Introduction
Lumbar disc herniation (LDH), a prevalent degenerative spinal disease, poses a significant clinical challenge. Treatment primarily encompasses conservative and surgical approaches [1,2]. Although conservative measures, which mainly focus on alleviating symptoms, benefit many patients, those who are unresponsive or experiencing progressive neurological decline often require surgical intervention [3]. Traditionally, open surgery has been the mainstay of surgical treatment, but its inherent drawbacks—extensive muscle dissection, bone resection, and potential complications—have led to the need for alternative approaches [4]. Minimally invasive spine surgery has emerged as a preferred technique in recent years, offering benefits such as reduced tissue trauma, faster recovery, and shorter hospital stays [5]. Techniques such as full endoscopic lumbar discectomy (FELD) have shown promising clinical efficacy in treating LDH [6,7]. However, both conservative and surgical interventions do not address the underlying disc degeneration process, highlighting the need for further therapeutic advancements.
Platelet-rich plasma (PRP) is a concentrated suspension of autologous platelets extracted from peripheral blood through centrifugation. Its therapeutic potential stems from its biological safety, ease of preparation and sourcing, and enrichment with multiple growth and anti-inflammatory factors [8,9]. This synergistic cocktail of bioactive molecules in PRP facilitates the repair of intervertebral disc tissues by promoting cellular regeneration and mitigating inflammatory responses [10]. Consequently, PRP holds promise in slowing, or even potentially reversing, the pathological progression of intervertebral disc degeneration [11].
The existing literature on the combined application of FELD and PRP injections for treating LDH is limited, with sparse evidence regarding its efficacy and safety. This meta-analysis aimed to systematically evaluate the available research on the synergistic effects of PRP injections post-FELD in patients with LDH. The primary objective was to determine whether FELD combined with PRP administration improves clinical outcomes and facilitates disc remodeling compared to FELD alone.
Materials and Methods
Search strategy
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework, we conducted a systematic search across established academic databases, including PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang Data. Conducted on December 20, 2023, the search employed a predefined set of keywords: (“lumbar disc herniation” OR “back pain” OR “full endoscopic lumbar discectomy” OR “percutaneous endoscopy” OR “full endoscopy” OR “FELD” OR “PELD” OR “PETD”) AND (“PRP” OR “platelet-rich plasma”). This search strategy aimed to identify all relevant studies investigating the efficacy and safety of PRP injections after FELD in the treatment of patients with LDH.
Additionally, the bibliographies of all included articles were manually screened to identify potentially relevant studies that were not captured by the initial database search [12]. This helped enhance both the breadth and depth of the literature review, ensuring the inclusion of potentially valuable research missed by the primary search strategy [13].
This is a meta-analysis study, so ethics committee approval was not required.
Inclusion and exclusion criteria
The inclusion criteria are as follows: (1) study design: randomized controlled trials (RCTs), cohort studies, and case-control studies; (2) study population: patients aged ≥18 years diagnosed with low back pain and/or unilateral radiating pain; unsuccessful conservative treatment for at least 3 months; confirmed diagnosis of simple LDH without stenosis of the spinal canal; treated through transforaminal FELD approach; (3) outcome measures: studies reporting at least one of the following outcomes: Visual Analog Scale (VAS) score for back and leg pain, Oswestry Disability Index (ODI), or complications; and (4) language of publication: English or Chinese.
The exclusion criteria are as follows: (1) studies enrolling patients with concurrent severe underlying medical or infectious diseases, spinal stenosis, spondylolisthesis, scoliosis, spinal tuberculosis, or tumors; (2) literature reviews, editorials, letters, and meeting abstracts; and (3) studies lacking essential clinical outcome data.
Data extraction
Two reviewers independently screened all retrieved articles against the predefined inclusion and exclusion criteria. Any discrepancies were resolved by consensus among the research team. During the initial screening, titles and abstracts were reviewed for relevance to the study objectives. For studies with unclear or insufficient information in the titles and abstracts, a full-text review was conducted to determine eligibility. This ensured the identification of all pertinent studies. For studies with missing data, the corresponding author was contacted by email to obtain the relevant data; however, no response was received.
Data extraction encompassed key elements from the included studies, categorized into three main domains: (1) basic information such as title, authors, publication year, and journal; (2) sample size, surgical segment, patient age and sex, and duration of follow-up; and (3) relevant clinical outcomes: VAS score, ODI score, Japanese Orthopaedic Association (JOA) score [14], disc height, complications, and Pfirrmann grade of disc degeneration [15].
Quality assessment and publication bias
The quality of the included non-randomized studies evaluated using the Newcastle-Ottawa Scale (NOS) [16]. The NOS facilitates a systematic evaluation of key study parameters across selection, comparability, and outcome assessment domains. Studies that achieve a predetermined threshold of five “stars” on the NOS scale, based on defined rating criteria, are considered to meet high quality standards.
Egger’s test was used to detect publication bias. Sensitivity analysis was performed by sequential exclusion of one study at a time from the meta-analysis (leave-one-out analysis) to evaluate the influence of individual studies on the overall results.
Further, this meta-analysis incorporates the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology [17]. GRADE systematically evaluates the credibility of pooled results by considering factors such as publication bias, the precision of the results, and the magnitude of the treatment effect. This comprehensive assessment ultimately assigns a quality grade to the resulting evidence, categorized into four distinct levels: high, moderate, low, and very low.
Statistical analysis
The meta-analysis was conducted using the Review Manager ver. 5.3 software (RevMan; Cochrane, London, UK). Weighted mean differences (WMD) with 95% confidence intervals (CI) were calculated for continuous variables. Odds ratios (OR) with their corresponding 95% CI were calculated for categorical variables. Heterogeneity among the studies was quantified using the I2 statistic. I2 values exceeding 50% were considered indicative of substantial heterogeneity. In the absence of significant heterogeneity (I2 <50%; p>0.1), a fixed-effects model was used for pooled analysis [18]. In case of significant heterogeneity (I2 ≥50%; p<0.1), a random-effects model was used [19]. The chi-square test or Fisher’s exact test was used for quantitative data. IBM SPSS ver. 23.0 (IBM Corp., Armonk, NY, USA) was used for statistical analysis [20]. All p-values <0.05 were considered indicative of statistical significance for all analyses. The impact of potential publication bias on the results of the meta-analysis was evaluated using funnel plots.
Results
Literature selection and characterization
A total of 210 articles were retrieved from databases. Of these, 204 articles were excluded according to predetermined criteria, resulting in the eventual inclusion of six articles (Fig. 1).
The characteristics of the six included studies are summarized in Table 1. These included two prospective studies and four retrospective studies [21–26]. Two studies were published in English and four in Chinese. All six studies were conducted in China. The combined study population consisted of 433 patients, with 214 assigned to the experimental group receiving FELD combined with PRP treatment (FELD+PRP group), and 219 receiving FELD alone (FELD group). All procedures were performed using the transforaminal approach. Table 2 presents the baseline comparisons between the two groups (FELD+PRP vs. FELD), including preoperative VAS, ODI, JOA scores, and Pfirrmann classification. There were no significant differences between the two groups regarding the baseline data prior to surgery.
Pain relief
VAS score for back pain
Both sensitivity analysis and heterogeneity analysis showed no statistically significant differences (p>0.05). All six studies had provided data on preoperative VAS score for back pain with no significant heterogeneity among the studies (I2=0%; p>0.05). With a total of 433 patients (214 in the FELD+PRP group and 219 in the FELD group), meta-analysis using a fixed-effects model revealed no significant differences between the two groups (WMD, 0.09; 95% CI, −0.16 to 0.33; p=0.48) (Fig. 2A).
Five studies reported VAS scores for back pain at 3 months after surgery, with a total of 360 patients (178 in the FELD+PRP group and 182 in the FELD group). Meta-analysis using a random-effects model (I2=63%) revealed a significantly lower mean VAS score in the FELD+PRP group compared to the FELD group (WMD, −0.58; 95% CI, −0.89 to −0.28; p=0.0002) (Fig. 2B), indicating potentially greater pain relief for patients receiving the combined therapy.
Four studies reported VAS scores for back pain at 6 months postoperatively, with a total of 299 patients (146 in the FELD+PRP group and 153 in the FELD group). Meta-analysis using a fixed-effects model (I2=25%) showed significantly lower mean VAS score in the FELF+PRP group compared to the FELD group (WMD, −0.24; 95% CI, −0.38 to −0.10; p=0.0007) (Fig. 2C), indicating potentially greater pain relief for patients receiving the combined therapy.
Four studies reported VAS scores for back pain at the final follow-up, with a total of 275 patients (134 in the FELD+PRP group and 141 in the FELD group). Meta-analysis using a fixed-effects model (I2=37%) showed significantly lower mean VAS score in the FELD+PRP group compared to the FELD group (WMD, −0.21; 95% CI, −0.34 to −0.07; p=0.002) (Fig. 2D), indicating potentially greater pain relief for patients receiving the combined therapy.
VAS score for leg pain
Three studies provided data on preoperative VAS scores for leg pain, with a total of 264 patients (130 in the FELD+PRP group and 134 in the FELD group). Meta-analysis using a fixed-effects model (I2=0%; p>0.05) revealed no significant between-group differences in this respect (WMD, −0.03; 95% CI, −0.44 to 0.39; p=0.89) (Fig. 3A). Sensitivity analysis and heterogeneity analysis showed no statistically significant differences (p>0.05).
Three studies reported VAS scores for leg pain 3 months after surgery. After conducting further heterogeneity and sensitivity analyses, we found some differences with the leave-one-out method. However, excluding any particular study did not alter the overall results. Therefore, we decided to retain the study by Li et al. [23] in 2024 in the analysis (Supplement 1). With a total of 264 patients (130 in the FELD+PRP group and 134 in the FELD group, meta-analysis using a random-effects model (I2=83%), showed no significant difference between the two groups (WMD, 0.03; 95% CI, −0.49 to 0.55; p=0.91) at 3 months postoperatively (Fig. 3B).
Two studies had reported VAS scores for leg pain at 6 months postoperatively, with a total of 166 patients (80 in the FELD+PRP group and 86 in the FELD group). Meta-analysis using a random-effects model (I2=91%) showed no significant difference between the two groups (WMD, −0.04; 95% CI, −0.91 to 0.83; p=0.93) at 6 months postoperatively (Fig. 3C). Both sensitivity analysis and heterogeneity analysis showed no statistically significant differences (p>0.05).
Two studies reported VAS scores for leg pain at 12 months postoperatively, with a total of 166 patients (80 in the FELD+PRP group and 86 in the FELD group). Meta-analysis using a random-effects model (I2=87%) showed no significant difference between the two groups (WMD, −0.00; 95% CI, −0.69 to 0.68; p=0.99) at 12 months postoperatively (Fig. 3D). Both sensitivity analysis and heterogeneity analysis showed no statistically significant differences (p>0.05).
Functional outcomes
ODI scores
Six studies provided data on preoperative ODI scores, with a total of 433 patients (214 in the FELD+PRP group and 219 in the FELD group). Meta-analysis using a fixed-effects model (I2=0%) revealed no significant between-group difference in terms of preoperative ODI scores (WMD, −0.12; 95% CI, −1.73 to 1.50; p=0.89) (Fig. 4A). Both sensitivity analysis and heterogeneity analysis showed no statistically significant differences (p>0.05).
Five studies reported ODI scores at 3 months postoperatively, with a total of 360 patients (178 in the FELD+PRP group and 182 in the FELD group). Meta-analysis using a random-effects model (I2=85%) showed no significant between-group difference (WMD, −1.13; 95% CI, −3.82 to 1.56; p=0.41) at 3 months postoperatively (Fig. 4B). Both sensitivity analysis and heterogeneity analysis showed no statistically significant differences (p>0.05).
Four studies reported ODI at 6 months postoperatively, with a total of 299 patients (146 in the FELD+PRP group and 153 in the FELD group). Although heterogeneity and sensitivity analyses revealed statistical differences, excluding the study by Lu et al. [25] in 2021 did not change the overall results. Therefore, we retained this study in the analysis (Supplement 2). Meta-analysis using a random-effects model (I2=82%) showed a significantly lower mean ODI score in the FELD+PRP group compared to the FELD group (WMD, −2.29; 95% CI, −4.61 to 0.02; p=0.05) at 6 months postoperatively (Fig. 4C).
Four studies reported ODI at final follow-up, with a total of 275 patients (134 in the FELD+PRP group and 141 in the FELD group). Meta-analysis using a fixed-effects model (I2=0%) showed significantly lower mean ODI score in the FELD+PRP group compared to the FELD group (WMD, −2.89; 95% CI, −3.59 to −2.20; p<0.0001) at final follow-up (Fig. 4D). Both sensitivity analysis and heterogeneity analysis showed no statistically significant differences (p>0.05).
JOA scores
Four studies provided data on preoperative JOA scores, with a total of 252 patients (127 in the FELD+PRP group and 125 in the FELD group). Further heterogeneity and sensitivity analyses revealed some differences in the leave-one-out method; however, the heterogeneity analysis showed no statistically significant differences. After careful consideration, we decided to retain the study by Du et al. [21] in 2023 in the analysis (Supplement 3). Meta-analysis using a fixed-effects model (I2=16%) revealed no significant between-group difference in terms of preoperative JOA scores (WMD, 0.39; 95% CI, −0.14 to 0.92; p=0.15) (Fig. 5A).
Four studies reported JOA scores at 3 months postoperatively, with a total of 252 patients (127 in the FELD+PRP group and 125 in the FELD group). Although the sensitivity analysis indicated statistical differences, the heterogeneity analysis showed none. Considering this, we decided to include the study by Lu et al. [25] in 2021 in the final analysis (Supplement 4). Meta-analysis using a random-effects model (I2=92%) showed significantly higher mean JOA score in the FELD+PRP group compared to the FELD group (WMD, 1.97; 95% CI, 0.02 to 3.93; p=0.05) at 3 months postoperatively (Fig. 5B).
Two studies reported JOA at 12 months postoperatively, with a total of 94 patients (47 in the FELD+PRP group and 47 in the FELD group). Meta-analysis using a fixed-effects model (I2=34%) showed significantly higher mean JOA score in the FELD+PRP group compared to the FELD group (WMD, 1.33; 95% CI, 0.69 to 1.97; p<0.0001) at 12 months postoperatively (Fig. 5C). Both sensitivity analysis and heterogeneity analysis showed no statistically significant differences (p>0.05).
Disc height
Both sensitivity analysis and heterogeneity analysis showed no statistically significant differences (p>0.05). Three studies provided data on preoperative disc height, with a total of 192 patients (97 in the FELD+PRP group and 95 in the FELD group). Meta-analysis using a fixed-effects model (I2=0%) revealed no significant between-group difference in terms of baseline disc height (WMD, 0.12; 95% CI, −0.14 to 0.38; p=0.37) (Fig. 6A).
Three studies reported postoperative disc height, with a total of 192 patients (97 in the FELD+PRP group and 95 in the FELD group). Meta-analysis using a fixed-effects model (I2=24%) showed significantly greater disc height in the FELD+PRP group compared to the FELD group (WMD, 0.76; 95% CI, 0.51 to 1.00; p<0.00001) at final follow-up (Fig. 6B).
Three studies reported a change in disc height after the procedure, with a total of 192 patients (97 in the FELD+PRP group and 95 in the FELD group). Meta-analysis using a fixed-effects model (I2=0%) showed significantly lesser loss of disc height in the FELD+PRP group compared to the FELD group (WMD, −0.64; 95% CI, −1.00 to −0.28; p=0.0005) (Fig. 6C).
Complications
Data on postoperative complications were reported by six studies with a total of 433 patients. Despite statistical differences observed in the sensitivity analysis, no significant differences were found in the heterogeneity analysis (Supplement 5). Meta-analysis using a fixed-effects model (I2=0%) revealed a significantly lower postoperative complication rate in the FELD+PRP group compared to the FELD group (WMD, 0.44; 95% CI, 0.19 to 0.98; p=0.04) (Fig. 6D). The incidence rates of complications in the FELD group and FELD+PRP group were 9.13% and 4.21%, respectively.
Pfirrmann grading
Data from five studies were employed to assess Pfirrmann grading of disc degeneration. Comparison of preoperative Pfirrmann grading between the two groups yielded no statistically significant differences (χ2=1.82; p=0.611). However, at the final follow-up, the FELD+PRP group showed significantly better Pfirrmann grading compared to the FELD group (χ2=16.53; p=0.002).
Quality analysis and publication bias
Table 3 presents the results of the risk-of-bias evaluation for all studies included in the meta-analysis. Each of the included studies surpassed predefined quality thresholds, achieving a NOS score of ≥5 stars. The impact of potential publication bias on the results of the meta-analysis was evaluated by visual inspection of the funnel plot (Fig. 7). The symmetrical distribution of the studies around the effect estimate reinforced the conclusion of a low risk of publication bias. Table 4 summarizes the application of the GRADE methodology to assess the overall credibility of the results, providing a transparent framework for interpreting the strength of the evidence.
Discussion
LDH clinically manifests as low back pain, radiating nerve root pain in the lower limbs, and possible sensory disturbances in the affected dermatomes [27]. For patients unresponsive to conservative measures, surgical intervention remains the mainstay of therapy. The emergence of minimally invasive techniques, particularly spinal endoscopy, has garnered enthusiasm due to its advantages of reduced tissue trauma and expedited recovery, yielding favorable clinical outcomes [28,29]. However, minimally invasive approaches, while preserving surrounding tissues, often necessitate fragmentation or removal of herniated disc material, compromising the structural integrity of the disc and potentially exacerbating postsurgical disc degeneration. Moreover, the avascular nature of the intervertebral disc poses a significant challenge, as its limited self-repair capacity hinders meaningful recovery from existing damage. In light of these limitations, developing novel therapeutic strategies that promote intervertebral disc tissue repair and regeneration while slowing the disc degeneration progression has become imperative. Innovative therapeutic approaches offer immense promise for the future management of LDH.
PRP is a platelet concentrate derived from the centrifugation of autologous peripheral blood [30]. PRP releases a multitude of biologically active substances with immunomodulatory, anti-inflammatory, and neuroprotective properties. These substances also promote Schwann cell activation and axonal regeneration, facilitating the repair of degenerated intervertebral discs [31–33]. The multifaceted attributes of PRP underscore its comprehensive therapeutic impact, making it a promising avenue for alleviating pathological nerve conditions.
The present study provides compelling evidence for the potential benefits of combining FELD with PRP injection for managing LDH. Our findings suggest the following potential effects of PRP: (1) Pain relief: Patients receiving FELD+PRP reported lower postoperative VAS scores for back pain, indicating greater pain relief and improved quality of life. (2) Functional improvement: Both JOA and ODI scores showed greater improvement in the FELD+PRP group, indicating better functional recovery. (3) Slowing disc degeneration: PRP’s regenerative properties promote repair and regeneration of the damaged intervertebral disc annulus fibrosus, potentially slowing disc degeneration and disc height loss. (4) Reduced postoperative complications: The FELD+PRP group experienced fewer postoperative complications, with a significantly lower recurrence rate compared to the FELD alone group, likely attributed to PRP’s ability to promote intervertebral disc repair and slow degeneration.
The combination of FELD and PRP confers distinct advantages compared to FELD alone. First, PRP stimulates the proliferation of intervertebral disc cells and facilitates the synthesis of extracellular matrix [34]. This, in turn, fosters tissue repair and delays the progression of intervertebral disc degeneration [35]. Second, the anti-inflammatory factors in PRP inhibit the release of cytokines, exerting anti-inflammatory effects [36]. Localized PRP injection has been shown to alleviate chemically-induced discogenic low back pain [37]. Third, due to the autologous origin of PRP, it poses a lower risk of infection and allergic reactions. The inherent antimicrobial properties of PRP further reduce the likelihood of postoperative infections [38]. Lastly, the utilization of intervertebral foraminoplasty enables the precise injection of PRP into the intervertebral disc through direct visualization from the annular fibrous rupture. This increased precision enhances the efficacy of PRP in mitigating disc degeneration, thereby optimizing its therapeutic impact [22].
Considerations for PRP injections under FELD include adhering to the principle that a concentrated application of platelets and growth factors directly to intervertebral disc cells is crucial for initiating the tissue repair cascade. Direct injection of liquid PRP into the intervertebral disc may result in substantial PRP outflow, reducing its content within the disc and compromising the efficacy of intervertebral disc repair. Moreover, surgical excision of the disc tissue during the procedure requires delicate balance. Removing too much tissue can cause postoperative lumbar instability, while removing too little can compromise decompression of the intervertebral spine, potentially leading to complications such as disc scar tissue proliferation, herniation, and nerve compression. Therefore, the extent of herniated disc removal during surgery is a crucial determinant of long-term outcomes. Furthermore, repair of the ruptured annulus fibrosus is a critical aspect of treatment, given its prolonged recovery duration. Premature and strenuous physical activity postoperatively may precipitate the protrusion of the nucleus pulposus from the ruptured annulus fibrosus. Some studies suggest that combining FELD with fibrous annular suturing is more effective in preserving disc height, thus reducing the recurrence of disc herniation [23,26]. Therefore, it is imperative to preserve annulus fibrosus integrity during surgery to minimize recurrence. Lastly, the efficacy of PRP is closely tied to the degree of disc degeneration. In patients with severe disc degeneration, the reduced number and activity of active cells within the intervertebral disc reduce the sensitivity to growth factors in PRP. Consequently, applying PRP in the treatment of young patients with LDH in the early stages of disc degeneration is of particular significance, as it leverages the relatively stronger disc cell bioactivity and favorable internal environment conducive to tissue repair.
To the best of our knowledge, this meta-analysis is the first comprehensive evaluation of the efficacy and safety of FELD combined with PRP for treating LDH. While it provides valuable insights into the potential benefits of FELD+PRP, some limitations must be acknowledged. The relatively small number of studies and sample size limit the generalizability of the findings. Additionally, the majority of studies were non-RCTs, introducing potential bias into the results. Furthermore, all studies originated from China, raising concerns about the generalizability of the findings to other populations with diverse genetic, environmental, and healthcare considerations. Finally, the possibility of publication bias cannot be ruled out, which could influence the observed effect size. Variations in follow-up time, postoperative Pfirrmann classification assessment timing, and inter-observer variability may also contribute to statistical bias.
Conclusions
This study reveals that combining FELD with PRP for treating LDH leads to better outcomes than FELD alone. These outcomes include better back pain relief, greater functional improvement, and fewer postoperative complications. This observed superiority is attributed to the synergistic effects of FELD and PRP, which not only alleviate back pain but also contribute to the repair of the annulus fibrosus of the intervertebral disc. Additionally, this combined approach helps ameliorate intervertebral disc degeneration and mitigate loss of disc height. These benefits suggest that combining FELD with PRP is a more effective and safer treatment option for LDH, which warrants consideration in clinical practice.
Key Points
Full endoscopic lumbar discectomy (FELD) combined with platelet-rich plasma (PRP) demonstrated superior clinical outcomes compared to FELD alone for lumbar disc herniation.
Postoperative pain relief (lower Visual Analog Scale scores) and functional recovery (improved Oswestry Disability Index and Japanese Orthopaedic Association scores) were significantly better in the FELD+PRP group.
Disc height preservation was greater, and the complication rate was lower with the combined treatment (p=0.0005).
Disc degeneration improvement, as assessed by Pfirrmann grading, was significantly enhanced in the FELD+PRP group (p=0.002).
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