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

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/m(2) vs 2.43‐fold in BMI < 25 kg/m(2)), 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.