Gender-specific patterns of external occipital protuberance hyperplasia: associations with nuchal ligament ossification and cervical sagittal imbalance in myelopathy patients
Article information
Abstract
Study Design
Retrospective cross-sectional analysis of 187 consecutive patients undergoing surgical treatment for cervical spondylotic myelopathy (CSM).
Purpose
To investigate sexual dimorphism in external occipital protuberance (EOP) hyperplasia morphology and elucidate its clinical correlation with ossification of the nuchal ligament (ONL) and cervical sagittal imbalance.
Overview of Literature
Emerging evidence implicates EOP hyperplasia as potential biomarker of chronic neck strain, yet its relationship with ONL and cervical sagittal imbalance remains underexplored in surgical CSM cohorts.
Methods
Cervical radiographs were analyzed. EOP hyperplasia was classified into three subtypes with standardized length measurements. Variables encompassed demographics, ONL-related indices, and sagittal parameters. Subtype comparisons and multivariate regression analyses (with EOP length as dependent variable) were conducted.
Results
Analysis of 187 CSM patients (64.2% male) identified gender-specific patterns: males exhibited greater EOP length (9.4±6.8 mm vs. 4.6±3.4 mm, p<0.001). Type III EOP demonstrated male predominance (82.4% vs. type I 31.8%, type II 51.4%; p<0.001), with associated longer hyperplasia length (11.6±6.6 mm vs. type II 5.1±1.9 mm, p<0.001). Type III EOP was associated with higher ONL prevalence (type III 64.8% vs. type I 45.5%, type II 41.9%; p=0.010) and longer ONL osteophyte length (type III 18.8±9.8 mm vs. type I 14.2±8.1 mm, type II 14.2±9.4 mm; p=0.046). Multivariate regression confirmed male sex (β=−3.82, p=0.009), ONL osteophyte length (β=0.16, p=0.017), T1 slope (β=0.27, p=0.041), and spino-cranial angle (β=−0.19, p=0.009) as factors independently associated with EOP length (adjusted R2=0.382).
Conclusions
Severe EOP hyperplasia exhibits a male-predominant distribution pattern and demonstrates significant radiological associations with ONL and cervical sagittal imbalance in CSM patients. These findings advocate for EOP evaluation in clinical evaluations to identify high-risk biomechanical profiles.
Introduction
The external occipital protuberance (EOP) is a bony prominence located on the posterior aspect of the occipital bone, serving as the attachment site for the nuchal ligament and trapezius muscle. Recent radiological studies classify EOP into three morphological types based on X-ray and computed tomography (CT) measurements: type I (flat type), type II (crest type), and type III (spine type) [1,2]. Type III, also known as the occipital spur, has been anthropologically linked to Neanderthals and is noted for its higher prevalence in males, making it a reference for gender identification in forensic medicine [2–4]. Biomechanical evidence suggests that chronic tensile forces from the nuchal ligament induce reactive osteogenesis at the EOP attachment site, a process analogous to enthesophyte formation in diffuse idiopathic skeletal hyperostosis [5]. Recent attention has turned to the potential pathological significance of EOP hyperplasia. Marshall et al. [6] reported cases of recurrent occipital-neck pain attributed to occipital spurs, alleviated effectively by surgical removal. Shahar and Sayers [7] conducted a survey revealing a 41% prevalence of EOP hyperplasia among young adults aged 18–30, suggesting a possible association with excessive smartphone use. However, conflicting evidence persists regarding smartphone-related biomechanical loading, with longitudinal studies showing no direct correlation between usage duration and EOP hyperplasia severity [8,9].
The nuchal ligament is a triangular, plate-like elastic membrane that extends from the tip of the cervical spinous process posteriorly. It attaches upward to the EOP, descends to the spinous process of the seventh cervical vertebra, and continues to the supraspinous ligament. This ligament physiologically restricts forward flexion of the cervical spine [10,11]. Ossification of the nuchal ligament (ONL) is commonly incidentally found on cervical spine radiographs and is more prevalent in Asian populations compared to Western populations [12–15]. Recent dynamic radiographs with flexion-extension protocols have demonstrated that ONL progression correlates with segmental instability [16]. Although typically asymptomatic, ONL is significantly associated with other spinal ossification disorders such as ossification of the posterior longitudinal ligament and ossification of the ligamentum flavum [17,18]. It serves as a predictor for cervical spine degenerative diseases [13,19].
Two critical gaps hinder clinical translation: First, the biomechanical interplay between EOP hyperplasia and ONL remains unexamined, particularly in surgical cohorts with cervical spondylotic myelopathy (CSM); Second, quantitative evidence is lacking to clarify how EOP features correlate with cervical sagittal balance parameters.
We hypothesize that EOP hyperplasia may exhibit significant associations with ONL and cervical sagittal alignment imbalance. This study investigates 187 cervical CSM patients to comprehensively analyze EOP morphology and length, ONL characteristics, and cervical sagittal alignment parameters. Our findings aim to establish EOP evaluation as a novel diagnostic tool for identifying high-risk biomechanical profiles in cervical spine.
Materials and Methods
Subject population
The study received approval from the Ethics Committee of Huashan Hospital, Fudan University under approval number KY2022-683, with informed consent obtained from all participants. We consecutively enrolled patients who underwent anterior or posterior cervical decompression and fusion for CSM between March and September 2023. Inclusion criteria required at least two myelopathic signs (e.g., hand clumsiness, gait disturbance, hyperreflexia) combined with magnetic resonance imaging (MRI)-confirmed spinal cord compression at one or more C3–C7 levels. Exclusion criteria encompassed traumatic or pathologic conditions (tumors, infections, deformities, prior cervical surgery), systemic diseases (rheumatoid arthritis, cerebral palsy), or concurrent thoracolumbar pathology. From an initial screening of 230 patients, 43 were excluded due to trauma history (n=9), prior spinal surgery (n=12), systemic diseases (n=5), or incomplete imaging (n=17), resulting in a final cohort of 187 patients.
Data collection
Demographic and clinical data were extracted from the hospital’s electronic medical records, including age, gender, symptom duration, and lesion characteristics. Cervical spine lesions were analyzed from C2 to C7, with disc degeneration defined as Pfirrmann grade III or higher on T2-weighted mid-sagittal MRI sequences, and spinal canal stenosis determined by a Pavlov ratio <0.8 on lateral radiographs [20]. Surgical details (anterior vs. posterior approach, instrumented levels) were recorded from operative reports.
Radiographic evaluation
Standardized lateral cervical radiographs were acquired using a Philips DigitalDiagnost C50 system (Philips, Amsterdam, Netherlands) with patients in a neutral standing position and the Frankfort plane parallel to the floor. All measurements were performed using INFINITT PACS ver. 5.0 software (INFINITT Healthcare, South Korea). The radiographic evaluation protocol included three key components as follows: (1) EOP: EOP morphology was classified into three types based on lateral X-ray measurements (Fig. 1): type I: flat type (Fig. 1A); type II: crest type (Fig. 1B); and type III: spine type (Fig. 1C). Measurements were performed at 200% magnification to minimize interobserver error. (2) ONL: ONL was assessed using the classification proposed by Wang et al. [21], which categorizes ossification into four types based on lateral radiograph morphology. On lateral cervical radiographs, the extent of cervical levels involved by ONL and the maximum osteophyte length were measured. (3) Cervical sagittal alignment parameters: Assessment involved categorizing cervical sagittal alignment based on the method proposed by Donk et al. [22]. Sagittal alignment was quantified using six parameters defined in Table 1: T1 slope (TS), spino-cranial angle (SCA), C0–C2 Cobb angle, cervical lordosis (CL), C2–C7 sagittal vertical axis (SVA), and forward head posture (FHP).
Representative images and external occipital protuberance (EOP) length measurement methods for three types of EOP. (A) Type I: flat type. (B) Type II: crest type. (C) Type III: spine type. Measurement method for type II: distance between the midpoint of crest-type hyperplasia and the furthest starting point of hyperplasia. measurement method for type III: distance between the tip of spine-type hyperplasia and the furthest starting point of hyperplasia. The yellow lines indicate the measurement methods for hyperplasia length.
Measurement methods for cervical sagittal parameters
All assessment data were evaluated twice, 4 weeks apart, by two experienced spinal surgeons. The inter-rater reliability between two senior spine surgeons was excellent for all parameters (intraclass correlation coefficient: 0.85–0.94).
Statistical analysis
All statistical analyses were performed using IBM SPSS ver. 20.0 (IBM Corp., Armonk, NY, USA). Categorical variables—including gender distribution, diagnosis subtypes, cervical sagittal alignment categories (lordotic/straight/kyphotic), EOP types (I–III), and ONL classifications—were compared using Pearson’s chi-square or Fisher’s exact tests as appropriate. Continuous variables—such as age, symptom duration, EOP hyperplasia length (mm), ONL osteophyte length (mm), and cervical sagittal parameters—demonstrated normality as confirmed by Shapiro-Wilk tests (all p>0.05), intergroup comparisons between two cohorts were analyzed using independent two-sample t-tests. For three-group comparisons, one-way analysis of variance was employed to assess between-group differences, followed by Bonferroni-adjusted post hoc comparisons to control for multiple testing. For ordinal/non-normally distributed data—specifically the number of pathology-affected segments, surgically intervened levels and ONL-involved vertebral levels—Mann-Whitney U tests were applied. To identify factors independently associated with EOP length, a multiple linear regression model was constructed with EOP length as the dependent variable. Independent variables included: demographics: age, gender (coded as 1=male, 2=female); ONL characteristics: osteophyte length; sagittal parameters: C0–C2 Cobb angle, CL, TS, SCA, CGH–C7 SVA, C2–C7 SVA, and FHP. Statistical significance threshold was set at α=0.05 (two-tailed).
Results
Patient demographics and clinical characteristics
The cohort comprised 187 surgically treated CSM patients (120 males, 64.2%; 67 females, 35.8%) with comparable age between genders (males: 56.7±10.8 years vs. female: 55.9±11.3 years, p=0.491). Key gender disparities emerged in symptom duration (males: 15.8±22.4 months vs. females: 25.3±32.7 months, p=0.002) and EOP hyperplasia length (males: 9.4±6.8 mm vs. females: 4.6±3.4 mm, p<0.001).
Anterior cervical discectomy and fusion (ACDF) was the predominant surgical approach (149 cases, 79.7%), with posterior laminoplasty performed in 38 patients (20.3%), showing equivalent gender distribution (p=0.614). The median number of pathologically involved segments was 4 (interquartile range [IQR], 1), while surgically intervened levels averaged 2 segments (IQR, 1), with no gender-based differences in segmental distribution patterns (pathology: p=0.561; surgery: p=0.662) (Table 2).
Demographic and clinical characteristics by gender
EOP morphology subgroup analysis
Stratification by EOP morphology revealed pronounced sexual dimorphism. Type III EOP demonstrated male predominance (82.4% vs. type I: 31.8%, p<0.001; vs. type II: 51.4%, p<0.001), whereas type I was predominantly female (68.2%). Age and EOP length differed significantly: type III patients were older than type II (58.3±10.8 years vs. 54.2±11.2 years, p=0.016) with greater EOP length (11.6±6.6 mm vs. 5.1±1.9 mm, p<0.001) (Table 3).
Comparative analysis of ONL by EOP morphological types
ONL profile
EOP morphology significantly correlated with ONL. The prevalence of ONL escalated with EOP severity: 45.5% (type I), 41.9% (type II), and 64.8% (type III), with type III demonstrating significantly higher rates than both type I (p=0.043) and type II (p=0.005). No significant differences were observed in the distribution of ONL morphology among the three EOP-type patient groups (p=0.099). However, type III EOP exhibited ONL osteophytes with both a greater number of involved segments and longer osteophyte length: three segments (IQR, 1) in type III vs. two segments (IQR, 1) in type II (p=0.046); 18.8±9.8 mm (type III) vs. 14.2±8.1 mm (type I, p=0.047) and 14.2±9.4 mm (type II, p=0.033) (Table 3).
Cervical sagittal alignment profiles
EOP morphology showed no significant association with cervical sagittal alignment profiles (Table 4). The distribution of cervical curvature types (lordotic/straight/kyphotic) remained comparable across EOP subtypes (p=0.420). Similarly, quantitative analyses revealed no intergroup differences in C0–C2 Cobb angle (p=0.642), SCA (p=0.431), TS (p=0.965), CL (p=0.557), CGH–C7 SVA (p=0.821), C2–C7 SVA (p=0.356), and FHP (p=0.537).
Comparison of cervical sagittal alignment in patients with different EOP types
Factors associated with EOP hyperplasia length: multivariate linear regression analysis
The multivariable model integrating demographic characteristics, ONL profiles, and sagittal alignment parameters explained 38.2% of the variance in EOP hyperplasia length (adjusted R2=0.382, p=0.028). Significant associations were observed as follows: male sex demonstrated 3.8 mm greater hyperplasia compared to females (β, −3.82; 95% CI, −6.672 to −0.975; p=0.009); ONL osteophyte length showed a positive graded relationship (0.16 mm increase in EOP per 1 mm ONL elongation; 95% CI, 0.029–0.283; p=0.017); T1 slope was positively correlated with EOP hyperplasia length (0.27 mm per degree increase; 95% CI, 0.011–0.533; p=0.041); SCA exhibited an inverse association with EOP hyperplasia length (−0.19 mm per degree decrease; 95% CI, −0.333 to −0.050; p=0.009) (Table 5).
Multivariate linear regression analysis with EOP length as the dependent variable
Discussion
While traditionally regarded as an anatomical landmark, contemporary evidence positions the EOP as a potential biomarker for cervical degeneration. Marshall et al. [6] first clinically correlated occipital spurs with refractory occipital neuralgia in 2015, sparking debate about its pathological significance. The smartphone-era hypothesis by Shahar and Sayers [7] and Shahar et al. [23] proposing FHP-induced enthesopathy contrasts sharply with transnational cohort studies demonstrating stable EOP prevalence across generations [8,9]. This dichotomy suggests EOP hyperplasia may have latent pathological potential. As the nuchal ligament’s cranial anchor, the EOP-nuchal ligament biomechanical continuum theoretically links EOP hyperplasia to cervical degeneration [10,24].
Sex/age associations and morphological discrepancies
The findings of this study demonstrate strong concordance with previously documented sexual dimorphism in the developmental characteristics of the EOP [2–4,25]. The observed male predominance (82.4%) and greater EOP length (11.6±6.6 mm) in type III EOP cases corroborate forensic anthropological evidence indicating that EOP morphology achieves 79% accuracy in sex determination [3]. Notably, the detection rate of type III EOP in our cohort reached 48.7%, significantly exceeding the 6.5% reported in the cadaveric study by Singal et al. [2]. This discrepancy primarily stems from three methodological considerations: (1) The study population comprised exclusively surgical candidates with CSM, exhibiting a higher mean age (56.4 years) than baseline values in prior EOP investigations; (2) Gender distribution skewed toward males (64.2%), consistent with CSM epidemiological patterns [26]; (3) The elevated detection rate of type III EOP and its pronounced hyperplasia magnitude in our cohort suggest a potential correlation between EOP proliferation and the severity of cervical degenerative changes.
EOP hyperplasia-ONL spectrum
Our findings establish a biomechanical continuum between EOP morphology and nuchal ligament pathology, evidenced by two distinct patterns: type III EOP demonstrated a nearly 1.5-fold higher ONL co-prevalence compared to types I/II, aligning with cadaveric studies documenting shared entheseal microtrauma [5,10]; longer ONL osteophytes correlate with EOP hyperplasia magnitude (0.16 mm increase in EOP per 1 mm ONL osteophyte elongation). Experimental evidence from animal enthesopathy models suggests that mechanical loading may activate signaling pathways such as transforming growth factor-β1/bone morphogenic protein-2 to promote ectopic ossification at ligament insertion sites [27]. While human tissue validation remains pending, this proposed mechanism could theoretically explain our observed EOP hyperplasia-ONL co-existence patterns. We hypothesize that the EOP, serving as the anatomical attachment site of the nuchal ligament, may form a biomechanical coupling system with the nuchal ligament. Under sustained abnormal biomechanical loading, this system might induce a cascade of ossification processes, manifesting as EOP hyperplasia and ONL. Therefore, we cautiously hypothesize that concurrent EOP hyperplasia and ONL could serve as composite imaging biomarkers for identifying abnormal biomechanical loading patterns in the cervical spine.
EOP length and cervical sagittal imbalance
This study investigates the spatial relationship between EOP hyperplasia and cervical sagittal parameters. While no significant differences in baseline sagittal alignment were observed across EOP subtypes (p>0.05), multivariate regression revealed two clinically relevant associations: each 1° increase in TS showed correlation with 0.27 mm EOP hyperplasia (β=0.27, p=0.041), whereas a 1° decrease in SCA correlated with 0.19 mm EOP hyperplasia (β=−0.19, p=0.009). Existing literature provides theoretical foundations for the clinical significance of TS and SCA. Specifically, TS as a crucial biomechanical parameter at the cervicothoracic junction requires dynamic equilibrium with CL. The formula CL=TS–16.5°±2° derived from asymptomatic populations [28] suggests that TS–CL mismatch may accelerate cervical degeneration and predict postoperative kyphotic deformity [29]. Furthermore, Le Huec et al. [30] demonstrated that maintaining SCA within the physiological range of 83°±9° optimizes load distribution, with deviations from this threshold inducing compensatory muscular efforts that accelerate degeneration. The significant correlations between EOP length and TS/SCA parameters revealed in our study suggest that EOP hyperplasia might indirectly correlate with symptom severity and surgical outcomes, requiring future multicenter prospective studies’ validation. Notably, our analysis of FHP parameters demonstrated neither intergroup variations nor correlation with EOP length, contrasting with the findings by Shahar et al. [23]—a discrepancy potentially attributable to population heterogeneity that warrants targeted investigation. A representative case illustrates this biomechanical-degenerative interplay (Fig. 2): A 43-year-old male with type III EOP exhibited 26.9 mm hyperplasia, continuous C3–C6 ONL, and severely reduced SCA (63.6°). The degeneration complex featured multilevel disc herniation, and characteristic “snake-eye” myelopathic changes. Postoperative neurological improvement following C3–6 ACDF underscores the clinical relevance of this biomechanical-degenerative profile.
A 43-year-old male presented to our hospital with “right upper limb soreness and unstable walking for over a year,” diagnosed with cervical spondylotic myelopathy. He underwent C3–6 anterior cervical discectomy and fusion, and his symptoms significantly improved postoperatively. (A) Preoperative lateral cervical spine X-ray showed type III external occipital protuberance (EOP) with a hyperplasia length of 26.9 mm. The patient had a T1 slope (TS) of 25.6° and a spino-cranial angle (SCA) of 63.6° (significantly below normal), and also had two continuous ossification of the nuchal ligaments (ONLs) with a total osteophyte length of 29.7 mm. (B) Preoperative magnetic resonance imaging indicated multilevel disc protrusions at C3–6 with dural sac compression. “Snake eye sign” was observed at the C5/6 segment due to spinal cord compression. (C, D) Postoperative day 3 lateral cervical spine X-ray.
Above all, building upon established correlations between EOP and demographic factors (gender/age), this study further elucidated morphological characteristics of EOP and their hyperplasia extent in relation to ONL and cervical sagittal alignment parameters. Key findings include: Type III EOP demonstrates not only increased ONL prevalence but also greater ONL osteophyte length. Significant linear correlations were identified between EOP hyperplasia and two cervical sagittal parameters: TS and SCA. These findings suggest EOP may serve as a morphological indicator reflecting biomechanical loading status in the cervical spine, though its precise mechanistic role requires multidisciplinary investigation.
Three primary limitations warrant consideration: First, as a retrospective cross-sectional study, the observed associations cannot establish causality. The temporal relationship and bidirectional interactions between EOP hyperplasia and cervical degeneration necessitate validation through longitudinal cohort studies. Second, while quantitative relationships between EOP hyperplasia and sagittal parameters were established, the absence of biomechanical loading threshold research impedes determination of clinically relevant cut-off values. Third, constrained by current medical data systems, patient-reported outcomes were not incorporated, potentially diminishing clinical translational value. Future investigations should prioritize developing dynamic biomechanical monitoring systems and constructing multimodal assessment models integrating symptomatic data with imaging features, thereby enabling comprehensive elucidation of EOP’s biomechanical significance in cervical degeneration.
Conclusions
Severe EOP hyperplasia exhibits a male-predominant distribution pattern and demonstrates significant radiological associations with ONL and cervical sagittal imbalance in CSM patients. These findings advocate for EOP evaluation in clinical evaluations to identify high-risk biomechanical profiles.
Key Points
Male patients demonstrated a significantly higher prevalence and greater severity of external occipital protuberance (EOP) hyperplasia compared to female patients.
Type III EOP hyperplasia was more frequently associated with ossification of the nuchal ligament (ONL) and correlated with longer ONL osteophyte length.
EOP length showed positive correlation with T1 slope and negative correlation with spinocranial angle based on multivariate regression analysis.
Notes
Conflict of Interest
No potential conflict of interest relevant to this article was reported.
Acknowledgments
Data can be obtained from the corresponding author upon reasonable request.
Funding
Funding was provided by the National Key Research and Development Program of China (2022YFC2407203).
Author Contributions
Conception and design: ZG, XL, FL, JJ, XM. Data acquisition: SL, XW, XX, FZ. Analysis of data: ZG, HS, DL, XW. Drafting of the manuscript: ZG. Critical revision: HS, DL, XL, XW, HW, XM. Obtaining funding: FL, JJ. Administrative support: XX, HW. Supervision: HW, XM. Final approval of the manuscript: all authors.