Correlation between lumbar sagittal alignment, Modic changes, and endplate erosion in patients with degenerative disease

Purpose To explore the role of lumbar sagittal alignment in the occurrence of Modicchanges and endplate defects (MC&ED) development in patients with a spinal degenerative disease, and the relationship between lumbar sagittal alignment and patient-report outcomes. Background Increasing attention has been focused on MC&ED as playing a potential role in the etiopathogenesis of lumbar degeneration. The precise understanding of the mechanisms leading to progression of MC&ED is lacking. Hence, we investigated how lumbar sagittal alignment influences the MC&ED. Patients and methods Ninety-six consecutive asymptomatic or symptomatic patients with Modic changes or endplate defect were retrospectively recruited in this study from August 2016 to December 2018. MC&ED were observed in 76 patients and not observed in 20 patients, representing two groups for comparison. The lumbar sagittal parameters were measured, including lumbar lordosis (LL),pelvic incidence (PI), sacral slope (SS), and pelvic tilt (PT). The lumbar lordosis index (LLI) and idea LL were then calculated. Clinical outcomes were assessed using a visual analog scale(VAS) and a Oswestry Disability Index (ODI) before and after operation. Results There were no significant differences in the distribution of demographics and baseline clinical variables between both groups. Mean age and BMI showed a significant difference between both groups (P<0.05). There were significant correlations between LL, LLI, Lossof LL, and Level 1 (r=0.281, 0.230, and 0.284, P<0.05) Also, PI, PT were significantly correlated with Level 4 (r=0.249, 0.202, P<0.05).Compared with presurgery scores, an improvement was seen in postoperative VAS and ODI scores (P<0.05). Further, the postoperative scores at 24 months in the without Modicor end plate defect group showed greater improvements compared with the with Modic or endplate defect group (P<0.05). Conclusion This analysis indicated that maintaining lumbar sagittal alignment was related to a lower risk of Modic changes in patients with the spinal degenerative logistic speculated that sagittal of


Introduction
Degenerative pathologies of the lumbar spine, including Modic changesandendplate defect, are common in the elderly population. [1] Modic changes (MCs) are shown as MRI signal variation in vertebral and subchondral bone marrow adjacentto the endplate. [2] MCs are assigned into three subtypes: TypeⅠ, Ⅱ, andⅢ accordingto T1-and T2-weighted MRI. [3,4] Radiological and histological examination analysis have revealed that differentsubtypes of MCs respectively displayed inflammatory responses, fatty marrow, and subchondral bone sclerosis. MCs are frequently observed inpathological structure changes like disc degeneration, disc herniation, and endplate defect. [5][6][7] A recent study demonstrated that there is an association between endplate defect and disc degeneration in a large-scale, population-based study. Several theories have been proposed with respect to the etiology of MCs and endplate defect. Recently, clinical studies have paid attention to endplate defects as acting as a concomitant role in the aetiopathogenesis of MCs. [8]Korres etal.
demonstratedthat the lumbar spine act as a role in maintaining the upright posture and formthe body trunk shape via maintaining proper sagittalalignment. [9] In fact, sagittal alignment has been related to various lumbar conditions. There are several reports demonstrated that sagittal malalignment contributes to lumbar disc degeneration. Buckland et al. reported that worsening sagittal malalignment associated with lumbar stenosis on stereoradiographs. [10]Ogura et al. showed that sagittal spinopelvic alignment as a significant impact on health-related quality of life and clinical outcomes after surgery. [11]Recent studies have demonstrated that patients with lumbar malalignment are frequently present sympathetic symptoms such as low back pain and.
The motion segment is composed of adjoining vertebrates, the lumbar disc, and adjoining ligaments between them, of which the endplate, located between the vertebrae and the intervertebral disc, is considered to be the most vulnerable structure. [12] It is obvious that both MCs and endplate defect is related to the lumbar degeneration. Therefore, it is considered and the lumbar sagittal malalignmentas a transitory stage of a lumbar degenerative process.
However, the role of lumbar sagittal alignment in the progression of Modic changes and endplate defects has not been illuminated. In the current study, we supposed that lumbar sagittal alignment patterns may be associated with the development of either Modicchanges or endplate defects. Thus, we explored whether differences in sagittal parameters and especially spinopelvic parameters, could predict the development ofeither Modic changes or endplate defects.

Study Population
This prospective study enrolled 96 symptomatic volunteers (age: mean

Lumbar sagittal parameters
Sagittal andaxial images were obtained on MRI scans from T12 upper endplate margin to S1 lower endplate margin.The measurements of the lumbarand pelvis sagittal parameters were: (1) lumbar lordosis (LL), LL was measured from the L1 superior endplate to S1 superior; (2)pelvic incidence (PI):

Assessment of endplate defects
The loss or disruption of the complete appearance was defined as endplate defects. Change of endplate defects visible on sagittal MR images was categorized into three grades according to Feng et al. [13]Type 1 endplate defect, focal endplate defect, was observed as a discontinuity or hollow on the endplate. Type 2endplate defect, corner endplate defect, was observed as a legible corner on the endplate. Type 3 endplate defect, erosive endplate defect, observed as the extensively irregular, serrated, or worm-eaten appearance. [14]Inter-rater agreement for the coding of endplate defect was calculated using Cohen's weighted kappa and Pearson's correlation.

Assessment of MCs
MCs were categorized into type 0, I, II and III using sagittal multi-positional MRI image. Type 0 MCs showed normal endplate, type I MCs showed low T1 and high T2 signal, type II MCs showed high T1 and T2 signals, and type III MCs showed low T1 and T2 signals.

Statistical analysis
All statistical analyses were performed using SPSS (version, 21.0 SPSS Inc, Chicago, IL). Demographic characteristics were expressed as means ± standard deviations (x ± s) for continuous variables.
Categorical variables were expressed as proportions and percentages. Mann-Whitney U test or chisquare test was used to compare parameters between groups. Moreover, Pearson correlation and linear regression analysis were also performed to analyze the relationship between lumbar sagittal alignment and the clinical outcomes. P less than 0.05 was considered statistically significant.

Demographics details
Distribution of demographic variables such as age, weight, smoking status, and duration of symptoms in the two groups was significantly different (P > 0.05); there was no significant difference in gender and BMI (P < 0.05). Moreover, Modic changes and/or endplate defects observed in79.16%of volunteers in group A (76/96), and in 20.83 of volunteers in group B(20/96), indicating no statistical difference in occurrence among groups. (Table 1) Table 4 Spearman's rank correlation coefficients between the lumbar sagittal parameters and clinical outcomes

Discussion
In this study, we showed two novel findings. First, patients with improper lumbar sagittal alignment had a higher occurrence of Modic and endplate defect.
Previous studies regarding sagittal balance have demonstrated that lumbar malalignmentafter spine surgery may cause poor clinical outcomes. [15,16] patients should be provided propercorrection of the spinal alignment in order to prevent complications to occur. However, there is no studies focus attention on the effectof lumbar sagittal alignmenton the progression of Modic changes and endplate defects before surgery until now. Thus, we conducted a study that mainly focused on the effect of lumbar sagittal alignment on the occurrence of Modic changes and endplate defects.
We think that the mechanism regarding the association between lumbar sagittal alignment and Modic changes or endplate defects is multifaceted. The lumbar segment with MCs or endplate defects tends to lumbar disk degeneration, the latter of which destabilizes the lumbar spine in turns and ultimately form a vicious cycle. Moreover, the vertebral endplate fulfills the critical function of disc nutrient transport. MCs decrease nutrition transmit ability of endplate, infection factors serving as initial pathogenesis. In addition, morphological changes such as fatty infiltration or change in crosssectional area of lumbar muscles were observed in patients with low back pain. Patients with low back pain demonstrate a significantly higher prevalence of MCs and endplate defect with an unclear mechanism. We hypothesize that the change of lumbar sagittal alignment leads to lumbar muscles of these MCs patients fail to support spinal stability and finally led to fatty infiltration or change in crosssectional area of lumbar muscles. The unstable lumbar spine is able to enlarge the range of movement, which accelerates the degeneration of endplate and lumbar disc. Finally, the interaction between the two makes the disease to develop into a serious direction. In this study lumbar sagittal parameter was measured in patients with low back pain and we found that lumbar sagittal parameter in volunteers with MCs or endplate defect was larger than those in subjects without MCs or endplate defect. A significant correlation between lumbar sagittal parameter, MCs, and endplate defect was found in logistic regression analysis. We speculated that increased lumbar sagittal alignment could increase lateral shear force, leading to the destroyed structure of endplate and formation of MCs.
In terms of the Modic and endplate defect, the prevalence of Modic and endplate defect was 79.16% (76/96) inwith Modic and endplate defect group and 21.5% (20/96) in without Modic and endplate defect group. Meanwhile, differences in the presurgical lumbar sagittal alignment were observed in two groups. Thus, we hypothesize that presurgical lumbar sagittal alignment, measured by PI, PT, SS, LL, and PI-LL, was related to the incidence of Modic and endplate defect in symptomatic subjects.
In terms of the lumbar parameters, the results indicated that PT, SS, and PI-LL in the without Modic and endplate defect group were significantly higher than those in the Modic  However, previous studies emphasized that there exist a relationship between sagittal alignment and degenerative changes only in the cervical spine. [17] In terms of the lumbar spine, Baron et al.
Showed that spinopelvic sagittal alignment plays a predisposingrole in the pathogenesis of lumbar degeneration. [18] Even though we couldn't confirm whether these characteristics were the effect or the predictor of lumbar degeneration in the current retrospective study, they have potential clinical implications.
Lumbar sagittal alignment plays a crucial role in predicting the development of Modic changes and endplate defects in symptomatic patients. Meanwhile, in the corrective surgery for patients with lumbar deformity, emphasis should be placed on the reconstruction of the lumbar sagittal alignment.
Furthermore, lower lumbar muscles dystrophy because of a surgical exposure can contribute to postoperative deformities. Li et al. reported that there is a correlation between spinopelvic alignment and degeneration of lower lumbar paraspinal muscles in elderly patients in a recent study. [19] Hence, the paraspinal muscle-strengthening exercises of lower lumbar levels could slow the progression of Modic changes and endplate defects. Longitudinal studies with subject outcomes need to be performed to validate our hypotheses.
Several limitations existed in this study. First, bias could not be avoided due to the nature of retrospective studies. Second, the study mainly focused on preoperative lumbar sagittal alignment and prevalence of Modic changes and endplate defects and not postoperative lumbar alignment or changes in lumbar alignment. Third, a high standard deviation of lumbar sagittal parameters reflects the flexibility of the lumbar spine. Thus, we should determine the reproducibility of lumbar sagittal parameters in further research. In addition, the lack of patient medical records made it difficult to verify the differences in clinical scores between patients with the imbalance and normal balance.

Conclusion
Lumbar sagittal alignment is a good predictor of the development of Modic changes and endplate defects for the association between them. Hence, maintaining a proper lumbar sagittal alignment was important in lumbar surgery, which seems to act as a vital role in the improved clinical outcomes.
Declarations Figures 14 Figure 1 The lumbar sagittal alignment of the lumbar spine. Abbreviations: PI, pelvic incidence; PT, with MC&ED group.