Risk factors and management of early pain non-response after vertebroplasty in osteoporotic vertebral compression fractures
Original Article

Risk factors and management of early pain non-response after vertebroplasty in osteoporotic vertebral compression fractures

Le Hoang Nha1, Do Cong Thuong1, Tran Kien Vu2

1Department of Neurosurgery, Tra Vinh General Hospital, Vinh Long, Vietnam; 2School of Medicine and Pharmacy, Tra Vinh University, Vinh Long, Vietnam

Contributions: (I) Conception and design: LH Nha, DC Thuong; (II) Administrative support: TK Vu; (III) Provision of study materials or patients: LH Nha, DC Thuong; (IV) Collection and assembly of data: LH Nha; (V) Data analysis and interpretation: LH Nha, TK Vu; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Correspondence to: Le Hoang Nha, MD, PhD. Department of Neurosurgery, Tra Vinh General Hospital, 399 Nguyen Dang Street, Nguyet Hoa Ward, 87117, Vinh Long Province, Vietnam. Email: lehoangnhatuyen@gmail.com.

Background: Percutaneous vertebroplasty is widely used to treat painful osteoporotic vertebral compression fractures (OVCFs), providing rapid pain relief in most patients. However, a subset of patients experiences early pain non-response, and the predictors and optimal management of this condition remain incompletely understood. This study aimed to identify risk factors associated with early pain non-response after vertebroplasty and to describe a practical management approach.

Methods: We retrospectively reviewed patients with OVCFs who underwent vertebroplasty at a tertiary referral center between January 2023 and December 2025. Pain intensity was assessed using the visual analog scale (VAS). Early pain non-response was defined as a postoperative VAS reduction of <2 points or a VAS score ≥5 within 72 hours after the procedure. Demographic, clinical, radiological, and procedural variables were analyzed using univariate and multivariate logistic regression models.

Results: A total of 837 patients were included, of whom 96 (11.5%) experienced early pain non-response after vertebroplasty. Multivariate analysis identified severe vertebral collapse (>50%), presence of an intravertebral cleft, multiple adjacent vertebral fractures, delayed intervention (>6 weeks after symptom onset), and discordance between magnetic resonance imaging (MRI) bone marrow edema and pain location as independent predictors of early pain non-response. Following targeted post-procedural management, including optimized medical therapy, facet joint interventions, repeat vertebral augmentation, or alternative stabilization procedures, 77.1% of non-responders achieved significant short-term pain improvement.

Conclusions: Early pain non-response after vertebroplasty is not uncommon and can be predicted using identifiable clinical and imaging factors. A cause-oriented, individualized management approach may improve short-term pain outcomes in patients with persistent pain after vertebroplasty.

Keywords: Vertebroplasty; osteoporotic vertebral compression fracture (OVCF); pain non-response; risk factors; management

Submitted Jan 08, 2026. Accepted for publication Feb 25, 2026. Published online Apr 20, 2026.

doi: 10.21037/jss-2026-1-0012

Highlight box

Key findings

• Approximately 11.5% of patients experienced early pain non-response after vertebroplasty for osteoporotic vertebral compression fractures.

• Severe vertebral collapse, intravertebral cleft, multiple adjacent fractures, delayed intervention, and MRI-clinical discordance were independent predictors of early pain non-response.

• A cause-oriented post-procedural management approach led to significant pain improvement in the majority of non-responders.

What is known and what is new?

• Vertebroplasty is effective for rapid pain relief in most patients with osteoporotic vertebral compression fractures.

• However, factors associated with early pain non-response and practical management strategies remain insufficiently defined.

• This study identifies key predictors of early pain non-response and proposes a structured, cause-oriented management approach based on real-world clinical practice.

What is the implication, and what should change now?

• Early pain non-response after vertebroplasty should prompt systematic clinical reassessment rather than be regarded as procedural failure.

• Preoperative risk stratification and individualized post-procedural management may improve short-term pain outcomes in high-risk patients.

Introduction

Osteoporotic vertebral compression fractures (OVCFs) are among the most common fragility fractures in the elderly and represent a major cause of back pain, functional impairment, and reduced quality of life worldwide (1,2). With the rapid aging of the global population, the incidence of OVCFs continues to increase, leading to substantial clinical and socioeconomic burden related to chronic pain, prolonged immobilization, and loss of independence (3,4).

Percutaneous vertebroplasty has been widely adopted as a minimally invasive treatment for painful OVCFs, particularly in patients who fail conservative management. By stabilizing the fractured vertebral body through polymethylmethacrylate cement injection, vertebroplasty has been shown to provide rapid pain relief, facilitate early mobilization, and improve functional outcomes in the majority of patients (5-7). As a result, vertebroplasty remains an important therapeutic option in daily clinical practice, especially for elderly patients with severe pain and limited tolerance for prolonged immobilization (8).

Despite its overall effectiveness, not all patients experience satisfactory pain relief after vertebroplasty. A subset of patients continues to report moderate to severe pain shortly after the procedure, which may result in prolonged hospitalization, repeated interventions, and dissatisfaction with treatment outcomes (9-11). Recent studies have shown that residual pain after vertebroplasty remains a clinically relevant issue, even in technically successful procedures (12,13). Previous reports have demonstrated wide variability in the incidence of early pain non-response, largely due to differences in study design, outcome definitions, and patient selection (12,14).

Although vertebroplasty has been extensively studied, most published reports have focused on overall pain reduction or long-term outcomes, while limited attention has been given specifically to patients who fail to achieve early pain relief. Existing studies addressing treatment failure often include heterogeneous patient populations or emphasize isolated risk factors without providing practical, cause-oriented management strategies (15-18). Consequently, clinicians frequently face uncertainty in evaluating persistent pain, identifying the dominant pain generator, and selecting appropriate subsequent interventions after vertebroplasty.

Therefore, the objectives of the present study were to identify clinical, radiological, and procedural risk factors associated with early pain non-response after vertebroplasty in patients with OVCFs, and to propose practical management strategies based on the underlying mechanisms of persistent pain. We present this article in accordance with the STROBE reporting checklist (available at https://jss.amegroups.com/article/view/10.21037/jss-2026-1-0012/rc).

Methods

Study design

This retrospective cohort study included patients with OVCFs treated with percutaneous vertebroplasty between January 2023 and December 2025 at Tra Vinh General Hospital, Vietnam.

Patient selection

Inclusion criteria were diagnosis of OVCF, treatment with vertebroplasty, and availability of pre- and postoperative visual analog scale (VAS) scores. Exclusion criteria included fractures due to malignancy or infection, combined fixation procedures, and incomplete data. The patient selection process is illustrated in Figure 1.

Figure 1 Flowchart of patient selection. OVCF, osteoporotic vertebral compression fracture; VAS, visual analog scale.

Definition of early pain non-response

Early pain non-response was defined as a VAS reduction <2 points or a postoperative VAS score ≥5 within 72 hours after vertebroplasty.

Variables collected

Collected variables included age, sex, fracture level and number, degree of vertebral collapse, magnetic resonance imaging (MRI) findings (bone marrow edema, intravertebral cleft), time from symptom onset to intervention, cement volume, cement leakage, and kyphotic deformity.

Statistical analysis

Continuous variables were compared using Student’s t-test or Mann-Whitney U test. Categorical variables were compared using chi-square or Fisher’s exact test. Variables with P<0.10 in univariate analysis were entered into multivariate logistic regression. Results were reported as odds ratios (ORs) with 95% confidence intervals (CIs). A P value <0.05 was considered statistically significant.

Ethics approval

This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This retrospective study was approved by the Institutional Review Board of Tra Vinh General Hospital (No. 15/QĐ-HĐKHKT, dated December 20, 2022). The requirement for informed consent was waived due to the retrospective nature of the study and the use of anonymized data.

Results

Patient characteristics

Baseline demographic, clinical, and radiological characteristics of the study population are summarized in Table 1.

Table 1

Baseline characteristics of patients with osteoporotic vertebral compression fractures treated by vertebroplasty

Characteristic Overall cohort (n=837)
Age (years), mean ± SD 72.6±8.9
Female sex, n (%) 612 (73.1)
Fracture level, n (%)
   Thoracolumbar junction (T11–L2) 572 (68.4)
   Other levels 265 (31.6)
Number of fractured vertebrae, n (%)
   Single level 604 (72.2)
   Multiple adjacent levels 233 (27.8)
Severe vertebral collapse (>50%), n (%) 212 (25.3)
Intravertebral cleft, n (%) 171 (20.4)
Bone marrow edema on MRI, n (%) 692 (82.7)
Time from symptom onset to vertebroplasty, n (%)
   ≤6 weeks 594 (71.0)
   >6 weeks 243 (29.0)
Cement volume (mL), mean ± SD 4.6±1.1
Asymptomatic cement leakage, n (%) 112 (13.4)
Preoperative VAS score, mean ± SD 7.8±1.1
Postoperative VAS score (72 h), mean ± SD 2.9±1.6

MRI, magnetic resonance imaging; SD, standard deviation; VAS, visual analog scale.

Incidence of early pain non-response

Ninety-six patients (11.5%) met the criteria for early pain non-response. Non-responders had a higher postoperative VAS score and smaller VAS reduction compared with responders (P<0.001).

Risk factor analysis

Univariate analysis showed significant associations between early pain non-response and severe vertebral collapse, intravertebral cleft, multiple adjacent fractures, delayed intervention, and MRI-clinical discordance (all P<0.05). Age, sex, cement volume, and asymptomatic cement leakage were not significant (Table 2).

Table 2

Univariate analysis of factors associated with insufficient pain relief after vertebroplasty

Variable Sufficient pain relief (n=741) Insufficient pain relief (n=96) P value
Age (years), mean ± SD 72.4±8.8 73.6±9.3 0.28
Female sex, n (%) 540 (72.9) 72 (75.0) 0.65
Severe vertebral collapse (>50%), n (%) 168 (22.6) 44 (45.8) <0.001
Intravertebral cleft, n (%) 133 (17.9) 38 (39.6) <0.001
Multiple adjacent vertebral fractures, n (%) 191 (25.8) 40 (41.7) 0.002
Delayed intervention (>6 weeks), n (%) 196 (26.4) 47 (48.9) <0.001
MRI edema-pain location discordance, n (%) 110 (14.8) 35 (36.5) <0.001
Cement volume (mL), mean ± SD 4.6±1.1 4.5±1.0 0.44
Asymptomatic cement leakage, n (%) 97 (13.1) 15 (15.6) 0.49

MRI, magnetic resonance imaging; SD, standard deviation.

Multivariate analysis confirmed all five variables as independent predictors of early pain non-response, with MRI-clinical discordance showing the strongest association (Table 3).

Table 3

Multivariate logistic regression analysis of factors associated with insufficient pain relief after vertebroplasty

Variable OR 95% CI P value
Severe vertebral collapse (>50%) 2.31 1.42–3.75 0.001
Intravertebral cleft 2.67 1.63–4.38 <0.001
Multiple adjacent vertebral fractures 1.94 1.18–3.19 0.009
Delayed intervention (>6 weeks) 2.08 1.26–3.42 0.004
MRI edema-pain location discordance 3.12 1.85–5.27 <0.001

CI, confidence interval; MRI, magnetic resonance imaging; OR, odds ratio.

Post-procedural management and outcomes

Among non-responders, optimized medical therapy alone achieved adequate pain relief in 39.6%, facet or medial branch block in 25.0%, repeat vertebral augmentation in 21.9%, and alternative stabilization in 13.5%. Overall, 77.1% achieved significant pain improvement within 2 weeks. The mean VAS score decreased from 5.8±0.9 to 3.1±1.4 (P<0.001). A proposed cause-oriented management algorithm is shown in Figure 2.

Figure 2 Morphology-based management algorithm for early pain non-response after vertebroplasty. Patients with persistent pain within 72 hours undergo reassessment and are stratified into structural instability-driven patterns (e.g., severe collapse >50%, intravertebral cleft) versus non-mechanical pain generators. Alternative stabilization may be considered in selected high-risk morphologies. VAS, visual analog scale

Discussion

Principal findings and morphology-driven implications

In this large single-center cohort of 837 patients, early pain non-response occurred in 11.5% of cases. Beyond statistical association, our findings suggest that early pain persistence may represent a biomechanical mismatch between fracture morphology and treatment strategy. Previous studies have reported that persistent pain after technically successful vertebroplasty remains a clinically relevant issue and may be influenced by fracture characteristics and patient selection (9,10,12).

Severe vertebral collapse (>50%) was present in 25.3% of patients and was independently associated with early non-response. Prior imaging-based investigations have demonstrated that vertebral endplate disruption and severe deformity are associated with residual pain after vertebral augmentation (9,16,17). In the subgroup demonstrating both severe collapse and intravertebral cleft formation, the rate of early non-response approached 47.9%, indicating a strong structural instability component. Intravertebral clefts have been previously associated with dynamic instability and variable outcomes after vertebroplasty (16,17,19,20).

These findings support the concept that severe collapse should not be interpreted solely as a radiographic severity marker but rather as a potential indicator of mechanical insufficiency in which vertebroplasty alone may be inadequate.

Mechanisms of instability-driven pain

Marked vertebral height loss may reflect endplate disruption, posterior wall compromise, and segmental micromotion. Vertebral endplate fractures have been identified as predictors of persistent pain following vertebroplasty (9). Although vertebroplasty increases local stiffness and stabilizes microfractures, it may not sufficiently control instability-driven pain when structural integrity is significantly compromised (10,15).

In this context, early pain non-response may reflect inappropriate index treatment selection rather than simple analgesic failure. Previous clinical analyses have emphasized the importance of appropriate patient selection and accurate identification of the dominant pain generator prior to vertebral augmentation (15).

Recent surgical literature has described cement-augmented short-segment fixation as an effective stabilization strategy in selected severely collapsed osteoporotic fractures. These techniques address both structural insufficiency and osteoporotic bone quality, potentially improving outcomes in high-risk morphologies (21).

Therefore, careful preoperative morphology-based stratification is essential.

Clinical decision-making and algorithm refinement

The revised management algorithm emphasizes differentiation between structural instability-driven pain and non-mechanical pain generators.

Structural instability-driven patterns include severe collapse (>50%), severe collapse with intravertebral cleft, and posterior wall involvement. These morphologies may reflect biomechanical insufficiency that is not fully corrected by cement augmentation alone (9,16,17).

Non-mechanical pain generators include facet-mediated pain, adjacent-level pathology, MRI-clinical discordance, and soft tissue sources. Facet joint and posterior element pain have been reported as contributors to persistent or recurrent pain after vertebroplasty and may respond to targeted interventions such as medial branch block (15,22). Moreover, mismatch between MRI bone marrow edema and the patient’s pain location has been shown to correlate with unsatisfactory outcomes after vertebral augmentation (23-25).

In selected high-risk morphologies, alternative stabilization may be considered as a primary strategy rather than solely as salvage treatment.

The 72-hour definition of early pain non-response was chosen pragmatically to detect early mechanical inadequacy. Cement polymerization and mechanical stabilization effects typically occur within the first 24–72 hours (5,6). While minor nociceptive pain may improve within one week, instability-related pain is unlikely to resolve spontaneously.

Strengths and limitations

This study benefits from a large real-world cohort and inclusion of management outcomes beyond risk factor identification alone. Few previous reports have combined risk factor analysis with structured post-procedural management outcomes (26,27).

However, several limitations should be acknowledged. First, the retrospective single-center design may introduce selection bias and limit generalizability. Second, functional outcomes such as the Oswestry Disability Index were not systematically recorded, and VAS alone may not fully capture disability or delayed mobilization. Third, quantitative analysis of cement distribution patterns was not performed, although cement distribution has been suggested as a factor influencing mechanical stability and outcomes (10,12). Finally, follow-up duration was relatively short.

External validation in multicenter prospective studies is warranted.

Conclusions

Early pain non-response after vertebroplasty is not uncommon and can be predicted using identifiable clinical and radiological factors. Persistent pain is multifactorial and should not be attributed solely to procedural failure. A systematic, individualized management strategy can achieve meaningful pain improvement in most affected patients and may optimize outcomes after vertebroplasty.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jss.amegroups.com/article/view/10.21037/jss-2026-1-0012/rc

Data Sharing Statement: Available at https://jss.amegroups.com/article/view/10.21037/jss-2026-1-0012/dss

Peer Review File: Available at https://jss.amegroups.com/article/view/10.21037/jss-2026-1-0012/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jss.amegroups.com/article/view/10.21037/jss-2026-1-0012/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. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This retrospective study was approved by the Institutional Review Board of Tra Vinh General Hospital (No. 15/QĐ-HĐKHKT, dated December 20, 2022). The requirement for informed consent was waived due to the retrospective nature of the study and the use of anonymized data.

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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Cite this article as: Nha LH, Thuong DC, Vu TK. Risk factors and management of early pain non-response after vertebroplasty in osteoporotic vertebral compression fractures. J Spine Surg 2026;12(4):52. doi: 10.21037/jss-2026-1-0012

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