Risk factors for intravertebral cleft in acute vertebral fractures and its relationship with bone cement leakage after vertebroplasty

Introduction

The occurrence of intravertebral cleft (IVC) is an important imaging characteristic that occurs in fractured vertebrae; this phenomenon is defined as a linear intravertebral lesion filled with liquid or gas in plain radiograms, computed tomography (CT) images, and magnetic resonance imaging (MRI) images. According to the literature, the main factors influencing the mechanism of IVC formation may include vertebral ischaemia, bone necrosis, and the movement of fluids or gases through negative pressure (1,2). However, IVC was long considered a phenomenon specific to Kummell’s disease (KD) (3,4), which was first described by Dr. Hermann Kummell in 1891 (5). The clinical features of KD include pain and progressive kyphosis due to delayed vertebral collapse after spinal trauma (6). In terms of pathology, KD is a chronic process of delayed union of a fracture. This disease has been described in many terms, including delayed posttraumatic vertebral osteonecrosis, intravertebral pseudarthrosis, intravertebral vacuum cleft, delayed vertebral collapse, and non-union of compression fracture (1,2,7). In summary, KD is a specific type of chronic fracture closely related to osteoporosis, while IVC refers to a group of imaging signs that can be observed not only in KD but also in other fractures.

In recent years, studies have indicated that IVC can occur in acute traumatic fractures (8,9). For example, Hutchins et al. reported that IVC was found in 44% of acute traumatic fractures, and it was speculated to be related to spinal instability, mobility, or negative pressure within the vertebral body (9). However, for these patients, the risk factors and pathogenesis of IVC are still unclear.

In clinical practice, percutaneous vertebroplasty (PVP) and kyphoplasty (PKP) have become widely accepted as treatments for acute vertebral fractures (AVF), osteoporosis and vertebral body metastases that cannot be resolved by conservative treatments (10-12). Compared with conventional invasive methods, PKP and PVP are characterized by high surgical safety, minimal invasion, rapid recovery, and rapid pain relief (13-15). For patients with AVF, bone cement leakage after PKP and PVP is a serious complication, Bone cement leakage is multifactorial (13), and the relationship between IVC and bone cement leakage is still unclear. Clarification could help doctors choose appropriate treatment plans and reduce the occurrence of complications. Therefore, in this study, a large sample of patients with AVFs was collected and analysed to explore the potential risk factors for IVC and its relationship with bone cement leakage after PVP or PKP. We present this article in accordance with the STROBE reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1186/rc).

Methods

Ethics statement

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Research Ethics Committee of Chongqing University Central Hospital (No. 2020-38) and individual consent was waived as it is a retrospective study. The First Affiliated Hospital of Chongqing Medical University was also informed and agreed the study.

Patients

A total of 2,176 patients diagnosed with AVFs from January 2019 to October 2022 in Chongqing University Central Hospital (1,137 patients) and The First Affiliated Hospital of Chongqing Medical University (1,039 patients) were retrospectively included.

The inclusion criteria were as follows:

• Patients older than 18 years;
• A diagnosis of vertebral fracture on CT and MRI by a team of two musculoskeletal radiologists with more than 6 years of experience;
• A history of trauma.

The exclusion criteria were as follows:

• Severe image artefacts;
• Incomplete clinical data;
• Fracture not on the same level as tenderness;
• A time interval of more than 2 weeks from trauma to CT/MR examination;
• Pathological fractures (tumour or infection).

A total of 126 patients (127 vertebrae) were diagnosed with intravertebral fissure sign and were included in the IVC group. A total of 125 age- and sex-matched patients (134 vertebrae) without IVC were included in the control group. At the time of enrolment, clinical information including sex, age, medical history, degree of osteoporosis, and time interval between fracture and imaging examination were collected from the local electronic medical records. The degree of osteoporosis was graded on the basis of the dual-energy X-ray absorptiometry (DXA) results. The bone density was considered normal if the bone mineral density (BMD) T score was greater than or equal to −1; osteopenia was considered to be present if the BMD T score was between −1 and −2.5; and osteoporosis was considered to be present if the BMD T score was equal to or less than −2.5. Among the included vertebrae, 64 in the IVC group and 61 in the control group underwent PKP or PVP 2–5 days after trauma and were followed up for three months. The criteria for PVP or PKP were as follows: (I) AVFs, especially for acute osteoporotic vertebral fractures; (II) no rotation, dislocation or spinal cord compression was present; and (III) conservative treatment was ineffective, and the patient hoped to quickly relieve the pain (13,14). A flow chart of the study design is shown in Figure 1.

Figure 1 The patient flow chart of the study. ^†, vertebral bodies. CT, computed tomography; IVC, intravertebral cleft; MR, magnetic resonance; MRI, magnetic resonance imaging; PKP, percutaneous kyphoplasty; PVP, percutaneous vertebroplasty.

Imaging parameters

All CT examinations were performed via two CT scanners (Revolution and Light Speed VCT, General Electric Medical Systems, USA) with a standardized protocol of 120 kV, 200–500 mA, and a matrix size of 512×512. All the images were reconstructed in 3D with a slice thickness of 0.625 mm using a bone reconstruction algorithm. MRI scans were performed on two 3.0 T MR scanners with a spine-array coil (Prisma, Siemens Healthcare, Germany, and Signa Excite, GE Healthcare, USA). The imaging protocol was as follows: (I) sagittal T2-weighted imaging [repetition time (TR)/echo time (TE), 2,500/90 or 2,490/72 ms] with a slice thickness of 4 mm, slice spacing of 20%, and a field of view (FOV) of 180 mm × 300 mm; (II) sagittal T1-weighted spin-echo images (TR/TE, 550/8 or 260/9.6 ms) with a slice thickness of 4 mm, slice spacing of 20%, and an FOV of 180 mm × 300 mm; (III) sagittal short-inversion-time inversion-recovery (STIR) images (TR/TE, 2,500/80 or 2,930/50 ms) with a slice thickness of 4 mm, slice spacing of 20%, and an FOV of 180 mm×300 mm; and (IV) axial T2-weighted spin-echo images (TR/TE 2,500/90 or 5,720/105 ms) with a slice thickness of 3 mm, slice spacing of 10%, and an FOV of 180 mm × 200 mm.

Image analysis

All the images were independently evaluated by two musculoskeletal radiologists (with 18 and 6 years of clinical experience, respectively). In the event of an initial disagreement, the two doctors reached an agreement through consultation. The degree of vertebral fractures was classified into grades 0–3 on the basis of the percentage of vertebral height loss: grades 0–0.5 (normal or very minimal deformity), with no obvious loss of height or loss of height less than 20%; grade 1 (minimal fracture), with 20% to 25% loss of height (grades 0–0.5 and grade 1 were merged and defined as mildly deformed); grade 2 (moderate fracture), with 25% to 40% loss of height (defined as moderately deformed); and grade 3 (severe fracture), with loss of height greater than 40% (defined as severely deformed). Vertebral parts including the superior endplate, anterior wall, left lateral wall, right lateral wall, inferior endplate and posterior wall were evaluated for fracture line involvement. The content of IVC was analysed in two categories: liquid and gas. Liquid IVC showed a linear shape with a similar density or signal intensity to cerebrospinal fluid on CT and MR imaging. The imaging features of gas IVC were a density similar to that of air on CT and a signal void on MRI. The presence of gas adjacent to the intravertebral disc was also analysed.

PVP or PKP was performed 2–5 days after trauma, The selection criteria for these two surgical procedures were determined based on previous relevant literature and guidelines (14,15). The program for PVP or PKP was the same as that previously reported (13). The culprit vertebra was accurately identified via MRI or CT combined with tenderness on physical examination before surgery. During the operation, under fluoroscopic guidance, the needle entered from the superolateral quadrant of the pedicle and ultimately reached the anterior to middle third of the vertebral body. Balloon dilation was applied in PKP. Bone cement and water were combined at a 2:1 ratio, then stirred to the consistency of toothpaste and slowly injected into the vertebral body. The volume of cement for the thoracic and lumbar vertebrae ranged from approximately 2.5–6 and 3–8 mL, respectively. The patient was maintained in a prone position for a period after the operation to allow further cement hardening (16). Bone cement leakage was classified into four types according to the literature (17): type B, leakage through the vertebral basal vein; type S, leakage through segmental veins; type C, leakage through cortical defects; and type D, leakage to the intravertebral disc.

Statistical analysis

Statistical analyses were performed with SPSS statistical software (version 26.0, SPSS). Age data were presented as medians with interquartile ranges (IQRs) and frequencies with percentages. Chi-squared tests were used to evaluate the differences in sex, osteoporosis severity, compression severity and the vertebral part with fracture line involvement between the two groups. Univariate logistic regression analysis was performed to identify the risk factors associated with IVC. A multiplicative model was adopted to analyse the effects of the interactions among all risk factors and quantify their independent and joint effects. The intraclass correlation coefficient (ICC) test was used to evaluate intrareader reliability. Statistical significance was indicated by a two-tailed P value <0.05.

Results

Demographic characteristics

Among the 2,176 patients reviewed in this study, 126 individuals were included in the IVC group (median age of 74 years; IQR, 63.00–82.25 years; 88 females and 38 males; 127 vertebral bodies in total). Another 125 age- and sex-matched individuals without IVC (median age of 76 years; IQR, 67.00–83.00 years; 87 females and 38 males; 134 vertebral bodies in total) were selected as the control group (Figure 1). The characteristics of the two groups are shown in Table 1.

Risk factors for IVC in AVFs

There were significant differences in compression severity and fracture line involvement of the inferior endplate, posterior wall and basivertebral foramen between the two groups (all P<0.05). No significant differences in age; sex; osteoporosis severity; or vertebral fracture line involvement of the superior endplate, anterior wall, left lateral wall or right lateral wall were detected (all P>0.05) (Table 1). Multivariate logistic regression analysis revealed that vertebral fracture line involvement of the basivertebral foramen was a risk factor for IVC [95% confidence interval (CI): 2.297 (1.303–4.048), P=0.004]. An interaction effect between the vertebral fracture line involvement of the basivertebral foramen and the posterior wall was found (P=0.029). The OR value of basivertebral foramen (+) × posterior wall (−) was 0.713 (0.165–1.260) (P=0.011), and the OR value of basivertebral foramen (+) × posterior wall (+) was 0.713 (0.165–1.260) (P=0.006); refer to Table 2.

For all the analyses by the two radiologists, the intrareader reliability was strong, with ICCs of 90.2% (95% CI: 87.6–92.2%) for compression severity, 95.1% (95% CI: 93.8–96.2%) for vertebral fracture line involvement of the basivertebral foramen, 97.3% (95% CI: 96.5–97.9%) for vertebral fracture line involvement of the superior endplate, 98.2% (95% CI: 97.7–98.6%) for vertebral fracture line involvement of the inferior endplate, 89.6% (95% CI: 86.7–91.9%) for vertebral fracture line involvement of the anterior wall, 98.3% (95% CI: 97.8–98.7%) for vertebral fracture line involvement of the posterior wall, 97.7 (95% CI: 97–98.2%) for vertebral fracture line involvement of the left lateral wall and 96.5 (95% CI: 95.5–97.3%) for vertebral fracture line involvement of the right lateral wall.

Relationship between IVC and bone cement leakage after PKP or PVP

In the IVC group, 64 vertebrae underwent PKP (n=42) or PVP (n=22), and 15 cases developed leakage (Figures 2,3), including 10 cases of PKP and 5 cases of PVP. Sixty-one vertebrae without IVC (Figure 4) in the control group underwent PKP (n=45) or PVP (n=16), with 6 cases developing leakage, including 3 cases of PKP and 3 cases of PVP. There was a significant difference in the bone cement leakage rate between the two groups (P=0.042). No significant difference was found in age or sex (Table 3). Among the types of bone cement leakage, type C was the most common in the IVC group (Figures 2,3), accounting for 86.7% (13 cases). Type D was found in 1 case (6.7%), and type B was found in 1 case (6.7%).

Figure 2 CT and MRI images showed a gas IVC in L4 (thin arrow). The vertebral fracture line involved the basivertebral foramen (fat arrow). After PKP in three months, cement leakage of type C occurred (dovetail arrow of X-ray). CT, computed tomography; IVC, intravertebral cleft; MRI, magnetic resonance imaging; PKP, percutaneous kyphoplasty; STIR, short-inversion-time inversion-recovery.

Figure 3 CT and MRI images showed a liquid IVC in L2 (thin arrow). The vertebral fracture line involved the basivertebral foramen (fat arrow). After PKP in three months, cement leakage of type C occurred (dovetail arrow of X-ray). CT, computed tomography; IVC, intravertebral cleft; MRI, magnetic resonance imaging; PKP, percutaneous kyphoplasty; STIR, short-inversion-time inversion-recovery.

Figure 4 CT and MRI images showed vertebral fracture and bone marrow edema (thin arrow) in L1. No IVC was found and the fracture line did not involve the basivertebral foramen (fat arrow). After PKP in three months, cement leakage did not occur (dovetail arrow of X-ray). CT, computed tomography; IVC, intravertebral cleft; MRI, magnetic resonance imaging; PKP, percutaneous kyphoplasty; STIR, short-inversion-time inversion-recovery.

Discussion

In recent years, it has been reported that IVC may also occur in AVF and that its pathogenesis and imaging characteristics differ from those of KD (18,19). However, the relevant factors and clinical implications of IVC in patients with AVFs remain unclear. In this study, we revealed that fracture line involvement of the basivertebral foramen was a risk factor for IVC and had an interaction effect with posterior wall fracture. Notably, analogous findings have been reported in prior studies on osteoporotic vertebral fracture (20-22), but not in AVF, which has important clinical significance. Our results suggest that for patients with basivertebral foramen and vertebral posterior wall injury found on plain films, further CT and MRI examinations are necessary to clarify the occurrence of IVC. The basivertebral foramen is an osseous channel located in the middle of the posterior wall of the vertebral body, occurring between the two pedicles in the median sagittal plane, and serves as a passageway for the entry and exit of vertebral blood vessels (mainly veins). When vertebral posterior wall fractures occur, the basivertebral foramen is prone to be affected. Additionally, the large diameter of the basivertebral foramen can lead to local weakness of the posterior wall. Compression fractures of the posterior wall can cause collapse of the basivertebral foramen, leading to IVC (23,24). The basivertebral foramen is also an important channel for blood vessels, including the vertebral venous plexuses, extravertebral venous plexuses, and vertebrobasilar vein (25). When acute fractures occur, venous injury or venous stasis can lead to local accumulation of fluid and the occurrence of IVC.

Given that there is an anatomical interaction between the basivertebral foramen and posterior wall of the vertebra, we performed multiplicative interaction analysis in this study to assess the combined effect of these two risk factors and to determine whether synergistic or antagonistic effects occur. The results revealed that, the interaction effect of Vertebral fracture line involvement of basivertebral foramen and posterior wall was significant. This indicates that there is a negative (antagonistic) multiplicative interaction between these two factors, which means that when both of these factors exist simultaneously, it is less than the product of the individual risks of each exposure factor. These results further clarify the clinical value of vertebral fracture line involvement of the basivertebral foramen. In contrast to the traditional clinical focus on the posterior wall of the vertebra alone, perhaps the basivertebral foramen merits more attention than it currently receives.

In this study, the severity of vertebral compression and fracture line involvement of the posterior wall and inferior endplate of the vertebral body were significantly different between the IVC group and the control group. These findings suggested that the occurrence of IVC in AVF was closely related to these factors. The severity of vertebral compression is a very important indicator for evaluating vertebral fractures in clinical work and scientific research (26). Fracture line involvement of the posterior wall and inferior endplate of the vertebral body is also closely related to the severity of the fracture. According to the Arbeitsgemeinschaft für Osteosynthesefragen Spine System, a fracture whose line involves the posterior wall of the vertebral body is a burst fracture, which is usually considered a serious injury (27). In clinical practice, inferior endplate fractures are not common. In some cases, an inferior endplate fracture is combined with a superior endplate fracture, forming a double endplate fracture (27).

This study was the first to investigate the relationship between IVC and the occurrence of bone cement leakage after PKP or PVP for AVF. Previously, IVC was considered to occur mainly in KD. Non-union of osteoporotic fractures and bone sclerosis at the edge of the IVC could easily lead to diffusion barriers or unstable fixation of bone cement within the vertebral body, leading to bone cement leakage. Therefore, PVP or PKP was not the preferred treatment method for KD (6,17). In this study, we revealed that IVC may also occur in patients with AVFs. Patients with IVC had a higher bone cement leakage rate than those without IVC.

For these patients, this study indicated that bone cement needs to be slowly injected and that high-viscosity bone cement should be used to reduce the incidence of bone cement leakage in clinical practice. In previously published research on KD patients, Wang et al. (28) confirmed through specimen experiments that when the fracture line involved the vertebral foramen, the vertebral foramen could be directly connected to the IVC, leading to bone cement leakage. Regarding the types of bone cement leakage in this study, C-type leakage was the most common type in the IVC group. C-type leakage is usually caused by cortical bone defects (29-32). Previous studies have reported that fracture severity and cortical destruction are risk factors for C-type leakage (33,34). IVC is often accompanied by severe vertebral fractures. High pressure in the IVC and cortical cracks can lead to bone cement leakage. However, owing to the relatively small number of cases with leakage and the further reduction in sample size after classification, the results of this research require more clinical research for verification.

This study exhibits several limitations. First, this was a retrospective case-control study and lacked long-term follow-up; such a design may impose limitations such as data dependence, information bias, selection bias, and other potential confounders. For instance, the controls were matched by age and sex, but osteoporosis severity and fracture type seemed unevenly distributed. Second, the majority of the participants did not undergo enhanced CT or MRI scanning. This might have affected the display of the lesions, as enhanced scanning can effectively increase the contrast between the lesions and the normal tissues and facilitate the visualization of the basivertebral foramen. Finally, the small sample size of patients with severe deformities in the classification of compression severity and the small number of follow-up patients with bone cement leakage might bias the results of this study. In the future, we will include more samples, including plain and enhanced CT and MRI scans, and we will conduct longitudinal dynamic studies to further validate our conclusions.

Conclusions

Vertebral fracture line involvement of the basivertebral foramen was a risk factor for IVC in patients with AVF. The risk of bone cement leakage after PVP or PKP was higher for AVF with IVC than for AVF without IVC. In clinical practice, attention should be given to the condition of the basivertebral foramen and IVC in patients with AVFs.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1186/rc

Data Sharing Statement: Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1186/dss

Funding: This work was supported by the Chongqing medical scientific research project (Joint project of Chongqing Health Commission and Science and Technology Bureau) (grant No. 2023MSXM016); Natural Science Foundation of Chongqing (No. CSTB2024NSCQ-MSX0630); Chongqing Key Laboratory of Emergency Medicine (grant Nos. 2024RCCX04, 2024RCCX05).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1186/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Research Ethics Committee of Chongqing University Central Hospital (No. 2020-38) and individual consent was waived as it is a retrospective study. The First Affiliated Hospital of Chongqing Medical University was also informed and agreed the study.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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