Study design and population
The subjects were from a 10-year longitudinal study on the degeneration of the spine and knee performed running in June 2014, and the basic data collection of this population was completed in 2017. Participants who are healthy community-dwelling adults, aged 20–60 years, not engaged in heavy physical activity, and residents in Beijing >5 years were included to facilitate follow-up and reveal the onset and development of the degeneration. Therefore, we use the baseline data to design a cross-sectional study to research LEPLs. The study was approved by the ethics committee of our hospital. The study was conducted under the Helsinki Declaration. Informed consent was obtained from all individual participants included in the study. The exclusion criteria were: autoimmune disease (e.g., rheumatoid arthritis), congenital disorders (e.g., juvenile idiopathic scoliosis), prior lumbar spine surgery, a history of metabolic bone disease, or chronic diseases related to calcium absorption (hyperparathyroidism), a history of malignant tumors, the use of medications known to affect bone metabolism, and pregnancy [13].
750 healthy volunteers were included in our study, who had experienced a lumbar quantitative computed tomography (QCT) and MRI scan within 48 hours. The lumbar spine disorders such as LDH, LDD (decreased signal intensity and losing the height of disc), and LEPLs were assessed by the radiologists by MRI examination performed by a 1.5 T scanner (Espree, SIEMENS, Munich, Germany). All subjects were scanned with the same multi-channel gradient waist coil. T2-weighted TSE imaging (TR/TE 2500/100 ms, slice thickness 4 mm, intersection gap 0.8 mm, voxel 240 × 282, FOV 180 × 280 mm) were performed in the sagittal plane. In the axial plane, T2-weighted TSE imaging was performed with TR/TE 2500/100 ms, slice thickness 4 mm, intersection gap 0.4 mm, voxel 248 × 198, and FOV 160 × 180 mm.
As part of the study protocol, the lumbar spines of all-volunteer scans were performed on a Toshiba CT scanner (Aquilion PRIME, Toshiba, Otawara, Japan). A QCT calibration phantom (Mindways Inc., Austin, TX, USA) was placed beneath the spine and scanned simultaneously according to the standard scanning protocol by Wang et al. [14]. The spine was kept parallel to the long axis of the calibration phantom, and minimal air gaps existed between the phantom and the volunteer. The scanning parameters were as follows: 120 kV 187 mAs, the field of view 50 cm, 1 mm slice thickness, and reconstruction matrix 512 × 512. Other methodological details have been described previously [15].
Demographic (sex, age), and physical (weight, height, waistline, and hipline) characteristics were collected from the enrolled population. Body mass index (BMI) was acquired as weight (kg) / height squared (m2).
Scoring system for the LEPLs and the lumbar disc disorders
Under the supervision of a senior radiologist, T2-weighted sagittal images were evaluated by two independent observers. All 30 out of 750 cases showing inter- and intra-observer differences in the assigned total score of LEPLs were re-evaluated by another expert radiologist. Ten endplates in the lumbar spine (L1-S1) were evaluated for the presence or absence of any type of defect. The score was calculated by labeling L1/L2 to L5/S1 intervertebral spaces as: “normal (1 point) = no lesions in the intervertebral space, physiological curvature of both EPs; wavy/irregular (2 points) = no specific lesions detectable in the intervertebral space, alterations in the physiological curvature of at least one of the EPs; notched (3 points) = a V-shaped or circular small lesion visible in at least one sagittal MRI slice; Schmorl’s node (4 points) = a deep focal defect of the vertebral EP with a smooth margin and a rounded appearance; fracture (5 points)” as previously reported by Brayda-Bruno et al. [5, 7]. For each of the five intervertebral levels, if two or more defects co-existed on an endplate or there were two types of defects in a disc level (including the upper and lower endplates), the higher score was counted. To conduct a comprehensive score for LEPLs of each individual, we define non-LEPLs (Grade I) when the upper and lower endplates of each of the five lumbar intervertebral discs were normal, mild LEPLs (Grade II) when one or more of the EPs was scored as 2(wavy/irregular) or 3(a V-shaped or circular small lesion) points, and severe LEPLs (Grade III) when the presentations of 4/5 points were evaluated (Fig. 1).
MRI degeneration of the L1/2–L5/S1 intervertebral discs in the whole cohort were assessed using a 5-point scoring system proposed by Pfirrmann et al. [16] as follows: Grade I: the homogeneous disc is with a bright hyperintense white signal intensity and a normal disc height. Grade II: The inhomogeneous disc with a hyperintense white signal and a normal disc height, and with or without horizontal gray bands. Grade III: the inhomogeneous disc with an intermediate gray signal intensity, with a normal or slightly decreased height, and indistinction between nucleus and annulus. Grade IV: the inhomogeneous disc with a hypointense dark gray signal intensity, with a normal or moderately decreased disc height, and the distinction between nucleus and annulus is lost. Grade V: the inhomogeneous disc with hypointense black signal intensity, the distinction between the nucleus and annulus is lost, and its space is collapsed. The intervertebral discs (IVD) were then classified into 3 groups. A subject was defined as having slight degeneration if their average grade of Pfirrmann stage was < 3, moderate degeneration if their average grade was ≥3 and < 4, and severe degeneration if their grade was ≥4 [17].
To describe the overall lumbar intervertebral disc herniation of each subject, we defined the non-LHD group as follows: normal, or bulge/protrusion with no evident contact of disk material with the nerve root, and without severe thecal sac compression or diminished dimensions of the neural foramen. The LDH group was defined as follows: the bulge, protrusion with the visible contract of disk material with the nerve root, severe thecal sac compression, and diminished dimensions of the neural foramen, extraction, and sequestration. The number of discs with herniation counts is distributed into the following 3 groups, non-lumbar intervertebral disc herniation, a single-level disc herniation, and ≥2 segments herniation.
Lumbar Vertebral Trabecular Volumetric Bone Mineral Density (Trab.vBMD) Measurement
After scanning, the CT DICOM images were transferred to the QCT workstation for further analysis with the QCT Pro 5.0.3 software (Mindways Inc.). lumbar vBMD was measured within a specific region of interest, which was defined as the oval-shaped areas containing the largest areas of the trabecular bone in the mid-plane of each vertebral body, not including the cortical bone or basivertebral vein [15, 18]. The Trab.vBMD values (mg/cm3) of L2–4 were recorded and analyzed, respectively, and the average was calculated [18].
Statistical Analysis.
Weighted Kappa statistic was used to assess the inter-and intra-observer reliability. The Kappa-values in intra-observer is 0.87, and the inter-observer values are 0.66, showing strong consistency.
The data were stratified into the male and female groups and then the normality was tested in the continuous variables. The descriptive statistics were presented as mean ± standard deviation for the normally distributed variables and as a median for the categorical and non-normally distributed variables. Then, the data were stratified by lumbar endplates condition, the normally distributed variables were analyzed using the one-way analysis of variance (ANOVA), and others were evaluated with the Kruskal–Wallis H test. The linear relationship of LEPLs with the stage of LDH and LDD was analyzed by Mantel-Haenszel chi-square tests. Finally, the ordinal logistic regression(OLR)was performed to estimate the effect of age, BMI, waistline, hipline, lumbar vBMD, lumbar intervertebral disc herniation, and lumbar disc degeneration on lumbar endplates lesions status and adjusting for confounding factors. Odds ratios (ORs) and 95% confidence intervals (CIs) for the occurrence of LEL were calculated as approximations of the relative risk estimates. A P-value <0.05 was considered statistically significant. SPSS 26.0 software was used to perform statistical analysis.