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The purpose of this study was to examine the association between non-traumatic VFs and degenerative changes of adjacent IVDs. Methods 98 consecutive patients undergoing spinal surgery were included in this study. VFs were semi-quantitatively evaluated by lateral lumbar radiography. 588 vertebral bodies (from T12 to L5) and 486 discs (from T12/L1 to L4/L5) were analyzed. The degree of IVD degeneration was evaluated by magnetic resonance imaging (MRI) and classified into two groups according to Pfirrmann’s classification. Grades I, II and III were defined as the early stage of IVD degeneration and Grades IV and V as the advanced stage. Intradiscal vacuum phenomena (VPs) were evaluated by computed tomography. Adjacent IVDs were categorized according to the locations of VFs (superior, inferior, and bilateral). Associations between the presence of VFs and the extent of IVD degeneration or the presence of VPs were statistically analyzed. Results IVDs adjacent to VFs were identified in 115 IVDs (31.1% of total; superior: 11.4%, bilateral: 8.6%, inferior: 11.1%). The presence of VFs was significantly associated with MRI grades of adjacent IVD degeneration (P<0.01) and the prevalence of VPs within adjacent IVDs (P<0.01). From logistic regression analysis, age, disc level, and VFs were independent related factors for disc degeneration (P<0.05). Conclusion This study showed that VFs were an independent related factor for adjacent disc degeneration and occurrence of intradiscal VPs. VFs may affect the micro-environment of adjacent IVDs, leading to disc degeneration and disc rupture. Orthopedics vertebral fracture disc degeneration intradiscal vacuum phenomenon magnetic resonance imaging (MRI) computed tomography (CT) Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Background Intervertebral discs (IVDs) consist of a central gelatinous nucleus pulposus and a surrounding fibrous annulus fibrosus (AF). IVDs are constrained within and connected to adjacent vertebral bodies by superior and inferior cartilaginous endplates (CEPs). Disc degeneration is considered to be caused by genetic predisposition, injury, aging, and environmental factors, or any combination thereof [1]. Blood flow to the vertebral bodies of the lumbar spine is abundantly supplied by the lumbar arteries, which are branches of the abdominal aorta [2]. IVDs are predominantly avascular and aneural tissues that exchange nutrients and metabolites primarily by diffusion to and from micro-vessels in the CEP and outer AF [3, 4]. The restricted transport and low cellularity of the discs limit repair. Therefore, endplate sclerosis, or an ischemic vertebra, is considered to be one of the factors responsible for IVD degeneration [1, 5]. Previous clinical studies reported that a thoracolumbar burst fracture with high energy spine trauma caused disc degeneration, and that, importantly, disc degeneration occurred at a level adjacent to the fractured vertebra [6-11]. One multicenter cohort study recently reported that progression of adjacent disc degeneration was observed at 6 months after osteoporotic VFs [12]. However, further study is needed to determine the association between non-traumatic VFs, including osteoporotic fractures, and the progression of disc degeneration adjacent to VFs. The purpose of this cross-sectional population study was to examine the effect of non-traumatic VFs on degenerative changes of adjacent IVDs using magnetic resonance imaging (MRI) and computed tomography (CT) analyses. Methods Subject: This IRB-approved retrospective study was conducted on spinal CT images of 98 consecutive patients (50 males and 48 females) undergoing spinal surgery (Table 1). Table 1. Patient characteristics Group Subjects (males/females) Average age (years)* VF-negative 50 (25/25) 60.6 (23-87) VF-positive 48 (25/23) 75.4 (56-90) Total 98 (50/48) 68.2 (23-90) VF: vertebral fracture. The numbar in the parenthesis in the average age column indicates the age range of subjects. *P<0.01 between VF-negative and VF-positive groups. The overall average age of the patients was 68.2 years-old (range 23-90). The clinical diagnoses of the patients were as follows: 74 lumbar spinal stenosis, 15 lumbar disc herniation, 6 cervical spinal diseases, and 3 others. Patients with VFs caused by high energy trauma were excluded from this study. Morphological classification of VFs: VFs were evaluated using lateral lumbar radiographs in all patients; 588 vertebral bodies from T12 to L5 were analyzed. VF deformities were classified into three groups (wedge, biconcave, or crush) using a semi-quantitative technique [13]. Classification of disc degeneration: MRI was performed in 74 patients. A total of 370 discs from T12/L1 to L4/L5 were analyzed with MRI. The degree of disc degeneration was evaluated with sagittal T2-weighted lumbar MRI, and graded according to Pfirrmann’s classification from Grades I to V [14]. Grades I, II and III were defined as the early stage of IVD degeneration and Grades IV and V as the advanced stage. Diagnosis of vacuum phenomena (VPs): Multi-detector CT (MDCT) (slice increment: 1.0 mm, slice thickness: 1.0 mm; Asteion TSX-021B, Toshiba Medical Systems Co., Otawara, Tochigi, Japan) was performed for all patients. A total of 486 discs from T12/L1 to L4/L5 were analyzed with MDCT. Four discs were excluded, because the T12/L1 disc was outside the range of CT analysis in four patients. Intradiscal VPs were evaluated by the presence of areas of gaseous radiolucency using MDCT imaging and those shapes were classified using sagittal imaging as previously reported [15]. In short, VP shapes were categorized according to three classifications: spot, linear, and island. A spot-type VP was defined as a point-like VP less than 2 mm in diameter. A linear-type rupture was defined as a radiating VP whose width was less than 2 mm. An island-type rupture was defined as a VP forming a wide cleft (>2 mm). Categorization of IVDs: IVDs were categorized according to the locations of adjacent VFs. The control (VF-negative) group was defined as those IVDs having no fracture in an adjacent vertebral body. The VF-positive group was defined as those IVDs having fractures in the adjacent vertebral body. Furthermore, the VF-positive group was further classified into three subgroups: those with IVDs superior to a VF (superior group), those with IVDs inferior to a VF (inferior group), and those with IVDs located between VFs (bilateral group) (Fig. 1). Statistical analysis: The morphological classification of VFs, the classification of disc degeneration and the diagnosis of VPs were evaluated by a single observer who was blinded to the categorization of the IVD groups. The Chi-square test and Student’s t-tests were used to compare the differences in gender and age between patients with VFs and those without VFs. The differences in the percentage of advanced stage of disc degeneration (MRI) or the prevalence of VP among the categorization of IVDs according to the locations of adjacent VFs were statistically assessed by a chi-square test followed by post hoc multiple comparisons using the Bonferroni method [15]. The post hoc test was performed to assess the probability values for each combination of independent category levels by using a Bonferroni correction to control for type I error inflation [16, 17]. Significance was determined by Chi-square test with post-hoc analysis by cellwise adjusted residual analysis in two-way contingency tables according to Garcia-Perez [16-18]. Post-hoc testing was performed with adjusted standardized residual analysis with an eight-fold Bonferroni-adjusted p-value (p<0.006) or sixteen-fold Bonferroni-adjusted p-value (p<0.003) [19]. The association between disc degeneration and the prevalence of an adjacent VF was evaluated by multiple logistic regression. Factors included in the multivariate model were age, gender, disc level, and adjacent VF(s). All the statistical analyses were performed using IBM SPSS Statistics (IBM Japan, Tokyo or IBM Corp., Armonk, NY, USA). Results Patient characteristics VFs were identified in 119 vertebrae (20.4%) of the 584 vertebral bodies analyzed (wedge type: 51.3%; biconcave type: 37.8%; crush type: 10.9%). The number of VFs was highest in the L1 vertebral body and lowest in the L3 (n [% of total VFs]: T12: 22 [18.5%]; L1: 28 [23.5%]; L2: 20 [16.8%]; L3: 12 [10.1%]; L4: 15 [12.6%]; L5: 22 [18.5%]) (Fig. 2). IVDs adjacent to VFs were identified in 115 IVDs (31.1%) of the 370 IVDs analyzed by MRI (superior: 42 [36.5%], bilateral: 32 [27.8%], inferior: 41 [35.7%]). IVDs adjacent to VFs were identified in 147 IVDs (30.2%) of the 486 IVDs analyzed by CT analysis (superior: 51 [34.7%], bilateral: 45 [30.6%], inferior: 51 [34.7%]). Association between VFs and disc degeneration Of all the discs analyzed by MRI (370 discs), 228 IVDs (61.6%) were classified as advanced degenerative stage, appearing most frequently in the L4/L5 disc and least frequently in the T12/L1 disc (T12/L1: 39.2%, L1/L2: 54.1%, L2/L3: 62.2%, L3/L4: 75.7%, L4/L5: 77.0%) (Fig. 3). A chi-square test showed a significant association between the presence of VFs and MRI grades of IVD degeneration adjacent to VFs (P<0.01) (Fig. 4A). The results of a post-hoc test showed that the numbers of IVDs with advanced stage degeneration were significantly lower than expected in the VF-negative group (P<0.006) (Fig. 4B). However, those with advanced stage degeneration were not significantly higher than expected in the IVDs of superior, bilateral, and inferior groups (superior: 78.6%, bilateral: 65.6%, inferior: 78.0%) (Fig. 4B). There were no significant differences in the prevalence of advanced stage IVD degeneration among the deformity types of adjacent VF by chi-square test (wedge: 77%; biconcave: 76%; crush: 100%). When the proportion of disc degeneration was analyzed by disc level, the percentages of advanced stage disc degeneration in T12/L1, L1/L2 and L2/L3 in the VF-positive group were significantly higher than those in the VF-negative group (Fig. 5). However, there were no significant differences in the percentages of advanced stage disc degeneration between the VF-positive group and the VF-negative group in L3/L4 and L4/L5. The results of logistic regression analysis showed that age, disc level, and adjacent VFs were independent factors that were significantly associated with the MRI-grade of IVD degeneration (Table 2). Table 2. Logistic regression analysis of significant related factors for advanced stage of disc degeneration and intradiscal vacuum phenomenon odds ratio (95%CI) p value DD age 1.050 (1.029 - 1.071) <0.001 disc level 1.687 (1.412 - 2.017) <0.001 adjacent VF 1.906 (1.079 - 3.368) 0.026 VP age 1.054 (1.034 - 1.076) <0.001 disc level 1.513 (1.298 - 1.764) <0.001 adjacent VF 2.476 (1.553 - 3.949) <0.001 DD: disc degeneration, VP: vacuum phenomenon, VF: vertebral fracture Association between VFs and intradiscal VPs VPs were found in 226 IVDs (46.5%) of the 486 IVDs analyzed. The number of discs with a VP was highest in the L4/5 level (55.1%). At other levels, VPs were found in 34-41% of the discs, with the exception of the T12/L1 level, where a VP was found in 20.2% of IVDs (Fig. 6). A chi-square test showed a significant association between the presence of VFs and VPs within IVDs adjacent to a VF (P<0.01) (Fig. 7A). The results of a post-hoc test showed that the numbers of IVDs with VPs were significantly lower than expected in the VF-negative group (29.2%) (P<0.006), and significantly higher than expected in superior and inferior groups (superior: 64.7%, inferior: 58.8%) (P<0.006) (Fig. 7B). In the VP shape analysis, the number of IVDs with an island shape VP was significantly lower than expected in the VF-negative group (P<0.003), and significantly higher than expected in the superior group (P<0.0006) (Table 3). A chi-square test showed a significant association between the deformity type of VF and the prevalence of a VP within IVDs adjacent to the VF (P<0.05). There was a tendency for the percentage of VPs to be lower in IVDs adjacent to wedge type VFs (52%). VPs were identified in all IVDs adjacent to crush type VFs (n=7). Table 3. Association between the location of intervertebral discs (IVDs) adjacent to vertebral fractures (VFs) and the shape of intradiscal vacuum phenomena (VPs) IVD location VP shape Total VP (-) Spot Linear Island VF (-) Count (% raw) 240** (70.8) 18 (5.3) 29 (8.6) 52* (15.3) 339 Exp. Count 221.4 25.8 37.0 64.9 Corrected P-value <0.0006 0.004 0.012 <0.003 Superior Count (% raw) 18** (35.3) 9 (17.6) 5 (9.8) 19** (37.3) 51 Exp. Count 31.8 3.9 5.6 9.8 Corrected P-value <0.0006 0.004 0.790 <0.0006 Bilateral Count (% raw) 24 (53.3) 5 (11.1) 10 (22.2) 6 (13.3) 45 Exp. Count 28.1 3.4 4.9 8.6 Corrected P-value 0.190 0.353 0.011 0.299 Inferior Count (% raw) 21* (41.2) 5 (9.8) 9 (17.6) 16 (31.4) 51 Exp. Count 31.8 3.9 5.6 9.8 Corrected P-value <0.003 0.533 0.103 0.019 Total 303 37 53 93 486 The results of a contingency-table test are presented. Intervertebral discs (IVDs) were categorized according to the locations of adjacent vertebral fractures (VFs). Percentages of the raw marginal total (% raw) are in parentheses. VF (-): no VF group; VP (-); no vacuum phenomena group; Exp. Count: expected count. *P < 0.003, **P < 0.0006 (by Bonferroni correction). The cells with counts above or below the expected count with statistical significance are shown in bold. When the prevalence of intradiscal VPs was analyzed by disc level, the percentages of VP-positive discs in T12/L1, L1/L2, L2/L3 and L3/L4 in the VF-positive group were significantly higher than those in the VF-negative group (Fig. 8). However, there was no significant difference in the percentages of VP-positive discs between the VF-positive and -negative groups in the L4/L5 level. A logistic regression analysis revealed that age, disc level, and adjacent vertebral fracture were independent factors that were significantly associated with the presence of intradiscal VPs (Table 2). Discussion We conducted a cross-sectional retrospective study of consecutive patients undergoing spinal surgery to evaluate the association between non-traumatic VFs and IVD degeneration adjacent to VFs. VFs were significantly associated with MRI grades of IVD degeneration and the presence of intradiscal VPs of discs adjacent to VFs. Logistic regression analysis showed that VF was one of the independent related factors for adjacent disc degeneration. Eight clinical studies have evaluated the association between thoracolumbar VFs with spine trauma and adjacent disc degeneration (Table 4). Among these, two studies focused on degenerative IVDs adjacent to a VF in children or young patients who were treated conservatively [6, 20]. Kerttula et al. investigated the occurrence of disc degeneration by MRI in young patients (average-age: 15.5 years) with a history of wedge type VFs [6]. They concluded that wedge type VFs, especially with endplate injury, in young people were significantly associated with the occurrence of disc degeneration [6]. Later, Moller et al. [20] evaluated whether VFs in children (average-age: 12 years) are a risk factor for adjacent IVD degeneration. They used MRI and the Oner classification scheme [21], which mainly classifies morphological changes of IVDs and endplate injuries, and reported no significant association between stable VFs and adjacent disc degeneration [20]. Because of differences in MRI assessments and type of injuries (Table 4), the relationship between VFs and adjacent disc degeneration in young people and children remains controversial. The other six clinical studies had evaluated disc degeneration following thoracolumbar VFs (AO classification [22]: type A1-4) treated with spine surgeries (Table 4). Posterior pedicle screw fixation was performed in four studies [7-9, 23] and instrumented kyphoplasty in two studies [10, 11]. Among six clinical studies, adjacent disc degeneration was evaluated by MRI in five studies [7-10, 23], and by radiograph in one study [11]. These studies have shown that adjacent disc degeneration had significantly progressed at 9 to 32 months after thoracolumbar burst fractures in comparison with those at the time of injury, except for one study reported by Verlaan et al. [23]. Three studies [8, 10, 11] have reported that disc degeneration was predominantly found at the superior adjacent disc. On the other hand, Sander et al. [9] reported that the disc degradation was identified both at superior and inferior adjacent discs after traumatic VFs. Toyone et al. [7] also showed that adjacent disc degeneration had progressed at two years after burst fractures; however, the degeneration of superior and inferior adjacent discs were not separately analyzed. Lastly, Verlaan et al. [23] reported that 10.5% of the superior adjacent discs and 15.8% of inferior adjacent discs showed progression of degeneration at 12 to 18 months after trauma. However, they concluded that no statistically significant progression in adjacent disc degeneration was found for superior or inferior discs. Table 4. Association between thoracolumbar vertebral fractures with spine trauma and the adjacent disc degeneration Author Year Subjects Age (averaged) Design Follow-up Type of injury Treatment MRI Assessment Kerttula 6 2000 14 15.5 [8.8- 20.8] Retrospective study 3.8 Y Wedge-type (14) Conservative Decrease in T2 signal intensity Moller 20 2007 20 12 [7 - 16] Observational cohort study 40 Y Stable (18), Denis type B (2) Conservative Oner classification Scheme 21 Verlaan 23 2013 20 42 [18 - 74] Prospective trial 12 to 18 M AO: A3 (20), A4 (1) PS fixation Pfirrmann classification 14 Toyone 7 2013 12 38 [14 - 59] Prospective consecutive series 10 Y AO: A3 (12) PS fixation Borenstein's report (score: 0-3) 37 Wang 8 2013 26 39.6 [21 - 54] Retrospective study 9-12 M AO: A3 (26) PS fixation Pfirrmann classification 14 Sander 9 2014 27 37.5 [16 - 59] Retrospective study 1 Y AO: A1 (5), A2 (14), A3 (8) PS fixation Original classification (Grade 0-3) Noriega 10 2016 20 50.7 [45 - 56] Retrospective study 32 M AO: A1 (10), A3 (10) IKP Diffusion-weighted MR imaging Descamps 11 2019 93 54 [18 - 83] Retrospective study 26.7 M AO: A1 (54), A2 (5), A3 (34) IKP Radiograph UCLA Grading Scale 38 Y: years, M: months, PS fixation: Pedicle screw fixation, AO: AO classification 19 , IKP: instrumented kyphoplasty. OVF: osteoporotic vertebral fracture Numbers in the brackets indicate the range of age. Number in the parentheses indicates the number of subjects. In contrast to these previous studies, the results of the current study showed a significant association between non-traumatic VFs and disc degeneration, at both superior and inferior adjacent levels, in a relatively older population. Rahmani et al. have recently evaluated whether endplate fracture (injury) and adjacent disc degeneration have a significant association with the occurrence of delayed union following osteoporotic VFs for 139 consecutive patients (average age: 79 years-old) who were treated conservatively [12]. They also evaluated signal changes of adjacent IVDs in MR T2-weighted images at enrollment and at 6 months follow-up based on a modified Pfirrmann grading system and reported that adjacent cranial disc degeneration had significantly progressed at 6 months post-injury. This suggests the possibility that disc degeneration would progress in the relatively short term after osteoporotic VFs. Next, to evaluate the effect of spinal levels on disc degeneration, the relationship between VFs and disc degeneration at different IVD levels was assessed (Fig. 5). Although there was no significant difference in the percentages of advanced stage of disc degeneration between VF-positive and VF-negative groups in L3/L4 and L4/L5, those percentages in T12/L1, L1/L2 and L2/L3 discs, which would be expected to have less degeneration than lower lumbar levels [24], were significantly higher in the VF-positive group than in the VF-negative group. This suggests that the effect of VFs on adjacent disc degeneration would be more pronounced at upper lumbar levels than those at middle/lower lumbar levels. There is also evidence to support this suggestion from cadaveric studies [25-29]. Dolan et al. [25] performed a mechanical and morphological study to evaluate how spinal level influences disc degeneration arising from endplate fracture. They reported that the effects of vertebral endplate fracture on disc mechanical function, and specifically on disc decompression, were greater at thoracic and upper lumbar levels than at lower lumbar levels. In addition, we evaluated the association between VFs and the presence of adjacent intradiscal VPs. Intradiscal VPs refer to the radiographic appearance of a lucency caused by the presence of gas, usually found in the lumbar region [30, 31]; this is one of the characteristics of IVD degeneration [15, 32]. Murata and colleagues showed that the presence of intradiscal VPs is associated with the MRI-grade of disc degeneration and radiographic disc height narrowing [15]. The results of the current study showed that the incidence of VPs, especially the island type, in the VF-positive group was significantly higher than that in the VF-negative group; this suggests that VFs have an impact, not only on the extent of MRI-graded disc degeneration, but also on the intradiscal ruptures evaluated by CT imaging as intradiscal VPs. The results of the analysis of intradiscal VPs by disc level were nearly identical to those of MRI-graded disc degeneration. Lafforgue and colleagues reported that VPs were grouped into collapse-related VPs and degenerative VPs [33]. They reported that collapse-related VPs, which were secondary to vertebral collapse, were located mainly in the thoracolumbar junction. Degenerative VPs, which were the result of disc degeneration, were located in lower lumbar discs. Therefore, in the current study, we speculate that intradiscal VPs in upper lumbar levels would be mainly attributed to VFs (vertebral collapse). According to the results of logistic regression analyses, age, disc level, and adjacent vertebral fracture were independent related factors for disc degeneration and intradiscal VPs (Table 2). It is well known that being elderly and lower disc level were significant related factors for disc degeneration [24, 34, 35]. The current study showed evidence that VFs are also an independent related factor for adjacent disc degeneration for the population with non-traumatic VFs. The following three patho-mechanisms are involved in the occurrence of adjacent disc degeneration. First, endplate and IVD injuries directly caused by VFs promote the progression of disc degeneration. Fujiwara and colleagues reported that endplate injuries were observed in 61%, and IVD lesions in 60% of patients with an acute, single osteoporotic VF [36]. Second, the progression of vertebral collapse is thought to cause impaired blood flow in vertebral bodies, to reduce blood flow and nutrient supply to the disc, and to cause disc degeneration [1, 5]. Imanishi and colleagues recently showed using a rabbit lumbar artery ligation model that ischemia of lumbar vertebrae initiated degenerative changes in IVDs [4]. Therefore, an ischemic vertebra is considered to be one of the important factors responsible for IVD degeneration. Third, mechanical stress is also involved in the progression of adjacent disc degeneration. Dolan et al. reported that vertebral endplate fracture reduced nucleus pressure and created abnormal stress distributions in the adjacent IVD, increasing the risk of internal disruption and degeneration [25]. Interestingly, Stefanakis et al. and Zehra et al. performed mechanical and morphological studies to determine whether high gradients of compressive stress within the IVD are associated with progressive disc degeneration [27, 29]. They reported that as the grade of disc degeneration increased, nucleus pressure decreased. However, stress gradients (concentration) in the annulus increased. A limitation of this study is that most of the subjects were patients who had been given pre-operative radiographs, CT, and MRI for elective spinal surgeries. Therefore, MRI grading of IVDs and percentage of intradiscal VPs would be much higher than those within a general population [24]. Another limitation is that VFs in our study excluded those caused by high energy trauma. Although the evaluation of osteoporosis was not performed in this study, most VFs in the subjects of this study would be osteoporotic VFs. Thirdly, the other risk factors associated with VFs, such as obesity and physical activity, and the clinical outcome including the subject’s low back pain have not been evaluated in this study. Further study would be needed to evaluate the risk factors of adjacent disc degeneration following VFs, and the association of adjacent disc degeneration and clinical outcomes. Conclusions This study showed that non-traumatic VFs are an independent related factor for adjacent disc degeneration and the occurrence of intradiscal VPs at the corresponding level. From the results of the current study, we speculate that VFs may affect the micro-environment of adjacent IVDs, leading to progression of disc degeneration and disc ruptures. Therefore, careful follow-up is necessary even for non-traumatic VFs (mostly osteoporotic VFs) and proper treatment, including surgical intervention, of VFs may prevent the progression of disc degeneration. Abbreviations VF: vertebral fracture; IVD: intervertebral disc; AF: annulus fibrosus; CEP: cartilaginous endplate; CT: computed tomography; MDCT: multi-detector CT; VP: vacuum phenomenon; MRI: magnetic resonance imaging Declarations Ethics approval and consent to participate Ethics were approved by the institutional review board of the Mie University Hospital (Tsu, Mie, Japan; IRB reference number: H2020-028). Written or oral informed consent was obtained from all the subjects. Consent for publication Not applicable. Availability of data and materials The datasets used and analyzed during the current study are available from the corresponding author at a reasonable request. Competing interests The authors declare that they have no conflict of interests. Funding Not applicable. Authors' contributions NT performed data acquisition and statistical analysis and drafted the manuscript. 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Moller A, Maly P, Besjakov J, Hasserius R, Ohlin A, Karlsson MK: A vertebral fracture in childhood is not a risk factor for disc degeneration but for Schmorl's nodes: a mean 40-year observational study . Spine (Phila Pa 1976) 2007, 32 (22):2487-2492. Oner FC, van der Rijt RR, Ramos LM, Dhert WJ, Verbout AJ: Changes in the disc space after fractures of the thoracolumbar spine . J Bone Joint Surg Br 1998, 80 (5):833-839. Magerl F, Aebi M, Gertzbein SD, Harms J, Nazarian S: A comprehensive classification of thoracic and lumbar injuries . Eur Spine J 1994, 3 (4):184-201. Verlaan JJ, Dhert WJ, Oner FC: Intervertebral disc viability after burst fractures of the thoracic and lumbar spine treated with pedicle screw fixation and direct end-plate restoration . Spine J 2013, 13 (3):217-221. Teraguchi M, Yoshimura N, Hashizume H, Muraki S, Yamada H, Minamide A, Oka H, Ishimoto Y, Nagata K, Kagotani R et al : Prevalence and distribution of intervertebral disc degeneration over the entire spine in a population-based cohort: the Wakayama Spine Study . Osteoarthritis Cartilage 2014, 22 (1):104-110. Dolan P, Luo J, Pollintine P, Landham PR, Stefanakis M, Adams MA: Intervertebral disc decompression following endplate damage: implications for disc degeneration depend on spinal level and age . Spine (Phila Pa 1976) 2013, 38 (17):1473-1481. Pollintine P, Dolan P, Tobias JH, Adams MA: Intervertebral disc degeneration can lead to "stress-shielding" of the anterior vertebral body: a cause of osteoporotic vertebral fracture? Spine (Phila Pa 1976) 2004, 29 (7):774-782. Stefanakis M, Luo J, Pollintine P, Dolan P, Adams MA: ISSLS Prize winner: Mechanical influences in progressive intervertebral disc degeneration . Spine (Phila Pa 1976) 2014, 39 (17):1365-1372. Adams MA, Pollintine P, Tobias JH, Wakley GK, Dolan P: Intervertebral disc degeneration can predispose to anterior vertebral fractures in the thoracolumbar spine . J Bone Miner Res 2006, 21 (9):1409-1416. Zehra U, Noel-Barker N, Marshall J, Adams MA, Dolan P: Associations Between Intervertebral Disc Degeneration Grading Schemes and Measures of Disc Function . J Orthop Res 2019, 37 (9):1946-1955. Vernon-Roberts B, Moore RJ, Fraser RD: The natural history of age-related disc degeneration: the pathology and sequelae of tears . Spine (Phila Pa 1976) 2007, 32 (25):2797-2804. Videman T, Nurminen M: The occurrence of anular tears and their relation to lifetime back pain history: a cadaveric study using barium sulfate discography . Spine (Phila Pa 1976) 2004, 29 (23):2668-2676. Li FC, Zhang N, Chen WS, Chen QX: Endplate degeneration may be the origination of the vacuum phenomenon in intervertebral discs . Med Hypotheses 2010, 75 (2):169-171. Lafforgue PF, Chagnaud CJ, Daver LM, Daumen-Legre VM, Peragut JC, Kasbarian MJ, Volot F, Acquaviva PC: Intervertebral disk vacuum phenomenon secondary to vertebral collapse: prevalence and significance . Radiology 1994, 193 (3):853-858. Boos N, Weissbach S, Rohrbach H, Weiler C, Spratt KF, Nerlich AG: Classification of age-related changes in lumbar intervertebral discs: 2002 Volvo Award in basic science . Spine (Phila Pa 1976) 2002, 27 (23):2631-2644. Kanayama M, Togawa D, Takahashi C, Terai T, Hashimoto T: Cross-sectional magnetic resonance imaging study of lumbar disc degeneration in 200 healthy individuals . J Neurosurg Spine 2009, 11 (4):501-507. Fujiwara T, Akeda K, Yamada J, Kondo T, Sudo A: Endplate and intervertebral disc injuries in acute and single level osteoporotic vertebral fractures: is there any association with the process of bone healing? BMC Musculoskelet Disord 2019, 20 (1):336. Borenstein DG, O'Mara JW, Jr., Boden SD, Lauerman WC, Jacobson A, Platenberg C, Schellinger D, Wiesel SW: The value of magnetic resonance imaging of the lumbar spine to predict low-back pain in asymptomatic subjects : a seven-year follow-up study . J Bone Joint Surg Am 2001, 83 (9):1306-1311. Ghiselli G, Wang JC, Bhatia NN, Hsu WK, Dawson EG: Adjacent segment degeneration in the lumbar spine . J Bone Joint Surg Am 2004, 86 (7):1497-1503. Cite Share Download PDF Status: Published Journal Publication published 27 Nov, 2020 Read the published version in BMC Musculoskeletal Disorders → Version 3 posted Submission checks completed at journal 19 Nov, 2020 Editorial decision: Accept 18 Nov, 2020 Editor assigned by journal 17 Nov, 2020 Editor invited by journal 17 Nov, 2020 You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-39669","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":5022289,"identity":"c2514a59-7026-4057-9b63-fcdc094b1654","order_by":0,"name":"Norihiko Takegami","email":"","orcid":"","institution":"Mie University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Norihiko","middleName":"","lastName":"Takegami","suffix":""},{"id":5022290,"identity":"93b8c6b3-e3c0-4364-a9da-daa6293d1a34","order_by":1,"name":"Koji Akeda","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0001-9468-9387","institution":"Mie University Graduate School of Medicine","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Koji","middleName":"","lastName":"Akeda","suffix":""},{"id":5022291,"identity":"21bc7457-dd4a-4e9a-a237-2430efd99631","order_by":2,"name":"Koichiro Murata","email":"","orcid":"","institution":"Mie University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Koichiro","middleName":"","lastName":"Murata","suffix":""},{"id":5022292,"identity":"c8d79f4e-2a63-40fe-bb71-8c263cf92f41","order_by":3,"name":"Junichi Yamada","email":"","orcid":"","institution":"Mie University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Junichi","middleName":"","lastName":"Yamada","suffix":""},{"id":5022293,"identity":"64205dc8-7d52-46c2-a566-a364865dca4a","order_by":4,"name":"Akihiro Sudo","email":"","orcid":"","institution":"Mie University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Akihiro","middleName":"","lastName":"Sudo","suffix":""}],"badges":[],"createdAt":"2020-07-01 13:29:39","currentVersionCode":3,"declarations":"","doi":"10.21203/rs.3.rs-39669/v3","doiUrl":"https://doi.org/10.21203/rs.3.rs-39669/v3","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12891-020-03814-0","type":"published","date":"2020-11-27T15:01:11+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":3790290,"identity":"7a7242f0-7ac0-4ee7-9291-5b8b0695a4c0","added_by":"auto","created_at":"2020-11-24 12:26:24","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":25003,"visible":true,"origin":"","legend":"Categorization of intervertebral discs (IVDs)\nIVDs were categorized according to the locations of adjacent vertebral fractures (VFs). The VF-negative (VF-) group was defined as those IVDs having no fracture in an adjacent vertebral body. The VF-positive (VF+) group was defined as those IVDs having a fracture in an adjacent vertebral body. The VF-positive group was further classified into three subgroups: those IVDs superior to the VF (superior), those IVDs inferior to the VF (inferior), and those IVDs located between VFs (bilateral).\n","description":"","filename":"Fig1.JPG","url":"https://assets-eu.researchsquare.com/files/rs-39669/v3/339ab1ac2cfa3b56bdac804e.JPG"},{"id":3790291,"identity":"972fc76c-f5fa-45b3-84b7-2c3e5f89e8b6","added_by":"auto","created_at":"2020-11-24 12:26:24","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":20818,"visible":true,"origin":"","legend":"Number of vertebral fractures (VFs) at different vertebral levels\nVFs were evaluated by lateral lumbar radiography. VFs were identified in 119 vertebrae (20.4%) of the 584 vertebral bodies analyzed.\n","description":"","filename":"Fig2.JPG","url":"https://assets-eu.researchsquare.com/files/rs-39669/v3/65effb6f4c1ba96a25a3c025.JPG"},{"id":3790292,"identity":"4fa75001-3114-4f5a-8c4b-a871b328a155","added_by":"auto","created_at":"2020-11-24 12:26:25","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":25099,"visible":true,"origin":"","legend":"Percentage of advanced stage disc degeneration at different intervertebral disc (IVD) levels\nThe degree of disc degeneration was evaluated by sagittal T2-weighted lumbar magnetic resonance imaging (MRI) and was graded according to Pfirrmann’s classification [14] from Grades I to V. Grades I, II and III were defined as early stage IVD degeneration and Grades IV and V as advanced stage.\n","description":"","filename":"Fig3.JPG","url":"https://assets-eu.researchsquare.com/files/rs-39669/v3/7da95710f610654ad68ef054.JPG"},{"id":3790293,"identity":"b86db0ed-183e-47bf-8c5e-82cf721e4409","added_by":"auto","created_at":"2020-11-24 12:26:25","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":35268,"visible":true,"origin":"","legend":"Percentage of advanced stage disc degeneration adjacent to vertebral fractures (VFs)\nA: The percentage of advanced stage disc degeneration evaluated by magnetic resonance imaging (MRI) was compared between VF-negative (VF-) and VF-positive (VF+) groups. **P \u003c 0.01 (by chi-square test). B: The VF+ group was classified into the following three subgroups: 1. IVDs superior to VFs (superior group), 2. IVDs inferior to VFs (inferior group), and 3. IVDs located between VFs (bilateral group). † P\u003c 0.006 (by Bonferroni correction).\n","description":"","filename":"Fig4.JPG","url":"https://assets-eu.researchsquare.com/files/rs-39669/v3/2e0cbbdbfd2449a8e4ca6aa7.JPG"},{"id":3790294,"identity":"0a82c27e-959f-403f-9df4-8a30d225e6a9","added_by":"auto","created_at":"2020-11-24 12:26:25","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":28270,"visible":true,"origin":"","legend":"Percentage of advanced stage disc degeneration adjacent to vertebral fractures (VFs) at different intervertebral disc levels\nThe percentages of advanced stage disc degeneration in T12/L1, L1/L2 and L2/L3 in the VF-positive group were significantly higher than those in the VF-negative group. However, there was no significant difference in the percentages of advanced stage disc degeneration between the VF-positive group and the VF-negative group in L3/L4 and L4/L5. *P\u003c0.05, **P\u003c0.01 between VF- and VF+.\n","description":"","filename":"Fig5.JPG","url":"https://assets-eu.researchsquare.com/files/rs-39669/v3/aeb7bb81a403198c339fcbc0.JPG"},{"id":3790295,"identity":"64d12bcc-74b4-4a1d-bffc-d759965690c4","added_by":"auto","created_at":"2020-11-24 12:26:25","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":22231,"visible":true,"origin":"","legend":"Number of vacuum phenomenon (VP)-positive discs at different intervertebral disc levels\nIntradiscal VP was evaluated by the presence of areas of gaseous radiolucency using multi-detector computed tomography (MDCT) imaging [15]. VPs were found in 226 IVDs (46.5%) of the 486 IVDs analyzed.\n","description":"","filename":"Fig6.JPG","url":"https://assets-eu.researchsquare.com/files/rs-39669/v3/816efeb1a9662d4ebb9c9228.JPG"},{"id":3790296,"identity":"217b0fcb-95b2-4ab9-86e3-9eba6717f835","added_by":"auto","created_at":"2020-11-24 12:26:25","extension":"jpg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":35393,"visible":true,"origin":"","legend":"Percentage of vacuum phenomenon (VP)-positive discs adjacent to vertebral fractures (VFs)\nA: Percentage of VP-positive discs between VF-negative (VF-) and VF-positive (VF+) groups. **P\u003c0.01 (by chi-square test). B: The VF+ group was classified into the following three subgroups: 1. IVDs superior to VFs (superior group), 2. IVDs inferior to VFs (inferior group), and 3. IVDs located between VFs (bilateral group). † P\u003c0.006 (by Bonferroni correction).\n","description":"","filename":"Fig7.JPG","url":"https://assets-eu.researchsquare.com/files/rs-39669/v3/8032c9d14787d0a557e188e3.JPG"},{"id":3790297,"identity":"41c19d9a-d493-46f7-bf2e-8c2963e0c1b4","added_by":"auto","created_at":"2020-11-24 12:26:25","extension":"jpg","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":25113,"visible":true,"origin":"","legend":"Percentage of vacuum phenomenon (VP)-positive discs adjacent to vertebral fractures (VFs) at different intervertebral disc levels\nThe percentages of VP-positive discs in T12/L1, L1/L2, L2/L3 and L3/L4 in the VF-positive group were significantly higher than those in the VF-negative group. *P\u003c0.05, **P\u003c0.01 between VF- and VF+ groups.\n","description":"","filename":"Fig8.JPG","url":"https://assets-eu.researchsquare.com/files/rs-39669/v3/98cc0217ae03514ddd59431b.JPG"},{"id":13620103,"identity":"d6ac935c-de34-4e77-be0f-ee601dca91a5","added_by":"auto","created_at":"2021-09-17 07:03:49","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1564467,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-39669/v3/8b74a00d-2bc9-40de-9ac2-aa155424e02d.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eAssociation between non-traumatic vertebral fractures and adjacent discs degeneration: a cross-sectional study and literature review\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eIntervertebral discs (IVDs) consist of\u0026nbsp;a central gelatinous nucleus pulposus and a surrounding fibrous annulus fibrosus (AF).\u0026nbsp;IVDs are constrained within and connected to adjacent vertebral bodies by superior and inferior cartilaginous endplates (CEPs).\u0026nbsp;Disc degeneration is considered to be caused by genetic predisposition, injury, aging, and environmental factors, or any combination thereof\u0026nbsp;[1].\u003c/p\u003e\n\u003cp\u003eBlood flow to the vertebral bodies of the lumbar spine is abundantly supplied by the lumbar arteries, which are branches of the abdominal aorta\u0026nbsp;[2].\u0026nbsp;IVDs are predominantly avascular and aneural tissues that exchange nutrients and metabolites primarily by diffusion to and from micro-vessels in the CEP and outer AF [3, 4]. The restricted transport and low cellularity of the discs limit repair. Therefore, endplate sclerosis, or an ischemic vertebra, is considered to be one of the factors responsible for IVD degeneration\u0026nbsp;[1, 5].\u003c/p\u003e\n\u003cp\u003ePrevious clinical studies reported that a thoracolumbar burst fracture with high energy spine trauma caused disc degeneration, and that, importantly, disc degeneration occurred at a level adjacent to the fractured vertebra [6-11].\u0026nbsp;One multicenter cohort study recently reported that progression of adjacent disc degeneration was observed at 6 months after osteoporotic VFs\u0026nbsp;[12]. However, further study is needed to determine the association between non-traumatic VFs, including osteoporotic fractures, and the progression of disc degeneration adjacent to VFs.\u003c/p\u003e\n\u003cp\u003eThe purpose of this cross-sectional population study was to examine the effect of non-traumatic VFs on degenerative changes of adjacent IVDs using magnetic resonance imaging (MRI) and computed tomography (CT) analyses.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eSubject: \u003c/strong\u003eThis IRB-approved retrospective study was conducted on spinal CT images of 98 consecutive patients (50 males and 48 females) undergoing spinal surgery (Table 1).\u003c/p\u003e\n\u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eTable 1. Patient characteristics\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable style=\"border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 104.1pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 27.55pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cstrong\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003eGroup\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 174.05pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 27.55pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cstrong\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003eSubjects (males/females)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 139.2pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 27.55pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cstrong\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003eAverage age (years)*\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 104.1pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 26.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003eVF-negative\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 174.05pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 26.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e50 (25/25)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 139.2pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 26.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e60.6 (23-87)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 104.1pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 27.55pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003eVF-positive\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 174.05pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 27.55pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e48 (25/23)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 139.2pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 27.55pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e75.4 (56-90)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 104.1pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 26.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003eTotal\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 174.05pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 26.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e98 (50/48)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 139.2pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 26.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e68.2 (23-90)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eVF: vertebral fracture. The numbar in the parenthesis in the average age column indicates the age range of subjects. *P\u0026lt;0.01 between VF-negative and VF-positive groups.\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003eThe overall average age of the patients was 68.2 years-old (range 23-90). The clinical diagnoses of the patients were as follows: 74 lumbar spinal stenosis, 15 lumbar disc herniation, 6 cervical spinal diseases, and 3 others. Patients with VFs caused by high energy trauma were excluded from this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMorphological classification of VFs:\u0026nbsp;\u003c/strong\u003eVFs were evaluated using lateral lumbar radiographs in all patients; 588 vertebral bodies from T12 to L5 were analyzed.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eVF deformities were classified into three groups (wedge, biconcave, or crush) using a semi-quantitative technique [13].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClassification of disc degeneration:\u0026nbsp;\u003c/strong\u003eMRI was performed in 74 patients. A total of 370 discs from T12/L1 to L4/L5 were analyzed with MRI. The degree of disc degeneration was evaluated with sagittal T2-weighted lumbar MRI, and graded according to Pfirrmann\u0026rsquo;s classification from Grades I to V\u0026nbsp;[14]. Grades I, II and III were defined as the early stage of IVD degeneration and Grades IV and V as the advanced stage.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiagnosis of vacuum phenomena (VPs):\u0026nbsp;\u003c/strong\u003eMulti-detector CT (MDCT) (slice increment: 1.0 mm, slice thickness: 1.0 mm; Asteion TSX-021B, Toshiba Medical Systems Co., Otawara, Tochigi, Japan) was performed for all patients. A total of 486 discs from T12/L1 to L4/L5 were analyzed with MDCT. Four discs were excluded, because the T12/L1 disc was outside the range of CT analysis in four patients. Intradiscal VPs were evaluated by the presence of areas of gaseous radiolucency using MDCT imaging and those shapes were classified using sagittal imaging as previously reported\u0026nbsp;[15]. In short, VP shapes were categorized according to three classifications: spot, linear, and island. A spot-type VP was defined as a point-like VP less than 2 mm in diameter. A linear-type rupture was defined as a radiating VP whose width was less than 2 mm. An island-type rupture was defined as a VP forming a wide cleft (\u0026gt;2 mm).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCategorization of IVDs:\u0026nbsp;\u003c/strong\u003eIVDs were categorized according to the locations of adjacent VFs. The control (VF-negative) group was defined as those IVDs having no fracture in an adjacent vertebral body. The VF-positive group was defined as those IVDs having fractures\u0026nbsp;in the adjacent vertebral body. Furthermore, the VF-positive group was further classified into three subgroups: those with IVDs superior to a VF\u0026nbsp;(superior group), those with IVDs inferior to a VF\u0026nbsp;(inferior group), and those with IVDs located between VFs (bilateral group) (Fig. 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe morphological classification of VFs, the classification of disc degeneration and the diagnosis of VPs\u0026nbsp;were evaluated by a single observer who was blinded to the categorization of the IVD groups. The\u0026nbsp;Chi-square test and Student\u0026rsquo;s t-tests were used to compare the differences in gender and age between patients with VFs and those without VFs.\u0026nbsp;The differences in the percentage of advanced stage of disc degeneration (MRI) or\u0026nbsp;the prevalence of VP among the categorization of IVDs according to\u0026nbsp;the locations of adjacent VFs were statistically assessed by a chi-square test followed by post hoc multiple comparisons using the Bonferroni method\u0026nbsp;[15]. The post hoc test was performed to assess the probability values for each combination of independent category levels by using a Bonferroni correction to control for type I error inflation\u0026nbsp;[16, 17].\u0026nbsp;Significance was determined by Chi-square test with post-hoc analysis by cellwise adjusted residual analysis in two-way contingency tables according to Garcia-Perez\u0026nbsp;[16-18]. Post-hoc testing was performed with adjusted standardized residual analysis with an eight-fold Bonferroni-adjusted p-value (p\u0026lt;0.006) or sixteen-fold Bonferroni-adjusted p-value (p\u0026lt;0.003) [19].\u003c/p\u003e\n\u003cp\u003eThe association between disc degeneration and the prevalence of an adjacent VF was evaluated by multiple logistic regression. Factors included in the multivariate model were age, gender, disc level, and adjacent VF(s). All the statistical analyses were performed using IBM SPSS Statistics (IBM Japan, Tokyo or IBM Corp., Armonk, NY, USA).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003ePatient characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eVFs were identified\u0026nbsp;in 119\u0026nbsp;vertebrae (20.4%) of the\u0026nbsp;584 vertebral bodies analyzed\u0026nbsp;(wedge type: 51.3%; biconcave type: 37.8%; crush type: 10.9%).\u0026nbsp;The number of VFs was highest in the L1 vertebral body and lowest in the L3 (n [% of total VFs]: T12: 22 [18.5%]; L1: 28 [23.5%]; L2: 20 [16.8%]; L3: 12 [10.1%]; L4: 15 [12.6%]; L5: 22 [18.5%]) (Fig. 2).\u0026nbsp;IVDs adjacent to VFs were identified in 115 IVDs (31.1%) of the 370 IVDs analyzed by MRI (superior: 42 [36.5%], bilateral: 32 [27.8%], inferior: 41 [35.7%]). IVDs adjacent to VFs were identified in 147 IVDs (30.2%) of the 486 IVDs analyzed by CT analysis (superior: 51 [34.7%], bilateral: 45 [30.6%], inferior: 51 [34.7%]).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssociation between VFs and disc degeneration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOf all the discs analyzed by MRI (370 discs), 228\u0026nbsp;IVDs (61.6%) were classified as advanced\u0026nbsp;degenerative\u0026nbsp;stage,\u0026nbsp;appearing most frequently in the L4/L5 disc and least frequently in the T12/L1 disc (T12/L1: 39.2%, L1/L2: 54.1%, L2/L3: 62.2%, L3/L4: 75.7%, L4/L5: 77.0%) (Fig. 3).\u003c/p\u003e\n\u003cp\u003eA chi-square test showed a significant association between the presence of VFs and MRI grades of IVD degeneration adjacent to VFs (P\u0026lt;0.01) (Fig. 4A).\u0026nbsp;The results of a post-hoc test showed that the numbers of IVDs with advanced stage degeneration were significantly lower than expected in the VF-negative group (P\u0026lt;0.006) (Fig. 4B). However, those with advanced stage degeneration were not significantly higher than expected in the IVDs of superior, bilateral, and inferior groups\u0026nbsp;(superior: 78.6%, bilateral: 65.6%, inferior: 78.0%) (Fig. 4B).\u003c/p\u003e\n\u003cp\u003eThere were no significant differences in the prevalence of advanced stage IVD degeneration among the deformity types of adjacent VF by chi-square test (wedge: 77%; biconcave: 76%; crush: 100%).\u003c/p\u003e\n\u003cp\u003eWhen the proportion of disc degeneration was analyzed by disc level, the percentages of advanced stage disc degeneration in T12/L1, L1/L2 and L2/L3 in the VF-positive group were significantly higher than those in the VF-negative group (Fig. 5). However, there were no significant differences in the percentages of advanced stage disc degeneration between the VF-positive group and the VF-negative group in L3/L4 and L4/L5.\u003c/p\u003e\n\u003cp\u003eThe results of logistic regression analysis showed that age, disc level, and adjacent VFs were independent factors that were significantly associated with the MRI-grade of IVD degeneration (Table 2).\u003c/p\u003e\n\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eTable 2. \u003cspan style=\"color:black;background:white;\"\u003eLogistic regression analysis of significant related factors for advanced stage of disc degeneration and intradiscal\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan style='line-height:200%;font-family:\"Times New Roman\",serif;'\u003evacuum phenomenon\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable style=\"width:425.0pt;border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:77.75pt;border:solid windowtext 1.0pt;padding:.75pt .75pt 0in .75pt;height:4.7pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width:99.2pt;border:solid windowtext 1.0pt;border-left: none;padding:.75pt .75pt 0in .75pt;height:4.7pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width:148.85pt;border:solid windowtext 1.0pt;border-left: none;padding:.75pt .75pt 0in .75pt;height:4.7pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eodds ratio (95%CI)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:99.2pt;border:solid windowtext 1.0pt;border-left: none;padding:.75pt .75pt 0in .75pt;height:4.7pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ep value\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width:77.75pt;border:solid windowtext 1.0pt;border-top:none;padding:.75pt .75pt 0in .75pt;height:8.65pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eDD\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:99.2pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:.75pt .75pt 0in .75pt;height:8.65pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eage\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:148.85pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:.75pt .75pt 0in .75pt;height:8.65pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e1.050 (1.029 - 1.071)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:99.2pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:.75pt .75pt 0in .75pt;height:8.65pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:99.2pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:.75pt .75pt 0in .75pt;height:8.65pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003edisc level\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:148.85pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:.75pt .75pt 0in .75pt;height:8.65pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e1.687 (1.412 - 2.017)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:99.2pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:.75pt .75pt 0in .75pt;height:8.65pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:99.2pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:.75pt .75pt 0in .75pt;height:8.65pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eadjacent VF\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:148.85pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:.75pt .75pt 0in .75pt;height:8.65pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e1.906 (1.079 - 3.368)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:99.2pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:.75pt .75pt 0in .75pt;height:8.65pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e0.026\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width:77.75pt;border:solid windowtext 1.0pt;border-top:none;padding:.75pt .75pt 0in .75pt;height:8.65pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eVP\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:99.2pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:.75pt .75pt 0in .75pt;height:8.65pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eage\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:148.85pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:.75pt .75pt 0in .75pt;height:8.65pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e1.054 (1.034 - 1.076)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:99.2pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:.75pt .75pt 0in .75pt;height:8.65pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:99.2pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:.75pt .75pt 0in .75pt;height:8.65pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003edisc level\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:148.85pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:.75pt .75pt 0in .75pt;height:8.65pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e1.513 (1.298 - 1.764)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:99.2pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:.75pt .75pt 0in .75pt;height:8.65pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:99.2pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:.75pt .75pt 0in .75pt;height:.7pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eadjacent VF\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:148.85pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:.75pt .75pt 0in .75pt;height:.7pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e2.476 (1.553 - 3.949)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:99.2pt;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:.75pt .75pt 0in .75pt;height:.7pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026lt;0.001\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cspan style='line-height:200%;font-family:\"Times New Roman\",serif;'\u003eDD: disc degeneration, VP: vacuum phenomenon, VF: vertebral fracture\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssociation between VFs and intradiscal VPs\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eVPs were found in 226 IVDs (46.5%) of the 486 IVDs analyzed. The number of discs with a VP was highest in the L4/5 level (55.1%). At other levels, VPs were found in 34-41% of the discs, with the exception of the T12/L1 level, where a VP was found in 20.2% of IVDs (Fig. 6).\u003c/p\u003e\n\u003cp\u003eA chi-square test showed a significant association between the presence of VFs and VPs within IVDs adjacent to a VF (P\u0026lt;0.01) (Fig. 7A). The results of a post-hoc test showed that the numbers of IVDs with VPs were significantly lower than expected in the VF-negative group (29.2%) (P\u0026lt;0.006), and significantly higher than expected in superior and inferior groups (superior: 64.7%, inferior: 58.8%) (P\u0026lt;0.006) (Fig. 7B).\u0026nbsp;In the VP shape analysis, the number of IVDs with an island shape VP was significantly lower than expected in the VF-negative group (P\u0026lt;0.003), and significantly higher than expected in the superior group (P\u0026lt;0.0006) (Table 3).\u003c/p\u003e\n\u003cp\u003eA chi-square test showed a significant association between the deformity type of VF and the prevalence of a VP within IVDs adjacent to the VF (P\u0026lt;0.05). There was a tendency for the percentage of VPs to be lower in IVDs adjacent to wedge type VFs (52%). VPs were identified in all IVDs adjacent to crush type VFs (n=7).\u003c/p\u003e\n\u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Century\",serif;line-height:200%;'\u003e\u003cstrong\u003e\u003cspan style='font-size:16px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eTable 3. Association between the location of intervertebral discs (IVDs) adjacent to vertebral fractures (VFs) and the shape of intradiscal vacuum phenomena (VPs)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable style=\"width:100.0%;border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width:20.22%;border:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:13.5pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003eIVD location\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width:25.2%;border:solid windowtext 1.0pt;border-left:none;padding:0in 5.4pt 0in 5.4pt;height:13.5pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width:45.5%;border:solid windowtext 1.0pt;border-left:none;padding:0in 5.4pt 0in 5.4pt;height:13.5pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003eVP shape\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width:9.06%;border:solid windowtext 1.0pt;border-left:none;padding:0in 5.4pt 0in 5.4pt;height:13.5pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003eTotal\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:13.0%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:13.5pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003eVP (-)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:9.72%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:13.5pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003eSpot\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:10.84%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:13.5pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003eLinear\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:11.94%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:13.5pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003eIsland\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width:20.22%;border:solid windowtext 1.0pt;border-top:none;padding:0in 5.4pt 0in 5.4pt;height:27.0pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003eVF (-)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:25.2%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:27.0pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003eCount\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e(% raw)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:13.0%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:27.0pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cstrong\u003e\u003cspan style='font-size:16px;font-family: \"Times New Roman\",serif;'\u003e240**\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cstrong\u003e\u003cspan style='font-size:16px;font-family: \"Times New Roman\",serif;'\u003e(70.8)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:9.72%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:27.0pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e18\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e(5.3)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:10.84%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:27.0pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e29\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e(8.6)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:11.94%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:27.0pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cstrong\u003e\u003cspan style='font-size:16px;font-family: \"Times New Roman\",serif;'\u003e52*\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cstrong\u003e\u003cspan style='font-size:16px;font-family: \"Times New Roman\",serif;'\u003e(15.3)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:9.06%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:27.0pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e339\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:25.2%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:13.5pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003eExp. Count\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:13.0%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:13.5pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cstrong\u003e\u003cspan style='font-size:16px;font-family: \"Times New Roman\",serif;'\u003e221.4\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:9.72%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:13.5pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e25.8\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:10.84%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:13.5pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e37.0\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:11.94%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:13.5pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cstrong\u003e\u003cspan style='font-size:16px;font-family: \"Times New Roman\",serif;'\u003e64.9\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:9.06%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:13.5pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:25.2%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:27.0pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003eCorrected P-value\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:13.0%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:27.0pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cstrong\u003e\u003cspan style='font-size:16px;font-family: \"Times New Roman\",serif;'\u003e\u0026lt;0.0006\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:9.72%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:27.0pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e0.004\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:10.84%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:27.0pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e0.012\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd 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5.4pt 0in 5.4pt;height:27.0pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e0.353\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:10.84%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:27.0pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e0.011\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:11.94%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:27.0pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e0.299\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:9.06%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:27.0pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width:20.22%;border:solid windowtext 1.0pt;border-top:none;padding:0in 5.4pt 0in 5.4pt;height:27.0pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003eInferior\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:25.2%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:27.0pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003eCount\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e(% raw)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:13.0%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:27.0pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cstrong\u003e\u003cspan style='font-size:16px;font-family: \"Times New Roman\",serif;'\u003e21*\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cstrong\u003e\u003cspan style='font-size:16px;font-family: \"Times New Roman\",serif;'\u003e(41.2)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:9.72%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:27.0pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e5\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e(9.8)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:10.84%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:27.0pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e9\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e(17.6)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:11.94%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:27.0pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e16\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e(31.4)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:9.06%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:27.0pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e51\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:25.2%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:13.5pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003eExp. Count\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:13.0%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:13.5pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cstrong\u003e\u003cspan style='font-size:16px;font-family: \"Times New Roman\",serif;'\u003e31.8\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:9.72%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:13.5pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e3.9\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:10.84%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:13.5pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e5.6\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:11.94%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:13.5pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e9.8\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:9.06%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:13.5pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:25.2%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:27.0pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003eCorrected P-value\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:13.0%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:27.0pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cstrong\u003e\u003cspan style='font-size:16px;font-family: \"Times New Roman\",serif;'\u003e\u0026lt;0.003\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:9.72%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:27.0pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e0.533\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:10.84%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:27.0pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e0.103\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:11.94%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:27.0pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e0.019\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:9.06%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:27.0pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:20.22%;border:solid windowtext 1.0pt;border-top:none;padding:0in 5.4pt 0in 5.4pt;height:13.5pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width:25.2%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:13.5pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003eTotal\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:13.0%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:13.5pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e303\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:9.72%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:13.5pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e37\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:10.84%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:13.5pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e53\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:11.94%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:13.5pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e93\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:9.06%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:13.5pt;\"\u003e\n \u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\"Century\",serif;'\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003e486\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\nThe results of a contingency-table test are presented. Intervertebral discs (IVDs) were categorized according to the locations of adjacent vertebral fractures (VFs). Percentages of the raw marginal total (% raw) are in parentheses. VF (-): no VF group; VP (-); no vacuum phenomena group; Exp. Count: expected count. *P \u003c 0.003, **P \u003c 0.0006 (by Bonferroni correction). The cells with counts above or below the expected count with statistical significance are shown in bold.\nWhen the prevalence of intradiscal VPs was analyzed by disc level, the percentages of VP-positive discs in T12/L1, L1/L2, L2/L3 and L3/L4 in the VF-positive group were significantly higher than those in the VF-negative group (Fig. 8). However, there was no significant difference in the percentages of VP-positive discs between the VF-positive and -negative groups in the L4/L5 level.\nA logistic regression analysis revealed that age, disc level, and adjacent vertebral fracture were independent factors that were significantly associated with the presence of intradiscal VPs (Table 2).\n"},{"header":"Discussion","content":"\u003cp\u003eWe conducted a cross-sectional retrospective study of\u0026nbsp;consecutive patients undergoing spinal surgery\u0026nbsp;to evaluate the association between non-traumatic VFs and IVD degeneration adjacent to VFs. VFs were significantly associated with MRI grades of IVD degeneration and the presence of intradiscal VPs of discs adjacent to VFs. Logistic regression analysis showed that VF was one of the independent related factors for adjacent disc degeneration.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Eight clinical studies have evaluated the association between thoracolumbar VFs with spine trauma and adjacent disc degeneration (Table 4). Among these, two studies focused on degenerative IVDs adjacent to a VF in children or young patients who were treated conservatively\u0026nbsp;[6, 20]. Kerttula et al. investigated the occurrence of disc degeneration by MRI in young patients (average-age: 15.5 years) with a history of wedge type VFs\u0026nbsp;[6]. They concluded that wedge type VFs, especially with endplate injury, in young people were significantly associated with the occurrence of disc degeneration\u0026nbsp;[6]. Later, Moller et al.\u0026nbsp;[20]\u0026nbsp;evaluated whether VFs in children (average-age: 12 years) are a risk factor for adjacent IVD degeneration. They used MRI and the Oner classification scheme\u0026nbsp;[21], which mainly classifies morphological changes of IVDs and endplate injuries, and reported no significant association between stable VFs and adjacent disc degeneration\u0026nbsp;[20]. Because of differences in MRI assessments and type of injuries (Table 4), the relationship between VFs and adjacent disc degeneration in young people and children remains controversial. The other six clinical studies had evaluated disc degeneration following thoracolumbar VFs (AO classification\u0026nbsp;[22]: type A1-4) treated with spine surgeries (Table 4).\u0026nbsp;Posterior pedicle screw fixation was performed in four studies\u0026nbsp;[7-9, 23]\u0026nbsp;and instrumented kyphoplasty in two studies\u0026nbsp;[10, 11]. Among six clinical studies, adjacent disc degeneration was evaluated by MRI in five studies [7-10, 23], and by radiograph in one study [11]. These studies have shown that adjacent disc degeneration had significantly progressed at 9 to 32 months after thoracolumbar burst fractures in comparison with those at the time of injury, except for one study reported by Verlaan et al. [23]. Three studies [8, 10, 11] have reported that disc degeneration was predominantly found at the superior adjacent disc. On the other hand, Sander et al. [9] reported that the disc degradation was identified both at superior and inferior adjacent discs after traumatic VFs. Toyone et al. [7] also showed that adjacent disc degeneration had progressed at two years after burst fractures; however, the degeneration of superior and inferior adjacent discs were not separately analyzed. Lastly, Verlaan et al. [23] reported that 10.5% of the superior adjacent discs and 15.8% of inferior adjacent discs showed progression of degeneration at 12 to 18 months after trauma. However, they concluded that no statistically significant progression in adjacent disc degeneration was found for superior or inferior discs.\u003c/p\u003e\n\u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cstrong\u003e\u003cspan style='font-size:16px;font-family:\"Times New Roman\",serif;'\u003eTable 4. Association between thoracolumbar vertebral fractures with spine trauma and the adjacent disc degeneration\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable style=\"border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1.5pt solid rgb(102, 102, 102);background: white;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAuthor\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57.2pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1.5pt solid rgb(102, 102, 102);background: white;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eYear\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1.5pt solid rgb(102, 102, 102);background: white;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eSubjects\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.7pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1.5pt solid rgb(102, 102, 102);background: white;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eAge (averaged)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 69.7pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1.5pt solid rgb(102, 102, 102);background: white;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eDesign\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.9pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1.5pt solid rgb(102, 102, 102);background: white;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eFollow-up\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86.75pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1.5pt solid rgb(102, 102, 102);background: white;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eType of injury\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66.25pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1.5pt solid rgb(102, 102, 102);background: white;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eTreatment\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73.2pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1.5pt solid rgb(102, 102, 102);background: white;padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eMRI Assessment\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73.5pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);background: rgb(204, 204, 204);padding: 0in 5.4pt;height: 61.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eKerttula\u003csup\u003e6\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57.2pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);background: rgb(204, 204, 204);padding: 0in 5.4pt;height: 61.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e2000\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);background: rgb(204, 204, 204);padding: 0in 5.4pt;height: 61.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e14\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.7pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);background: rgb(204, 204, 204);padding: 0in 5.4pt;height: 61.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e15.5 [8.8- 20.8]\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 69.7pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);background: rgb(204, 204, 204);padding: 0in 5.4pt;height: 61.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eRetrospective study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.9pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);background: rgb(204, 204, 204);padding: 0in 5.4pt;height: 61.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e3.8 Y\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86.75pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);background: rgb(204, 204, 204);padding: 0in 5.4pt;height: 61.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eWedge-type (14)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66.25pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);background: rgb(204, 204, 204);padding: 0in 5.4pt;height: 61.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eConservative\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73.2pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid rgb(102, 102, 102);background: rgb(204, 204, 204);padding: 0in 5.4pt;height: 61.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eDecrease in T2 signal intensity\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73.5pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eMoller\u003csup\u003e20\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57.2pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e2007\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e20\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.7pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e12 [7 - 16]\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 69.7pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eObservational cohort study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.9pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e40 Y\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86.75pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eStable (18), Denis type B (2)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66.25pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eConservative\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73.2pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid rgb(102, 102, 102);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eOner classification Scheme\u003csup\u003e21\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73.5pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);background: rgb(204, 204, 204);padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eVerlaan\u003csup\u003e23\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57.2pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);background: rgb(204, 204, 204);padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e2013\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);background: rgb(204, 204, 204);padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e20\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.7pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);background: rgb(204, 204, 204);padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e42 [18 - 74]\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 69.7pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);background: rgb(204, 204, 204);padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eProspective trial\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.9pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);background: rgb(204, 204, 204);padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e12 to 18 M\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86.75pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);background: rgb(204, 204, 204);padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eAO: A3 (20), A4 (1)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66.25pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);background: rgb(204, 204, 204);padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003ePS fixation\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73.2pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid rgb(102, 102, 102);background: rgb(204, 204, 204);padding: 0in 5.4pt;height: 18.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003ePfirrmann classification\u003csup\u003e14\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73.5pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);padding: 0in 5.4pt;height: 56.25pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eToyone\u003c/span\u003e\u003csup\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e7\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57.2pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);padding: 0in 5.4pt;height: 56.25pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e2013\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);padding: 0in 5.4pt;height: 56.25pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e12\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.7pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);padding: 0in 5.4pt;height: 56.25pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e38 [14 - 59]\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 69.7pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);padding: 0in 5.4pt;height: 56.25pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eProspective consecutive series\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.9pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);padding: 0in 5.4pt;height: 56.25pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e10 Y\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86.75pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);padding: 0in 5.4pt;height: 56.25pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAO: A3 (12)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66.25pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);padding: 0in 5.4pt;height: 56.25pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePS fixation\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73.2pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid rgb(102, 102, 102);padding: 0in 5.4pt;height: 56.25pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eBorenstein\u0026apos;s report (score: 0-3)\u003csup\u003e37\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73.5pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);background: rgb(204, 204, 204);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eWang\u003c/span\u003e\u003csup\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e8\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57.2pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);background: rgb(204, 204, 204);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e2013\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);background: rgb(204, 204, 204);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e26\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.7pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);background: rgb(204, 204, 204);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e39.6 [21 - 54]\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 69.7pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);background: rgb(204, 204, 204);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eRetrospective study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.9pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);background: rgb(204, 204, 204);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e9-12 M\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86.75pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);background: rgb(204, 204, 204);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eAO: A3 (26)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66.25pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);background: rgb(204, 204, 204);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003ePS fixation\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73.2pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid rgb(102, 102, 102);background: rgb(204, 204, 204);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003ePfirrmann classification\u003csup\u003e14\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73.5pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eSander\u003c/span\u003e\u003csup\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e9\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57.2pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e2014\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e27\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.7pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e37.5 [16 - 59]\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 69.7pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eRetrospective study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.9pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e1 Y\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86.75pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAO: A1 (5), A2 (14), A3 (8)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66.25pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003ePS fixation\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73.2pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid rgb(102, 102, 102);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eOriginal classification (Grade 0-3)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73.5pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);background: rgb(204, 204, 204);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eNoriega\u003c/span\u003e\u003csup\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e10\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57.2pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);background: rgb(204, 204, 204);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e2016\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);background: rgb(204, 204, 204);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e20\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.7pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);background: rgb(204, 204, 204);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e50.7 [45 - 56]\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 69.7pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);background: rgb(204, 204, 204);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eRetrospective study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.9pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);background: rgb(204, 204, 204);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003e32 M\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86.75pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);background: rgb(204, 204, 204);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eAO: A1 (10), A3 (10)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66.25pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);background: rgb(204, 204, 204);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eIKP\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73.2pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid rgb(102, 102, 102);background: rgb(204, 204, 204);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;color:black;'\u003eDiffusion-weighted MR \u003cu\u003eimaging\u003c/u\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73.5pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eDescamps\u003csup\u003e11\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57.2pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e2019\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48.75pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e93\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.7pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e54 [18 - 83]\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 69.7pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eRetrospective study\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51.9pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e26.7 M\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86.75pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eAO: A1 (54), A2 (5), A3 (34)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66.25pt;border-top: none;border-left: none;border-bottom: 1pt solid rgb(102, 102, 102);border-right: 1pt solid rgb(102, 102, 102);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eIKP\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73.2pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid rgb(102, 102, 102);padding: 0in 5.4pt;height: 37.5pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eRadiograph\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eUCLA Grading Scale\u003csup\u003e38\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;'\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-size:16px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eY: years, M: months, PS fixation:\u0026nbsp;\u003c/span\u003e\u003cspan style='font-size:16px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003ePedicle screw fixation, AO: AO classification\u003csup\u003e19\u003c/sup\u003e, IKP: instrumented kyphoplasty.\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-size:16px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eOVF: osteoporotic vertebral fracture\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\"Yu Mincho\",serif;line-height:200%;'\u003e\u003cspan style='font-size:16px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eNumbers in the brackets indicate the range of age. Number in the parentheses indicates the number of subjects.\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;In contrast to these previous studies, the results of the current study showed a significant association between non-traumatic VFs and disc degeneration, at both superior and inferior adjacent levels, in a relatively older population.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Rahmani et al. have recently evaluated whether endplate fracture (injury) and adjacent disc degeneration have a significant association with the occurrence of delayed union following osteoporotic VFs for 139 consecutive patients (average age: 79 years-old) who were treated conservatively [12]. They also evaluated signal changes of adjacent IVDs in MR T2-weighted images at enrollment and at 6 months follow-up based on a modified Pfirrmann grading system and reported that adjacent cranial disc degeneration had significantly progressed at 6 months post-injury. This suggests the possibility that disc degeneration would progress in the relatively short term after osteoporotic VFs.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Next, to evaluate the effect of spinal levels on disc degeneration, the relationship between VFs and disc degeneration at different IVD levels was assessed (Fig. 5). Although\u0026nbsp;there was no significant difference in the percentages of advanced stage of disc degeneration between VF-positive and VF-negative groups in L3/L4 and L4/L5, those percentages in T12/L1, L1/L2 and L2/L3 discs, which would be expected to have less degeneration than lower lumbar levels\u0026nbsp;[24], were significantly higher in the VF-positive group than in the VF-negative group. This suggests that the effect of VFs on adjacent disc degeneration would be more pronounced at upper lumbar levels than those at middle/lower lumbar levels.\u0026nbsp;There is also evidence to support this suggestion from cadaveric studies [25-29]. Dolan et al. [25]\u0026nbsp;performed a mechanical and morphological study to evaluate how spinal level influences disc degeneration arising from endplate fracture. They reported that the effects of vertebral endplate fracture on disc mechanical function, and specifically on disc decompression, were greater at thoracic and upper lumbar levels than at lower lumbar levels.\u003c/p\u003e\n\u003cp\u003eIn addition, we evaluated the association between VFs and the presence of adjacent intradiscal VPs. Intradiscal VPs refer to the radiographic appearance of a lucency caused by the presence of gas, usually found in the lumbar region [30, 31]; this is one of the characteristics of IVD degeneration [15, 32]. Murata and colleagues showed that the presence of intradiscal VPs is associated with the MRI-grade of disc degeneration and radiographic disc height narrowing\u0026nbsp;[15]. The results of the current study showed that the incidence of VPs, especially the island type, in the VF-positive group was significantly higher than that in the VF-negative group; this suggests that VFs have an impact, not only on the extent of MRI-graded disc degeneration, but also on the intradiscal ruptures evaluated by CT imaging as intradiscal VPs.\u003c/p\u003e\n\u003cp\u003eThe results of the analysis of intradiscal VPs by disc level were nearly identical to those of MRI-graded disc degeneration. Lafforgue and colleagues reported that VPs were grouped into collapse-related VPs and degenerative VPs\u0026nbsp;[33]. They reported that collapse-related VPs, which were secondary to vertebral collapse, were located mainly in the thoracolumbar junction. Degenerative VPs, which were the result of disc degeneration, were located in lower lumbar discs. Therefore, in the current study, we speculate that intradiscal VPs in upper lumbar levels would be mainly attributed to VFs (vertebral collapse).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;According to the results of logistic regression analyses, age, disc level, and adjacent vertebral fracture were independent related factors for disc degeneration and intradiscal VPs (Table 2). It is well known that being elderly and lower disc level were significant related factors for disc degeneration\u0026nbsp;[24, 34, 35]. The current study showed evidence that VFs are also an independent related factor for adjacent disc degeneration for the population with non-traumatic VFs.\u003c/p\u003e\n\u003cp\u003eThe following three patho-mechanisms are involved in the occurrence of adjacent disc degeneration. First, endplate and IVD injuries directly caused by VFs promote the progression of disc degeneration.\u0026nbsp;Fujiwara and\u0026nbsp;colleagues reported that endplate injuries were observed in 61%, and IVD lesions in 60% of patients with an acute, single osteoporotic VF\u0026nbsp;[36].\u0026nbsp;Second, the progression of vertebral collapse is thought to cause impaired blood flow in vertebral bodies, to reduce\u0026nbsp;blood flow and\u0026nbsp;nutrient supply to the disc, and to cause disc degeneration\u0026nbsp;[1, 5]. Imanishi and\u0026nbsp;colleagues recently\u0026nbsp;showed using a rabbit lumbar artery ligation model that ischemia of lumbar vertebrae initiated degenerative changes in IVDs\u0026nbsp;[4].\u0026nbsp;Therefore, an ischemic vertebra is considered to be one of the important factors responsible for IVD degeneration.\u0026nbsp;Third, mechanical stress is also involved in the progression of adjacent disc degeneration. Dolan et al. reported that vertebral endplate fracture reduced nucleus pressure and created abnormal stress distributions in the adjacent IVD, increasing the risk of internal disruption and degeneration [25]. Interestingly, Stefanakis et al. and Zehra et al. performed mechanical and morphological studies to determine whether high gradients\u0026nbsp;of compressive stress within the IVD are associated with progressive disc degeneration [27, 29]. They reported that as the grade of disc degeneration increased, nucleus pressure decreased. However, stress gradients (concentration) in the annulus increased.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA limitation of this study is that most of the subjects were patients who had been given pre-operative radiographs, CT, and MRI for elective spinal surgeries. Therefore, MRI grading of IVDs and percentage of intradiscal VPs would be much higher than those within a general population [24]. Another limitation is that VFs in our study excluded those caused by high energy trauma. Although the evaluation of osteoporosis was not performed in this study, most VFs in the subjects of this study would be osteoporotic VFs. Thirdly, the other risk factors associated with VFs, such as obesity and physical activity, and the clinical outcome including the subject\u0026rsquo;s low back pain have not been evaluated in this study. Further study would be needed to evaluate the risk factors of adjacent disc degeneration following VFs, and the association of adjacent disc degeneration and clinical outcomes.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis study showed that non-traumatic VFs are an independent related factor for adjacent disc degeneration and the occurrence of intradiscal VPs at the corresponding level. From the results of the current study, we speculate that VFs may affect the micro-environment of adjacent IVDs, leading to progression of disc degeneration and disc ruptures. Therefore, careful follow-up is necessary even for non-traumatic VFs (mostly osteoporotic VFs) and proper treatment, including surgical intervention, of VFs may prevent the progression of disc degeneration.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eVF: vertebral fracture; IVD: intervertebral disc; AF: annulus fibrosus; CEP: cartilaginous endplate; CT: computed tomography; MDCT: multi-detector CT; VP: vacuum phenomenon; MRI: magnetic resonance imaging\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthics were approved by the institutional review board of the Mie University Hospital (Tsu, Mie, Japan; IRB reference number: H2020-028). Written or oral informed consent was obtained from all the subjects.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and analyzed during the current study are available from the corresponding author at a reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflict of interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNT performed data acquisition and statistical analysis and drafted the manuscript. KA helped to perform data acquisition and statistical analyses, drafted the manuscript, conceived of this study, and made substantial contributions to study design. KM and JY performed data acquisition, and revised the manuscript. AS contributed to the study design and coordination and revised the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eVo NV, Hartman RA, Patil PR, Risbud MV, Kletsas D, Iatridis JC, Hoyland JA, Le Maitre CL, Sowa GA, Kang JD: \u003cstrong\u003eMolecular mechanisms of biological aging in intervertebral discs\u003c/strong\u003e. \u003cem\u003eJ Orthop Res \u003c/em\u003e2016, \u003cstrong\u003e34\u003c/strong\u003e(8):1289-1306.\u003c/li\u003e\n\u003cli\u003eHassler O: \u003cstrong\u003eThe human intervertebral disc. 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\u003cstrong\u003e80\u003c/strong\u003e(5):833-839.\u003c/li\u003e\n\u003cli\u003eMagerl F, Aebi M, Gertzbein SD, Harms J, Nazarian S: \u003cstrong\u003eA comprehensive classification of thoracic and lumbar injuries\u003c/strong\u003e. \u003cem\u003eEur Spine J \u003c/em\u003e1994, \u003cstrong\u003e3\u003c/strong\u003e(4):184-201.\u003c/li\u003e\n\u003cli\u003eVerlaan JJ, Dhert WJ, Oner FC: \u003cstrong\u003eIntervertebral disc viability after burst fractures of the thoracic and lumbar spine treated with pedicle screw fixation and direct end-plate restoration\u003c/strong\u003e. \u003cem\u003eSpine J \u003c/em\u003e2013, \u003cstrong\u003e13\u003c/strong\u003e(3):217-221.\u003c/li\u003e\n\u003cli\u003eTeraguchi M, Yoshimura N, Hashizume H, Muraki S, Yamada H, Minamide A, Oka H, Ishimoto Y, Nagata K, Kagotani R\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003ePrevalence and distribution of intervertebral disc degeneration over the entire spine in a population-based cohort: the Wakayama Spine Study\u003c/strong\u003e. \u003cem\u003eOsteoarthritis Cartilage \u003c/em\u003e2014, \u003cstrong\u003e22\u003c/strong\u003e(1):104-110.\u003c/li\u003e\n\u003cli\u003eDolan P, Luo J, Pollintine P, Landham PR, Stefanakis M, Adams MA: \u003cstrong\u003eIntervertebral disc decompression following endplate damage: implications for disc degeneration depend on spinal level and age\u003c/strong\u003e. \u003cem\u003eSpine (Phila Pa 1976) \u003c/em\u003e2013, \u003cstrong\u003e38\u003c/strong\u003e(17):1473-1481.\u003c/li\u003e\n\u003cli\u003ePollintine P, Dolan P, Tobias JH, Adams MA: \u003cstrong\u003eIntervertebral disc degeneration can lead to \"stress-shielding\" of the anterior vertebral body: a cause of osteoporotic vertebral fracture?\u003c/strong\u003e \u003cem\u003eSpine (Phila Pa 1976) \u003c/em\u003e2004, \u003cstrong\u003e29\u003c/strong\u003e(7):774-782.\u003c/li\u003e\n\u003cli\u003eStefanakis M, Luo J, Pollintine P, Dolan P, Adams MA: \u003cstrong\u003eISSLS Prize winner: Mechanical influences in progressive intervertebral disc degeneration\u003c/strong\u003e. \u003cem\u003eSpine (Phila Pa 1976) \u003c/em\u003e2014, \u003cstrong\u003e39\u003c/strong\u003e(17):1365-1372.\u003c/li\u003e\n\u003cli\u003eAdams MA, Pollintine P, Tobias JH, Wakley GK, Dolan P: \u003cstrong\u003eIntervertebral disc degeneration can predispose to anterior vertebral fractures in the thoracolumbar spine\u003c/strong\u003e. \u003cem\u003eJ Bone Miner Res \u003c/em\u003e2006, \u003cstrong\u003e21\u003c/strong\u003e(9):1409-1416.\u003c/li\u003e\n\u003cli\u003eZehra U, Noel-Barker N, Marshall J, Adams MA, Dolan P: \u003cstrong\u003eAssociations Between Intervertebral Disc Degeneration Grading Schemes and Measures of Disc Function\u003c/strong\u003e. \u003cem\u003eJ Orthop Res \u003c/em\u003e2019, \u003cstrong\u003e37\u003c/strong\u003e(9):1946-1955.\u003c/li\u003e\n\u003cli\u003eVernon-Roberts B, Moore RJ, Fraser RD: \u003cstrong\u003eThe natural history of age-related disc degeneration: the pathology and sequelae of tears\u003c/strong\u003e. \u003cem\u003eSpine (Phila Pa 1976) \u003c/em\u003e2007, \u003cstrong\u003e32\u003c/strong\u003e(25):2797-2804.\u003c/li\u003e\n\u003cli\u003eVideman T, Nurminen M: \u003cstrong\u003eThe occurrence of anular tears and their relation to lifetime back pain history: a cadaveric study using barium sulfate discography\u003c/strong\u003e. \u003cem\u003eSpine (Phila Pa 1976) \u003c/em\u003e2004, \u003cstrong\u003e29\u003c/strong\u003e(23):2668-2676.\u003c/li\u003e\n\u003cli\u003eLi FC, Zhang N, Chen WS, Chen QX: \u003cstrong\u003eEndplate degeneration may be the origination of the vacuum phenomenon in intervertebral discs\u003c/strong\u003e. \u003cem\u003eMed Hypotheses \u003c/em\u003e2010, \u003cstrong\u003e75\u003c/strong\u003e(2):169-171.\u003c/li\u003e\n\u003cli\u003eLafforgue PF, Chagnaud CJ, Daver LM, Daumen-Legre VM, Peragut JC, Kasbarian MJ, Volot F, Acquaviva PC: \u003cstrong\u003eIntervertebral disk vacuum phenomenon secondary to vertebral collapse: prevalence and significance\u003c/strong\u003e. \u003cem\u003eRadiology \u003c/em\u003e1994, \u003cstrong\u003e193\u003c/strong\u003e(3):853-858.\u003c/li\u003e\n\u003cli\u003eBoos N, Weissbach S, Rohrbach H, Weiler C, Spratt KF, Nerlich AG: \u003cstrong\u003eClassification of age-related changes in lumbar intervertebral discs: 2002 Volvo Award in basic science\u003c/strong\u003e. \u003cem\u003eSpine (Phila Pa 1976) \u003c/em\u003e2002, \u003cstrong\u003e27\u003c/strong\u003e(23):2631-2644.\u003c/li\u003e\n\u003cli\u003eKanayama M, Togawa D, Takahashi C, Terai T, Hashimoto T: \u003cstrong\u003eCross-sectional magnetic resonance imaging study of lumbar disc degeneration in 200 healthy individuals\u003c/strong\u003e. \u003cem\u003eJ Neurosurg Spine \u003c/em\u003e2009, \u003cstrong\u003e11\u003c/strong\u003e(4):501-507.\u003c/li\u003e\n\u003cli\u003eFujiwara T, Akeda K, Yamada J, Kondo T, Sudo A: \u003cstrong\u003eEndplate and intervertebral disc injuries in acute and single level osteoporotic vertebral fractures: is there any association with the process of bone healing?\u003c/strong\u003e \u003cem\u003eBMC Musculoskelet Disord \u003c/em\u003e2019, \u003cstrong\u003e20\u003c/strong\u003e(1):336.\u003c/li\u003e\n\u003cli\u003eBorenstein DG, O'Mara JW, Jr., Boden SD, Lauerman WC, Jacobson A, Platenberg C, Schellinger D, Wiesel SW: \u003cstrong\u003eThe value of magnetic resonance imaging of the lumbar spine to predict low-back pain in asymptomatic subjects : a seven-year follow-up study\u003c/strong\u003e. \u003cem\u003eJ Bone Joint Surg Am \u003c/em\u003e2001, \u003cstrong\u003e83\u003c/strong\u003e(9):1306-1311.\u003c/li\u003e\n\u003cli\u003eGhiselli G, Wang JC, Bhatia NN, Hsu WK, Dawson EG: \u003cstrong\u003eAdjacent segment degeneration in the lumbar spine\u003c/strong\u003e. \u003cem\u003eJ Bone Joint Surg Am \u003c/em\u003e2004, \u003cstrong\u003e86\u003c/strong\u003e(7):1497-1503.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"
[email protected]","identity":"bmc-musculoskeletal-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmsd","sideBox":"Learn more about [BMC Musculoskeletal Disorders](http://bmcmusculoskeletdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://author-welcome.nature.com/12891","title":"BMC Musculoskeletal Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"vertebral fracture, disc degeneration, intradiscal vacuum phenomenon, magnetic resonance imaging (MRI), computed tomography (CT)","lastPublishedDoi":"10.21203/rs.3.rs-39669/v3","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-39669/v3","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\u003cp\u003ePrevious clinical studies reported that thoracolumbar vertebral fractures (VFs) associated with high energy spine trauma cause adjacent intervertebral disc (IVD) degeneration; however, the effect of non-traumatic VFs on the progression of adjacent disc degeneration remains to be determined. The purpose of this study was to examine the association between non-traumatic VFs and degenerative changes of adjacent IVDs.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\u003cp\u003e98 consecutive patients undergoing spinal surgery were included in this study. VFs were semi-quantitatively evaluated by lateral lumbar radiography. 588 vertebral bodies (from T12 to L5) and 486 discs (from T12/L1 to L4/L5) were analyzed. The degree of IVD degeneration was evaluated by magnetic resonance imaging (MRI) and classified into two groups according to Pfirrmann’s classification. Grades I, II and III were defined as the early stage of IVD degeneration and Grades IV and V as the advanced stage. Intradiscal vacuum phenomena (VPs) were evaluated by computed tomography. Adjacent IVDs were categorized according to the locations of VFs (superior, inferior, and bilateral). Associations between the presence of VFs and the extent of IVD degeneration or the presence of VPs were statistically analyzed.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eIVDs adjacent to VFs were identified in 115 IVDs (31.1% of total; superior: 11.4%, bilateral: 8.6%, inferior: 11.1%). The presence of VFs was significantly associated with MRI grades of adjacent IVD degeneration (P\u0026lt;0.01) and the prevalence of VPs within adjacent IVDs (P\u0026lt;0.01). From logistic regression analysis, age, disc level, and VFs were independent related factors for disc degeneration (P\u0026lt;0.05).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eThis study showed that VFs were an independent related factor for adjacent disc degeneration and occurrence of intradiscal VPs. VFs may affect the micro-environment of adjacent IVDs, leading to disc degeneration and disc rupture.\u003c/p\u003e","manuscriptTitle":"Association between non-traumatic vertebral fractures and adjacent discs degeneration: a cross-sectional study and literature review","msid":"","msnumber":"","nonDraftVersions":[{"code":3,"date":"2020-11-24 12:26:23","doi":"10.21203/rs.3.rs-39669/v3","editorialEvents":[{"type":"communityComments","content":0},{"type":"checksComplete","content":"","date":"2020-11-19T14:31:09+00:00","index":"","fulltext":""},{"type":"decision","content":"Accept","date":"2020-11-19T00:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2020-11-18T00:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-11-17T23:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"
[email protected]","identity":"bmc-musculoskeletal-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmsd","sideBox":"Learn more about [BMC Musculoskeletal Disorders](http://bmcmusculoskeletdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://author-welcome.nature.com/12891","title":"BMC Musculoskeletal Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":2,"date":"2020-10-26 23:37:59","doi":"10.21203/rs.3.rs-39669/v2","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2020-10-29T00:00:00+00:00","index":2,"fulltext":"Recommendation: Accept after minor essential revisions\nForm responses:\n---\n\nComments to Author:\n---\nThe authors have clarified the statistical analysis and improved the presentation of the results. However, a few remaining points need to be addressed, as outlined below.\n\n\nResults\n\nPage 9 lines 14 and 16. I suggest amending the text to \"….advanced stage degeneration…..\"\n\nDiscussion\n\nThe authors have incorporated some new information into the Discussion but detail is lacking in places which makes it difficult to follow. For example, on page 14, the authors refer to several earlier studies which examined links between traumatic vertebral fractures and adjacent disc degeneration. The findings of the first two studies, carried out in children and young people who were treated conservatively, are clearly summarised. However, the findings of the other six studies in patients who underwent spine surgery are not mentioned. If the authors wish to compare the current findings in people with non-traumatic fractures with those observed previously in subjects with traumatic fractures, it is important to present the findings of these earlier investigations and, if they contrast with those of the current study, to explain possible reasons why this might be. In this respect, it would also be helpful to have more details of the subjects involved in the study by Rhamani et al regarding the nature of their fractures and whether they were treated conservatively, especially if the authors believe these factors are relevant to the progression of degeneration. \n\nPage 15, line 9. Does cranial disc degeneration refer to degeneration of discs lying immediately above the fractured vertebra? Please clarify.\n\nPage 19, line 1. Should this be \"….the subject's low back pain……\"?\n\nFigure legends\n\nPage 25, line 11 and Page 26, line 14. In the legends for Figure 4B and Figure 7B, please insert \"P\" when indicating the level of significance (i.e. † P\u003c0.006).\n\nTables\n\nIn Table 4, \"imaging\" is spelt incorrectly in the final column for the Noriega study.\n* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **No**\n* Declaration of competing interests: **I declare that I have no competing interests.**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **Yes**\n* Are the methods sufficiently described to allow the study to be repeated?: **Yes**\n* Is the use of statistics and treatment of uncertainties appropriate?: **Yes**\n* Is the presentation of the work clear?: **Yes**\n* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**\n"},{"type":"decision","content":"Minor revision","date":"2020-10-29T00:00:00+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-10-16T12:00:00+00:00","index":2,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-10-14T12:00:00+00:00","index":1,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-10-14T12:00:00+00:00","index":1,"fulltext":"Recommendation: Accept without revision\nForm responses:\n---\n\nComments to Author:\n---\nPlease include all comments for the authors in this box rather than uploading your report as an attachment. Please only upload as attachments annotated versions of manuscripts, graphs, supporting materials or other aspects of your report which cannot be included in a text format.\nPlease overwrite this text when adding your comments to the authors.* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **Yes**\n* Declaration of competing interests: **nothing**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **Yes**\n* Are the methods sufficiently described to allow the study to be repeated?: **Yes**\n* Is the use of statistics and treatment of uncertainties appropriate?: **Yes**\n* Is the presentation of the work clear?: **Yes**\n* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**\n"},{"type":"editorAssigned","content":"","date":"2020-10-13T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewersInvited","content":"","date":"2020-10-13T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-10-12T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-10-12T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"
[email protected]","identity":"bmc-musculoskeletal-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmsd","sideBox":"Learn more about [BMC Musculoskeletal Disorders](http://bmcmusculoskeletdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://author-welcome.nature.com/12891","title":"BMC Musculoskeletal Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2020-07-14 17:05:37","doi":"10.21203/rs.3.rs-39669/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2020-09-10T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-08-19T12:00:00+00:00","index":3,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-08-16T12:00:00+00:00","index":2,"fulltext":"Recommendation: Accept after minor essential revisions\nForm responses:\n---\n\nComments to Author:\n---\nThis study examined the effect of non-traumatic vertebral fractures on degenerative changes in adjacent intervertebral discs in 98 patients undergoing spinal surgery. Vertebral fractures and vacuum phenomena were evaluated in all patients from radiographs and CT scans, respectively. Disc degeneration was assessed in 74 patients from MRI scans. The results show that vertebral fractures were associated significantly with advanced disc degeneration and the presence of vacuum phenomena in adjacent intervertebral discs.\n\nThis is a very interesting and important study that has investigated a variety of parameters, such as the location and type of fracture that may have some influence on adjacent disc degeneration. The study is well designed and the manuscript is generally well-written. The one area that needs improvement is the presentation of the results of the post-hoc tests where it is often unclear whether comparisons are being made within a particular group or between groups. Some examples where clarification is required are given below along with some additional comments and queries.\n\nAbstract\n\nPage 2, line 10. Did the authors only evaluate non-traumatic vertebral fractures?\n\nPage 2, line 11. Please indicate which spinal levels were examined for vertebral fractures and intervertebral disc degeneration.\n\nPage 2, line 12. On the MRIs, was Pfirmann grading used to assess disc degeneration and, if so, which grades were considered to represent \"early\" or \"advanced\" degeneration?\n\n\nMaterials and Methods\n\nPage 6, lines 7-8. The title of the paper suggests that the study is investigating the effects of non-traumatic vertebral fractures on adjacent level disc degeneration so is there evidence that biconcave, wedge and crush fractures are always non-traumatic? \n\nPage 6, line 15. Amend text to \"….and those shapes were classified…..\"\n\nResults\n\nPage 8, line 12. The authors indicate that 115 intervertebral discs representing 31.1% of the total were identified as being adjacent to a fracture. However, 486 discs across 98 patients were examined in total so presumably this 31.1% refers only to those discs examined in the 74 patents who underwent MRI. This should be clarified in the text as should the number of vertebral fractures in these 74 patients because these represent the subgroup on which the analyses relating to disc degeneration were performed. It would also be helpful to know how many of the 498 discs assessed by CT were adjacent to a fracture as presumably the analyses relating to vacuum phenomena would be based on these larger numbers.\n\nPage 9, lines 2-4. Did the VF-negative group have a significantly higher proportion of early stage IVD degeneration when compared with each of three VF-positive groups or did the post-hoc test show a significantly higher proportion of early stage degeneration than advanced stage degeneration within the VF-negative group? Please clarify in the text.\n\nPage 9, lines 5-6. Again it is unclear what comparisons are being made by the post-hoc tests. Are they comparing the proportion of advanced stage degeneration to the proportion of early stage degeneration separately within each of the three VF-positive groups or are they comparing the proportion of advanced stage degeneration between the three VF-positive groups?\n\nPage 10, line 4. 226 represents 46.5% of the 486 discs that were analysed.\n\nPage 10, line 10 to page 11, line 1. Again, please clarify if the post hoc tests were comparing the proportion of discs with VPs to those without VPs within each of the four VF groups shown in Fig 7B?\n\nPage 11, line 2. To clarify what comparisons are being made here, I suggest amending the text to indicate that the percentage of island shape VPs was significantly lower than expected in the IVDs of the VF-negative group and significantly higher than expected in the VF+ superior group.\n\nPage 12, lines 16-18. These results relate to comparisons between fracture type and disc degeneration so would be better placed in the preceding section \"Association between VFs and disc degeneration\".\n\nDiscussion\n\nPage 13, lines 14-19. This information relating to Table 4 can be omitted here as it is included at the end of the manuscript along with the actual table.\n\nPage 14, line 13. Please clarify what is meant by \"….adjacent disc degeneration in children has not been unfiled.\"\n\nPage 15, lines 1-2. I'm unsure of the message here. The authors state that most studies reported the occurrence of adjacent disc degeneration following thoracolumbar VFs treated by spine surgeries but then suggest that surgical procedures that correct kyphosis and/or restore the end-plate will alleviate the progression of adjacent disc degeneration. What is the evidence for this latter statement?\n\nPage 15, lines 10-11. The authors don't know that these discs originally had less degeneration so I suggest amending the text as follows;\"……those percentages in T12/L1, L1/L2 and L2/L3 discs, which would be expected to have less degeneration than lower lumbar levels [21], were significantly higher in the VF-positive group than in the VF-negative group.\"\n\nPage 15, lines 12-14. There is also evidence to support this suggestion from cadaveric studies. These showed that the effects of vertebral endplate fracture on disc mechanical function, and specifically on disc decompression, were greater at thoracic and upper lumbar levels than at lower lumbar levels (Dolan et al., 2013. Intervertebral Disc decompression following endplate damage: implications for disc degeneration depend on spinal level and age. Spine 38 (17):1473-1481) and that such mechanical disruption is associated with the presence and progression of intervertebral disc degeneration (see for example, Zehra et al., 2019. Associations between intervertebral disc degeneration grading schemes and measures of disc function. J Orthop Res 37:1946-1955; Stefanakis et al. 2014. ISSLS Prize Winner: Mechanical influences in progressive intervertebral disc degeneration. Spine 39 (17):1365 - 1372).\n\nPage 17, lines 14-15. Again, evidence to support these suggestions is provided in the papers cited above.\n\nFigure legends\n\nPage 25, line 6. In the legend for Figure 1, I suggest amending the text to \"…..those IVDs having no fracture in an adjacent vertebral body.…\" to avoid implying that there is only one adjacent vertebral body.\n\nPage 26, line 10. In the legend for Figure 4B, should this be P\u003c0.006 and, if so, why is it different from the value of P\u003c0.05 given in the text when referring to this figure (page 9, line 4). Also, please indicate what comparison this p value relates to. Is it the proportion of early compared to advanced stage degeneration within the VF-negative group?\n\nPage 27, line 6. In the legend for Figure 6, 226 actually represents 46.5% of the 486 discs that were analysed so this should be corrected.\n\nPage 27, line 13. In the legend for Figure 7B, should this be P\u003c0.006? Again, please clarify whether this p value refers to comparisons made within each group or between the groups. \n\nTables\n\nIn Table 4, \"imaging\" is spelt incorrectly in the final column for the Noriega study, Also, what does the asterisk represent in the final column for the Descamps study?\n* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **No**\n* Declaration of competing interests: **I declare that I have no competing interests.**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **Yes**\n* Are the methods sufficiently described to allow the study to be repeated?: **Yes**\n* Is the use of statistics and treatment of uncertainties appropriate?: **Yes**\n* Is the presentation of the work clear?: **No**\n* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**\n"},{"type":"editorInvitedReview","content":"","date":"2020-08-16T12:00:00+00:00","index":1,"fulltext":"Recommendation: Major revisions required\nForm responses:\n---\n\nComments to Author:\n---\nThis study showed the association of non-traumatic vertebral fracture with DD. However, there are several problems.\n\n\u003e Authors demonstrated that 'there has been no study that evaluates the effect of non-traumatic VFs on the progression of adjacent disc degeneration.' However, there is a study which revealed the progression of DD after VFs in a longitudinal study design. (The degeneration of adjacent intervertebral discs negatively influence union rate of osteoporotic vertebral fracture: A multicenter cohort study. Rahmani MS, Takahashi S, Hoshino M, Takayama K, Sasaoka R, Tsujio T, Yasuda H, Kanematsu F, Kono H, Toyoda H, Nakamura H. J Orthop Sci. 2018 Jul;23(4):627-634.) Therefore, authors should show what is the new knowledge from this study based on the previous study. Please change the several sentences.\n\u003e The study subjects were consecutive patients who underwent spine surgery. Was patients who had received lumbar spine surgery excluded?\nAuthors analyzed the vertebrae from T12-L5 in 98 patients. Finally, 486 discs and 584 vertebral body were analyzed. Why were several discs and vertebral body excluded?\n\u003e Why were only 31% of adjacent IVD examined?\n\u003e What is the reason of the non-traumatic fracture? Secondary osteoporosis? Authors mentioned that most of them were osteoporotic fracture. Did author check the status of osteoporosis? What is the definition of non-traumatic fracture? Specific disease might affect the results.\n\u003e Was disc level used as continuous variable in logistic regression?\n\u003e Did authors check other well-known risk factors such as obesity and physical activity?\n\u003e What are the p-values in Table 3? What did authors compare? Residual analysis?\n\u003e Did authors check back pain? Was the DD after VFs related to any clinical outcome?\n\n* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **Yes**\n* Declaration of competing interests: **I declare that I have no competing interests.**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please publish my name with my report.**\n* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **No**\n* Are the methods sufficiently described to allow the study to be repeated?: **Yes**\n* Is the use of statistics and treatment of uncertainties appropriate?: **No**\n* Is the presentation of the work clear?: **Yes**\n* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**\n"},{"type":"reviewerAgreed","content":"","date":"2020-07-24T12:00:00+00:00","index":2,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-07-21T12:00:00+00:00","index":1,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2020-07-19T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2020-07-12T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-07-10T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-07-10T12:00:00+00:00","index":"","fulltext":""},{"type":"submitted","content":"","date":"2020-07-01T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"
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