Efficacy and Safety of Platelet-rich Plasma in the Management of Lumbar Disc Herniation: A Systematic Review and Meta-analysis

Abdulsalam Mohammed Aleid; MOHEMED SAMI AL BOHASSAN; Mohammed yousef Alessa; Loai Saleh Albinsaad; Mutlaq Alsubaie; Abdulwahab Ahmed Alzahrani; Hasan Ali Abdullah Alaidarous; Yousef Khalaf A Alghamdi; Abdullah Alamer; Saud Nayef Aldanyowi

doi:10.12688/f1000research.159329.1

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Systematic Review

Efficacy and Safety of Platelet-rich Plasma in the Management of Lumbar Disc Herniation: A Systematic Review and Meta-analysis

[version 1; peer review: 1 approved with reservations]

Abdulsalam Mohammed Aleid¹, MOHEMED SAMI AL BOHASSAN¹, Mohammed yousef Alessa¹, [...] Loai Saleh Albinsaad¹, Mutlaq Alsubaie², Abdulwahab Ahmed Alzahrani³, Hasan Ali Abdullah Alaidarous³, Yousef Khalaf A Alghamdi³, Abdullah Alamer⁴, Saud Nayef Aldanyowi ¹

Abdulsalam Mohammed Aleid¹, MOHEMED SAMI AL BOHASSAN¹, [...] Mohammed yousef Alessa¹, Loai Saleh Albinsaad¹, Mutlaq Alsubaie², Abdulwahab Ahmed Alzahrani³, Hasan Ali Abdullah Alaidarous³, Yousef Khalaf A Alghamdi³, Abdullah Alamer⁴, Saud Nayef Aldanyowi ¹

PUBLISHED 06 Dec 2024

Author details Author details

¹ Departement of Surgery, College of Medicine., King Faisal University, Al Ahsa, Eastern Province, 31982, Saudi Arabia
² Orthopedic Department, National Gaurd Hospital, Alahsa, Eastern Province, Saudi Arabia
³ Department of Surgery, Faculty of Medicine., Albaha University, Albaha, Albaha Province, Saudi Arabia
⁴ Pediatric Orthopedic Department, King Faisal Hospital, AlHofuf, Eastern Province, Saudi Arabia

Abdulsalam Mohammed Aleid
Roles: Conceptualization, Writing – Original Draft Preparation, Writing – Review & Editing

MOHEMED SAMI AL BOHASSAN
Roles: Conceptualization, Writing – Original Draft Preparation, Writing – Review & Editing

Mohammed yousef Alessa
Roles: Conceptualization, Writing – Original Draft Preparation, Writing – Review & Editing

Loai Saleh Albinsaad
Roles: Conceptualization, Writing – Original Draft Preparation, Writing – Review & Editing

Mutlaq Alsubaie
Roles: Conceptualization, Writing – Original Draft Preparation, Writing – Review & Editing

Abdulwahab Ahmed Alzahrani
Roles: Conceptualization, Writing – Original Draft Preparation, Writing – Review & Editing

Hasan Ali Abdullah Alaidarous
Roles: Conceptualization, Writing – Original Draft Preparation, Writing – Review & Editing

Yousef Khalaf A Alghamdi
Roles: Conceptualization, Writing – Original Draft Preparation, Writing – Review & Editing

Abdullah Alamer
Roles: Conceptualization, Writing – Original Draft Preparation, Writing – Review & Editing

Saud Nayef Aldanyowi
Roles: Conceptualization, Writing – Original Draft Preparation, Writing – Review & Editing

OPEN PEER REVIEW

REVIEWER STATUS

Abstract

Background

Lumbar radicular discomfort is often induced by mechanical compression of the nerve root and inflammatory reactions. Platelet-rich plasma (PRP) is an efficacious therapy modality, albeit ongoing controversies regarding its effectiveness, and it possesses the advantage of minimal side effects. Therefore, we conducted the current systematic review and meta-analysis to investigate the efficacy and safety of PRP in the treatment of lumbar disc herniation (LDH).

Methods

We conducted our database searching on PubMed, Scopus, and Web of Science from inception till August 2024 to look for articles that fulfil our aim. The search strategy was based on three main keywords: “Platelet-rich plasma” AND “Lumbar” AND “Hernia*”. We conducted the pooled analysis of continuous variables using mean difference (MD) and we used pooled odds ratio (OR) for dichotomous variables with 95% confidence intervals (CI).

Results

The use of PRP was statistically significant associated with reduced visual analogue scale (VAS) compared with no PRP with MD of -0.44 (95%CI:-0.76, -0.11, p=0.008), and Oswestry Disability Index (ODI) with MD of -5.36 (95%CI: -8.25, -2.48, p=0.0003). However, no significant difference was observed regarding Japanese Orthopedic Association (JOA) with MD of 2.52 (95%CI:-0.8, 5.84, p=0.14) with non-significant heterogeneity. PRP was also associated with reduced risk of complications with OR of 0.22 (95%CI:0.07, 0.68, p=0.009) and non-significant heterogeneity.

Conclusion

PRP use in patients with LDH is associated with positive outcomes presented in reduction of pain, and disability (decrease in ODI scale) in addition to being safe with less incidence of complications compared with patients not receiving PRP.

Keywords

Lumbar, Hernia, Platelet-rich plasma, Disc.

Corresponding author: Saud Nayef Aldanyowi

Competing interests: No competing interests were disclosed.

Grant information: 'This work was supported by the Deanship of Scientific Research, Vice Presidency for Graduate Studies and Scientific Research, King Faisal University, Saudi Arabia [Grant No. KFU242482]'
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright: © 2024 Aleid AM et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to cite: Aleid AM, AL BOHASSAN MS, Alessa My et al. Efficacy and Safety of Platelet-rich Plasma in the Management of Lumbar Disc Herniation: A Systematic Review and Meta-analysis [version 1; peer review: 1 approved with reservations]. F1000Research 2024, 13:1500 (https://doi.org/10.12688/f1000research.159329.1) First published: 06 Dec 2024, 13:1500 (https://doi.org/10.12688/f1000research.159329.1) Latest published: 06 Dec 2024, 13:1500 (https://doi.org/10.12688/f1000research.159329.1)

Introduction

Lumbar radicular discomfort is often induced by mechanical compression of the nerve root and inflammatory reactions.^1–3 Conservative care, including rest, physical therapy, and oral medicines, constitutes the primary approach in the treatment of lumbar disc herniation (LDH). Nonetheless, merely 70% saw substantial alleviation of discomfort, and as much as 20% encountered recurring symptoms.⁴ Transforaminal epidural steroid injection (ESI) has served as a method to alleviate radicular discomfort prior to surgical intervention.^5,6 The medicinal drug triamcinolone is extensively utilized for its anti-inflammatory properties and minimal complications. Nonetheless, other cases have indicated significant side effects, including infection, allergic reactions, and endocrine suppression.^7,8 Numerous randomized studies have shown substantial enhancement in pain alleviation within the initial three months. Controversial results have emerged regarding pain reduction in long-term follow-up and the incidence of further operations at one year.⁹

High amounts of platelet-rich plasma (PRP) facilitate recovery and the anti-inflammatory process through the secretion of growth factors and cytokines.^10,11 PRP injections have garnered interest as an innovative therapeutic approach for orthopedic and rheumatologic conditions, including osteoarthritis, tendinopathies, and ligament tears.¹² Data about their efficacy in treating intervertebral disc degeneration and low back pain is lacking.¹³ While their therapeutic potential in discogenic and facet joint pain is intriguing,¹⁴ the effectiveness of PRP injections administered to the epidural area for radiculopathy remains uncertain. Baig et al.¹⁵ indicated that the epidural space remains an unexplored domain for PRP injections in radiculopathy treatment, noting just two clinical investigations utilizing PRP injections as an alternative to steroids in their literature analysis.^16,17 PRP is an efficacious therapy modality, albeit ongoing controversies regarding its effectiveness, and it possesses the advantage of minimal side effects.^15–17 Therefore, we conducted the current systematic review and meta-analysis to investigate the efficacy and safety of PRP in the treatment of LDH.

Methods

We used the guidelines of Cochrane handbook for systematic reviews and meta-analysis in addition to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to conduct this study.¹⁸

Database searching

We conducted our database searching on PubMed, Scopus, and Web of Science from inception till August 2024 to look for articles that fulfil our aim. The search strategy was based on three main keywords: “Platelet-rich plasma” AND “Lumbar” AND “Hernia*”. The resulting articles were gathered together and uploaded to Rayyan.¹⁹

Eligibility criteria and screening

We included articles which were randomized controlled trials (RCTs), and cohort studies investigating the use of PRP in patients with LDH. We excluded reviews, and case reports. We conducted the title and abstract screening to find whether the articles matched our criteria or not. This process was followed by full-text screening to ensure that the included articles from the previous step were eligible for inclusion.

Data extraction and outcome measures

We extracted the baseline data of the included studies including study ID, groups, sample size, study design, age, gender cointervention with PRP, and the herniated spine. Regarding the outcomes, we extracted the following: baseline and post-treatment values of visual analogue scale (VAS), Oswestry Disability Index (ODI), and Japanese Orthopedic Association (JOA) in addition to the incidence of complications.

Quality and risk of bias assessment

We conducted quality assessment for the cohort studies using New Castle Ottawa scale tool (NOS),²⁰ while we conducted risk of bias assessment for RCTs using Cochrane Risk of Bias-2 tool (Rob-2).²¹

Statistical analysis

All the statistical procedures were done using Review Manager software version 5.4.²² We conducted the pooled analysis of continuous variables using mean difference (MD) and we used pooled odds ratio (OR) for dichotomous variables. We used the random effect model for heterogeneous outcomes, and the fixed effect model for homogeneous outcomes, at confidence interval (CI) of 95%, and p-value of 0.05. I² was utilized to measure the heterogeneity at p-value of 0.05.

Results

Screening results

After searching the databases, the search strategy yielded a total of 109 articles. We removed 42 duplicates and conducted title and abstract screening for 67 articles. We excluded a total of 58 articles and conducted full-text screening for the remaining 9 articles to include 7 of them in the meta-analysis^23–29 ( Figure 1).

Figure 1. PRSIMA flow diagram of searching and screening.

Quality and risk of bias assessment

According to NOS, the included cohort studies were deemed to have high quality ( Table 1). Moreover, the included RCTs were observed to have low risk of bias ( Figure 2).

Table 1. Quality assessment of cohort studies using NOS.

Study name	Representativeness of the exposed cohort (⋆)	Selection of the non exposed cohort (⋆)	Ascertainment of exposure (⋆)	Demonstration that outcome of interest was not present at start of study (⋆)	Comparability of cohorts on the basis of the design or analysis (max⋆⋆)	Assessment of outcome (⋆)	Was follow-up long enough for outcomes to occur? (⋆)	Adequacy of follow up of cohorts (⋆)	Quality level
Demirci 2022	☆	☆	☆	☆	☆☆	☆	☆	☆	High
Jiang 2022	☆	☆	☆	☆	☆☆	☆	☆	☆	High
Li 2024	☆	☆	☆	☆	☆☆	☆	☆	☆	High
Zhang 2023	☆	☆	☆	☆	☆☆	☆	☆	☆	High

Figure 2. Risk of bias assessment of RCTs using Rob-2.

Baseline characteristics

We included three RCTs, and four cohort studies in the present systematic review and meta-analysis comparing patients with LDH who received PRP with those who didn’t receive. Those who didn’t receive were mostly treated with corticosteroids. Discectomy was mostly performed with the treatment ( Table 2).

Table 2. Baseline characteristics of the include studies.

Study ID	Design	PRP	Control	Cointervention with PRP	Sample size		Age, mean (SD)		Male, n (%)		Spine
Study ID	Design	PRP	Control	Cointervention with PRP	PRP	control	PRP	control	PRP	control	Spine
Demirci 2022	Cohort	Epidural injection of 7-8 ml of PRP	Corticosteroids	Epiduroscopy procedure	31	31	49.6 (13.0)	46.8 (11.6)	8 (25.81)	14 (45.16)	L3-L4, L4-L5, L5-S1
Tuakli-Wosornu 2016	RCT	Intradiskal 3-4 ml of PRP	Contrast agent	Provocative diskography	29	18	41.40 (8.08)	43.80 (8.91)	14 (48.3)	2 (15.8)	Lumbar
Wongjarupong 2023	RCT	epidural injection 4 ml	Triamcinolone	NR	15	15	39.73 (7.04)	39.13 (7.21)	9 (60)	8 (53.3)	L4/5, L5/S1
Gupta 2023	RCT	2 ml	Corticosteroids	NR	23	23	40.64	38.92	14 (60.86)	17 (73.91)	L4–5, L5–S1
Xu 2021	RCT	3 ml	Corticosteroids	Ultrasound-guided transforaminal injections	61	63	53.5 (11.76)	55 (6.82)	28 (45.9)	37 (58.73)	Lumbar
Jiang 2022	Cohort	4 ml	No PRP	Transforaminal endoscopic lumbar discectomy	51	57	48.1 (10.25)	45.9 (9.83)	33 (57.9%)	32 (62.7%)	L3/L4, L4/L5, L5/S1
Li 2024	Cohort	4 ml	No PRP	Percutaneous endoscopic lumbar discectomy	75	80	43.61 (11.72)	44.25 (11.56)	39 (52.0)	46 (57.5)	L3-4, L4-5, L5-S1
Zhang 2023	Cohort	3.5–4 ml	No PRP	Percutaneous endoscopic lumbar discectomy	50	48	41.5 (9.8)	45.8 (11.0)	28 (56%)	26 (54.2%)	L3/4, L4/5, L5/S1

Meta-analysis

The use of PRP was statistically significant associated with reduced VAS compared with no PRP with MD of -0.44 (95%CI:-0.76, -0.11, p=0.008), and ODI with MD of -5.36 (95%CI: -8.25, -2.48, p=0.0003) ( Figures 3 and 4). However, no significant difference was observed regarding JOA with MD of 2.52 (95%CI:-0.8, 5.84, p=0.14) with non-significant heterogeneity ( Figure 5). PRP was also associated with reduced risk of complications with OR of 0.22 (95%CI:0.07, 0.68, p=0.009) and non-significant heterogeneity ( Figure 6).

Figure 3. Comparison between PRP and no PRP regarding the change in VAS.

Figure 4. Comparison between PRP and no PRP regarding the change in ODI.

Figure 5. Comparison between PRP and no PRP regarding the change in JOA.

Figure 6. Comparison between PRP and no PRP regarding the incidence of complications.

Discussion

Main findings

The present systematic review and meta-analysis of RCTs investigating the use of PRP in LDH showed promising results. PRP was associated with better outcomes regarding pain reduction, decreased ODI, and less incidence of complications compared to patients with LDH who didn’t receive PRP.

Clinical implications

Standard interventions for LDH include a multifaceted approach comprising activity limitation, physical therapy, non-steroidal anti-inflammatory medications, and analgesic injections, which have demonstrated efficacy in symptom relief but do not alter disease progression. PRP, an FDA-approved therapeutic approach, has been effectively utilized by orthopedic physicians for musculoskeletal disorders for decades.³⁰ Positive results have been documented in clinical studies concerning elbow pathology,³¹ rotator cuff tendons,³² and knee articular cartilage.³³ The mechanism of PRP’s function provides a beneficial matrix for cellular proliferation and supplies various bioactive factors, including vascular endothelial growth factor and platelet-derived growth factor, which facilitate the recruitment of cells such as mesenchymal stromal cells and fibroblasts to the injury site, thereby stimulating subsequent proliferation and biosynthetic activity.³⁴ In vitro investigations of animal and human disc cells have proven the positive benefits of PRP.³⁵ Disc cells exhibit enhanced proteoglycan production and annulus fibrosus cell proliferation when grown with PRP.³⁶ PRP demonstrates an inhibitory effect on the harmful inflammation caused by TNF-alpha and interleukin-1 in human nucleus pulposus cells.³⁷ Currently, research on the combination of PRP injection and percutaneous endoscopic lumbar discectomy (PELD) surgery is few. Numerous papers examine clinical outcomes after intradiscal injections of PRP in individuals with degenerative disc degeneration. Hirase et al.³⁸ conducted a meta-analysis encompassing five retrospective investigations, concluding that intradiscal PRP injection for degenerative lumbar disc degeneration yields a statistically significant enhancement in VAS, accompanied by low rates of complications and re-injections. Zhang et al.²³ concurred that PRP is a localized annular treatment; hence, if the endplates exhibit severe degeneration and the protrusion is substantial, the injection of PRP hydrogel in conjunction with PELD would yield no clinical advantage.

Zhang et al.²³ indicated that patients administered PRP hydrogel in conjunction with PELD exhibited greater enhancements in low back pain, JOA, and ODI scores at three months post-surgery compared to those receiving PELD alone, implying that PRP hydrogel injection may release factors that mitigate inflammation and ameliorate symptoms. This study also aimed to evaluate alterations in disc degeneration subsequent to PRP hydrogel injection by radiographic analyses. This research differs from studies on PRP injection for degenerative lumbar disc degeneration in two respects. The superior articular process was excised, and an annuloplasty was conducted using a bipolar radiofrequency ablator during the procedure. Collectively, these two elements may expedite disc degeneration. A notable restorative effect on disc height was seen, indicating that PRP hydrogel injection enhanced disc remodeling. The Pfirrmann grade assesses alterations in the structural organization of the intervertebral disc. A notable disparity in the Pfirrmann grade at the final follow-up was observed between the two groups,²³ aligning with prior findings.³⁹

As PRP is derived from autologous blood, it poses little danger of immunological rejection, along with a minimal likelihood of infection and allergic reactions.⁴⁰ Moreover, PRP has been documented to possess antibacterial characteristics that may mitigate the risk of infection.⁴¹ Zhang et al.²³ indicated that the PRP group exhibited no signs of nerve root irritation, and there were no drug-related problems or puncture-related injuries to the traversing nerve root, exiting nerve root, or dura mater.

Comparison with literature

Prolotherapy employs a technique of inflammatory induction to attract cytokines and growth factors, thereby facilitating the healing cascade. The justification for utilizing PRP is its high concentration of cytokines and growth factors, which are produced over time.⁴² Additional benefits of PRP include its autologous nature and antibacterial characteristics. The application of PRP has been investigated in orthopedic spine surgery, primarily for the management of degenerative disc disease. Before the application of PRP, Becker’s RCT demonstrated the efficacy of PRP over triamcinolone in LegVAS outcomes by the utilization of Autologous Conditioned Serum (ACS), an alternative orthobiologic, for the treatment of LDH via several injections.⁴³ Recently, interlaminar and transforaminal epidural injections have been employed to address radicular pain resulting from herniated discs using various substances, including ACS,⁴⁴ platelet-rich growth factor (PRGF),⁴⁵ PRP,¹⁶ and plasma lysate.⁴⁶ The results of leg pain alleviation were effective for up to three months. A study indicated substantial pain alleviation and enhancement of disability over a period of six months in twenty patients.⁴⁴ The safety of epidural injection with plasma lysate was evaluated in 470 registries, also showing encouraging outcomes in VAS, functional rating index (FRI), and a modified single assessment numeric evaluation (SANE) over a two-year follow-up period.⁴⁶ Wongjarupong et al.²⁴ demonstrated that PRP yielded improved outcomes compared to triamcinolone on LegVAS at 6, 12, and 24 weeks. This may stem from the reparative and regenerative effects of PRP.^47,48

Research indicates that the efficacy of PRP was established in a 2016 pilot trial including a small cohort with 10 conditions, where epidural PRP was delivered for radiculopathy with a brief follow-up period.¹⁶ A series of clinical investigations have delineated the efficacy of intradiscal PRP injections for lumbar pain attributable to disc degeneration, associated with therapeutic and inflammatory effects on type 1 Modic alterations.^13,49–51 Singla et al.⁵² conducted a comparison of PRP and corticosteroid injections for the treatment of sacroiliac joint discomfort, yielding positive results for PRP administration. Despite the widespread use of epidural corticosteroid injections, controversies regarding their efficacy persist due to the absence of rigorously performed randomized controlled trials.^53,54 Positive outcomes were achieved with epidural steroid injections for alleviating persistent low back pain resulting from lumbar spine issues, discogenic pain, and radicular pain.^54,55

Strengths and limitations

The present systematic review and meta-analysis gathered evidence from all available RCTs investigating the use of PRP in the treatment of LDH. Consistent findings without heterogeneity were observed in addition to showing the effectiveness of PRP making it a promising treatment for LDH. It is limited by the small sample size in JOA and the difference comparison groups used in LDH.

Recommendations

We recommend that future RCTs should identify the best treatment combinations to be used involving PRP in patients with LDH.

Conclusion

PRP use in patients with LDH is associated with positive outcomes presented in reduction of pain, and disability (decrease in ODI scale) in addition to being safe with less incidence of complications compared with patients not receiving PRP.

Author contributions

Conceptualization, Writing – original draft, Writing – review & editing: All author.

Data availability statement

No data are associated with this article.

Reporting guidelines

Figshare: Efficacy and Safety of Platelet-rich Plasma in the Management of Lumbar Disc Herniation: A Systematic Review and Meta-analysis. DOI: https://doi.org/10.6084/m9.figshare.27854955.v2.⁵⁶

The project contains the following reporting guidelines:

• PRISMA_2020_checklist (3)
• Fig 1, flow chart

Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).

Acknowledgments

The authors acknowledge the Deanship of Scientific Research at King Faisal University for obtaining financial support for research, authorship, and the publication of research under Research proposal Number (KFU242482).

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