

Sensitivity analysis through excluding 1 study at a time. The middle line represents the pooled effect value. The bilateral lines represent the 95% confidence interval (CI).

Fig. 6

Forest plot of remaining studies estimating the risk of cervical ossification of the posterior longitudinal ligament and ossification of the nuchal ligament after a sensitivity analysis. The diamond represents the pooled odds ratio (OR) and 95% confidence interval (CI).

Fig. 7

Forest plot of 2 studies estimating the types of ossification of the nuchal ligament and the length of cervical ossification of the posterior longitudinal ligament. The diamond represents the pooled odds ratio (OR) and 95% confidence interval (CI).

Fig. 8

Subgroup analysis on the association between risk of cervical ossification of the posterior longitudinal ligament and ossification of the nuchal ligament according to study design. CI, confidence interval; OR, odds ratio.

Fig. 9

Subgroup analysis on the association between risk of cervical ossification of the posterior longitudinal ligament and ossification of the nuchal ligament according to male–female ratio. CI, confidence interval; OR, odds ratio.

Fig. 10

Subgroup analysis on the association between risk of cervical ossification of the posterior longitudinal ligament and ossification of the nuchal ligament according to age. CI, confidence interval; OR, odds ratio.

Fig. 11

Subgroup analysis on the association between risk of cervical ossification of the posterior longitudinal ligament and ossification of the nuchal ligament according to body mass index.

Fig. 12

A schematic illustrative diagram showing the relationship of ossification of the nuchal ligament (ONL) and cervical ossification of the posterior longitudinal ligament (OPLL) and related risk factors.