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Reporting Bias is Highly Prevalent in Systematic Reviews and Meta-Analyses of Platelet Rich Plasma Injections for Hip Osteoarthritis
Kim, D., Bashrum, B. S., Kotlier, J. L., Mayfield, C. K., Thompson, A. A., Abu-Zahra, M., Hwang, M., Bolia, I. K., Petrigliano, F. A., Liu, J. N.
Arthroscopy, sports medicine, and rehabilitation. 2024;6(1):100851
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Editor's Choice
Abstract
PURPOSE To describe the incidence and types of spin in systematic reviews of platelet-rich plasma (PRP) injections for hip osteoarthritis (OA) and to determine whether patterns in study characteristics could be identified among studies with identifiable spin. METHODS The PubMed, Scopus, and SPORTDiscus databases were queried. Inclusion criteria were systematic reviews or meta-analyses that included an assessment of intra-articular PRP injections as a stand-alone treatment for hip OA. Two authors independently assessed the presence of spin in the included studies and recorded general study characteristics. The prevalence of the 15 different categories of spin was quantified using descriptive statistics. RESULTS Fifteen studies met inclusion criteria for this study. All studies contained at least two types of spin (range 2-9), with a median of 2. The most common type of spin was type 14 ("Failure to report a wide confidence interval of estimates"), which was observed in 10 studies. The second most common type of spin was type 13 ("Failure to specify the direction of the effect when it favors the control intervention"), found in 6 studies. CONCLUSIONS Spin is highly prevalent in abstracts of systematic reviews of PRP in the treatment of hip OA. Several associations were found between spin types and the study characteristics of AMSTAR 2 rating, Scopus CiteScore, journal impact factor, and PROSPERO preregistration. When present, spin in the abstracts of reviewed studies tended to favor the use of PRP in hip osteoarthritis. CLINICAL RELEVANCE It is important to understand the prevalence of spin in published abstracts, especially in areas of great impact or interest, so authors and readers can have a greater awareness of this potential form of bias.
PICO Summary
Population
Patients with hip osteoarthritis (15 systematic reviews).
Intervention
Systematic review to describe the incidence and types of spin bias in systematic reviews of platelet-rich plasma injections for hip osteoarthritis and to determine whether patterns in study characteristics could be identified among studies with identifiable spin.
Comparison
Outcome
All studies contained at least two types of spin (range 2-9), with a median of 2. The most common type of spin was type 14 ("Failure to report a wide confidence interval of estimates"), which was observed in 10 studies. The second most common type of spin was type 13 ("Failure to specify the direction of the effect when it favors the control intervention"), found in 6 studies. Several associations were found between spin types and the study characteristics of AMSTAR 2 rating, Scopus CiteScore, journal impact factor, and PROSPERO preregistration.
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Comparative effectiveness of intra-articular therapies in knee osteoarthritis: a meta-analysis comparing platelet-rich plasma (PRP) with other treatment modalities
Khalid, S., Ali, A., Deepak, F., Zulfiqar, M. S., Malik, L. U., Fouzan, Z., Nasr, R. A., Qamar, M., Bhattarai, P.
Annals of medicine and surgery (2012). 2024;86(1):361-372
Abstract
INTRODUCTION Knee osteoarthritis (KOA) is a progressive joint disease commonly treated with intra-articular injections, including platelet-rich plasma (PRP), hyaluronic acid (HA), or corticosteroids (CS). This updated meta-analysis aims to enhance the statistical power of the results and provide comprehensive clinical evidence that reflects the most current research. By doing so, the authors aim to suggest a reliable estimate for the development of guidelines, addressing the pressing need for effective and minimally invasive treatment options. METHODS PubMed, Scopus, clinicaltrials.gov, Cochrane Central were searched until March 2023, for randomized controlled trials (RCTs) comparing the effectiveness of intra-articular injectable therapies, including PRP, HA, CS, and placebo, in KOA. Data extraction involved baseline characteristics and outcome measures [Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores, Visual Analog Scale (VAS) pain scores, KOOS, and IKDC scores] at 1, 3, 6 and 12 months. Statistical analysis, including subgroup analysis, assessment of heterogeneity, and publication bias, was conducted using Review Manager. RESULTS Our meta-analysis of 42 studies involving 3696 patients demonstrated that PRP treatment resulted in significant pain relief compared to HA injections, as evidenced by improved WOMAC pain (MD: -0.74; 95% CI: -1.02 to -0.46; P≤0.00001; I (2)=94%) and VAS pain (MD: -0.65; 95% CI: -1.24 to -0.06; P=0.03; I(2)=97%) outcomes. Similarly, PRP showed greater efficacy in reducing WOMAC pain (MD: -8.06; 95% CI: -13.62 to -2.51: P=0.004; I (2)=96%) and VAS pain (MD: -1.11; 95% CI: -1.64 to -0.59; P≤0.0001; I (2)=68%) compared to CS injections, with the most significant improvement observed at 6 months. CONCLUSIONS PRP is an effective treatment for KOA. It provides symptomatic relief, has the potential to reduce disease progression, and has sustained effects up to 12 months. PRP offers superior pain relief and functional enhancement compared to CS and HA injections.
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Adipose Tissue-Derived Minimally Manipulated Products versus Platelet-Rich Plasma for the Treatment of Knee Osteoarthritis: A Systematic Review of Clinical Evidence and Meta-Analysis
Veronesi, F., Andriolo, L., Salerno, M., Boffa, A., Giavaresi, G., Filardo, G.
Journal of clinical medicine. 2023;13(1)
Abstract
The use of minimally manipulated adipose tissue (MM-AT) products is gaining increasing interest for the treatment of knee osteoarthritis (OA). MM-AT represents an easy way to exploit adipose tissue properties, although clinical evidence is still limited, as well as their benefits with respect to more documented orthobiologics like platelet-rich plasma (PRP). A systematic review and meta-analysis were performed to evaluate the safety and efficacy of MM-AT products for knee OA management. The risk of bias of the included studies was evaluated using the Dawns and Black checklist for all the included studies and RoB-2.0 for randomized controlled trials (RCTs). Thirty-three clinical studies were included in the qualitative analysis: 13 prospective case series, 10 retrospective case series, 7 RCTs, 2 retrospective comparative studies, and 1 prospective comparative study. An overall clinical improvement and few minor adverse events were observed. Five RCTs comparing MM-AT and PRP injections were meta-analyzed, showing comparable results. The analysis also highlighted the limits of the literature, with only a few high-level trials and an overall low quality. Even though the current literature is still limited, the available evidence suggests the safety and overall positive results of the intra-articular injections of MM-AT products for knee OA treatment.
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Leukocyte and platelet rich fibrin in the management of medication-related osteonecrosis of the jaw: A systematic review and meta-analysis
Muñoz-Salgado A, Silva FF, Padín-Iruegas ME, Camolesi GC, Bernaola-Paredes WE, Veronese HR, Celestino MD, Filho WJ, Lorenzo-Pouso AI, Pérez-Sayáns M
Medicina oral, patologia oral y cirugia bucal. 2023
Abstract
BACKGROUND Osteonecrosis of the jaw (ONJ) has a frequent adverse effect after the administration of nitrogenous bisphosphonates, as non-nitrogenous bisphosphonates are metabolized more rapidly and would produce this effect to a lesser extent. The objective of this study is to analyze the results obtained in the literature with the use of L-PRF in the treatment of ONJ through a systematic review and meta-analysis. MATERIAL AND METHODS Medline (via PubMed), Cochrane, Web of Science and Grey Literature Database was screened from which 10 were selected. RESULTS In the meta-analysis with full resolution, combining the use of L-PRF in the treatment of ONJ, a weighted proportion (PP) of 94.3% of complete resolution is obtained (95% CI: 91.2-97.4, p<0.001), with a low degree of heterogeneity, statistically significant (I2 = 29.02%; p<0.001). When analyzing the non-resolution data, a weighted proportion (PP) of 7.7% (95% CI: 3.6-11.9; p<0.001) was obtained with moderate heterogeneity (I2: 41.87%; p=0.112). In the meta-regression, no significant correlation was found between complete resolution and year of publication (intercept = 2.88, p=0.829). In consistency analysis no major changes in PP are identified when any of the studies are eliminated, demonstrating a high reliability in the combined results. CONCLUSION L-PRF alone or in combination with other therapies in treatment of ONJ achieved high percentages of complete lesion resolution (94.3%). In studies where L-PRF is combined with other therapies, and where the effectiveness of the other therapy alone is analyzed, L-PRF has been shown higher percentages of resolution.
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Platelet-Rich Plasma Therapy: An Effective Approach for Managing Knee Osteoarthritis
Crowley, J. L., Soti, V.
Cureus. 2023;15(12):e50774
Abstract
Platelet-rich plasma (PRP) is a promising non-invasive therapeutic intervention for knee osteoarthritis (KOA) that has generated significant interest due to anecdotal accounts of its efficacy, resulting in reduced recovery time in various orthopedic interventions. This systematic review examines the effectiveness of PRP in managing KOA. Specifically, it seeks to determine the extent to which PRP can treat KOA patients effectively, alleviate KOA symptoms, and improve patient outcomes. Additionally, the review aims to identify the optimal concentration and composition of PRP required to achieve therapeutic results in KOA. Furthermore, the review investigates whether PRP can modify the synovial environment structurally and immunologically to improve outcomes in KOA patients. We conducted a comprehensive literature search on PubMed, Orthogate, Clinicaltrials.gov, and Embase of clinical trials investigating PRP treatment in KOA patients in the last five years. The results indicated that PRP is effective in treating KOA patients. Evidence shows that PRP therapy can alleviate pain, enhance joint function, increase range of motion, and improve mobility in KOA patients. PRP was effective in treating KOA when the mean platelet concentration of PRP treatment was 4.83 to 5.91 times higher than the baseline whole blood platelet concentration. However, studies investigating PRP with a mean platelet concentration of 3.48 to 4.04 times higher than baseline failed to demonstrate statistically significant improvements. PRP therapy slowed down KOA progression, which validates its effectiveness in impeding further structural damage and arresting the degenerative impact of the disease. Nonetheless, further investigation is necessary to examine how PRP therapy can modify the progression of the disease. Furthermore, future research should identify the most effective platelet concentration levels that provide optimal symptom relief. There is a need for further research to identify the specific PRP configuration that is most pertinent in a clinical setting, as there is a lack of standardization in PRP manufacturing protocols, including the variety of experimental setups and dosing schedules utilized in different studies.
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Comparing Intra-articular Platelet-Rich Plasma With Hyaluronic Acid for the Treatment of Hip Osteoarthritis: A Systematic Review and Meta-Analysis
Sambe, H. G., Yasir, M., Man, R. K., Gogikar, A., Nanda, A., Janga, L. S. N., Hamid, P.
Cureus. 2023;15(10):e47919
Abstract
Hip osteoarthritis (HOA), a prevalent condition among those aged 55 years and above, is a significant cause of joint pain and functional impairment and it contributes to the overall burden of chronic pain experienced by the elderly population. While platelet-rich plasma (PRP) and hyaluronic acid (HA) injections have emerged as innovative therapeutic approaches for managing osteoarthritis, their effectiveness in HOA remains a subject of contention. Therefore, the objective of this review was to assess the efficacy of PRP versus HA in terms of pain relief and functional outcomes for the management of HOA. We searched PubMed, Cochrane Library, and Google Scholar databases from 2013 to 2023 to identify pertinent randomized controlled trials (RCTs). A total of seven trials (478 participants) were included. The selected studies underwent quality assessment using the updated Cochrane risk of bias tool. The pain and functional outcomes were examined using measures of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scale, visual analog scale (VAS), and Harris hip score (HHS). In the meta-analysis, standard mean differences (SMDs) along with 95% confidence intervals (CIs) to estimate overall effect magnitudes for continuous outcomes were extracted. Statistical significance was determined using p-values below 0.05. At six months, the PRP group experienced a significantly lower standard mean WOMAC pain score (SMD = -0.38, CI = -0.64 - 0.13; p = 0.03). No significant differences in WOMAC pain scores were noted at one to two months (SMD = 0.09, CI = -0.24, 0.43; p = 0.59), and at 12 months (SMD = -0.85, CI = -1.81, 0.12; p = 0.09). Similarly, for VAS, patients on PRP showed a slight improvement in their VAS scores at six months (SMD = -0.50, CI = -0.89, -0.12; p < 0.01). However, no significant differences in VAS between the PRP groups and the HA groups were observed at one to two months (SMD = -0.22, CI = -0.49, 0.04; p = 0.10) and at 12 months (SMD = -0.22, CI: -0.63, 0.19; p = 0.29). In terms of hip dysfunction, there was no statistically significant standard mean difference in HHS between the PRP and HA groups at six months (SMD = 0.02, CI = -0.40, 0.44; p = 0.93), and at 12 months (SMD = -0.31, CI = -0.32, 0.22; p = 0.73). This review and meta-analysis provide insights into emerging treatments for HOA, especially considering that PRP shows potential benefits and safety for patients with HOA during mid-term follow-up in a 12-month period. Nevertheless, it is necessary to conduct research that includes high-quality designs and larger sample sizes to validate the comparative efficacy of these treatments.
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Platelet-rich plasma injection for the treatment of ankle osteoarthritis: a systematic review and meta-analysis
Laohajaroensombat S, Prusmetikul S, Rattanasiri S, Thakkinstian A, Woratanarat P
Journal of orthopaedic surgery and research. 2023;18(1):373
Abstract
BACKGROUND Platelet-rich plasma (PRP) injection for ankle osteoarthritis (OA) treatment showed contradictory results. This review was aimed to pool individual studies which assessed the efficacy of PRP for ankle OA treatment. METHODS This study was conducted following the preferred report items of systematic review and meta-analysis guideline. PubMed and Scopus were searched up to January 2023. Meta-analysis, or individual randomised controlled trial (RCT), or observational studies were included if they involved ankle OA with aged ≥ 18 years, compared before-after receiving PRP, or PRP with other treatments, and reported visual analog scale (VAS) or functional outcomes. Selection of eligible studies and data extraction were independently performed by two authors. Heterogeneity test using Cochrane Q test and the I(2)-statistic were assessed. Standardised (SMD) or unstandardised mean difference (USMD) and 95% confidence interval (CI) were estimated and pooled across studies. RESULTS Three studies from meta-analysis and two individual studies were included, which consisted of one RCT and four before-after studies with 184 ankle OAs and 132 PRP. The average age was 50.8-59.3 years, and 25-60% of PRP injected cases were male. The number of primary ankle OA was accounted to 0-100%. When compared to before treatment, PRP significantly reduced VAS and functional score at 12 weeks with pooled USMD of - 2.80, 95% CI - 3.91, - 2.68; p < 0.001 (Q = 82.91, p < 0.001; I(2) 96.38%), and pooled SMD of 1.73, 95% CI 1.37, 2.09; p < 0.001 (Q = 4.87, p = 0.18; I(2) 38.44%), respectively. CONCLUSION PRP may beneficially improve pain and functional scores for ankle OA in a short-term period. Its magnitude of improvement seems to be similar to placebo effects from the previous RCT. A large-scale RCT with proper whole blood and PRP preparation processes is required to prove treatment effects. Trial registration PROSPERO number CRD42022297503.
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The Efficacy of Platelet-Rich Plasma Injection Therapy in the Treatment of Patients with Achilles Tendinopathy: A Systematic Review and Meta-Analysis
Arthur Vithran DT, Xie W, Opoku M, Essien AE, He M, Li Y
Journal of clinical medicine. 2023;12(3)
Abstract
BACKGROUND Over the past few years, many studies have been conducted to evaluate the effectiveness of platelet-rich plasma (PRP) in treating musculoskeletal conditions. However, there is controversy about its benefits for patients with Achilles tendinopathy. OBJECTIVE This study aimed to investigate whether platelet-rich plasma injections can improve outcomes in patients with Achilles tendinopathy. METHODS A comprehensive literature search was conducted in PubMed, Embase, Cochrane Library, Web of Science, China Biomedical CD-ROM, and Chinese Science and Technology Journal databases to identify randomised controlled clinical trials that compared the efficacy of PRP injection in patients with Achilles tendinopathy (AT) versus placebo, published between 1 January 1966 and 1 December 2022. Review Manager 5.4.1 software was used for the statistical analysis, and the Jadad score was used to assess the included literature. Only 8 of the 288 articles found met the inclusion criteria. RESULTS Our work suggests that: The PRP treatment group had a slightly higher VISA-A score than the placebo group at 6 weeks [MD = 1.92, 95% CI (-0.54, 4.38), I(2) = 34%], at 12 weeks [MD = 0.20, 95% CI (-2.65 3.05), I(2) = 60%], and 24 weeks [MD = 2.75, 95% CI (-2.76, 8.26), I(2) = 87%]). However, the difference was not statistically significant. The Achilles tendon thickness was higher at 12 weeks of treatment in the PRP treatment group compared to the control group [MD = 0.34, 95% CI (-0.04, 0.71), p = 0.08], but the difference was not statistically significant. The VAS-improvement results showed no significant difference at 6 and 24 weeks between the two groups, respectively (MD = 6.75, 95% CI = (-6.12, 19.62), I(2) = 69%, p = 0.30), and (MD = 10.46, 95% CI = (-2.44 to 23.37), I(2) = 69%, p = 0.11). However, at 12 weeks of treatment, the PRP injection group showed a substantial VAS improvement compared to the control group (MD = 11.30, 95% CI = (7.33 to 15.27), I(2) = 0%, p < 0.00001). The difference was statistically significant. The return to exercise rate results showed a higher return to exercise rate in the PRP treatment group than the placebo group [RR = 1.11, 95% CI (0.87, 1.42), p = 0.40]; the difference was not statistically significant. CONCLUSION There is no proof that PRP injections can enhance patient functional and clinical outcomes for Achilles tendinopathy. Augmenting the frequency of PRP injections may boost the outcomes, and additionally, more rigorous designs and standardised clinical randomised controlled trials are needed to produce more reliable and accurate results.
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Statistical Fragility of Randomized Controlled Trials Evaluating Platelet-Rich Plasma Use for Knee Osteoarthritis: A Systematic Review
Chan, J. P., Vrla, M., Thompson, C., Trofa, D. P., Li, X., Wang, D., Parisien, R. L.
Orthopaedic journal of sports medicine. 2023;11(8):23259671231187894
Abstract
BACKGROUND Numerous studies have been published on the use of platelet-rich plasma (PRP) for knee osteoarthritis (OA), with conflicting results. PURPOSE To determine the fragility index (FI) and fragility quotient (FQ) of randomized controlled trials (RCTs) that evaluated the use of PRP to treat knee OA. STUDY DESIGN Systematic review. METHODS RCTs evaluating the efficacy of PRP injections for knee OA from 2000 to 2020 were included for analysis according to PRISMA guidelines. The FI was determined by calculating the number of outcome event reversals required to change the statistical significance. The associated FQ was determined by dividing the FI by the sample size. RESULTS Our initial search resulted in 41,149 studies, of which 8 RCTs (678 patients, 72 outcome events) were included in the analysis. One study failed to report PRP formulation details, whereas 87.5% of studies reported using either leukocyte-rich or leukocyte-poor PRP. The platelet concentration was reported in 25% of the included trials. The overall FI of the 72 outcome events was 8.5. Accounting for sample size, the associated FQ was determined to be 0.14, suggesting that the reversal of 14% of outcome events was required to change outcome significance. There were 51 statistically significant outcomes, of which the FI and FQ were 12 and 0.164, respectively. CONCLUSION Comprehensive fragility analysis suggested that the published literature evaluating the efficacy of PRP use for knee OA may lack statistical stability. We recommend the reporting of both an FI and FQ in addition to P value analysis to provide a clear and thorough understanding of the statistical integrity of studies reporting on PRP use for knee OA.
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Efficacy and safety of platelet-rich plasma injections for the treatment of osteoarthritis: a systematic review and meta-analysis of randomized controlled trials
Xiong, Y., Gong, C., Peng, X., Liu, X., Su, X., Tao, X., Li, Y., Wen, Y., Li, W.
Frontiers in medicine. 2023;10:1204144
Abstract
BACKGROUND In recent years, platelet-rich plasma (PRP) injections for osteoarthritis (OA) have been widely promoted in clinical practice, but their effectiveness is controversial. Therefore, we conducted a meta-analysis of relevant randomized controlled trials (RCTs) to determine the efficacy and safety of PRP injections for the treatment of OA. METHODS We searched databases including Embase, Web of Science, Medline, PubMed, and the Cochrane Library for relevant studies. Two researchers (YQX and CG) performed literature screening, baseline data extraction, literature quality assessment, and heterogeneity analysis of RCTs from the retrieved studies. Based on the magnitude of heterogeneity I(2), random-effects or fixed-effects models were selected for the meta-analysis. RESULTS We included 24 RCTs comprising 1344 patients with OA who met the inclusion criteria, with the main types of morbidity being knee osteoarthritis (KOA), hip osteoarthritis (HOA), ankle osteoarthritis (AOA), and temporomandibular joint osteoarthritis (TMJOA). Our results indicate that PRP injections were effective in improving Visual Analog Scale (VAS) pain scores in patients with KOA, HOA, and AOA compared to controls (AOA, MD = -1.15, CI = 95% [-1.74, -0.56], I(2) = 40%, P < 0.05; KOA, MD = -1.03, CI = 95% [-1.16, -0.9], I(2) = 87%, P < 0.05; TMJOA, MD = -1.35, CI = 95% [-1.74, -0.97], I(2) = 92%, P < 0.05) but showed no significant efficacy in patients with HOA (MD = -0.27, CI = 95% [-0.8, 0.26], I(2) = 56%, P>0.05). Compared to controls, PRP injections were effective in improving Knee Injury and Osteoarthritis Outcome Score (KOOS), including the patient's pain symptoms, activities of daily living (ADL), and adhesion symptomatology, but not for that of sports function (KOOS-pain, MD = 2.77, CI = 95% [0, 5.53], I(2) = 0%, P < 0.05; KOOS-symptoms, MD = 3.73, CI = 95% [0.76, 6.71], I(2) = 0%, P < 0.05; KOOS-ADL, MD = 3.61, CI = 95% [0.79, 6.43], I(2) = 0%, P < 0.05; KOOS-QOL, MD = 4.66, CI = 95% [0.98, 8.35], I(2) = 29%, P < 0.05, KOOS-sport, MD = 0.48, CI = 95% [-3.02, 3.98], I(2) = 0%, P > 0.05). PRP injections were effective in improving Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores, including pain, stiffness, and functional joint motion, in patients with OA compared with the control group (WOMAC-pain, MD = -1.08, CI = 95% [-1.62, -0.53], I(2) = 87%, P < 0.05; WOMAC-stiffness, MD = -1.17, CI = 88% [-1.72, -0.63], I(2) = 87%, P < 0.05; WOMAC-function, MD = -1.12, CI = 95% [-1.65, -0.58], I(2) = 87%, P < 0.05). In addition, subgroup analysis showed that leukocyte-poor (LP) PRP injections were more effective than leukocyte-rich (LR) PRP injections in improving pain symptoms in patients with OA (VAS, LR-PRP, MD = -0.81, CI = 95% [-1.65, -0.03], I(2) = 83%, P = 0.06 > 0.05; LP-PRP, MD = -1.62, CI = 95% [-2.36, -0.88], I(2) = 92%, P < 0.05). A subgroup analysis based on injection sites showed that no statistical difference in efficacy between intra-articular (IA) combined with intra-osseous (IO) simultaneous PRP injections. IA PRP injections only improved VAS pain scores in patients with OA (IA+IO PRP injections, MD = -0.74, CI =95% [-1.29, -0.18], I(2) = 61%, P < 0.05; IA PRP injections, MD = -1.43, CI = 95% [-2.18, -0.68], I(2) = 87%, P < 0.05, test for subgroup differences, P > 0.05, I(2) = 52.7%). CONCLUSION PRP injection therapy can safely and effectively improve functional activity in patients with OA and produce positive analgesic effects in patients with KOA, TMJOA, and AOA. However, PRP injection therapy did not significantly reduce pain symptoms in patients with HOA. In addition, the analgesic effect of LP-PRP was greater than that of LR-PRP. SYSTEMATIC REVIEW REGISTRATION https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022362066.