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Review Article
2024
:3;
100248
doi:
10.1016/j.jorep.2023.100248

Navigating the treatment landscape: Choosing between platelet-rich plasma (PRP) and hyaluronic acid (HA) for knee osteoarthritis management – A narrative review

, ,
Department of Pharmacy Practice, Teerthanker Mahaveer College of Pharmacy, Teerthanker Mahaveer University, Moradabad, Uttar Pradesh, India

∗Corresponding author: Abhijith Murali. abhijithmurali69@gmail.com

Received: , Accepted: ,
The Authors
Disclaimer:
This article was originally published by Reed Elsevier India Pvt. Ltd. and was migrated to Scientific Scholar after the change of Publisher.

Abstract

Abstract

Knee osteoarthritis (KOA) is one of the most prevalent forms of OA and causes pain, joint instability, and functional limitations. The management of KOA involves a wide range of therapies, including surgical interventions, medications, exercise prescription, physical agent modalities, and patient education. While knee arthroplasty is an effective treatment for severe KOA, it is not suitable for younger patients or those with non-end-stage disease due to its cost and potential complications. Pharmacological therapy options for KOA include analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), and corticosteroid injections, but they can have significant adverse effects. In recent years, platelet-rich plasma (PRP) and hyaluronic acid (HA) have emerged as promising treatments for KOA.

We conducted a literature review to explore the effectiveness of both PRP and HA in treating knee osteoarthritis. We compared some studies to know their effectiveness in patients, when given alone and with combination.

PRP injections have consistently outperformed HA injections in treating knee osteoarthritis, offering pain relief and improved function, but the potential benefits of combining PRP with HA remain inconclusive, necessitating further research to ascertain their effectiveness and safety in combination treatment. This narrative review serves as a guide to evidence-based treatment.

Abstract

Highlights

•Knee Osteoarthritis (KOA) significantly impacts movement and quality of life in the elderly population.•Platelet-Rich Plasma (PRP) and Hyaluronic Acid (HA) as promising treatments for KOA.•PRP shown greater effectiveness than HA in reducing pain and improving function in KOA patients.

Keywords

Knee osteoarthritis
Platelet-rich plasma (PRP)
Hyaluronic acid (HA)
Growth factors
Cartilage repair
Intra-articular injections
Viscosupplementation
1

1 Introduction

OA is a chronic condition which affects the bones and joints that significantly impacts mobility and quality of life, particularly among the elderly population.1–4 It is characterized by cartilage loss, subchondral bone changes, and joint inflammation. As one of the most common causes of disability worldwide, OA's prevalence is projected to rise due to factors such as increased lifespans, the obesity epidemic, and physical activity trends.5,6 Knee osteoarthritis (KOA) is particularly prevalent and can lead to pain, joint instability, and functional limitations.7 Various approaches, including surgical interventions, medications, exercise, and non-pharmacological therapies, are employed for KOA management.8 Platelet-rich plasma (PRP) and hyaluronic acid (HA) injections have gained attention as potential treatments, either individually or in combination, to alleviate symptoms and promote tissue repair.9,10

2

2 Methods

The literature review was conducted through Pubmed. “Knee osteoarthritis”, “treatment for knee osteoarthritis”, “platelet rich plasma”, “use of PRP for treatment of knee osteoarthritis”, “use of Hyaluronic Acid (HA) for treatment of knee osteoarthritis” and “combination of PRP and HA for treating knee osteoarthritis” were some of the search phrases used for the review. Based on the study question, which compared Platelet-Rich Plasma (PRP) and Hyaluronic Acid (HA) for managing knee osteoarthritis, published from the earliest date feasible through 2023, these search phrases were chosen. The research question focused on the qualities connected to all possible therapies for knee osteoarthritis. This made it possible to conduct an extensive review of the relevant literature that has so far been published. Following the initial search, the papers were assessed for their applicability to the study issue. After excluding publications that were not pertinent to the study, the remaining articles underwent a second evaluation to determine their calibre and relevancy. The studies that offered insights into the efficient treatment of knee osteoarthritis were those that were chosen for inclusion in the study.

3

3 Discussion

3.1

3.1 Osteoarthritis

Osteoarthritis (OA) isa multifaceted chronic bone and joint disease that affects people's movement and quality of life and is one of the main causes of disability among the elderly.1–4 It is characterized by articular cartilage loss, subchondral bone alterations, and nonbacterial synovitis. Osteoarthritis (OA) ranks as the fourth most frequent global cause of years lived with a disability. The expense along with prevalence of OA are predicted to increase further as a result of longer lifespans, the obesity epidemic, and the resulting drive to exercise, frequently through sports.5,6 The joint that OA affects most frequently is the knee.11 The second largest joint that is most frequently affected by osteoarthritis (OA) is the hip joint.12 In the population, up to 40 % of people over 65 may suffer from symptomatic osteoarthritis in their knee or hip.13,14

3.2

3.2 Knee osteoarthritis

Knee osteoarthritis (KOA) is among the major and most frequent causes of disabilities and a need of dependency in the elderly population, a frequent progressive degenerative musculoskeletal illness.15,16 The weight of this disease on societies and the detrimental consequences it has on an individual's well-being and quality of life which include loss of employment, premature retirement, and arthroplasty.17 It is distinguished by subchondral bone hyperplasia, cartilage degeneration, and cartilage exfoliation, and it causes knee discomfort, joint instability, as well as functional limitations.7 3.8 % is the estimated global prevalence of symptomatic knee OA.18 Over twenty percent of people over 45 are affected.19 When non-operative treatments fail, this frequently results in arthroplasty.20Fig. 1 shows the X-ray of a severe bilateral knee osteoarthritis.21

X-ray of a severe bilateral knee osteoarthritis.
Fig. 1 X-ray of a severe bilateral knee osteoarthritis.
3.3

3.3 Approaches for management of knee osteoarthritis

There are numerous potential treatments for this ailment, some of them involving surgical management, prescription drugs, physical activity, traditional and novel physical therapy methods.8 While arthroplasty is a successful final treatment for severe KOA, it is not recommended for younger patients or those with non-end-stage illness. However, it is pricey and exposes patients to the possibility of major postoperative problems.22,23 There isn't a one well-known or widely accepted drug that can halt the development of KOA, hence patients frequently undergo numerous therapies to halt the progress.24,25

According to a definition put forth by the American College of Rheumatology (ACR), conservative approach encompasses both drug- and non-drug-based treatment.26 General and muscular exercise are also non-drug treatments, but they frequently rely largely on compliance from patients and are challenging to manage.26 The three main pharmaceutical therapies are analgesics, NSAIDs, and corticosteroid injections.27 The mainstays of pharmacological therapy for KOA are shown in Fig. 2.28

Mainstay of pharmacological therapy for Knee Osteoarthritis.
Fig. 2 Mainstay of pharmacological therapy for Knee Osteoarthritis.

However, there are frequently negative effects associated with the use of NSAIDs and analgesics.29 Although the aforementioned pharmacological regimens are somewhat effective, they also have significant adverse effects.27,30

A significant amount of research has been done over the past 20 years to develop non-surgical or less invasive treatments for OA symptoms or to halt the disease's progression. Regarding the common management strategies, though, no agreement has yet been established.31–35 Intra-articular injections are one of the minimally invasive techniques advised for managing knee OA. Corticosteroids, dextrose, hyaluronic acid (HA), plasma derivatives including platelet-rich plasma (PRP) and plasma rich in growth factors (PRGF), as well as ozone, have all been used for these injections.9,10 Ozone provides effective treatment due to its visco-induction properties of increasing joint lubrication.36,37

3.4

3.4 Harnessing platelet – rich plasma (PRP) for the management of knee osteoarthritis

Muscle and injuries to the musculoskeletal system are to blame for the worldwide decline in health-related quality of life.38 Clinical and social issues arise since the current studies on the treatment of such injuries have not shown any encouraging results. In their research, scientists are focusing on the biological techniques for repairing injured tissues.39 When treating injured tissues, therapies that promote rapid repair of tissues and functional healing as well as biologically based therapeutic modalities are addressed. PRP is a significant step in this direction.40 For OA patients wishing to improve the state of the joint, platelet-rich plasma (PRP), a form of biological treatment, has more recently come to the fore.20,41,42

PRP is created by centrifuging autologous blood, which roughly tenfold increases the platelet content. It has roughly 1500 proteins which, when triggered, can release macrophages along with growth factors that are beneficial for eliminating necrotic tissue, minimising inflammation, and regenerating and repairing articular cartilage.43–45 It is a kind of autologous blood extract with a significant platelet concentration. It is thought to contain a range of growth factors along with other bioactive compounds that regulate abnormal inflammatory processes and so promote tissue healing.46

Here, vascular endothelial growth factor, epidermal growth factor, and platelet-derived growth factor are all present in high amounts. These growth factors function to mobilise local stem cells as well as fibroblasts to areas of damage or injury, stimulate local angiogenesis, control inflammation, block breakdown enzymes (catabolic) and cytokines, and encourage healthy neighbouring cells to produce more growth factors.47–49 Therefore, it is believed that applying PRP locally and directly to the site of a cartilage damage will promote the body's own healing process and accelerate the development of cartilage repair tissue.20,50,51 Regardless of the encouraging preclinical results and numerous clinical applications, The benefits and possible risks of PRP injection for knee osteoarthritis continue to be crucial issues.

Large amounts of growth factors are present in platelets - granules and are then concentrated and given into the knee joint to aid in the control of inflammation and promote healing of the tissues, including cartilage restoration, bone and vascular remodelling, as well as participation in the process.20,52

PRP injection has been shown to be an effective treatment for knee OA in numerous research conducted internationally.53 PRP has been employed in numerous research in a variety of contexts, and obtained findings suggest that PRP might function as an anti-nociceptive and encourage cell proliferation.54 The supraphysiologic quantities of biological substances and growth factors found in platelet granules may also contribute to the therapeutic effects of PRP, which may be able to combat the catabolic conditions associated with OA, restore the joint's homeostasis, and ultimately encourage cartilage repair.53,55 The widespread use of intraarticular platelet-rich plasma for the treatment of osteoarthritis of the knee in clinical practise, however, is not well documented in the literature, much like what was discussed about the HA.56 Blood platelets were made to disperse out their granule elements, which led to the production of PRGF, biologic activators that are compatible with the body have been employed to get around this obstacle.57 PRGF is the end result of PRP; it is devoid of leukocytes and cytokines that induce inflammation and has only a specified quantity of cytokines as well as growth factors. In comparison to PRP, this makes PRGF more efficient and reduces its negative effects, such as swelling and pain.56

PRP has chondroprotective effects by boosting the synthesis of cartilage matrix and endogenous HA, which may alleviate pain and modify the OA process. It also has anti-nociceptive and anti-inflammatory effects.20,58,59

The best PRP dosage and frequency for treating knee OA, which can range from weekly to every three to four weeks with a single to numerous injections, are still up for debate.60–62

Autologous PRP has been used extensively to treat rotator cuff tendinopathy because there is little chance of immunological reactions and the spread of contagious infections.63 In the past, Lin et al.'s RCT study64 found that intraarticular administrations of leukocyte-poor PRP can offer patients with mild-to-moderate knee osteoarthritis clinically meaningful functional improvement for a minimum of a year.

Increasingly, platelet-rich therapies are utilised to treat injuries to musculoskeletal soft tissue which include tendinopathies and rips of the ligaments, muscles, and tendons. These treatments can be applied following reconstructive surgery or reconstruction as an augmentation therapy or as the primary mode of treatment. Platelet-rich therapies are made by centrifuging a certain amount of the individual's own blood and extracting the active, platelet-rich fraction. The wounded tissue is treated with the platelet-rich fraction, perhaps by injection. These treatments ought to improve tissue repair because numerous growth factors can be produced by platelets. It is necessary to evaluate whether this has clinical value.65

A straightforward, affordable alternative that offers an abundance of naturally existing, autologous growth factors which are derived from patients’ own blood, is platelet-rich plasma (PRP) which can be utilised to accelerate tissue regeneration.66,67 Researchers have looked into how GFs affect cartilage repair and found that they encourage cellular anabolism and regeneration of tissues.68–70 Apoptosis, the production of extracellular matrix, the regulation of angiogenesis, as well as inflammation are just a few of the biological processes that are thought to be significantly controlled by PRP.69 The research has shown the most effectiveness with intra-articular infiltrative therapy using PRP, with evidence of reduced pain and improved function in knee OA.64,70–73

Although the advantages of this approach over viscosupplementation are supported by some evidence in the current literature, no research investigations have been carried out to compare the effects over the long term. Based on promising in vitro findings that show the injection of platelet-derived growth stimulating factors together with other bioactive molecules could delay the onset of musculoskeletal degenerative disorders, such as tendinopathies and osteoarthritis (OA), interest in the use of blood-derived products has risen over the past ten years.55,74,75 Because it has the ability to alter the environment inside joints utilising biological agents, platelet-rich plasma (PRP) is used for the management of OA. This could reduce inflammatory discomfort and promote the anabolism of diverse tissues.44,76

The PRP is designed to offer a substantial amount of growth factors that facilitate cartilage recovery and remodelling in order to enhance clinical and structural outcomes.77 The clinical application of intra-articular PRP for osteoarthritis of the knee is controversial. Because the existing evidence is of low quality, PRP should not be used to treat knee OA, according to the American College of Rheumatology and Osteoarthritis Research Society International recommendations for treatment.30,78 Following intra-articular PRP injection, Previous studies have shown a clinical improvement in terms of pain sensation and standard of life, along with cartilage thickness, which can be determined by magnetic resonance imaging (MRI) or ultrasonography (USG), indicating its chondroprotective effect.79,80

PRP has grown in popularity because it releases local growth factors into the environment, enabling non-pharmaceutical and biologic repair-oriented recuperation. Additionally, it performs coagulation and homeostatic activities. It involves PLT, a substance rich in cytokines and growth factors necessary for bone mineralization and tissue repair.81 Additionally, it contains a large number of growth factors, many of which have protein or peptide structures and are crucial for the production of tissue matrix.82 PRP usage has recently emerged as a stand-alone therapy option.83 PRP has been demonstrated to be efficient in treating KOA in a number of studies.84–86 PRP injection is a straightforward, minimally invasive alternative to knee arthroplasty that delivers concentrated growth factors suitable for intra-articular injection.87

The regenerative, analgesic, anti-inflammatory, and antibacterial effects of PRP are hypothesised.88 Research has examined the use of PRP as an adjuvant for the healing of bones,89–91 cartilage healing, and chronic tendinopathy,92,93 and in conjunction with surgical treatments such rotator cuff repair,94 Achilles tendon repair,95 and the anterior cruciate ligament rebuilding.96–98 The foundation for this interest was created by in vitro as well as ex vivo studies. PRP has been shown to have beneficial effects, including the differentiation of pluripotent mesenchymal cells into cartilage by chondrogenic differentiation with expression of genes specific to cartilage, chondrocyte proliferation, improved extracellular matrix production, and suppression of catabolic processes.47,99–103 Despite being encouraging, two meta-analyses and qualitative evaluations could not support PRP's effectiveness in this situation.6,104,105 In reality, the American Academy of Orthopaedic Surgeons Clinical Practise Guidelines group came to the conclusion that they were unable to advise PRP in the management of symptomatic KO, either in favour of or against it. Leukocyte content in PRP has received particular focus. The production of catabolic pathways and inflammatory indicators like interleukin-1 and tumour necrosis factor-alpha has been demonstrated to increase in the presence of high quantities of WBC.106,107

Although PRP in orthopaedic and sports medicine has shown encouraging outcomes in multiple published research, its practical use and effectiveness are yet unknown. PRP lacks the optimum treatment for various phases of gonarthrosis and proper standardisation for the quantity or frequency of injections. Additionally, recently published meta-analyses and systematic reviews44,85,108,109 have looked at the impact of PRP for knee OA, but these studies produced contradictory findings.25,85 For instance, Kanchanatawan, W. et al.'s meta-analysis85 found insufficient evidence to support PRP's ability to improve WOMAC stiffness, pain, and function scores when compared to HA or a placebo in the management of knee OA. In comparison to HA, saline control, ozone, or corticosteroids, PRP showed significantly better results in the WOMAC pain and physical performance subscores, two more meta-analyses by Shen, L. et al.110 and Han, Y. et al.25 support this.

3.5

3.5 Harnessing hyaluronic acid (HA) for the management of knee osteoarthritis

HA stands for hyaluronic acid, a complex glycosaminoglycan made up of repeating disaccharide units that create a linear polymeric substance by combining, is disrupted by intra-articular cytokines that promote inflammation and proteinases in OA, resulting in HA with a considerably decreased molecular weight with a decrease in the viscoelasticity of synovial fluid.111,112 It is produced by chondrocytes as well as fibroblasts and oversees giving the knee joint its viscoelasticity and lubrication.113 The synovial fluid's viscoelastic properties are based on HA, which is present in joints.114 Articular cartilage deteriorates and the mechanical homeostasis within the joint is disturbed when HA loses its usual properties.115 A growing body of research has shown that HA can enhance joint functionality, reduce pain, and lower analgesic usage.116

There has been speculation that intra-articular HA injections may alleviate knee discomfort and functional impairment because the breakdown of hyaluronate in synovial fluid is a result of knee osteoarthritis. When it comes to treating knee OA, as a pharmacologic substitute, HA has been accepted by the FDA since 1997. Additionally, it was suggested to be an effective remedy for treating knee OA. in the American College of Rheumatology's guideline in 2000.117,118

The concentration of HA is lower than usual in the OA-affected joints. Exogenous HA makes synovial fluid more viscous and improves its capacity for shock absorption and lubrication. Additionally, it has been demonstrated to activate synovial areas' intrinsic HA synthesis by interacting to CD44 receptors.119 By restoring metabolic equilibrium, HA lessens the deterioration and discomfort of articular cartilage.120

An pricey and sometimes harmful single intra-articular HA injection did not reduce the joint's inflammatory process.121–123 When numerous injections are administered to patients, viscosupplementation appears to delay the requirement for a joint replacement procedure by up to 3–6 years in comparison to placebo, and the arthroplasty survivability is higher in the first five years of follow-up.124,125

3.6

3.6 Maximizing knee osteoarthritis treatment: exploring the superiority of PRP, HA, or their synergistic combination

Injections of hyaluronic acid (HA) as well as platelet-rich plasma (PRP) for treating knee osteoarthritis (KOA) were compared in a meta-analysis by Tang et al. (2020), and PRP injection into the joint was demonstrated to be more efficient than HA injection regarding quick functional recovery. The study also discovered that PRP injection provided more long-lasting pain alleviation and improved function than HA injection. Additionally, there was no appreciable distinction between both treatment modalities in terms of adverse events.126

At 6 and 12 months of follow-up, PRP injections in knee osteoarthritis were found to be more successful at reducing pain than HA injections, according to a different meta-analysis conducted by Zhang et al. (2018). According to the study, PRP injection is a viable treatment for KOA.116

PRP injection was reported to be more effective than HA therapy for KOA by Tan et al. (2021) considerably decreased early discomfort and enhanced function when compared to HA. The study demonstrated the effectiveness and safety of PRP for KOA and revealed no discernible difference in adverse events among the two groups.127

Another systematic review and meta-analysis by Zhang et al. (2022) concluded that PRP exhibited more benefits in the conservative management of KOA compared to HA, including decreased chronic pain, and enhanced knee joint performance. The study emphasized the comparable safety of PRP and HA treatments.128

According to Ayhan et al. (2014), PRP injections have demonstrated both safety and effectiveness in the treatment of osteoarthritis of the knee with no elevated possibility of side events. They emphasized other advantages of PRP therapy, such as the decrease in inflammatory markers and synovial fluid.35

Han et al. (2019) found that when PRP and HA injections were compared in the treatment of patients with knee osteoarthritis, PRP had a good effect on levels of pain and performance outcomes. The study discovered no discernible difference in the incidence of adverse events between Platelet-rich plasma and Hyaluronic Acid injections.25

According to Kanchanatawan et al. (2016), who conducted a study on the short-term outcomes of PRP injections for osteoarthritis of knee PRP was superior to HA and a placebo in terms of relieving symptoms, improving function, and enhancing quality of life for patients with mild-to-moderate KOA. For individuals who failed to respond to traditional therapy, they recommended PRP as an alternative option.85

In a meta-analysis of the effects of injections of PRP in knee and hip osteoarthritis, Dong et al. (2021) found that when compared to other intra-articular injections, intra-articular platelet-rich plasma injections were far more effective, especially in the short-term follow-up for pain relief and function improvement in knee osteoarthritis.129

The administration of platelet-rich plasma (PRP) and hyaluronic acid (HA) together improved both pain and function among individuals with chronic symptomatic knee degenerative alterations and osteoarthritis, according to Di Martino et al.'s double-blind randomized controlled trial, which was published in 2019.130

A study by Lana et al. (2016) compared PRP, HA, and their use in combination to treat mild & moderate knee osteoarthritis. They discovered that using PRP and HA together produced favourable outcomes for the development of functional capacity and pain alleviation.131 Similar to this, Saturveithan et al. (2016) performed a retrospective analysis and found that intra-articular administration of PRP and HA combined with functional advantages for patients with advanced stages of grade III along with grade IV knee osteoarthritis.132

Due to their various biological mechanisms, according to some studies, using PRP and HA in combination can be advantageous.132–143 According to Chen et al. (2014), the combination of HA and PRP improved cartilage regeneration by increasing chondrocyte proliferation and reducing inflammation.144 When PRP and HA were combined, Abate and Verna (2015) also found that it was effective and safe for treating knee osteoarthritis.145

It is important to keep in mind, nevertheless, that not all research have demonstrated that PRP and HA are superior to PRP alone. For instance, Zhang et al. (2022) found that PRP with HA supplementation and PRP alone showed no appreciable differences in terms of relieving pain and enhancing function in knee osteoarthritis patients.128 In a similar vein, Huang et al.'s clinical trial from 2022 discovered that both PRP in combination with Artz and PRP in combination with HYAJOINT Plus were efficient and secure for 6 months among patients with symptomatic knee osteoarthritis, but there was no superior combination.146

4

4 Conclusion

Based on the studies cited, it can be said that PRP injections into joints has always surpassed HA injection in treating knee osteoarthritis. PRP injections have shown advantages such as pain relief, enhanced function, thereby providing an appealing option for knee osteoarthritis patients' treatment. Regarding the possible benefits of combining PRP with HA, there is, however, still conflicting data for treating knee osteoarthritis. To fully comprehend the effectiveness and safety of platelet-rich plasma and HA in a combination treatment for knee osteoarthritis, more research is required.

Authors contribution

AM: Methodology, Writing - Original Draft, IK: Conceptualization, Writing - Review & Editing, Supervision. ST: Conceptualization, Resources, Writing - Review & Editing, Supervision.

Funding/sponsorship

This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

Ethical committee approval

As a narrative review, this study is not subject to ethical approval.

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