Abstract
Background
Prolapsed lumbar intervertebral disc (IVD) is a prevalent spinal cause of low back pain associated with radicular pain. Platelet-rich plasma (PRP) has emerged as a potential alternative to epidural steroid injections. This review aimed to compare the efficacy of epidural PRP and epidural steroid injections in treating low back pain due to prolapsed lumbar IVD, assessed using a pain scale and Oswestry's disability index (ODI).
Methods
A systematic search of 4 databases (PubMed, Scopus, ScienceDirect, and Cochrane Central Register of Controlled Trials) up to July 2024 for randomized controlled trials comparing epidural PRP with steroids. Risk of Bias 2 was used for bias assessment. Pain and ODI mean differences (MDs) were calculated using RevMan v5.4. Heterogeneity was measured using I2, with random or fixed effects applied accordingly. The combined outcome progression of pain and ODI scores were computed using STATA/MP 17.0 software.
Results
Three trials (n=132) were included. At 1 month, epidural steroid injections showed lower pain scores than PRP (standard MD=1.04, 95% confidence interval [CI]: 0.63-1.46, p<0.00001, I2=0%). At 6 months, epidural PRP injection demonstrated greater pain relief (MD=−1.51, 95% CI: −1.98 to −1.05, p<0.00001, I2=0%) and lower ODI (MD=−9.71, 95% CI: −16.63 to −2.78, p=0.006, I2=75%). Epidural steroids showed significant worsening in pain score (1 vs 3 months, p=0.001; 3 vs 6 months, p=0.003).
Conclusions
Epidural PRP provides sustained and gradual improvement of pain and ODI for patients with prolapsed lumbar IVD over months of follow-up, while steroids provide initial relief at 1 month but are associated with worsening at later follow-ups.
Keywords: lumbar, prolapsed disc, epidural, platelet-rich plasma, steroid, meta-analysis
Introduction
The prolapsed lumbar intervertebral disc (IVD) is one of the most common spinal disorders leading to low back pain (LBP) associated with radicular pain that propagates to the lower extremities1). Both inflammation of these discs and herniation compressing nerve roots lead to radicular pain. Furthermore, the inflammatory response has been identified as an important factor in disc degeneration and pain generation, which worsens as the patient ages2).
Conservative interventions such as non-steroidal anti-inflammatory drugs, physical therapy, and steroid injections have been the mainstay treatment for treating LBP with radiculopathies2). Autologous platelet-rich plasma (PRP), derived from the patient's blood, is rich in growth factors (GFs) and bioactive proteins, such as Platelet-derived, transforming, vascular endothelial, insulin-like, and epidermal GF, and promotes repair and healing by influencing processes like hemostasis, inflammation, proliferation, and remodeling3,4). Injection of PRP in the epidural space has shown the potential to address the underlying causes of LBP associated with herniated IVD4).
We aimed to (1) evaluate the efficacy of epidural injection of PRP compared to epidural injection of steroids in treating LBP due to prolapsed lumbar IVD, as measured by the pain scale and Oswestry's disability index (ODI), and (2) evaluate pain scores and ODI of each group over time.
Materials and Methods
Search Strategy
This study was carried out in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines5). PubMed, Scopus, ScienceDirect, and Cochrane Central Register of Controlled Trials databases up to July 2024 were searched. We employed Medical Subject Headings terms and keywords in 2 blocks: (1) PRP; and (2) prolapsed disc or herniated disc or nerve root compression or radiculopathies.
Inclusion and Exclusion Criteria
The inclusion criteria were as follows: (1) patients with symptomatic prolapsed lumbar IVD; (2) participant groups treated with either epidural PRP or epidural steroid injection alone; (3) not a combination of PRP and steroids; (4) at least 1 efficiency and safety outcome measurement available; (5) limited to randomized controlled trials (RCTs); (6) a study population of more than 10; and (7) English language documents. Articles that did not meet the inclusion criteria were excluded.
Quality Appraisal, and Risk of Bias Assessment
Articles were collected and then independently reviewed by 2 authors (H.C and M.S.F) for identification, selection, and assessment. Data were then extracted. Discrepancies between reviewers were rediscussed and reevaluated with another author (R.E). Jadad's score was used to evaluate the methodological quality of the analysis. The Revised Cochrane Risk of Bias tool for Randomized Trials (Risk of Bias 2) was used to assess the risk of bias6). The level of evidence was assessed using the Oxford Centre for Evidence-based Medicine guidelines7).
Data Extraction and Analysis
The data extracted from the studies included: authors, year of publication, study design, sample size, age, gender, level of disease, intervention, follow-up time, pain scores, and ODI scores. Mean difference (MD) calculations were conducted using RevMan 5.4 (Cochrane, London, UK). Standard MD (SMD) or MD along standard deviation (SD) with a 95% confidence interval (CI) were employed for effect determination. Heterogeneity among trials was identified through the I2 value. Initially, a random-effects model was used, and a fixed-effects model was applied if I2<50% and heterogeneity was not significant (p>0.05).
To evaluate the overall progression of pain and ODI scores over time, meta-analyses of the combined mean and SD of baseline and each follow-up of all included studies were calculated according to the method described in the Cochrane Handbook for Systematic Reviews of Interventions by Higgins et al.8). The calculations were conducted using STATA/MP 17.0 software (Stata Corp., College Station, TX, USA). To determine significance, MDs between baselines and follow-ups were calculated using RevMan 5.4. The method for calculating the combined mean was also applied to 1 study to calculate the overall pain score.
Results
Study Selection
From the initial search, 531 studies were obtained (Fig. 1). Forty duplicates were removed, leaving 491 articles. A total of 487 articles were excluded through title and abstract screening. Of the 4 remaining studies, 1 presented the median instead of the mean and SD9). Three studies were included in the meta-analysis after the full-text assessment10-12).
Figure 1.
PRISMA flow diagram of study selection. PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses
Risk of Bias and Quality of Study
All studies were marked as high-quality studies with a low risk of bias (Tables S1 and S2). All 3 RCTs have a level of evidence of 2.
Demographic Characteristics of Included Studies
Three RCTs were included in this meta-analysis. A total of 132 patients with prolapsed discs, including 65 and 67 patients treated with PRP and steroids, respectively. The summary of the intervention of the included studies can be seen in Table S3. The demographic characteristics of our study are summarized in Table 1. Both groups were statistically comparable (p>0.05).
Table 1.
Demographic characteristics of included studies.
| Characteristics(n=available data) | PRP | Steroid | p Value |
|---|---|---|---|
| Age (years, mean±SD) (n=132) |
43.01±10.43 | 43.29±11.26 | 0.93 |
| Body weight (kg) (n=72) | 68.40±13.47 | 68.33±11.80 | 0.95 |
| BMI (kg/m2) (n=90) | 24.81±5.20 | 23.19±3.77 | 0.09 |
| Male, n (%) (n=132) | 36 (55.3) | 38 (56.7) | 0.87 |
| Level of pathology | 0.76 | ||
| L3/L4 (n=102) | 2 | 4 | |
| L4/L5 (n=132) | 37 | 36 | |
| L5/S1 (n=132) | 26 | 27 |
PRP: platelet-rich plasma; SD: standard deviation
Pain Score between Groups
All studies presented pain scores. Two studies measured pain with a visual analog scale (VAS)10,12), and 1 study employed a numeric rating scale (NRS)11). SMD and sensitivity analysis were employed to mitigate the difference. One study12) presented back and leg VAS, and the Cochrane method was used to calculate the combined mean and SD8).
No significant difference was found in the baseline pain scores between the PRP and steroid groups (p=0.65) (Table S4). At the 1-month follow-up, the steroid group's pain score was significantly lower than that of the PRP group (p<0.00001). However, at the 6-month follow-up, the PRP group showed a favorable significance (p=0.008). No significant difference was observed at the 3-month follow-up (Fig. 2).
Figure 2.
Pain score at one-, three-, and six-month follow-ups.
High heterogeneity was observed at the 3-month and 6-month follow-ups (Fig. 2B and C). In the sensitivity analysis, we omitted a study by Singh et al.11), resulting in I2=0%, with the reasons for using NRS instead of VAS possibly contributing to the result differences. Adjusted results showed no significant pain score difference between groups at the 3-month follow-up (p=0.97, I2=0%), and a significant difference was observed at the 6-month follow-up (p<0.00001, I2=0%) (Fig. 2D and E).
ODI Score between Groups
Two studies presented ODI scores (Fig. 3). No difference was found in both group's baseline (p=0.50) (Table S5). We found no significant difference in ODI scores at the 3-month follow-up. A significant difference was found at the 6-month follow-up, favoring PRP (p=0.006). A sensitivity analysis couldn't be conducted since only 2 studies were included.
Figure 3.
ODI score at three- and six-month follow-ups. ODI: Oswestry’s disability index
Pain and ODI Scores over Time
The combined pain and ODI scores of included studies were calculated and summarized in Table 2, and the data were plotted in a graph (Fig. 4). MDs were calculated to determine the significance between the baseline and each follow-up and between follow-ups (Tables S4 and S5).
Table 2.
Meta-analysis of combined pain and ODI scores mean and SD of studies at baseline and each follow-up.
| Measurement | Baseline | 1-month follow-up | 3-month follow-up | 6-month follow-up |
|---|---|---|---|---|
| Pain score (mean±SD) | ||||
| PRP | 6.72±1.23 | 4.62±1.23 | 2.98±1.27 | 2.41±1.51 |
| Steroid | 6.81±1.34 | 3.35±1.15 | 3.82±1.68 | 4.76±1.34 |
| ODI (mean±SD) | ||||
| PRP | 53.01±11.62 | - | 30.02±12.57 | 27.09±12.85 |
| Steroid | 51.74±12.16 | - | 32.33±12.11 | 38.35±14.66 |
ODI: Oswestry’s disability index; PRP: platelet-rich plasma; SD: standard deviation
Figure 4.
Graph showing the progression of combined mean and SD of (A) pain and (B) ODI scores through follow-ups. Only significant differences were presented (*significant, p<0.05). ODI: Oswestry’s disability index; SD: standard deviation
Pain Score Progression over Time
A constant reduction in pain could be observed in the PRP group over time (Fig. 4A). There was a significant reduction in pain scores from baseline to 1-month follow-up (p=0.002). However, there was no significant difference between follow-ups of the 1-month vs 3-month (p=0.12) and the 3-month vs 6-month (p=0.06) in the PRP group. All follow-up pain scores of the PRP group were significantly different when compared to the baseline (p<0.05).
A greater reduction in pain score was observed in the steroid group compared to the PRP group at the 1-month follow-up (Fig. 4A), and it was statistically significant based on the previous meta-analysis (Fig. 2). In the steroid group, the pain scores worsened at the 3-month and 6-month follow-ups, both statistically significant (1-month vs 3-month, p=0.001; 3-month vs 6-month, p=0.003). All follow-up pain scores of the steroid group were significantly different when compared to the baseline (p<0.05) (Fig. 4A).
ODI Score Progression over Time
A constant reduction in ODI score over time could be observed in the PRP group (Fig. 4B). Both baseline vs 3-month and baseline vs 6-month ODI scores in the PRP group were significant, with both p<0.00001. There was no significant difference in ODI scores of the PRP group at the 3-month vs 6-month follow-ups (p>0.05).
The ODI score in the steroid group significantly decreased when compared to baseline, (baseline vs 3-month, p<0.00001; baseline vs 6-month, p=0.01). At the 6-month follow-up, the ODI score in the steroid group worsened but it was not significant when compared to the 3-month follow-up (p=0.36) (Fig. 4B).
Discussion
Autologous PRP is a fraction of a blood centrifugation product harvested from fresh peripheral blood, characterized by a small amount of plasma with a significant platelet count compared to baseline values as its main constituent13,14). While adverse events have been reported15), its autologous nature provides an inherently safe application16). Furthermore, the cost of PRP injections is known to be comparable to steroids17).
Singjie et al.18) conducted a meta-analysis of RCTs comparing PRP injection vs controls in chronic back pain. In this study, lidocaine, contrast agent, or corticosteroid were grouped as the control arm. The injection site was either intradiscal, epidural, or lumbosacral ligaments. The result revealed that PRP performed significantly better than control groups, as pain scores reduced in the first, third, and sixth months of follow-up18).
Peng et al.19) conducted a meta-analysis comparing corticosteroid injection and PRP in rotator cuff disease. Corticosteroids showed functional improvement in the short-term (2-6 weeks). However, the long-term (>12 weeks) results showed that PRP was more favorable. There was no difference between the 2 groups in the middle of the terms (6-12 weeks). The corticosteroids were able to alleviate pain better than PRP during follow-ups, but no difference could be found in the short-, mid-, and long-term subgroups19).
Another meta-analysis, by Li et al.20) showed that corticosteroid injections demonstrated a favorable short-term (4 and 8 weeks) outcome when compared with local PRP treatments for lateral elbow epicondylitis. In the long-term follow-up (24 weeks), PRP injections improved pain and function more effectively than corticosteroid injections20).
A prospective study by Singh et al. was conducted to compare the addition of intra-articular lumbar facet joint PRP and steroid injections to radiofrequency ablation in chronic LBP patients. The VAS score of the group with additional PRP injections was significantly better at 3 and 6 months than with steroid or radiofrequency ablation alone. Furthermore, a consistent reduction of VAS and ODI scores could be observed in the PRP group. No difference could be found on the first day, or at the first, third, and sixth months of the steroid group or the radiofrequency ablation alone. Although significance was not calculated, a consistent increase in the mean VAS and ODI scores of the steroid group at the first, third, and sixth months was observed21).
On the contrary, Zielinski et al.22) and Schepers et al.23) showed no significant difference between the administration of intradiscal PRP vs saline-based controls for lumbar discogenic pain. This difference might be due to the differences in dose and concentration of administered PRP.
The current meta-analysis showed that epidural PRP is better than epidural steroids in treating LBP with prolapsed lumbar IVD. This was shown by the progression of the MD at the 1-, 3-, and 6-month post-injection and a steady decline in the pain score over time. Epidural PRP also showed superiority regarding a lower disability index in the sixth month compared to epidural steroid injections.
Interestingly, we found that in the steroid group, albeit still significant from the baseline, the pain scores of the third and sixth months were worse than the first-month post-injection. This worsening of pain in the steroid group suggests a diminishing effect of epidural steroid injection over time, with sharp initial relief of pain followed by a rebound, which was not observed in the PRP group. The rebound could also be observed in the 6-month disability index of the steroid group, while the PRP group preserved its improvement.
We found that while steroids could provide short-term improvement, the effect is relatively temporary. Epidural PRP injections showed gradual improvement and lasted longer, which may be attributed to their regenerative properties24,25).
The strength of our study was that we utilized 4 databases and strictly only included high-quality RCTs, contributing to the robustness of this meta-analysis. We acknowledge the limitation of this study: we were only able to include 3 studies, which can limit the strength of the statistical results. Furthermore, we could not control for the discrepancy in the PRP preparation protocol, which resulted in different concentrations, and the different doses and preparation of the steroid arm. Additionally, the variation of PRP, such as leukocyte-rich or leukocyte-poor, was not mentioned in any of the included studies14).
We propose that further PRP studies should at least mention the increase of platelets from baseline, platelet concentration, administered PRP volume, and total delivered platelets, as variations in these parameters may show clinical differences. Variations or subtypes of PRP should be mentioned if possible14). Moreover, larger, randomized high-quality studies are needed to compare the effects of epidural PRP injection and steroids.
This meta-analysis suggests that epidural PRP provides sustained and gradual improvement for patients with lumbar disc prolapse in terms of pain relief and functional improvement in the first, third, and sixth months. These results also showed that epidural steroids showed greater pain reduction in the first month, but were associated with the risk of worsening in the third and sixth months of pain score, and sixth month of ODI score. We suggest that epidural PRP should be considered as a stronger alternative to steroid injection for patients with prolapsed lumbar IVD.
Author Contributions: Writing- Review and Editing, Investigation, Supervision: RE. Conceptualization, Writing-Original Draft, Methodology, Resources: HC, MSF. Data Curation, Visualization: GM, AA. Validation, Supervision, Project Administration: BSJ, IY, MA
Conflicts of Interest: The authors declare that there are no relevant conflicts of interest.
Ethical Approval: Our institutional review board approved this study. Ethics approval was not required.
Informed Consent: This study did not require informed consent, as secondary data was used for systematic review and meta-analysis. We ensured that no identifiable information of the participants was included in the manuscript.
Supplementary Material
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