Skip to main content
Download PDF
  • Systematic Review
  • Open access
  • Published:

Comparison of hyaluronic acid and platelet-rich plasma in knee osteoarthritis: a systematic review

BMC Musculoskeletal Disorders volume 26, Article number: 236 (2025) Cite this article

Abstract

Background

Knee osteoarthritis (KOA) is a common joint disorder, and intra-articular injections of hyaluronic acid (HA) or platelet-rich plasma (PRP) are frequently employed therapeutic interventions. However, there remains controversy regarding their efficacy. This systematic review aims to compare the effectiveness and safety of HA and PRP through a meta-analysis, with the objective of identifying the optimal treatment protocol for KOA and enhancing its management.

Methods

Randomized controlled trials evaluating the clinical outcomes of patients receiving intra-articular injections of either HA or PRP were included as eligible studies. Two independent investigators assessed the selected studies and evaluated their risk of bias. Primary outcome measures included the Visual Analog Scale (VAS) score, the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score, and other relevant assessment indices. Dichotomous variables were analyzed using risk ratios (RR) with 95% confidence intervals (CI). Data analysis was conducted using RevMan software (version 5.3).

Results

A total of forty-two randomized controlled trials were included in this meta-analysis. No significant differences were observed between the patient populations in the two groups. The analysis demonstrated that PRP resulted in lower VAS and WOMAC scores compared to HA. Additionally, PRP exhibited superior performance across other evaluation indices. Notably, the incidence of adverse events was higher in the PRP group; however, all reported complications were mild.

Conclusions

Based on the current evidence, intra-articular injection of PRP appears to be more effective than HA for the treatment of KOA, as indicated by the analysis of VAS, WOMAC scores, and other evaluation indices.

Trial registration

Retrospectively registered.

Peer Review reports

Background

Knee osteoarthritis (KOA), a prevalent joint disease, is emerging as one of the leading causes of global disability. The incidence and prevalence of KOA in the general population have been increasing over the years. From 2008 to 2014, approximately 32.5 million individuals, representing 14% of the American population, were affected by osteoarthritis. It is estimated that the global prevalence of symptomatic knee osteoarthritis, confirmed by X-ray or other imaging modalities, was around 3.8%. However, this prevalence increased to 10% or more in individuals aged 60 years and older. Hereditary vulnerabilities, elevated body mass, certain occupations, and traumatic injuries are likely to augment the risk of developing KOA, while age remains the predominant risk factor [1]. KOA is with high health burden on patients, their families, and the society [2]. It is emerging as a major challenge for global health systems, particularly in the context of global aging and rising obesity rates [3].

Arthritis patients typically experience joint pain, stiffness, and difficulty in physical activity [1]. The impact of osteoarthritis (OA) on joints is gradual and progressive, leading to the continuous degradation of articular cartilage, subchondral bone, and surrounding synovial structures [4]. Approximately 80% of OA patients suffer from movement limitations, and one in four are unable to perform essential daily activities [5]. KOA constitutes at least 80% of all OA cases, and more than 19% of adults aged 45 and older in the United States have KOA [6]. KOA results in knee pain and functional impairment due to cartilage degeneration and joint space narrowing [7, 8].

The treatment of KOA aims to reduce pain and improve patient function. Most treatments, particularly invasive procedures such as total knee arthroplasty, carry potential adverse effects. While total knee arthroplasty is a surgical option, it is complex and associated with risks. However, this procedure is complicated and carries risks. Consequently, non-surgical interventions, including intra-articular injections, oral nonsteroidal anti-inflammatory drugs (NSAIDs), and physical therapy, have been extensively investigated. For patients with KOA, intra-articular injections are widely utilized. The most commonly administered injections are HA and PRP [9].

HA is a natural glycosaminoglycan in synovial fluid that enhances joint lubrication and improves viscoelastic properties. HA mechanically lubricates the joints to protect them from loads and impacts, and to restore the fluidity synovial fluid [10]. Additionally, HA interacts with inflammatory mediators to inhibit pain transmission, promote cartilage growth and extracellular matrix protein synthesis, and reduce apoptosis in osteoarthritic cartilage [11,12,13,14]. Consequently, HA functions as a physiologically active molecule and is commonly used as intra-articular injections [15,16,17]. Studies have demonstrated that HA can facilitate functional improvements in knee, hip, and ankle osteoarthritis [18, 19].

PRP, an autologous blood product, contains growth factors that promote angiogenesis, modulate inflammation, and recruit stem cells and fibroblasts to the injured area [20]. A small volume of peripheral blood is centrifuged to concentrate the platelets in the plasma. The concentration quality depends on the centrifugation equipment, gravity, centrifugation time and initial blood sample [21, 22]. Platelet α-granules (TGF-β1, bFGF, EGF and so on) contain a large number of growth factors. These factors can promote tissue healing such as cartilage repair, vascular remodeling and help regulate inflammation, when concentrated and injected into the knee joint [23, 24]. PRP has become an increasingly common and promising treatment for KOA in clinical practice in recent years.

The effectiveness of each intra-articular injection is controversial. While HA injections are common treatment for KOA, with its potential to benefit patients, studies on the efficacy have been inconsistent. The effectiveness of PRP injections appears to be less favorable in severe KOA patients. Additionally, the relatively expensive cost and the safety performance are questioned. This review aims to compare the effectiveness of PRP and HA or KOA through a meta-analysis. The goal is to determine the optimal treatment protocol for this condition and identify more effective management strategies.

Methods

Search strategy

PubMed, Web of science and the Cochrane Central Register of Controlled Trials were searched for randomized controlled trials (RCTs). Medical Subject Headings (MeSH) were used including ‘knee osteoarthritis’, ‘hyaluronic acid’, ‘platelet-rich plasma’ and “intra-articular”.

Inclusion/exclusion criteria

Inclusion criteria primarily included: (1) clinical trial was randomly controlled, (2) random allocation was performed, (3) key data was recorded, including but not limited to age, sex, BMI, OA Grade, intervention, clinical outcomes including follow-up, VAS score, Western Ontario and McMaster Universities Arthritis Index (WOMAC score), International Knee Documentation Committee score (IKDC score), Knee injury and osteoarthritis outcome score (KOOS score), EuroQol visual analog scale (EQ-VAS), Lequesne index, satisfaction rate, Tegner activity scale and adverse events.

Exclusion criteria mainly including: (1) case report or review, (2) not involved with KOA treatment, (3) superfluous data were mixed in the comparison between PRP and HA, (4) without an English version. Disagreement was resolved through collective discussion.

Risks of bias assessment

Risks of bias were assessed according to the Cochrane Handbook for Systematic Reviews of Interventions. This included selection bias, performance bias, detection bias, attrition bias and reporting bias.

Potential effect modifiers and reasons for heterogeneity

Risk ratio (RR) and 95% confidence interval (CI) were calculated. Heterogeneity among the included studies was assessed using the I2 statistic at a significance level of α = 0.05. A fixed-effect model was used if there was no evidence of heterogeneity (I2 ≤ 50%), otherwise a random effect model was used. The result robustness was tested by sequentially eliminating each study one by one and studies with I2 > 50% were excluded. A funnel plot was used to assess the potential publication bias if more than ten studies were included.

Data extraction

The following data were extracted: number of patients, characteristics of patients (age, sex, BMI, OA Grade, intervention), clinical outcomes including follow-up, VAS score, WOMAC score (total score, pain score, stiffness score), EQ-VAS score, Lequesne index, satisfaction rate, IKDC score, KOOS score and adverse events. Data extraction was conducted by reviewing the full test, and all relevant figures and tables were extracted end interpreted.

Data synthesis

Rev Man software (version 5.3) was employed for data analysis.

Ethical statement

Ethical approval was not required for this mete-analysis as all data were obtained from published studies.

Results

Study selection

Three hundred and sixty-one articles were identified from database searches. One hundred and forty-three duplicates were removed. Strict inclusion and exclusion criteria were applied. After reviewing the abstracts, ninety-eight records were excluded. Following full-text assessment, an additional thirty-eight studies were excluded. Ultimately, thirty-seven articles met the primary inclusion criteria and were included in this meta-analysis. Additionally, we manually reviewed the reference lists of relevant reviews to identify any additional eligible studies, which resulted in the inclusion of five more RCTs. The selection process is illustrated in the PRISMA Flow Diagram (Fig. 1).

Fig. 1
figure 1

PRISMA flow diagram

Full size image

Study characteristics

The forty-two identified RCTs [16, 25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65] included one RCT [58] conducted on KOA patients following knee arthroscopic debridement. Basic information was summarized in Table 1. A total of 3660 KOA patients were enrolled across the 42 RCTs, with 1839 assigned to the PRP group and 1821 to the HA group. The sample size of the these RCTs ranged from 21 to 192 patients. The majority of studies had a follow-up period of at least six months, with the shortest follow-up being three months. The OA severity was assessed using Kellgren and Lawrence (KL), Ahlbäck or Shahriaree Classification System, including patients with grades 0–4.

Table 1 Basic information of all the identified RCTs
Full size table

One article [45] did not report the mean age of each group, while two others [34, 53] reported the mean age without the standard deviation (SD). The remaining 39 RCTs indicated that patients in the PRP group were, to some extent, younger than those in the HA group (p = 0.001, Supplementary Fig. 1). Subgroup was employed to reduce I2, and the result of 33 RCTs showed a similar trend (p = 0.03, Supplementary Fig. 1).

One article [56] did not provide the sex ratio and another [45] included only male patients The remaining 40 RCTs showed no statistic difference in sex ratio (p = 0.23, Supplementary Fig. 2).

Four articles [28, 42, 45, 65] did not report the mean BMI of each group, while another three [26, 34, 53] reported the mean BMI without the SD. The remaining 35 RCTs showed no statistic difference (p = 0.28, Supplementary Fig. 3). Subgroup was employed to reduce I2 based on the funnel plot. And the result of 34 RCTs showed a similar trend (p = 0.44, Supplementary Fig. 3).

Data on OA grade were available in 30 studies, with one [34] not reporting the SD. No statistic difference was found in the OA grade (p = 0.96, Supplementary Fig. 4). Subgroup was employed. The result of 28 RCTs showed a similar trend (p = 0.86, Supplementary Fig. 4).

Risk of bias

Random sequence generation was reported in all RCTs. In most studies, random sequence generation was achieved using computers or other technology. Sealed envelope technique was employed in 25 studies. Blinding of participants was not achieved in 8 studies, leading to a high risk of performance bias. Evaluators were not concealed of the grouping in 6 studies, resulting in a high risk of detection bias (blinding of outcome assessment). Attrition bias and reporting bias were assessed as low or unclear. The authors’ judgments regarding the risk of bias are summarized in Figs. 2 and 3.

Fig. 2
figure 2

Risks of bias graph

Full size image
Fig. 3
figure 3

Risks of bias summary

Full size image

VAS score

VAS score before intra-articular injection was available in 25 studies, with one [53] not reporting the SD. Data from 29 studies were used for analysis and no statistic difference was found (p = 0.05, Fig. 4). The VAS score at one to three months post-injection was available in 20 studies. The analysis revealed that patients in the PRP group had significantly lower VAS score (p < 0.01, Fig. 5). VAS score at 6 months post-injection was available in 18 studies and the PRP group again showed significantly lower VAS scores (p < 0.01, Fig. 6). One-year follow-up analysis, based on 12 studies, also demonstrated the same trend (p < 0.01, Fig. 7).

Fig. 4
figure 4

VAS score before treatment

Full size image
Fig. 5
figure 5

VAS score, 3 months after treatment

Full size image
Fig. 6
figure 6

VAS score, 6 months after treatment

Full size image
Fig. 7
figure 7

VAS score, 12 months after treatment

Full size image

WOMAC score

WOMAC total score

WOMAC total score before intra-articular injection was available in 28 studies. Analysis revealed no statistic difference (p = 0.1, Fig. 8). The follow-up at one to three months post-injection was available in 19 studies. Analysis showed that WOMAC total score was significantly lower in the PRP group (p < 0.01, Fig. 9). Same trend was observed at the six-month follow-up (23 RCTs, p < 0.01, Fig. 10) and one-year follow-up (16 RCTs, p < 0.01, Fig. 11).

Fig. 8
figure 8

WOMAC total score before treatment

Full size image
Fig. 9
figure 9

WOMAC total score, 3 months after treatment

Full size image
Fig. 10
figure 10

WOMAC total score, 6 months after treatment

Full size image
Fig. 11
figure 11

WOMAC total score, 12 months after treatment

Full size image

WOMAC pain score

WOMAC pain score before injection was available in 20 studies. Analysis revealed no statistic difference (p = 0.7, Fig. 12). The follow-up at one to three months post-injection was available in 11 studies. Analysis showed no statistic (p = 0.12, Fig. 13). The follow-up at six months post-injection was available in 14 studies, and analysis showed that WOMAC pain score was significantly lower in the PRP group (p < 0.01, Fig. 14). At one year follow-up, the PRP group continued to perform better (12 RCTs, p < 0.01, Fig. 15).

Fig. 12
figure 12

WOMAC pain score before treatment

Full size image
Fig. 13
figure 13

WOMAC pain score, 3 months after treatment

Full size image
Fig. 14
figure 14

WOMAC pain score, 6 months after treatment

Full size image
Fig. 15
figure 15

WOMAC pain score, 12 months after treatment

Full size image

WOMAC stiffness score

WOMAC stiffness score before injection was available in 18 studies. Analysis revealed that WOMAC stiffness score was lower in the HA group (p < 0.01, Fig. 16). Subgroup analysis was then employed and the result of 17 RCTs showed the same trend (p < 0.01). No statistic difference was found at the one to three-month follow-up (9 RCTs, p = 0.87, Fig. 17) or the six-month follow-up (12 RCTs, p = 0.61, Fig. 18). However, one year later, the situation reversed, with the WOMAC stiffness score being higher in the HA group (p < 0.01, Fig. 19).

Fig. 16
figure 16

WOMAC Stiffness score before treatment

Full size image
Fig. 17
figure 17

WOMAC Stiffness score, 3 months after treatment

Full size image
Fig. 18
figure 18

WOMAC Stiffness score, 6 months after treatment

Full size image
Fig. 19
figure 19

WOMAC Stiffness score, 12 months after treatment

Full size image

WOMAC function score

WOMAC function score before injection was available in 16 studies. Analysisrevealed no statistic difference (p = 0.17, Fig. 20). At the one to three-month, the function score was lower in the PRP group (9 RCTs, p < 0.01, Fig. 21). Same trend was fobserved at the six-month follow-up (11 RCTs, p < 0.01, Fig. 22) and one year (9 RCTs, p < 0.01, Fig. 23).

Fig. 20
figure 20

WOMAC Function score before treatment

Full size image
Fig. 21
figure 21

WOMAC Function score, 3 months after treatment

Full size image
Fig. 22
figure 22

WOMAC Function score, 6 months after treatment

Full size image
Fig. 23
figure 23

WOMAC Function score, 12 months after treatment

Full size image

IKDC score

Ten RCTs recorded the IKDC score before injection. No statistic difference was found (p = 0.82, Supplementary Fig. 7.1). After intra-articular injection, the result at any follow-up point consistently showed that the IKDC score was higher in the PRP group (Supplementary Fig. 7.2, 7.3, 7.4).

KOOS score

Only 6 RCTs mentioned the KOOS score. The analysis found no statistic difference between the two groups before injection, at 6 months, or at 12 months post-injection (Supplementary Fig. 8.1, 8.2, 8.3). However, at one to three-month follow-up, the KOOS score was higher in the PRP group (6 RCTs, p = 0.03, Supplementary Fig. 8.4).

EQ-VAS score

Only 4 RCTs reported the EQ-VAS score. The analysis found no statistic difference before the injection (p = 0.45, Supplementary Fig. 9.1). During the first six months of follow-up, the EQ-VAS score was higher in the PRP group (Supplementary Fig. 9.2,9.3). Follow-up data at one year post-injection were not available.

Lequesne index

Six RCTs reported the Lequesne index score before injection and no statistic difference was found (p = 0.78, Supplementary Fig. 10.1). No difference was observed at the one to three-month follow-up (p = 0.39, Supplementary Fig. 10.2). However, at the six-month and one-year follow-ups, the score was lower in the PRP group (p < 0.01, Supplementary Fig. 10.3, 10.4).

Satisfaction rate

Satisfaction rate was reported in only in 5 RCTs post-injection. Despite the small number of included studies, subgroup analysis was employed due to the extreme heterogeneity of one study [38]. In the remaining 4 studies, satisfaction rate was 81.2% in the PRP group and 78.92% in the HA group, with no statistic difference (p = 0.58, Supplementary Fig. 11). In Kon, E.’s study [38], satisfaction rate was obviously higher in the PRP group (82% vs 33%).

Adverse event

Adverse events, occurring after the injection or during the follow-up, were reported in 21 RCTs. The adverse event rate was higher in the PRP group (12.86% vs 9.27%, p = 0.02, Supplementary Fig. 12). However, all studies declared that the adverse events were mild and could be treated with oral medications or required no treatment.

Discussion

This meta-analysis was designed to compare the efficacy of the PRP and HA in the treatment of KOA within 12 months. The primary evaluating indicators included VAS score and WOMAC score (total score, pain score, stiffness score). Additional recorded measures were EQ-VAS score, Lequesne index, satisfaction rate, IKDC score, and adverse events. Statistical analysis indicated that PRP, in some respects, achieved better performance compared to HA.

Pain is typically the chief complaint of KOA patients. The analgesia effect assessment of injection is a crucial indicator. PRP achieves lower VAS score at all follow-up times within 12 months. Regarding another assessment criterion, WOMAC pain score, the analysis showed no statistic difference between the two groups during the first three months of follow-up. However, the WOMAC pain score was lower in the PRP group at six months and one year post injection. Last year, Khalid S and colleagues published a systematic review on a similar topic. They found that PRP treatment resulted in significant pain relief compared to HA injections, as evidenced by improved WOMAC pain and VAS scores, with the most significant improvement observed at 6 months [19]. Costa LAV’s review also reported that at 6-month follow-up, PRP was as effective as and, in some studies, more effective than other therapies in terms of pain, function, and stiffness [66]. These findings are consistent with our clinical experience, where patients often report better pain relief after using PRP.

Analysis of WOMAC stiffness and function score indicated that PRP performed better. The WOMAC stiffness score was lower in the HA group before injection, and showed no statistic difference three months post-injection. However, one year later, it was higher in the HA group, reversing initial trend. The WOMAC function score showed no statistic difference before injection but was lower in the PRP group in subsequent evaluations within 12 months.

The IKDC score was used to comprehensively evaluate the subjective symptoms and objective signs of KOA patients. KOOS score is a scale assessing the extent of knee injury and the effectiveness of treatment for osteoarthropathy. This scale evaluates pain, symptoms, the ability to perform activities of daily living, sports and recreation, and life quality related to the knee joint in KOA patients. EQ-VAS score was used to measure the general health of the patients. Lequesne index, initially developed in France, is a tool for assessing the severity and functional status of KOA patients. Though these scales were less used than the VAS score and WOMAC score in the included studies, data analysis showed better performance of PRP. Satisfaction rate was available only in 5 RCTS, with most showing no statistic difference between the two groups. However, in Kon, E.’s study [38], the satisfaction rate was significantly higher in the PRP group.

According to the review and analysis, the adverse event rate was higher in the PRP group. It was declared that the adverse events were all mild, which could be treated with oral medications or required no therapy. Both treatment methods were effective in improving pain and function over the study period and proven to be safe.

Though it was demonstrated that intra-articular injections (PRP and HA) were beneficial for pain treatment and function recovery in KOA patients, their effects tend to deteriorate over time and virtually disappear after the treatment [16, 26, 30]. Filardo’s study declared that the effect of PRP or HA remain virtually stable nearly two months [16]. However, Sdeek, M. found the opposite conclusion, indicating that the benefits could persist for nearly one and half a year. PRP was found to be even better, although a second injection was required by the third year [53].This meta-analysis compared the treatment effect of PRP and HA for KOA patients only within 12 months, with no longer follow-up data available for analysis. It appears that both PRP and HA lose their therapeutic effects 6 months after injection, particularly HA.

Biochemical changes in articular cartilage are the primary features of KOA. This degenerative disease leads to progressive joint cartilage destruction and has a very limited self-renewal and repair capability.

HA is widely present in human tissues, particularly in synovial fluid, where it lubricates joint to prevent cartilage mechanical degradation. The synthesis and degradation of HA are abnormal in KOA patients, leading to reduced HA concentration and molecular weight. This lesion decreases the bioviscolelasticity of synovial fluid and damages cartilage. HA also has the anti-inflammatory effects to relieve pain and reduce damage [39]. However, HA can only alleviate pain and inflammation; it cannot prevent the degeneration and destruction of articular cartilage. Moreover, its effect tend to deteriorate gradually within one to six months, and the patients may return to their pre-treatment status [67].

PRP injections, as an alternative to HA, can relieve pain in patients with mild KOA. PRP’s regenerative and anti-inflammatory effects are biochemically significant in cartilage repair. Macrophages and growth factors released by PRP can help to repair and regenerate articular cartilage, destroy necrotic tissue and reduce inflammatory response [22, 68]. In PRP, concentrated platelet-derived growth factors can stimulate chondrocyte proliferation and matrix secretion, and reduce the inflammatory factors expression and chondrocytes apoptosis [24]. PRP is also believed to stimulate the migration and proliferation of mesenchymal stem cells and their differentiation into joint chondrocytes, thereby ameliorating cartilage degeneration [39]. The controversial effects of PRP may be attributed to the different components of PRP used in various studies, particularly the concentration of white blood cells. Based on the concentration of white blood cells, PRP can be roughly categorized into two categories, leukocyte- and platelet-rich plasma (L-PRP) and pure platelet-rich plasma (P-PRP) [69]. The concentrations of IL-1βand TNF-α in PRP are closely related to the concentration of leukocyte, and they should perform adverse effects on chondrocytes [70, 71]. Therefore, the high concentration of leukocytes in L-PRP may adversely affect cartilage repair by releasing IL-1β and TNF-α, potentially counteracting the positive effects of growth factors on cartilage repair and ultimately impacting the efficacy of L-PRP in treating osteoarthritis.

Clinicians tend to administer regular, multiple injections to stabilize the effect of PRP or HA. A new treatment combining HA and PRP has been proposed. Xu,Z and his team found the combination of HA and PRP is more effective than PRP or HA alone in inhibiting synovial inflammation and can effectively improve pain and function while reducing adverse reactions [63]. Gao et al. found the combination did not differ significantly from PRP alone but performed better than HA monotherapy with a lower incidence of adverse events [72]. Michelangelo Palco and his group combined HA and PRP in the conservative treatment of KOA and hip osteoarthritis (HOA) [73, 74]. They found the combination showed better results in improving knee mobility and function, while for HOA, L-PRP demonstrated better results in reducing VAS score over time. Li, B. performed a network meta-analysis in 2020 and found the combination with best clinical efficacy in improving physical performance, stiffness, and total scores, while PRP alone was more effective in relieving pain [75]. However, another review published in 2022 did not confirm the superior therapeutic effect of such combination, but considered it safer than PRP injections alone, based on the incidence of adverse events [76]. Further research is needed to determine whether the combination of HA and PRP is a better treatment option.

Patients with mild, moderate or severe OA should respond differently to injections. However, in this review, the clinical outcomes were not analyzed according to the KL-grade. Consequently, this review was unable to assess the effects in KOA patients with different KL-grades. Furthermore, the published studies vary in terms of injection frequency, making direct comparisons challenging. This variability may explain the differences in outcome. Intra-articular injections, with strong placebo effect, made subjective evaluation indices such as pain, stiffness and satisfaction susceptible more susceptible to bias. Significant heterogeneity in some of the analyses suggests the evidence is mixed in certain areas. The reasons of this heterogeneity are diverse, primarily including variations in PRP preparation methods, differences in hyaluronic acid molecular weight and concentration, and differences in patient characteristics (age, BMI, OA grade) across studies. Khalid S [19] highlighted similar issues, noting the presence of high unexplained heterogeneity. ‘Caution is advised when interpreting the results, and additional studies are required to gain a more thorough and unbiased understanding of the topic’.

Conclusions

Current evidence suggests that intra-articular injection of PRP shows potential advantages compared to HA for the KOA patients, based on the analysis of VAS score, WOMAC score, IKDC score, KOOS score and EQ-VAS score. However, significant heterogeneity in some analyses indicates that the evidence is mixed in certain areas, and further studies are needed to confirm these findings across diverse patient populations and KOA grades. Future studies with larger study cohorts are warranted to validate our findings.

Data availability

The data used to support the findings of this study are included within the article.

Abbreviations

KOA:

Knee osteoarthritis

HA:

Hyaluronic acid

PRP:

Platelet-rich plasma

RCT:

Randomized controlled trial

VAS:

Visual analog scale

WOMAC:

Western Ontario and McMaster Universities Arthritis Index score

IKDC:

International Knee Documentation Committee score

KOOS:

Knee injury and osteoarthritis outcome score

EQ-VAS:

EuroQol visual analog scale

KL:

Kellgren and Lawrence

RR:

Risk ratio

CI:

Confidence interval

CI:

Confidence interval

SD:

Standard deviation

References

  1. Brophy RH, Fillingham YA. AAOS Clinical Practice Guideline Summary: Management of Osteoarthritis of the Knee (Nonarthroplasty), Third Edition. The Journal of the American Academy of Orthopaedic Surgeons. 2022;30(9):e721-e9.

  2. Hunter DJ, Schofield D, Callander E. The individual and socioeconomic impact of osteoarthritis. Nat Rev Rheumatol. 2014;10(7):437–41.

    Article  PubMed  Google Scholar 

  3. Cross M, Smith E, Hoy D, Nolte S, Ackerman I, Fransen M, et al. The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis. 2014;73(7):1323–30.

    Article  PubMed  Google Scholar 

  4. Hunter DJ, Bierma-Zeinstra S. Osteoarthritis. Lancet (London, England). 2019;393(10182):1745–59.

    Article  CAS  PubMed  Google Scholar 

  5. Hu X, Lai Z, Wang L. Effects of Taichi exercise on knee and ankle proprioception among individuals with knee osteoarthritis. Res Sports Med. 2020;28(2):268–78.

    Article  PubMed  Google Scholar 

  6. Wallace IJ, Worthington S, Felson DT, Jurmain RD, Wren KT, Maijanen H, et al. Knee osteoarthritis has doubled in prevalence since the mid-20th century. Proc Natl Acad Sci U S A. 2017;114(35):9332–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Phillips M, Vannabouathong C, Devji T, Patel R, Gomes Z, Patel A, et al. Differentiating factors of intra-articular injectables have a meaningful impact on knee osteoarthritis outcomes: a network meta-analysis. Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA. 2020;28(9):3031–9.

    Article  PubMed  Google Scholar 

  8. Kennedy MI, Whitney K, Evans T, LaPrade RF. Platelet-Rich Plasma and Cartilage Repair. Curr Rev Musculoskelet Med. 2018;11(4):573–82.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Alden KJ, Harris S, Hubbs B, Kot K, Istwan NB, Mason D. Micronized Dehydrated Human Amnion Chorion Membrane Injection in the Treatment of Knee Osteoarthritis-A Large Retrospective Case Series. J Knee Surg. 2021;34(8):841–5.

    Article  PubMed  Google Scholar 

  10. Trueba Davalillo CA, Trueba Vasavilbaso C, Navarrete Alvarez JM, Coronel Granado P, Garcia Jimenez OA, Gimeno Del Sol M, et al. Clinical efficacy of intra-articular injections in knee osteoarthritis: a prospective randomized study comparing hyaluronic acid and betamethasone. Open Access Rheumatol. 2015;7:9–18.

    PubMed  PubMed Central  Google Scholar 

  11. Yu CJ, Ko CJ, Hsieh CH, Chien CT, Huang LH, Lee CW, et al. Proteomic analysis of osteoarthritic chondrocyte reveals the hyaluronic acid-regulated proteins involved in chondroprotective effect under oxidative stress. J Proteomics. 2014;99:40–53.

    Article  CAS  PubMed  Google Scholar 

  12. Waddell DD, Kolomytkin OV, Dunn S, Marino AA. Hyaluronan suppresses IL-1beta-induced metalloproteinase activity from synovial tissue. Clin Orthop Relat Res. 2007;465:241–8.

    Article  PubMed  Google Scholar 

  13. Peng H, Zhou JL, Liu SQ, Hu QJ, Ming JH, Qiu B. Hyaluronic acid inhibits nitric oxide-induced apoptosis and dedifferentiation of articular chondrocytes in vitro. Inflamm Res. 2010;59(7):519–30.

    Article  CAS  PubMed  Google Scholar 

  14. Karna E, Miltyk W, Palka JA, Jarzabek K, Wolczynski S. Hyaluronic acid counteracts interleukin-1-induced inhibition of collagen biosynthesis in cultured human chondrocytes. Pharmacol Res. 2006;54(4):275–81.

    Article  CAS  PubMed  Google Scholar 

  15. Berenbaum F, Grifka J, Cazzaniga S, D’Amato M, Giacovelli G, Chevalier X, et al. A randomised, double-blind, controlled trial comparing two intra-articular hyaluronic acid preparations differing by their molecular weight in symptomatic knee osteoarthritis. Ann Rheum Dis. 2012;71(9):1454–60.

    Article  CAS  PubMed  Google Scholar 

  16. Filardo G, Di Matteo B, Di Martino A, Merli ML, Cenacchi A, Fornasari P, et al. Platelet-Rich Plasma Intra-articular Knee Injections Show No Superiority Versus Viscosupplementation: A Randomized Controlled Trial. Am J Sports Med. 2015;43(7):1575–82.

    Article  PubMed  Google Scholar 

  17. Juni P, Reichenbach S, Trelle S, Tschannen B, Wandel S, Jordi B, et al. Efficacy and safety of intraarticular hylan or hyaluronic acids for osteoarthritis of the knee: a randomized controlled trial. Arthritis Rheum. 2007;56(11):3610–9.

    Article  CAS  PubMed  Google Scholar 

  18. Bowman S, Awad ME, Hamrick MW, Hunter M, Fulzele S. Recent advances in hyaluronic acid based therapy for osteoarthritis. Clin Transl Med. 2018;7(1):6.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Khalid S, Ali A, Deepak F, Zulfiqar MS, Malik LU, Fouzan Z, et al. Comparative effectiveness of intra-articular therapies in knee osteoarthritis: a meta-analysis comparing platelet-rich plasma (PRP) with other treatment modalities. Ann Med Surg (Lond). 2024;86(1):361–72.

    Article  PubMed  Google Scholar 

  20. Spreafico A, Chellini F, Frediani B, Bernardini G, Niccolini S, Serchi T, et al. Biochemical investigation of the effects of human platelet releasates on human articular chondrocytes. J Cell Biochem. 2009;108(5):1153–65.

    Article  CAS  PubMed  Google Scholar 

  21. Kaushik A, Kumaran MS. Platelet-Rich Plasma: The Journey so Far ! Indian Dermatol Online J. 2020;11(5):685–92.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Bennell KL, Hunter DJ, Paterson KL. Platelet-Rich Plasma for the Management of Hip and Knee Osteoarthritis. Curr Rheumatol Rep. 2017;19(5):24.

    Article  PubMed  Google Scholar 

  23. Sundman EA, Cole BJ, Karas V, Della Valle C, Tetreault MW, Mohammed HO, et al. The anti-inflammatory and matrix restorative mechanisms of platelet-rich plasma in osteoarthritis. Am J Sports Med. 2014;42(1):35–41.

    Article  PubMed  Google Scholar 

  24. Le ADK, Enweze L, DeBaun MR, Dragoo JL. Current Clinical Recommendations for Use of Platelet-Rich Plasma. Curr Rev Musculoskelet Med. 2018;11(4):624–34.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Ahmad HS, Farrag SE, Okasha AE, Kadry AO, Ata TB, Monir AA, et al. Clinical outcomes are associated with changes in ultrasonographic structural appearance after platelet-rich plasma treatment for knee osteoarthritis. Int J Rheum Dis. 2018;21(5):960–6.

    Article  CAS  PubMed  Google Scholar 

  26. Arliani GG, Durigon TS, Pedroso JP, Ferreira GF, Oksman D, Oliveira VO. Intra-articular Infiltration of Platelet-Rich Plasma versus Hyaluronic Acid in Patients with Primary Knee Osteoarthritis: Preliminary Results from a Randomized Clinical Trial. Revista brasileira de ortopedia. 2022;57(3):402–8.

    PubMed  Google Scholar 

  27. Buendía-López D, Medina-Quirós M, Fernández-Villacañas MM. Clinical and radiographic comparison of a single LP-PRP injection, a single hyaluronic acid injection and daily NSAID administration with a 52-week follow-up: a randomized controlled trial. Journal of orthopaedics and traumatology : official journal of the Italian Society of Orthopaedics and Traumatology. 2018;19(1):3.

    Article  PubMed  Google Scholar 

  28. Cerza F, Carnì S, Carcangiu A, Di Vavo I, Schiavilla V, Pecora A, et al. Comparison between hyaluronic acid and platelet-rich plasma, intra-articular infiltration in the treatment of gonarthrosis. Am J Sports Med. 2012;40(12):2822–7.

    Article  PubMed  Google Scholar 

  29. Cole BJ, Karas V, Hussey K, Pilz K, Fortier LA. Hyaluronic Acid Versus Platelet-Rich Plasma: A Prospective, Double-Blind Randomized Controlled Trial Comparing Clinical Outcomes and Effects on Intra-articular Biology for the Treatment of Knee Osteoarthritis. Am J Sports Med. 2017;45(2):339–46.

    Article  PubMed  Google Scholar 

  30. Di Martino A, Di Matteo B, Papio T, Tentoni F, Selleri F, Cenacchi A, et al. Platelet-Rich Plasma Versus Hyaluronic Acid Injections for the Treatment of Knee Osteoarthritis: Results at 5 Years of a Double-Blind, Randomized Controlled Trial. Am J Sports Med. 2019;47(2):347–54.

    Article  PubMed  Google Scholar 

  31. Dong C, Zhao C, Wang F. Clinical benefit of high tibial osteotomy combined with the intervention of platelet-rich plasma for severe knee osteoarthritis. J Orthop Surg Res. 2022;17(1):405.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Dulic O, Rasovic P, Lalic I, Kecojevic V, Gavrilovic G, Abazovic D, et al. Bone marrow aspirate concentrate versus platelet rich plasma or hyaluronic acid for the treatment of knee osteoarthritis. Medicina (Kaunas, Lithuania). 2021;57(11). https://doiorg.publicaciones.saludcastillayleon.es/10.3390/medicina57111193.

  33. Duymus TM, Mutlu S, Dernek B, Komur B, Aydogmus S, Kesiktas FN. Choice of intra-articular injection in treatment of knee osteoarthritis: platelet-rich plasma, hyaluronic acid or ozone options. Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA. 2017;25(2):485–92.

    Article  PubMed  Google Scholar 

  34. Filardo G, Kon E, Di Martino A, Di Matteo B, Merli ML, Cenacchi A, et al. Platelet-rich plasma vs hyaluronic acid to treat knee degenerative pathology: study design and preliminary results of a randomized controlled trial. BMC Musculoskelet Disord. 2012;13:229.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Gormeli G, Gormeli CA, Ataoglu B, Colak C, Aslanturk O, Ertem K. Multiple PRP injections are more effective than single injections and hyaluronic acid in knees with early osteoarthritis: a randomized, double-blind, placebo-controlled trial. Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA. 2017;25(3):958–65.

    Article  PubMed  Google Scholar 

  36. Huang Y, Liu X, Xu X, Liu J. Intra-articular injections of platelet-rich plasma, hyaluronic acid or corticosteroids for knee osteoarthritis : A prospective randomized controlled study. Der Orthopade. 2019;48(3):239–47.

    Article  PubMed  Google Scholar 

  37. Kesiktas FN, Dernek B, Sen EI, Albayrak HN, Aydin T, Yildiz M. Comparison of the short-term results of single-dose intra-articular peptide with hyaluronic acid and platelet-rich plasma injections in knee osteoarthritis: a randomized study. Clin Rheumatol. 2020;39(10):3057–64.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Kon E, Mandelbaum B, Buda R, Filardo G, Delcogliano M, Timoncini A, et al. Platelet-rich plasma intra-articular injection versus hyaluronic acid viscosupplementation as treatments for cartilage pathology: from early degeneration to osteoarthritis. Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association. 2011;27(11):1490–501.

    Article  Google Scholar 

  39. Küçükakkaş O, Aydin T, Yurdakul OV. Evaluation of the effect of intra-articular platelet-rich plasma and hyaluronic acid injections on femoral cartilage thickness in chronic knee osteoarthritis. Acta Orthop Belg. 2022;88(4):811–9.

    Article  PubMed  Google Scholar 

  40. Lana JF, Weglein A, Sampson SE, Vicente EF, Huber SC, Souza CV, et al. Randomized controlled trial comparing hyaluronic acid, platelet-rich plasma and the combination of both in the treatment of mild and moderate osteoarthritis of the knee. Journal of stem cells & regenerative medicine. 2016;12(2):69–78.

    Article  Google Scholar 

  41. Lin KY, Yang CC, Hsu CJ, Yeh ML, Renn JH. Intra-articular Injection of Platelet-Rich Plasma Is Superior to Hyaluronic Acid or Saline Solution in the Treatment of Mild to Moderate Knee Osteoarthritis: A Randomized, Double-Blind, Triple-Parallel, Placebo-Controlled Clinical Trial. Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association. 2019;35(1):106–17.

    Article  Google Scholar 

  42. Lisi C, Perotti C, Scudeller L, Sammarchi L, Dametti F, Musella V, et al. Treatment of knee osteoarthritis: platelet-derived growth factors vs. hyaluronic acid. A randomized controlled trial. Clinical rehabilitation. 2018;32(3):330–9.

    Article  PubMed  Google Scholar 

  43. Louis ML, Magalon J, Jouve E, Bornet CE, Mattei JC, Chagnaud C, et al. Growth Factors Levels Determine Efficacy of Platelets Rich Plasma Injection in Knee Osteoarthritis: A Randomized Double Blind Noninferiority Trial Compared With Viscosupplementation. Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association. 2018;34(5):1530–40.e2.

    Article  Google Scholar 

  44. Montañez-Heredia E, Irízar S, Huertas PJ, Otero E, Del Valle M, Prat I, et al. Intra-articular injections of platelet-rich plasma versus hyaluronic acid in the treatment of osteoarthritic knee pain: a randomized clinical trial in the context of the Spanish national health care system. Int J Mol Sci. 2016;17(7). https://doiorg.publicaciones.saludcastillayleon.es/10.3390/ijms17071064.

  45. Papalia R, Zampogna B, Russo F, Vasta S, Tirindelli MC, Nobile C, et al. Comparing hybrid hyaluronic acid with PRP in end career athletes with degenerative cartilage lesions of the knee. J Biol Regul Homeost Agents. 2016;30(4 Suppl 1):17–23.

    CAS  PubMed  Google Scholar 

  46. Park YB, Kim JH, Ha CW, Lee DH. Clinical Efficacy of Platelet-Rich Plasma Injection and Its Association With Growth Factors in the Treatment of Mild to Moderate Knee Osteoarthritis: A Randomized Double-Blind Controlled Clinical Trial As Compared With Hyaluronic Acid. Am J Sports Med. 2021;49(2):487–96.

    Article  PubMed  Google Scholar 

  47. Paterson KL, Nicholls M, Bennell KL, Bates D. Intra-articular injection of photo-activated platelet-rich plasma in patients with knee osteoarthritis: a double-blind, randomized controlled pilot study. BMC Musculoskelet Disord. 2016;17:67.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Raeissadat SA, Ghazi Hosseini P, Bahrami MH, Salman Roghani R, Fathi M, Gharooee Ahangar A, et al. The comparison effects of intra-articular injection of Platelet Rich Plasma (PRP), Plasma Rich in Growth Factor (PRGF), Hyaluronic Acid (HA), and ozone in knee osteoarthritis; a one year randomized clinical trial. BMC Musculoskelet Disord. 2021;22(1):134.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Raeissadat SA, Rayegani SM, Ahangar AG, Abadi PH, Mojgani P, Ahangar OG. Efficacy of Intra-articular Injection of a Newly Developed Plasma Rich in Growth Factor (PRGF) Versus Hyaluronic Acid on Pain and Function of Patients with Knee Osteoarthritis: A Single-Blinded Randomized Clinical Trial. Clinical medicine insights Arthritis and musculoskeletal disorders. 2017;10:1179544117733452.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Raeissadat SA, Rayegani SM, Hassanabadi H, Fathi M, Ghorbani E, Babaee M, et al. Knee Osteoarthritis Injection Choices: Platelet- Rich Plasma (PRP) Versus Hyaluronic Acid (A one-year randomized clinical trial). Clinical medicine insights Arthritis and musculoskeletal disorders. 2015;8:1–8.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Sánchez M, Fiz N, Azofra J, Usabiaga J, Aduriz Recalde E, Garcia Gutierrez A, et al. A randomized clinical trial evaluating plasma rich in growth factors (PRGF-Endoret) versus hyaluronic acid in the short-term treatment of symptomatic knee osteoarthritis. Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association. 2012;28(8):1070–8.

    Article  Google Scholar 

  52. Say F, Gurler D, Yener K, Bulbul M, Malkoc M. Platelet-rich plasma injection is more effective than hyaluronic acid in the treatment of knee osteoarthritis. Acta Chir Orthop Traumatol Cech. 2013;80(4):278–83.

    Article  CAS  PubMed  Google Scholar 

  53. Sdeek M, Sabry D, El-Sdeek H, Darweash A. Intra-articular injection of Platelet rich plasma versus Hyaluronic acid for moderate knee osteoarthritis. A prospective, double-blind randomized controlled trial on 189 patients with follow-up for three years. Acta orthopaedica Belgica. 2021;87(4):729–34.

    Article  PubMed  Google Scholar 

  54. Spaková T, Rosocha J, Lacko M, Harvanová D, Gharaibeh A. Treatment of knee joint osteoarthritis with autologous platelet-rich plasma in comparison with hyaluronic acid. Am J Phys Med Rehabil. 2012;91(5):411–7.

    Article  PubMed  Google Scholar 

  55. Su K, Bai Y, Wang J, Zhang H, Liu H, Ma S. Comparison of hyaluronic acid and PRP intra-articular injection with combined intra-articular and intraosseous PRP injections to treat patients with knee osteoarthritis. Clin Rheumatol. 2018;37(5):1341–50.

    Article  PubMed  Google Scholar 

  56. Szwedowski D, Mobasheri A, Moniuszko A, Zabrzyński J, Jeka S. Intra-articular injection of platelet-rich plasma is more effective than hyaluronic acid or steroid injection in the treatment of mild to moderate knee osteoarthritis: a prospective, randomized, triple-parallel clinical trial. Biomedicines. 2022;10(5). https://doiorg.publicaciones.saludcastillayleon.es/10.3390/biomedicines10050991.

  57. Tavassoli M, Janmohammadi N, Hosseini A, Khafri S, Esmaeilnejad-Ganji SM. Single- and double-dose of platelet-rich plasma versus hyaluronic acid for treatment of knee osteoarthritis: A randomized controlled trial. World journal of orthopedics. 2019;10(9):310–26.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Trueba Vasavilbaso C, Rosas Bello CD, Medina Lopez E, Coronel Granado MP, Navarrete Alvarez JM, Trueba Davalillo CA, et al. Benefits of different postoperative treatments in patients undergoing knee arthroscopic debridement. Open Access Rheumatol. 2017;9:171–9.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Tschopp M, Pfirrmann CWA, Fucentese SF, Brunner F, Catanzaro S, Kuhne N, et al. A randomized trial of intra-articular injection therapy for knee osteoarthritis. Invest Radiol. 2023;58(5):355–62.

    Article  CAS  PubMed  Google Scholar 

  60. Vaquerizo V, Plasencia M, Arribas I, Seijas R, Padilla S, Orive G, et al. Comparison of intra-articular injections of plasma rich in growth factors (PRGF-Endoret) versus Durolane hyaluronic acid in the treatment of patients with symptomatic osteoarthritis: a randomized controlled trial. Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association. 2013;29(10):1635–43.

    Article  Google Scholar 

  61. Wang YC, Lee CL, Chen YJ, Tien YC, Lin SY, Chen CH, et al. Comparing the efficacy of intra-articular single platelet-rich plasma (PRP) versus novel crosslinked hyaluronic acid for early-stage knee osteoarthritis: a prospective, double-blind, randomized controlled trial. Medicina (Kaunas, Lithuania). 2022;58(8). https://doiorg.publicaciones.saludcastillayleon.es/10.3390/medicina58081028.

  62. Wang Z, Wang R, Xiang S, Gu Y, Xu T, Jin H, et al. Assessment of the effectiveness and satisfaction of platelet-rich plasma compared with hyaluronic acid in knee osteoarthritis at minimum 7-year follow-up: A post hoc analysis of a randomized controlled trial. Frontiers in bioengineering and biotechnology. 2022;10:1062371.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Xu Z, He Z, Shu L, Li X, Ma M, Ye C. Intra-Articular Platelet-Rich Plasma Combined With Hyaluronic Acid Injection for Knee Osteoarthritis Is Superior to Platelet-Rich Plasma or Hyaluronic Acid Alone in Inhibiting Inflammation and Improving Pain and Function. Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association. 2021;37(3):903–15.

    Article  Google Scholar 

  64. Yaradilmis YU, Demirkale I, Safa Tagral A, Caner Okkaoglu M, Ates A, Altay M. Comparison of two platelet rich plasma formulations with viscosupplementation in treatment of moderate grade gonarthrosis: A prospective randomized controlled study. J Orthop. 2020;20:240–6.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Yu W, Xu P, Huang G, Liu L. Clinical therapy of hyaluronic acid combined with platelet-rich plasma for the treatment of knee osteoarthritis. Exp Ther Med. 2018;16(3):2119–25.

    PubMed  PubMed Central  Google Scholar 

  66. Costa LAV, Lenza M, Irrgang JJ, Fu FH, Ferretti M. How Does Platelet-Rich Plasma Compare Clinically to Other Therapies in the Treatment of Knee Osteoarthritis? A Systematic Review and Meta-analysis. Am J Sports Med. 2023;51(4):1074–86.

    Article  PubMed  Google Scholar 

  67. Cerza F, Carni S, Carcangiu A, Di Vavo I, Schiavilla V, Pecora A, et al. Comparison between hyaluronic acid and platelet-rich plasma, intra-articular infiltration in the treatment of gonarthrosis. Am J Sports Med. 2012;40(12):2822–7.

    Article  PubMed  Google Scholar 

  68. Zhao J, Huang H, Liang G, Zeng LF, Yang W, Liu J. Effects and safety of the combination of platelet-rich plasma (PRP) and hyaluronic acid (HA) in the treatment of knee osteoarthritis: a systematic review and meta-analysis. BMC Musculoskelet Disord. 2020;21(1):224.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Dohan Ehrenfest DM, Andia I, Zumstein MA, Zhang CQ, Pinto NR, Bielecki T. Classification of platelet concentrates (Platelet-Rich Plasma-PRP, Platelet-Rich Fibrin-PRF) for topical and infiltrative use in orthopedic and sports medicine: current consensus, clinical implications and perspectives. Muscles, ligaments and tendons journal. 2014;4(1):3–9.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Burguera EF, Vela-Anero A, Magalhaes J, Meijide-Failde R, Blanco FJ. Effect of hydrogen sulfide sources on inflammation and catabolic markers on interleukin 1beta-stimulated human articular chondrocytes. Osteoarthritis Cartilage. 2014;22(7):1026–35.

    Article  CAS  PubMed  Google Scholar 

  71. Sundman EA, Cole BJ, Fortier LA. Growth factor and catabolic cytokine concentrations are influenced by the cellular composition of platelet-rich plasma. Am J Sports Med. 2011;39(10):2135–40.

    Article  PubMed  Google Scholar 

  72. Gao J, Ma Y, Tang J, Zhang J, Zuo J. Efficacy and safety of platelet-rich plasma and hyaluronic acid combination therapy for knee osteoarthritis: a systematic review and meta-analysis. Arch Orthop Trauma Surg. 2024;144(9):3947–67.

    Article  PubMed  Google Scholar 

  73. Palco M, Fenga D, Basile GC, Rizzo P, Cavalieri B, Leonetti D, et al. Platelet-rich plasma combined with hyaluronic acid versus leucocyte and platelet-rich plasma in the conservative treatment of knee osteoarthritis. a retrospective study. Medicina (Kaunas, Lithuania). 2021;57(3). https://doiorg.publicaciones.saludcastillayleon.es/10.3390/medicina57030232.

  74. Palco M, Rizzo P, Basile GC, Alito A, Bruschetta D, Accorinti M, et al. Short- and midterm comparison of platelet-rich plasma with hyaluronic acid versus leucocyte and platelet-rich plasma on pain and function to treat hip osteoarthritis. a retrospective study. Gels. 2021;7(4). https://doiorg.publicaciones.saludcastillayleon.es/10.3390/gels7040222.

  75. Li B, Zhang Y, Bi L. Comparative efficacy of treatments for patients with knee osteoarthritis: a network meta-analysis. Eur J Med Res. 2020;25(1):27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Zhang Q, Liu T, Gu Y, Gao Y, Ni J. Efficacy and safety of platelet-rich plasma combined with hyaluronic acid versus platelet-rich plasma alone for knee osteoarthritis: a systematic review and meta-analysis. J Orthop Surg Res. 2022;17(1):499.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

None.

Funding

Young Innovative Talents Support Program of Zhejiang Medical and Health Science and Technology Project (grant number: 2022499572).

Young Innovative Talents Support Program of Zhejiang Chinese Medicine Science Technology Project (grant number:2024025437,2024ZR152).

Hangzhou Biomedical and Health Industry Development Support Project (2023WJC063).

Author information

Author notes

  1. Hong Xu and Weifeng Shi contributed equally to this work.

Authors and Affiliations

  1. Department of Orthopaedics, Hangzhou Xiaoshan Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang Province, China

    Hong Xu, Weifeng Shi, Hong Liu, Shasha Chai, Jindi Xu, Qingyu Tu, Jinwei Xu & Wei Zhuang

  2. Zhejiang Chinese Medical University, Zhejiang Province, China

    Jindi Xu & Qingyu Tu

Authors
  1. Hong Xu
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Weifeng Shi
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Hong Liu
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Shasha Chai
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Jindi Xu
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Qingyu Tu
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Jinwei Xu
    View author publications

    You can also search for this author inPubMed Google Scholar

  8. Wei Zhuang
    View author publications

    You can also search for this author inPubMed Google Scholar

Contributions

HX, WS, JX and WZ had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: HX and WS. Acquisition, analysis, or interpretation of data: HX, WS and HL Drafting of the manuscript: HX and WS. Critical revision of the manuscript for important intellectual content: All authors.

Corresponding authors

Correspondence to Jinwei Xu or Wei Zhuang.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

I confirm that this original manuscript has been read and approved by all named authors for publication, and that the work is not under consideration in any other journal.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xu, H., Shi, W., Liu, H. et al. Comparison of hyaluronic acid and platelet-rich plasma in knee osteoarthritis: a systematic review. BMC Musculoskelet Disord 26, 236 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12891-025-08474-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12891-025-08474-6

Keywords

BMC Musculoskeletal Disorders

ISSN: 1471-2474

Contact us