Combined vertebroplasty and pregabalin versus vertebroplasty alone for osteoporotic thoracolumbar fractures with referred pain: a retrospective cohort study

Abstract

Background

Osteoporotic thoracolumbar vertebral fractures are frequently accompanied by referred pain. Although percutaneous vertebroplasty (PVP) effectively alleviates local pain, its efficacy for referred pain remains limited. Pregabalin reduces neural sensitization and may enhance analgesic outcomes. This study aimed to investigate the effect of combining PVP with pregabalin on referred pain.

Methods

In this retrospective cohort study, 108 patients were allocated to either a combination therapy group (PVP plus pregabalin, n = 55) or a PVP-alone group (n = 53). The Visual Analog Scale (VAS), Pain Sensitivity Questionnaire (PSQ), and Oswestry Disability Index (ODI) scores were assessed preoperatively and at 1 week, 1 month, 2 months, and 3 months postoperatively.

Results

The combination group demonstrated significantly lower VAS and PSQ scores at 1 week and 1 month postoperatively compared to the PVP-alone group (all P < 0.05). However, no significant differences were observed at 3 months. No significant intergroup differences were found in ODI scores throughout the follow-up period. Patients with high baseline VAS scores or high pain sensitivity (as indicated by PSQ) exhibited more pronounced early pain improvement in the combination group.

Conclusion

The combination of PVP with pregabalin provides more effective relief of early postoperative referred pain, particularly in patients with high pain sensitivity. The baseline VAS score is a key predictor of early pain improvement. These findings suggest that postoperative analgesic strategies should be tailored to individual baseline pain sensitivity levels.

Background

Osteoporotic vertebral fracture (OVF) is a major global health issue, with its incidence increasing annually due to the aging population [1]. Owing to the unique anatomical characteristics of the thoracolumbar spine, most fractures occur in the thoracolumbar region (T11–L2). Patients with such fractures exhibit considerable variability in clinical manifestations, which can lead to delays in diagnosis and treatment [2]. Recent studies have reported that patients with OVF may experience non-midline pain in areas such as the chest, abdomen, lumbosacral region, iliac crest, groin, thigh, or even the calf—this is referred to as referred pain—rather than pain confined solely to the affected vertebra [2].

PVP is widely used in the treatment of osteoporotic vertebral compression fractures. This procedure can rapidly alleviate back pain and significantly improve patients’ quality of life [3]. However, clinically, it has been observed that patients often report referred pain after PVP, which affects their daily activities. Studies have shown that activation and upregulation of NMDA and NK1 receptors play a key role in central sensitization induced by spinal surgery, which manifests as mechanical hyperalgesia outside the surgical area [4]. Pregabalin, which modulates the nervous system to reduce the release of excitatory neurotransmitters and thereby decrease central sensitization, has become a key drug for pain management after spinal surgery [5].

Nevertheless, there is a lack of clinical studies on the effectiveness of PVP combined with pregabalin for the treatment of thoracolumbar fractures accompanied by referred pain. Unlike previous research, this study incorporates the degree of central sensitization and further analyzes the impact of pregabalin on postoperative outcomes of PVP based on baseline pain sensitivity levels. The aim is to provide a reliable new strategy for clinical postoperative pain management.

Materials and methods

General information

Inclusion criteria

• ① Age ≥ 60 years, with bone mineral density T-score ≤ − 2.5 SD; We used ≥ 60 years to balance representativeness of the typical OVCF population and adequate sample size in our center.

• ② History of minor trauma or stress to the lower back, accompanied by significant low back pain or distal pain;

• ③ Availability of complete preoperative imaging examinations (X-ray, CT, MRI) and bone mineral density measurement, with a confirmed diagnosis;

• ④ Single-segment thoracolumbar vertebral fracture (T11–L2);

• ⑤ Absence of nerve root or spinal cord compression symptoms.

Exclusion criteria

• ① Pathological fractures secondary to spinal tumors or metastases;

• ② Pre-existing chronic low back pain lasting > 6 weeks prior to the acute fracture event;

• ③ Previous spinal surgery or vertebroplasty/kyphoplasty for OVCF;

• ④ Concomitant lumbar degenerative disease or instability (e.g., disc herniation, spinal stenosis, degenerative spondylolisthesis, or radiographic/clinical evidence of lumbar segmental instability) that could confound pain assessment.

• ⑤ Pre-existing neurological deficits or radiculopathy;

• ⑥ Major systemic comorbidities contraindicating surgery or anesthesia;

• ⑦ New vertebral fracture occurring during the follow-up period;

• ⑧ Alternative diagnoses for distal pain, such as piriformis syndrome, sacroiliac joint dysfunction, or superior cluneal nerve entrapment;

• ⑨ History of psychiatric disorders, cognitive impairment, or any condition that could impede accurate pain evaluation or follow-up compliance.

Study population

A total of 108 patients with acute single-level OVCF (T11–L2) were enrolled in this study. All procedures (PVP with or without pregabalin) were performed in our Department of Spinal Surgery between January 2022 and January 2024.Patients were allocated into two groups: the combination therapy group (PVP plus pregabalin, n = 55; 20 males, 35 females; mean age 72.1 ± 5.5 years, range: 61–88) and the PVP-alone group (n = 53; 18 males, 35 females; mean age 72.4 ± 5.2 years, range: 60–89).The diagnosis of acute OVCF was confirmed by imaging: vertebral compression and height loss on radiographs and CT, and bone marrow edema within the vertebral body on MRI, which identified the symptomatic level.For all patients, two senior orthopedic surgeons conducted a comprehensive review of the medical history, imaging findings, and physical examination results to rigorously exclude other potential causes of distal pain.The preoperative baseline demographics and clinical characteristics were well-balanced between the two groups, with no significant differences observed (p > 0.05; see Table 1).

Table 1.

Baseline Characteristics and Preoperative Scores ()

Variable	PVP (n = 53)	PVP + Pregabalin (n = 55)	P-Value
Age (years)	72.4 ± 5.2	72.1 ± 5.5	0.770
Male, n(%)	18 (34.0)	20 (36.4)	0.782
Bone mineral density (T-score)	-3.21 ± 0.21	-3.18 ± 0.25	0.507
BMI (kg/m²)	20.9 ± 1.6	21.1 ± 1.8	0.538
Cement volume (mL)	4.52 ± 0.85	4.63 ± 0.91	0.519
Vertebra of fracture, n(%)			0.956
T11, n(%)	10 (18.9)	11 (20.0)
T12, n(%)	16 (30.2)	18 (32.7)
L1, n(%)	18 (34.0)	18 (32.7)
L2, n(%)	9 (17.0)	8 (14.5)
Preoperative Scores
VAS (score)	7.21 ± 0.82	7.13 ± 0.67	0.577
PSQ (score)	7.60 ± 1.03	7.42 ± 0.83	0.303
ODI (%)	71.5 ± 3.71	71.98 ± 4.5	0.299

Notes: Data are presented as mean ± standard deviation or number (percentage). Intergroup comparisons were performed using independent samples *t*-test or χ² test. No significant differences were found in baseline characteristics (P > 0.05).Abbreviations: PVP Percutaneous Vertebroplasty, BMI Body Mass Index, VAS Visual Analogue Scale, PSQ Pain Sensitivity Questionnaire, ODI Oswestry Disability Index

Surgical technique and postoperative management

All 108 surgical procedures were performed by the same surgical team. Under local anesthesia, patients were placed in a prone position. The fractured vertebral level was identified using fluoroscopic guidance. Following routine surgical disinfection and draping, local anesthesia was administered via infiltration with 5 mL of 1% lidocaine. A unilateral transpedicular approach was utilized. The puncture needle was advanced to a position approximately 0.5 cm beyond the posterior vertebral wall. After removing the inner stylet, a working cannula was inserted sequentially. Polymethylmethacrylate (PMMA) bone cement was prepared to a viscous state and injected slowly under continuous fluoroscopic monitoring to assess its dispersion and to detect any potential leakage. The injection was ceased immediately if leakage into the venous plexus, intervertebral disc, or spinal canal was observed, or once the cement reached the posterior quarter of the vertebral body. Postoperatively, patients were closely monitored for vital signs and neurological function (sensation and movement of both lower limbs). The puncture site was covered with a sterile dressing. All patients were instructed to wear a lumbar support brace and were allowed to ambulate under supervision on the first postoperative day.

Standard anti-osteoporosis medication was initiated for all patients postoperatively, including:

• Salmon calcitonin nasal spray (1 spray, twice daily);

• Oral calcium carbonate with vitamin D chewable tablets (800 mg, once daily);

• Oral alfacalcidol (0.5 µg, once daily).

Additionally, patients in the PVP plus pregabalin group received oral pregabalin (75 mg, twice daily) for 3 consecutive months.

Outcome evaluation and follow-up

The visual analog scale (VAS [6]; range: 0 [no pain] to 10 [worst pain imaginable]) was used to evaluate the intensity of both local and distant pain at 1 week, 1 month, 2 months, and 3 months postoperatively. The Pain Sensitivity Questionnaire (PSQ [7]; total score range 0–10, with higher scores indicating greater sensitivity) was employed to assess the degree of central sensitization. Functional disability related to low back pain was measured using the Oswestry Disability Index (ODI [8]). Safety was assessed by documenting the incidence of adverse reactions associated with pregabalin, including dizziness, somnolence, and gastrointestinal disturbances. Follow-up data were collected through a combination of clinical outpatient reviews, telephone interviews, and analysis of medical records and imaging studies.

Statistical analysis

Statistical analyses were performed using SPSS software (version 27.0). Continuous variables are presented as mean ± standard deviation (SD). Inter-group comparisons of VAS, PSQ, and ODI scores at different time points were conducted using independent samples t-tests. Categorical data were compared between groups using the chi-square (χ²) test. A two-tailed P-value of less than 0.05 was considered statistically significant.

Results

All 108 patients in this study successfully underwent the procedure without any surgery-related complications. Representative cases are illustrated in Fig. 1. All patients were followed up for a period of 3 months. The volume of bone cement injected was 3–6 mL (4.3 ± 1.1 mL) in the PVP with pregabalin group and 3–6 mL (4.5 ± 1.0 mL) in the PVP-alone group. Postoperative pain levels (as reflected by VAS score) were significantly reduced in both groups at 1 week compared to preoperative values (Fig. 2A). The VAS and PSQ scores in the PVP with pregabalin group were significantly lower than those in the PVP-alone group at 1 week and 1 month after surgery, indicating the improvement of the pain relief with the combination treatment (P < 0.05; Table 2; Fig. 2A and B). However, there was no significant difference in ODI improvement between the two groups (P > 0.05; Fig. 2C). Regarding safety: In the combination group, one 88-year-old patient experienced dizziness and lethargy; these symptoms resolved after discontinuation of pregabalin. No other adverse reactions were observed.

Fig. 1.

Imaging findings of a 77-year-old female with a T12 vertebral compression fracture. The patient presented with lumbosacral pain that was exacerbated upon getting out of bed, and a Visual Analogue Scale (VAS) score of 7. After treatment with percutaneous vertebroplasty (PVP) combined with pregabalin and a 3-month follow-up, the patient’s lumbosacral pain significantly improved, with a VAS score of (1) (A-C) Preoperative magnetic resonance imaging (MRI). (D, E) Preoperative lumbar spine radiographs. (F) Preoperative lumbar spine computed tomography (CT). Fracture level indicated by arrow. (G, H) Lumbar spine radiographs on postoperative day (2) (I, J) Lumbar spine radiographs at the 3-month postoperative follow-up

Fig. 2.

Changes in (A) VAS, (B) PSQ, and (C) ODI scores over time in the two treatment groups (PVP alone vs. PVP + pregabalin). The time points are defined as “Pre-op” (baseline, before surgery), “Post-1w” (1 week after surgery), “Post-1m” (1 month after surgery), “Post-2m” (2 months after surgery), and “Post-3m” (3 months after surgery). Between-group comparisons at each time point were performed using independent t-tests. To account for multiple comparisons across time points within each outcome, p-values were adjusted using the Benjamini–Hochberg false discovery rate procedure, and adjusted q-values are displayed on the plots. Significance levels are marked as: *** q < 0.001; ** q < 0.01; * q < 0.05; ns = not significant

Table 2.

Changes in primary outcome measures over time

Measure	Time Point	PVP Group	PVP + Pregabalin Group	P-Value
VAS	1 week	3.40 ± 0.44	2.67 ± 0.47	< 0.001
	1 month	3.05 ± 0.31	2.17 ± 0.54	< 0.001
	2 months	2.08 ± 0.68	1.97 ± 0.60	0.409
	3 months	1.14 ± 0.32	1.12 ± 0.23	0.663
ODI	1 week	31.70 ± 2.83	31.18 ± 2.71	0.334
	1 month	26.96 ± 3.03	26.40 ± 2.79	0.318
	2 months	19.49 ± 3.50	20.33 ± 2.68	0.165
	3 months	14.40 ± 2.12	14.73 ± 2.28	0.437
PSQ	1 week	7.51 ± 1.10	6.91 ± 0.95	0.003
	1 month	5.04 ± 0.85	4.51 ± 0.50	< 0.001
	2 months	4.39 ± 0.42	3.51 ± 0.55	< 0.001
	3 months	2.19 ± 0.37	2.11 ± 0.28	0.211

Notes: Data are presented as mean ± standard deviation .Intergroup comparisons at each postoperative time point were performed using independent samples *t*-test

To further identify potential predictors of postoperative pain relief, we analyzed the correlation between the improvement in VAS scores at one week postoperatively (calculated as preoperative VAS minus VAS at one week after surgery) and various baseline characteristics. A strong positive correlation was observed between baseline VAS and the degree of VAS improvement in the PVP-alone group (r = 0.90, Fig. 3A, left). Similarly, a significant positive correlation was also found in the PVP with pregabalin (PVP+PRBL) group (r = 0.83, Fig. 3A, right), with both correlations being highly statistically significant (p < 0.001). These results indicate that patients with higher initial pain levels tend to exhibit greater improvement after surgery.

Fig. 3.

Potential physiological predictors influencing postoperative VAS improvement. (A) Correlation between improvement in VAS score at 1 week postoperatively and baseline VAS score. X-axis: baseline VAS score; Y-axis: improvement in VAS score at 1 week postoperatively. Left panel: PVP group; Right panel: PVP + Pregabalin group. (B) Correlation between improvement in VAS score at 1 week postoperatively and baseline PSQ score. X-axis: baseline PSQ score; Y-axis: improvement in VAS score at 1 week postoperatively. Left panel: PVP group; Right panel: PVP + Pregabalin group. (C) Association between improvement in VAS score at 1 week postoperatively and gender. X-axis: gender; Y-axis: improvement in VAS score at 1 week postoperatively. Left panel: PVP group; Right panel: PVP + Pregabalin group. (D) Correlation between improvement in VAS score at 1 week postoperatively and age. X-axis: age; Y-axis: improvement in VAS score at 1 week postoperatively. Left panel: PVP group; Right panel: PVP + Pregabalin group. (E) Correlation between improvement in VAS score at 1 week postoperatively and bone mineral density. X-axis: bone mineral density (T-score); Y-axis: improvement in VAS score at 1 week postoperatively. Left panel: PVP group; Right panel: PVP + Pregabalin group. (F) Correlation between improvement in VAS score at 1 week postoperatively and BMI. X-axis: BMI; Y-axis: improvement in VAS score at 1 week postoperatively. Left panel: PVP group; Right panel: PVP + Pregabalin group

We further evaluated the association between other baseline factors and postoperative VAS improvement. No strong correlations were identified for any of the following factors: baseline PSQ (PVP group: r = 0.04; PVP+PRBL group: r = 0.21, Fig. 3B), sex (PVP group: p = 0.11; PVP+PRBL group: p = 0.074, Fig. 3C), age (PVP group: p = 0.06; PVP+PRBL group: p = 0.37, Fig. 3D), bone mineral density (T-score) (PVP group: r = -0.01; PVP+PRBL group: r = -0.15, Fig. 3E), or BMI (PVP group: r = 0.24; PVP+PRBL group: r = -0.22, Fig. 3F).These findings suggest that baseline pain intensity, as measured by VAS, is a strong predictor of short-term pain reduction after surgery. In contrast, general demographic and physiological factors—including central sensitization status, bone mineral density, age, BMI, and sex—demonstrated limited predictive value for postoperative pain improvement.

We further investigated the clinical scenarios in which combined therapy (PVP with pregabalin) demonstrates superior efficacy over PVP alone. Based on the median baseline PSQ score of 7.0, patients were stratified into a “high PSQ group” (n = 93) and a “low PSQ group” (n = 15). The improvement in VAS scores at one week postoperatively was compared between the treatment groups within each stratum (Fig. 4). In the high PSQ group, the mean VAS improvement was 3.84 ± 0.99 points in the PVP-alone group and 4.52 ± 0.82 points in the PVP with pregabalin group, with the difference being statistically significant (p < 0.001). In contrast, in the low PSQ group, the mean VAS improvement was 3.67 ± 1.15 points in the PVP-alone group and 3.92 ± 0.92 points in the combination group; this difference did not reach statistical significance (p = 0.65).

Fig. 4.

Difference in VAS improvement at 1 week postoperatively between patients with different central sensitization levels treated with PVP alone versus PVP combined with pregabalin. The X-axis represents patient groups stratified by different levels of central sensitization; within each group, the blue bars represent treatment with PVP alone, and the red bars represent treatment with PVP combined with pregabalin. The Y-axis represents the difference in the improvement of VAS scores

These results indicate that the addition of pregabalin significantly enhances the analgesic effect of PVP in patients with elevated baseline central sensitization (high PSQ), whereas no significant additional benefit was observed in patients with low baseline neurosensitization.

Discussion

Baseline VAS score was identified as a significant predictor of early postoperative pain improvement, whereas other demographic and physiological factors demonstrated limited predictive value. The combination of PVP and pregabalin significantly enhanced analgesic efficacy during the early postoperative period in patients with high central sensitization levels, while its effect was comparable to that in patients with low central sensitization levels. These findings highlight the potential clinical relevance of selecting adjunct postoperative analgesia based on individualized baseline pain sensitivity.

Clinical characteristics of referred pain associated with osteoporotic fractures

Osteoporotic vertebral compression fractures (OVCF) predominantly occur in the thoracolumbar region (T11–L2). The typical clinical presentation consists of severe back pain, usually localized to the level of the affected vertebra. The pain is exacerbated by changes in position and alleviated by bed rest [9]. However, clinical experience has shown that some patients with osteoporotic thoracolumbar fractures exhibit clear bone marrow edema on MRI, yet report pain not only at the fracture site but also in regions distal to the injured vertebra, such as the lower lumbar area, peri-iliac crest region, or buttocks. This type of pain is referred to as distal pain or non-midline pain [10]. In some cases, patients diagnosed with OVCF may present exclusively with distal pain, with little or no discomfort at the fracture level itself. Without a thorough understanding of this pathophysiology, such cases are prone to misdiagnosis or underdetection [11]. In 1991, Patel et al. [12] documented 30 cases of distal pain in OVCF patients, though no subclassification was proposed. Friedrich et al. [13] categorized pain distributions in 51 patients with T8–L2 OVCF into three types: upper back pain, lower lumbosacral pain, and combined pain. Later, in 2008, Doo et al. [14] further classified pain into four patterns according to location: Type A (peri-midline pain near the affected vertebra, 13%); Type B1 (localized back pain, 27%); Type B2 (pain radiating to the anterior chest, 17%); and Type C (lumbosacral or lower limb pain distant from the fracture, 43%).

More recently, Shi et al. [15] proposed a detailed classification system for distal pain, categorizing it into types A through E based on pain distribution: Type A: pain in the lumbosacral area and buttocks; Type B: pain in the abdomen, anterior superior iliac spine (ASIS) region, or groin; Type C: pain in the back or anterolateral thigh; Type D: pain extending to the knee, posterior calf, or anterolateral lower leg; Type E: pain occurring in two or more of the regions described in types A–D. This study found that distal pain in OVCF patients was predominantly concentrated in Type A. We previously referred to this type as “initiation pain,” as it is primarily triggered by changes in body position—becoming noticeable upon rising or turning—and tends to subside when the patient is lying down.

Pathogenesis of referred pain

Currently, there is no consensus on the mechanism by which thoracolumbar vertebral compression fractures cause referred pain, and understanding primarily centers around the following three aspects.

• ① Referred Pain of Neurogenic Origin

Thoracolumbar vertebral fractures, accompanied by injuries to the surrounding soft tissues and facet joints, can stimulate the sympathetic ganglia, leading to referred pain.Kim et al. [16], through anatomical studies, divided the sinuvertebral nerve into four branches: N1: an ascending branch within the bone, extending toward the posterior margin of the vertebral body; N2: a descending branch coursing along the posterior longitudinal ligament and intervertebral disc; N3: a branch reaching the intervertebral disc; N4: a branch diverging from N1 near the pedicle into the vertebral body (also termed the “basivertebral nerve”), distributed near the superior and inferior endplates.

• ② Vertebrogenic Referred Pain

The convergence-projection hypothesis posits that primary afferent nerve fibers from two distinct regions converge onto the same secondary neuron within the spinal cord, resulting in the central nervous system’s misinterpretation of the pain’s origin [17]. Regarding referred pain associated with the thoracolumbar fascia, a growing body of evidence now indicates that the thoracolumbar fascia is innervated [18].

• ③ Other Etiological Factors

Sagittal imbalance, recurrent fractures, pain originating from facet joint injuries, and postural fatigue syndrome [19]. Soft tissue injuries, age, number of vertebral fractures, lumbar comorbidities, psychological factors, and the location of the fracture are significant independent risk factors for low back pain in OVCF patients following PVP [20, 21]. In summary, and based on the findings of this study, we propose that the primary cause of referred pain associated with OVCF is damage to the sinuvertebral nerves within the fractured vertebral body and stimulation of the posterior rami of the spinal nerves, which induces central nervous system sensitization and subsequently leads to the development of referred pain.

Treatment options

Currently, two main approaches are employed in the management of this condition:

• ① Conservative Treatment

This primarily involves bed rest and immobilization. However, prolonged recumbency increases the risk of deep vein thrombosis, pneumonia, and pressure ulcers. Clinically, OVCF has been associated with an eightfold increase in mortality—a risk comparable to that of hip fractures in the elderly [22]. Cho et al. [23] suggested that absolute bed rest for three days may be appropriate for conservative management of OVCF, taking into account radiographic outcomes, prognosis, potential complications, patient convenience, and economic factors, followed by brace-assisted ambulation. Nevertheless, studies have indicated that while braces may improve comfort in some patients with acute fractures, no significant differences were observed between braced and non-braced groups in long-term outcomes or changes in height [24]. Moreover, due to low bone density, osteoporotic fractures are more prone to progressive vertebral collapse and delayed union [25]. Jeon et al. [26] further identified paraspinal muscle fatty infiltration as a predictor of progressive collapse in OVCF. Thus, conservative treatment carries notable limitations and risks.

• ② Surgical Treatment

Percutaneous vertebroplasty (PVP) is a safe and effective intervention for patients with recent OVCF whose clinical symptoms align with imaging findings. PVP provides rapid pain relief, reduces kyphotic deformity, improves quality of life, and decreases long-term mortality [9]. Li et al. [27] reported that both PVP and percutaneous kyphoplasty (PKP) effectively alleviate distal lumbosacral pain associated with thoracolumbar OVCF, suggesting that such pain may be of vertebrogenic referred origin. Lin et al. [28] demonstrated that PKP combined with local anesthetic and steroid injection more effectively reduced early postoperative distal lumbosacral pain compared with PKP alone, thereby encouraging earlier mobilization and functional rehabilitation. PVP not only improves local pain and Oswestry Disability Index (ODI) scores at the fracture level but also ameliorates accompanying distal lumbosacral pain symptoms. Additionally, the choice of puncture approach does not appear to influence the degree of pain relief or functional improvement [29].

• ③ Rehabilitation and Physical Therapy

In addition to vertebral augmentation and pharmacologic analgesia, physical therapy (PT) is an integral component of comprehensive care for patients with OVCF, particularly for restoring mobility and function in older adults. In this context, PT refers to a structured rehabilitation program that may include graded mobilization, postural training, back-extensor strengthening, balance training, functional task practice, and patient education, with adjunct modalities or manual techniques used selectively when appropriate. Current guidance supports physiotherapist-supervised exercise after vertebral fracture, which has been shown to improve pain and physical performance, and recommends initiating back-extensor training in unloaded positions when pain limits activity (NOGG 2024, Sect. 8).

Importantly, the potential impact of PT is particularly relevant to multidimensional functional outcomes such as the ODI. Unlike pain intensity alone, ODI reflects broader physical capacity and participation domains (e.g., standing, walking, lifting, and social activities) and may therefore depend more on progressive improvements in muscle strength, endurance, and movement confidence than on short-term analgesia.

In the present retrospective cohort, postoperative PT/rehabilitation was not standardized and was implemented according to routine clinical practice, which may have introduced heterogeneity in rehabilitation exposure and thereby attenuated between-group differences in ODI trajectories within the 3-month follow-up window. Future studies should incorporate a protocolized PT pathway (e.g., early supervised mobilization followed by progressive extensor-strengthening and balance training) and evaluate longer-term outcomes to better define the additive value of rehabilitation alongside PVP and individualized analgesic strategies.

While previous studies have primarily focused on PVP or PKP alone for managing distant pain, few have investigated combination therapy involving PVP and adjuvant pharmacologic treatment. In the present study, follow-up assessment of VAS, PSQ, and ODI scores in 108 patients revealed that PVP combined with pregabalin effectively alleviated both local and distal pain during the early postoperative period. Compared with PVP alone, the combination group showed significantly greater improvement in VAS and PSQ scores at early timepoints (1 week and 1 month postoperatively; P < 0.05), consistent with earlier findings. A novel aspect of this study is the incorporation of the Pain Sensitivity Questionnaire (PSQ) as a patient-reported measure of pain sensitivity. Although PSQ is not a direct physiological assessment of central sensitization, it may reflect individual differences in pain sensitivity and central pain processing. In our cohort, patients with higher baseline PSQ showed greater early pain improvement with adjunct pregabalin following PVP compared with PVP alone. However, this subgroup finding should be interpreted as exploratory and hypothesis-generating, particularly given the relatively small sample size in the low-PSQ subgroup (n = 15). Future prospective studies with larger, balanced subgroups and objective sensitization-related measures are warranted to determine whether baseline pain sensitivity meaningfully modifies the analgesic response to pregabalin after vertebral augmentation.

• ④ Pregabalin Treatment

Pregabalin exerts its analgesic effect by binding to the α2-δ subunit of presynaptic voltage-gated calcium channels in both the central and peripheral nervous systems. This binding reduces the release of excitatory neurotransmitters and attenuates spinal cord sensitization [30]. Due to this mechanism, pregabalin has become an established cornerstone of postoperative pain management in spinal surgery. It is recommended in several clinical guidelines, including the Enhanced Recovery After Surgery (ERAS) protocols for spinal procedures and the North American Spine Society (NASS) Clinical Guidelines for Multidisciplinary Spine Care [31]. Khalil Komlakh et al. [32] demonstrated that pregabalin significantly contributes to pain relief in patients undergoing spinal surgery and endorsed its use in the postoperative period. Similarly, Tsai et al. [33] reported that preoperative administration of pregabalin effectively reduced postoperative pain and decreased opioid consumption in spinal surgery patients. Through its modulation of neuropathic pain pathways, pregabalin facilitates functional recovery, particularly within the first week to one month after surgery.

This study found that most patients with OVCF and concomitant distant pain who underwent PVP alone also exhibited significant reductions in VAS, ODI, and PSQ scores. Their distant pain was alleviated to some extent, and quality of life was markedly improved. At the 3-month follow-up, clinical symptoms remained favorable in both groups, with no statistically significant differences observed between them. This convergence in outcomes may be attributed to fracture healing and neural adaptation by 3 months post-surgery, potentially diminishing the differential effect of medication. These findings are consistent with the follow-up results reported by Lin [28] and Li [27]. Therefore, our findings should be interpreted as supporting short-term analgesic and sensitization-related benefit, rather than durable clinical superiority. Longer-term, prospective studies with extended follow-up are warranted to determine whether early improvements translate into sustained functional gains, reduced recurrence of pain, or other clinically meaningful long-term outcomes. Safety assessments indicated that pregabalin is effective in alleviating post-spinal surgery pain, as supported by Park et al. [34], with no significant side effects observed at a low dose of 25 mg. Pregabalin was the first drug approved by the U.S. Food and Drug Administration (FDA) for the treatment of diabetic neuropathy and postherpetic neuralgia. Clinical trials of up to 12 weeks’ duration demonstrated that both peripheral and central neuropathic pain decreased within the first week of treatment and remained reduced throughout the treatment period [33]. According to Filippo Migliorini et al. [5], a daily dose of 450 mg pregabalin was most effective in improving symptoms of fibromyalgia, while 600 mg/day resulted in better sleep quality. The incidence of adverse events at 300 mg/day was lower than that at higher doses. In the present study, one elderly patient experienced dizziness and lethargy after taking pregabalin; these symptoms resolved following drug discontinuation. Previous studies have indicated that adverse reactions to pregabalin occur primarily at high doses. In this trial, a low dose of 150 mg/day was used, which was associated with a low incidence of adverse events.

In addition to pain improvement, both treatment groups—PVP with or without pregabalin—exhibited significant improvement in ODI scores. However, the addition of pregabalin did not yield a statistically significant enhancement in ODI improvement compared to PVP alone. This observation may be attributed to the multidimensional nature of the ODI scale, which evaluates not only pain intensity but also functional capacities across 10 domains, including personal care, lifting, walking, standing, sleeping, and social activities. Changes in ODI scores thus reflect a comprehensive functional status influenced by physical, psychological, and motor factors, rather than pain relief alone. Furthermore, elderly patients generally have low activity levels, and early postoperative functional exercises are often conducted under the protection of a lumbar brace, which imposes certain restrictions on mobility. A randomized controlled trial [35] compared ODI changes in patients who received systematic back muscle training after PVP versus those who did not. The results showed no significant difference in ODI between the two groups at 3 days and 1 month postoperatively. However, at 6 months, 1 year, and 2 years after surgery, the group that underwent rehabilitation training showed significantly better ODI scores than the control group. This suggests that functional recovery depends not only on acute pain relief but also on long-term improvements in physiological indicators such as muscle strength and exercise endurance. Thus, sustained rehabilitation interventions may demonstrate more substantial benefits within multidimensional functional assessments like the ODI.

Although statistically significant between-group differences in VAS (and PSQ) were observed early, their magnitude requires consideration of clinical relevance. The minimal clinically important difference (MCID), defined as the smallest patient-perceived beneficial change, is commonly used to distinguish clinical from statistical significance in pain and disability outcomes. Here, the early VAS advantage with PVP plus pregabalin was modest and did not lead to detectable ODI improvement, suggesting that short-term analgesic benefits may not correspond to clinically meaningful functional gains within 3 months. Future studies should predefine MCID-based responder analyses (e.g., proportion achieving MCID in VAS/ODI) and include longer follow-up to better evaluate the patient-centered impact of adjunct pregabalin.

We also evaluated the predictive value of various baseline characteristics for early VAS improvement following PVP, with or without pregabalin. Baseline VAS emerged as a strong independent predictor, indicating that patients with more severe preoperative pain experienced greater early postoperative improvement. In contrast, other demographic and physiological parameters—such as baseline PSQ, age, sex, bone mineral density, and BMI—showed limited predictive value.Additionally, when patients were stratified according to baseline central sensitization (as measured by PSQ), those with high central sensitization who received PVP plus pregabalin showed significantly greater pain reduction in the early postoperative period compared to those treated with PVP alone. This result suggests that pregabalin provides particular benefit to patients with elevated central sensitization shortly after surgery.

Routine postoperative MRI follow-up was not performed in this retrospective cohort due to real-world resource and cost constraints for patients, which limited our ability to correlate symptom trajectories with radiological evolution (e.g., changes in vertebral bone marrow edema). Prior studies have shown that bone marrow edema may gradually decrease over months after vertebroplasty on serial MRI, and imaging follow-up could therefore provide complementary information regarding fracture healing and edema resolution [36]. Future prospective studies incorporating standardized MRI surveillance would help clarify radiological–clinical associations in patients with OVCF and distal pain.

Limitations

1. This single-center study with a relatively small sample size may limit the generalizability of the findings.

2. The absence of long-term follow-up data beyond three months precludes the evaluation of long-term complications or recurrence rates.

3. Follow-up MRI assessments were not available.

4. Control of confounding factors: Potential confounding variables, such as patients’ baseline medications and psychological status, were not analyzed.

Conclusion

Combining PVP with pregabalin can more effectively alleviate early postoperative referred pain in patients with heightened pain sensitivity by reducing central neural sensitization, although the long-term outcomes show no significant difference compared to PVP alone. Baseline VAS is identified as a key predictive factor for early postoperative pain improvement. This finding supports the selection of postoperative analgesic strategies based on individualized baseline pain sensitivity levels.

Abbreviations

PVP

Percutaneous vertebroplasty

VAS

Visual Analog Scale

PSQ

Pain Sensitivity Questionnaire

ODI

Oswestry Disability Index

OVF

Osteoporotic vertebral fracture

OVCF

Osteoporotic vertebral compression fracture

Authors’ contributions

Zhang X.D. was responsible for drafting the initial manuscript and creating the tables and figures. Cheng H. collected and organized patient data and follow-up statistics. Li L. proofread the manuscript, collected additional data, and provided feedback on the overall design and formatting. Cui W. performed statistical analysis and interpretation, and critically revised the manuscript.

Funding

The authors did not receive support from any organization for the submitted work.

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Declarations

Ethics approval and consent to participate

This study was designed as a retrospective cohort study and was approved by the Ethics Review Committee of Shaanxi Nuclear Industry 215 Hospital. Informed consent was obtained from all patients prior to surgery. All procedures performed in this study were in ac cordance with the ethical standards of the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.