Comparison of platelet rich plasma and injectable steroids in the treatment of oral lichen planus: A systematic review and meta-analysis

Abstract

Oral lichen planus (OLP) is the common acute or chronic, potentially malignant disorder of the oral mucosa. Steroids the primary treatment for OLP; however, their chemical composition often leads to significant side effects. Platelet-rich plasma (PRP), an autologous biologically active material has been explored as an alternative treatment option. This systematic review evaluates the effects of autologous platelet-rich plasma compared to injectable steroids for treatment of OLP. A comprehensive search for randomized controlled trials were conducted in PubMed, Web of Science, Google Scholar, and Scopus using search terms such as “oral lichen planus and corticosteroids and platelet rich plasma injection,” “oral lichen planus and corticosteroids,” “oral lichen planus and corticosteroids and PRP,” “oral lichen planus and PRP,” “OLP and PRP and steroid.” Articles selection followed the Preferred Reporting Items for Systematic Reviews and meta-analysis guidelines. A meta-analysis was performed to group studies and determine summary effect estimates. A total of nine Randomized Controlled Trials (RCT) involving 266OLP patients were included in the analysis. Both treatment methods demonstrated a statistically significant improvements in outcome parameters including lesion size, pain scores, and burning sensations from baseline to the end of treatment and during follow-up visits. Patients treated with autologous PRP reported lower levels of pain and burning sensations compared to those treated with corticosteroids. A significant difference was observed between the two treatments with PRP showing greater effectiveness in alleviating pain and burning sensation than injectable steroids. Both platelet-rich plasma and injectable steroids effectively reduce lesion size and pain in OLP patients as measured by the Visual Analog Scale (VAS). However, the difference in efficacy between the two treatments was not statistically significant. Nonetheless, platelet-rich plasma can be considered promising alternative treatment to injectable steroids.

INTRODUCTION

Oral Lichen Planus (OLP) is an autoimmune disorder of unclear pathogenesis that affects the oral mucosa and significantly impacts the quality-of-life[1] Lichen planus can involve oral and genital mucous membranes, nails, skin, and scalp.[2] Its prevalence is ranges from 0.1% and 5% globally with an average of 1% and an incidence rate of around 2.2%.[3] It has a female predilection of 2 to 1 and commonly affects individuals aged 50 and 70 years, while it is relatively rare in children.[4,5] Around 77% of OLP cases present with oral manifestations.[6]

The exact etiology of OLP remains unidentified, however, it is considered a complex condition influenced by various triggers, including mechanical and electrolytic trauma, psychological stress, infections, nutritional deficiencies, mucous irritations, allergens, hormonal imbalances, salivary glands dysfunction, genetic susceptibility, and immunological factors.[7] The progression of a chronic, abnormal immune response to OLP-related antigens triggers an upregulation of cytokines, chemokines, and adhesion molecule expression ultimately leading to keratinocyte apoptosis, basement membrane damage, and persistent disease.[8] CD4+ and CD8+ lymphocytes are key factors in altering the immune response.

Clinically, OLP often presents as white striae, also known as Wickham’s striae, which are a hallmark of the condition. The disease manifests in different forms, including reticular, popular, plaque-like, erosive, atrophic, and bullous types. The atrophic, erosive, and bullous forms are associated with significant pain and burning sensation.[9] OLP disrupts daily activities such as eating, drinking, speaking, and socializing, thereby affecting patients’ overall well-being.[10]

Approximately 1.1% of OLP lesions progress to OSCC, with a greater likelihood in individuals, who smoke, consume alcohol, or have hepatitis C virus infection.[11] WHO classifies OLP as an oral potentially malignant disorder (OPMD).[12]

Current treatments for OLP aims to alleviate symptoms and heal ulcerations and extends periods of remission.[13] The treatments for OLP includes topical agents (dexamethasone, clobetasol, fluocinonide, triamcinolone, betamethasone, fluocinolone, tacrolimus, pimecrolimus, cyclosporine, amlexanox, retinoids, tocopherol), systemic therapies (retinoids, levamisole), intra-lesional therapies (triamcinolone, Bacillus Calmette-Guerin, polysaccharide nucleic acid), natural alternatives (aloe vera, Ignatia, lycopene), and advanced techniques like LASER and photodynamic therapy.[14] Ozone therapy is emerging as a promising treatment option for all forms of oral lichen planus.[15]

Corticosteroids remain the first line drug therapy for most clinicians due to their anti-inflammatory properties and can be administered through various routes including topical and systemic.[16] Topical or oral Corticosteroids are associated with risks such as of oral candidiasis and tachyphylaxis.[17] Long-term use of can lead to serious side effects including Cushing’s syndrome, hypertension, diabetes, gastric ulcers, and immunosuppression.[18]

Aims of this study

Autologous platelet-rich plasma (PRP) is frequently used in both medical and dental practices. The treatment involves extracting specific components from the patient’s blood and using them to promote tissue regeneration. PRP, the first type of platelet concentrate developed, accelerates the healing of both soft and hard tissues.[19] These concentrates are rich in growth factors, with typically 1 to 2 ml of PRP being used per session. To achieve optimal tissue regeneration and healing, 2 to 3 sessions are usually required.[20] The growth factors in PRP play a miracle role in cell proliferation, inflammation, and soft tissue remodeling during wound healing process. These factors promote natural cell growth, angiogenesis, detoxification, and cell regeneration. No side effects have been observed with the use of platelet-rich plasma.[21] Numerous studies have examined the impact of PRP on oral lichen planus compared to injectable steroids. This systematic review and meta-analysis aim to evaluate and compare the overall effects of PRP versus injectable steroids in the treatment of OLP.

METHODS

This systematic review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, updated to incorporate advancements in systematic methodologies.[22] The study protocol was registered in PROSPERO (Registration ID: CRD42024623582).

The research question was developed using the “PICO” framework:

Population- Patients diagnosed with oral lichen planus requiring treatment Intervention- Platelet-Rich Plasma

Comparison- Injectable steroids

Outcome-Changes in pain as (measured using Numerical Rating Scale (NRS) or Visual Analog Scale (VAS), clinical presentations (based on the Thongprasom scale) and lesion size. Thus, the research question was: Comparison of platelet rich plasma and injectable steroids on the oral lichen planus?”

Search strategy

An electronic search was conducted across four major databases without restrictions on publication start dates, up to 27 November 2024.

1) PubMed, 2) Web of Science, 3) Google Scholar, and 4) Scopus. Various combinations of search terms using “OR” and “AND” operators were applied. Additionally, the reference lists of the included studies were reviewed to identify further relevant research. The search terms used included “oral lichen planus,” “platelet-rich plasma,” and “injectable steroids.” EndNote Basic software was employed to manage the references; the duplicate entries were identified and removed.

Eligibility criteria

Only RCTs and case reports were included in the study. The inclusion criteria were limited to studies published in English within the last 10 years. Studies were excluded if they were semi-experimental, in-vitro research, animal studies, articles reusing data from the same sample. Additionally, letters to the editor, correspondence, review articles, and studies lacking sufficient information- particularly those that did not report exact frequencies of outcomes and independent variables- were excluded.

Screening and selection

The Screening process began with two independent reviewers, Ajay Kumar (A.K.) and Neha Sah (N.S.), who first examined the titles of the articles. Then they analyzed the abstracts to ensure they met the specified eligibility criteria. Following this, the full texts of the articles were reviewed to select the final studies that met the inclusion requirements. Any disagreements between the reviewers were resolved through discussion with a third reviewer, Adit Srivastav (A.S.). Cohen’s Kappa score was used to evaluate the level of agreement between the reviewers.

Data extraction

After the final selection of studies, the required information was extracted and summarized using a table created in the Microsoft Excel. The extracted data included the first author and year of publication, study design, country, gender of participants, mean age, total sample size, OLP types, intervention groups, evaluation methods (VAS), follow-up (in months), outcome and adverse effects. Two independent reviewers (A.K. and N.S.) performed the data extraction.

Risk of bias assessment

Two independent reviewers (A.K. and N.S.) assessed the risk of bias using the updated Cochrane risk-of-bias tool for Randomized Controlled Trials (RoB2).[23] Any disagreements were resolved through discussion with a third reviewer, Sachin Jadhav (S.J.) and Sivani Darjee SD. The RoB2 is organized into five domains, culminating in an overall judgment of the risk of bias.

Outcome parameters

The outcomes discussed in this article, based on the “PICO” framework, include changes in lesion and alterations in pain and burning sensations assessed using either the VAS or the NRS. Both the VAS and NRS are validated tools for measuring acute and chronic pain. While NRS and the Visual Analogue Scale (VAS) are not identical, they share similarities making them comparable in meta-analyses using standard methods.[24]

VAS scores are recorded on a 10-cm line, with one end labelled “no pain = 0” and the other labelled “worst pain = 10.” Patient indicates their pain level by marking a point along the line.[25] The NRS is an 11-point scale, where 0 represents “no pain” and 10 represents either “the worst possible pain” or “the most intense pain imaginable.”[26]

Statistical analysis

Standardized Mean Differences (SMD), endpoint scores, or change scores were used as effect sizes due to the different measurement scales (NRS and VAS) employed across the studies. These values were compared between the intervention and control groups. The SMD was calculated by determining the difference between the intervention and control group values and then dividing it by the pooled Standard Deviation (SD). Pooled SMDs and 95% confidence intervals (CIs) were computed using the Der Simonian and Laird method with a random-effects model. To evaluate heterogeneity across studies, Cochran’s Q test and I² statistics were applied.[27] All statistical analyses were performed using STATA 14.0 (Stata Corp, College Station, TX, US).

RESULTS

The electronic search across the specified databases identified 514 articles. After eliminating duplicates, 71 articles were reviewed, of which 11 were relevant to the topic, including two case reports. After excluding of case report, a total of nine articles met the inclusion criteria. The results of the search are summarized in the PRISMA flow diagram [Figure 1].

Figure 1.

PRISMA flow diagram showing study selection process

Characteristics of the studies

The key characteristics of the included studies are presented in Table 1. A total of 266 participants were involved across nine studies, all of which were randomized controlled trials (RCTs) published between 2017 and 2023. Of the participants, 193 were male and 73 were female. Nine studies used the VAS to evaluate pain before and after treatment.

Table 1.

Characteristics of included randomized controlled trials comparing platelet-rich plasma and injectable steroids in oral lichen planus.

First author, year	Study design	Country	Female/Male	Mean age	Sample size		OLP type	Intervention		Evaluation methods (VAS)	Follow up Period	Outcome	Adverse effect
					Experiment group	Control group		Experiment group	Control group
Laura Piñasa et al. 2017	RCT	Spain	10/0	48±12	10	10	Atrophic Erosive	Plasma Rich in Growth Factors PRGF/PRP	Corticosteroid	Histopathological	13±1 month	1 Infiltration Of PRP In eight Patients and two infiltrations required two patients patients’ complete response	No Side Effects
Bruno Loré et al. 2018	RCT	Italy	8/12	56 (40–74)	20	20	Erosive	PRP gel	Cyclosporine Mouthwash	VAS	2,4,8,12 Weeks	Seven patients’ complete response seven patients a partial response, six patients no response.	No Side Effects
Ahuja 2020	RCT	India	2/18	44.5	10	10	Erosive	PRP	Steroid	VAS	2 Month	Mean Pain Scores Steroid and PRP Group 8.70/8.90 % Reduction Of Pain in Group I And Group II 82.55% /93.5% Less Recurrence	No Side Effects
Una El Shinnawi and Bassant Mowafey 2021	RCT	Egypt	3/7	50–65	10	10	Erosive	PRP	Steroid	VAS	2 Month	Result Was Satisfactory	No Side Effects
Hijazi et al. 2022	RCT	Egypt	2/18	Intervention 42.6 Control 50.3	10	10	Erosive	PRP	Steroid	VAS	3 Month	PRP group 80% Steroid group 70%	No Side Effects
ElGhareeb et al. 2023	RCT	Egypt	10/14	Intervention 47 Control 52.17	12	12	Erosive	PRP	Steroid	VAS	3 Month	PRP is a good and safe. there were some side effects and recurrence of disease	Increase pain due to PRP Recurrence of the disease within 3 months
Sobhy, a., et al 2023	RCT	Egypt	11/7	30–65	9	9	Erosive	PRP	Steroid	VAS	3 months	Improved after 5 sessions of PRP injection. REU scoring, mean Before treatment 7.73±3.12 After treatment 1.03±0.77	No Side Effects
Sharma S et al. 2023	RCT	India	15/5	35.75	20	20	Erosive	PRP	Steroid	VAS	4 months	PRP shows slightly better results OLP.	No Side Effects
Akshi Choudhary et al. 2023	RCT	India	Not mention	Not mention	28	28	Erosive	PRP	Steroid	VAS	2 months	PRP is good in resistant cases of OLP	No Side Effects

In the study by Ahuja et al.,[28] one group of patients received bilateral intralesional injections of 10 mg/ml triamcinolone acetonide (TA), while another group was treated with bilateral intralesional autologous PRP injections. These injections were administered weekly over 8-week period. Both groups initially received a local anesthetic with a vasoconstrictor through a field block. A volume of 0.5 ml of either corticosteroid or PRP was injected for every 1 cm² of the lesions. The mean lesion size was assessed in both groups, but the P values comparing the two treatments were found to be statistically insignificant.

In the study conducted by El Ghareeb et al.,[29] one group received PRP injections at four points along the perimeter of the lesion (superior, inferior, left, and right), while the other group was given intralesional triamcinolone acetonide injections at 1 cm intervals, with 0.2 ml per injection. The triamcinolone acetonide (40 mg/ml) was combined with 1 ml of 2% lidocaine, resulting in a final concentration of 20 mg/ml. Both groups received injections every two weeks for two months. After treatment, no significant differences in pain scores (NRS) were observed between the two groups.

In the study by Hijazi et al.,[30] two groups of patients were treated with intralesional injections of either PRP or 40 mg/ml of TA. Each injection consisted of 0.5 ml per 1 cm² of the ulcerated mucosa. Before administering the injections, a field block was performed using 3% Mepivacaine anesthetic without a vasoconstrictor. Both groups received weekly injections for four weeks. No significant differences were found between the two groups in terms of pain, clinical score, or remission.

In the study by Laura Piñas et al.,[31] two groups of patients received intralesional injections of either PRP or corticosteroids, both leading to successful outcomes. However, in 2 out of 6 patients, no plasma cells (PRP) were needed after two infiltrations.

In the study by Bruno Loré et al.,[32] three groups were treated with different therapies: cyclosporine mouthwash, 0.05% retinoic acid lotion, and autologous PRP gel for reticular, plaque-like, and erosive types, respectively. The treatments were administered as follows: retinoic acid twice daily for 8 weeks, cyclosporine mouthwash once daily for 8 weeks, and PRP once a week for 8 weeks.

In the study by Una El Shinnawi and Bassant Mowafey, ten patients with a histopathological diagnosis of oral erosive lichen planus (seven females and three males), aged between 50 and 65 years, were included. These patients were resistant to conventional treatment. Each patient received an injection of 0.5 ml of autologous PRP per 1 cm² of ulcerated mucosa using a 25-gauge needle, administered once weekly for 4 weeks.[33]

In the study by Sobhy et al.,[34] 18 patients with OLP underwent five sessions of intralesional PRP injections, with a 2-week interval between each session. No side effects were reported following the PRP treatment.

In the study by Sharma S et al.,[35] 40 patients aged 18 to 60 years with erosive lichen planus were treated. Triamcinolone 40 mg (1 mg/ml) mixed with 2% lignocaine hydrochloride (1:80,000) was injected into the lesion on one side, while autologous PRP was prepared and injected into the other side of the same patients. During each visit, all patients were assessed for pain, burning sensation, lesion size, and severity.

In the study by Akshi Choudhary et al.,[36] a total of 56 lesion sites were divided into two groups of 28 each. Group 1 received intralesional PRP, while Group two was treated with intralesional steroids. The outcomes of the group treated with PRP were compared to those of the group receiving intralesional steroids.

Assessing the risk of bias

The risk of bias across included studies was evaluated using standard domains. Most studies demonstrated a low risk of bias in critical areas such as random sequence generation and allocation concealment, ensuring robust methodology.

Performance bias and detection bias were generally well-controlled, as indicated by proper blinding of participants, personnel, and outcome assessors in most studies. Attrition bias and reporting bias were also adequately addressed, with all included studies providing complete outcome data and avoiding selective reporting.

However, some uncertainties were noted in studies such as El Ghareeb et al.,[29] and Sharma S et al.[35] concerning random sequence generation and allocation concealment. Similarly, El Ghareeb et al.,[29] and El-Shinnawi U[33] presented unclear risks for certain biases due to insufficient reporting. Despite these minor concerns, the overall methodological quality of the included studies remains robust, supporting the reliability of the review’s conclusions.

The summary uses a colour-coded system

Green (+) indicates a low risk of bias. Yellow (?) indicates an unclear risk of bias. Red (-) indicates a high risk of bias. Among the studies, most demonstrate a low risk of bias in random sequence generation and allocation concealment. However, performance and detection bias are evident in a few studies, particularly unclear risks are noted in certain domains for studies like El Ghareeb et al.,[29] and Sobhy A et al.,[34] reflecting gaps in reporting or methodology. Overall, while several studies exhibit strong methodological rigor, others reveal areas needing improvement to ensure reliability and validity.

Risk of bias graph illustrates that most studies were methodologically sound, with low risk across various domains. Nonetheless, minor concerns were identified, particularly in the areas of allocation concealment and blinding, emphasizing the need for detailed reporting in future studies to further enhance transparency and validity [Figure 2].

Figure 2.

Risk of bias summary of included studies (RoB 2 tool)

Meta-analysis

Statistical analysis

The meta-analyses, using the random effects model, were applied with RevMan 5.4 (RevMan 5.4, The Nordic Cochrane Centre, Copenhagen). Heterogeneity was assessed by a Q test and quantified with I2 statistics. Data on pain/burning sensation among the two groups were obtained from selected studies. For analyses, if the test showed substantial heterogeneity (I² >50%), a random effects model was applied, or else (I² ≤50%), a fixed effects model would be used.

RESULTS

Meta-analysis was performed on four studies that qualified with the required data outcome that could be analyzed quantitatively. The results of the overall comparison have been depicted as a forest plot. With the meta-analysis conducted for selected studies, heterogeneity was greater than 50% (I² = 85%); hence, a random effects model was applied. The post-operative pain score in the PRP group was lower than that of the Steroid group; however, the difference between the two groups was statistically non-significant with a standardized mean difference of −0.16 (95% CI = −1.13 to 0.80; Z value = 0.33; P = 0.74) [Table 2].

Table 2.

Forest plot of standardized mean differences (PRP vs Steroid)

DISCUSSION

This systematic review examined PRP therapy as a potential alternative to injectable steroids for the treatment of symptomatic OLP. Lichen planus is an inflammatory condition that affects both the oral mucous membranes and the skin, with an unknown origin.[15] The existing treatments only help to reduce the symptoms.[37] A range of treatment options are employed for managing OLP, such as corticosteroids, immunosuppressive drugs (e.g., Cyclosporin, Azathioprine), and immunomodulatory agents (e.g., levamisole).[38] Platelet concentrates, primarily in the form of PRP, are autologous biological products derived from blood. These products are considered safe for clinical use because they are sourced from the patient’s own blood.[39]

Autologous PRP has been utilized in both medicine and dentistry for regenerative treatments, primarily promoting soft tissue wound healing by providing concentrations of autologous growth factors that are higher than natural levels.[40] APCs contain growth factors and cytokines, which, when released locally from platelet alpha granules, help speed up tissue repair and enhance wound healing. This effect is further enhanced when combined with the fibrinolytic system, which plays a key role in achieving full regeneration.[41] The development of OLP is influenced by several cellular mechanisms that are regulated by various cytokines. Tumor necrosis factors α, IL-1, and IL-4 is particularly important in driving the progression of the disease.[8] PRP stimulates the production of anti-inflammatory cytokines, which assist activated macrophages in controlling the effects of pro-inflammatory cytokines. These anti-inflammatory cytokines help manage inflammation by interacting with soluble cytokine receptors and cytokine inhibitors.[42] additionally, oxidative stress may play a role in the development of OLP.[43] Studies have demonstrated that PRP treatment can protect against oxidative damage by activating nuclear factor type 2, that enhances the signaling of antioxidant response elements.[44] Regarding lesion recurrence and treatment side effects, most studies reported either no recurrence or only mild symptoms, along with minimal side effects from the treatment. In Ahuja et al.’s[28] study, during the 2-month follow-up after treatment, patients treated with PRP experienced little to no recurrence, with only one out of ten patients showing mild erythema and slight burning at the 15^th week. In contrast, three patients in the corticosteroid group experienced lesion recurrences during follow-up, with increased pain and erythema compared to the 8^th week. Additionally, two patients in the steroid group reported mild side effects, while no adverse effects were reported by any of the patients treated with PRP. In the study by El Ghareeb et al.,[29] there was a notable increase in the frequency of side effects, particularly pain, among patients, who received PRP compared to those treated with steroids. This finding contrasts with the results of the other two studies that used PRP. This difference may be attributed to the shorter injection intervals in this study and the use of lidocaine as a local anesthetic in the triamcinolone acetonide (TA) injections. Additionally, there was a significant rise in the recurrence rate among patients treated with PRP compared to those treated with TA. The authors suggested that this could be due to the depletion of growth factors at the lesion site after a short period or the prolonged immunosuppressive effect of corticosteroids. In the study by Sobhy A et al.,[34] significant improvement in erosive lichen planus lesions was observed after five sessions, with no side effects reported and no recurrence noted. In the next study Sharma S et al.[35] on the 20 patients, PRP shows slightly better results on erosive OLP. in one study of Akshi Choudhary et al.[36] reviled in her study PRP is more effective in resistant OLP cases without any side effects. Una El Shinnawi and Bassant Mowafey reported in her study about the PRP treatment on the erosive lichen planus Result Was only Satisfactory during 2 month follow-up.[33] on the other side one study finished in Italy Bruno Loré et al. with PRP gel on the 20 patients, 8 was female and 12 was male after follow-up period of 2, 4, 8, 12 Weeks seven patients gain complete response, seven was partial response and six patients has no response with PRP as gel.[32] One study performed Laura Piñas et al.[31] in Spain, the fallow-up periods of 13 ± 1 month, only one injection required in eight patients, and two injections used in another two patients; complete remission of the disease was achieved. Out of oral cavity, Behrangi et al.[45] was gives the recent study, (clobetasol > prp) topical clobetasol lesion was more effective then PRP in scalp region. Platelets not only play a role in hemostasis but also possess regenerative capabilities. PRP is a concentrated blend of growth factors and cytokines that can impact inflammation, cell proliferation, stem cell migration, tissue repair, and angiogenesis.[46]

While the exact cause of OLP remains unknown, it has been demonstrated that various cytokines and inflammatory processes play a significant role in its development.[47] Corticosteroids are the most widely used treatment for OLP because of their anti-inflammatory properties; however, they do not provide a permanent cure and only help in alleviating the symptoms.[48]

Further research is needed to assess the long-term and potentially definitive effects of these treatments. This review indicates that PRP shows promise in relieving the symptoms of OLP, with minimal side effects and a low recurrence rate. The outcomes of PRP treatment for OLP are comparable to those of topical steroids, offering the added benefit of fewer side effects, such as oral candidiasis, which is commonly associated with corticosteroids. Therefore, PRP may be recommended, particularly for patients who do not respond well to topical steroids. Additionally, more studies are needed to explore PRP as a potential alternative to corticosteroids. While there was not sufficient data to directly compare PRP with corticosteroids, PRP may offer a quicker clinical response in managing OLP. Further research is required to compare these two treatments. This review has some limitations, including the small number of studies that compared PRP with topical steroids, resulting in a small overall sample size, variability in outcome measures, and differences in injection intervals across studies. Additionally, varying follow-up durations could impact the results. Despite these limitations, our study suggests that PRP may be effective in treating oral lichen planus, with results like those of topical or injectable steroids, though it does not show superior benefits in reducing pain or improving clinical appearance. Future studies with larger sample sizes and longer follow-up periods are recommended, along with research to establish a standardized treatment protocol for the duration and intervals of PRP use in OLP patients.

CONCLUSION

PRP was found to reduce lesion size, Thongprasom score, and pain in OLP patients; however, no significant differences were observed between PRP and topical steroids. Therefore, PRP could be considered a potential alternative to topical steroids. Nevertheless, the results should be interpreted with caution due to the high variability among the studies and the small number of participants. Additional well-designed prospective randomized clinical trials with larger sample sizes and longer follow-up periods are needed.

Author contributions

AS contributed to the study’s conceptualization and reviewed the identified articles for eligibility. AK and NS were responsible for screening the articles, extracted data, and drafting the manuscript. SJ assessed the risk of bias, and performed the meta-analysis. NS and Sivani Darjee SD carried out the systematic search in databases and revised the manuscript. Amlendu Shekhar AS revised the manuscript and handled the Prospero registration. All authors have read and approved the final manuscript.

Ethics approval

This study has been approved by the PROSPERO (Registration ID: CRD42024623582).

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.