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 Table of Contents  
EDITORIAL
Year : 2020  |  Volume : 15  |  Issue : 3  |  Page : 159-161

Platelet-rich plasma therapy for knee osteoarthritis: The jury is still out


Consultant Rheumatologist, Wockhardt Hospital, TUIMSR, Mumbai, Maharashtra, India

Date of Submission14-Jul-2020
Date of Acceptance14-Jul-2020
Date of Web Publication3-Sep-2020

Correspondence Address:
Dr. Nilesh Nolkha
Wockhardt Hospital, Mumbai, TUIMSR, Mira Road, Mumbai - 401 107, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-3698.294310

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How to cite this article:
Nolkha N. Platelet-rich plasma therapy for knee osteoarthritis: The jury is still out. Indian J Rheumatol 2020;15:159-61

How to cite this URL:
Nolkha N. Platelet-rich plasma therapy for knee osteoarthritis: The jury is still out. Indian J Rheumatol [serial online] 2020 [cited 2020 Sep 20];15:159-61. Available from: http://www.indianjrheumatol.com/text.asp?2020/15/3/159/294310



Symptomatic knee osteoarthritis (KOA) affects 6%–15% of people above 50 years of age and is considered as one of the top ten causes of disability in the world.[1] Currently, there are no disease modifying therapies for KOA and treatment is directed at symptom alleviation and preserving function. The nonoperative pharmacological management of KOA includes options such as topical or oral agents and intra-articular therapies. Corticosteroids (IACS), visco-supplementation with hyaluronic acid injections (IHA), platelet-rich plasma (PRP), and stem cells are the most widely used intra-articular therapies in KOA.[2]

PRP is more or less defined as any preparation of autologous blood which contains a higher concentration of platelets than peripheral blood. The literature regarding preparation of PRP is extremely heterogeneous and advent of multiple proprietary systems makes this scenario further confusing.[3] [Table 1] outlines certain important (not all-inclusive) variations in PRP preparation techniques and injection methods. In addition, there are other reported formulations such as autologous conditioned serum (ACS– a cell-free serum), plasma rich in growth factors, and platelet-rich fibrin (PRF). Thus, PRP used in studies done by individual working groups is theoretically unique and difficult to compare with others.
Table 1: Different variations in platelet rich plasma preparation technique and injection methods

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Platelets contain multiple growth factors, cytokines, and adhesion molecules. There are many reportedin vitro andin vivo animal model studies on effects of PRP. The claimed positive results of PRP in various settings may be explained by its stimulatory effect on chondrocytes, mesenchymal stem cells and synoviocytes, its variable anti-inflammatory effect in osteoarthritic milieu, and its effects on repair of cartilage or chondral defects.[4] It may stimulate growth of some mechanistic osteochondral tissue, but no clear hyaline cartilage formation is seen.[4] Overall, all these studies are heterogenous, effects are inconsistent, and more work is needed to elucidate the mechanism underlying PRP's reported beneficial effects. A majority of trials of PRP in KOA have reported improvement in subjective parameters, without studying its objective effects on intra-articular markers or structural pathology. A review of imaging studies in KOA patients receiving PRP, suggested possible stabilising effect in cartilage thickness, improvement in cartilage volume and reduced synovitis in some.[5] However, due to low-quality nature of these studies, additional work is needed before commenting on PRP's favourable effects on structural changes in KOA.

In this issue of Indian Journal of Rheumatology, Arjun et al. have reported the outcomes of a prospective observational study, comparing two doses of intra-articular PRP versus (vs.) two doses of IACS (methylprednisolone acetate, MPA 80 mg), given 12 weeks apart, in patients with moderate KOA (Kellgren-Lawrence scale grade 2–3).[6] The PRP was freshly prepared and preparation technique was not elucidated. The baseline characteristics, including the total Western Ontario and McMaster Universities Index (WOMAC) score, different components of WOMAC score (pain, physical function, and stiffness) and pain Visual Analog Scale (VAS), were comparable between the PRP versus MPA group (n = 30 each). The primary outcomes (pain VAS and WOMAC score) and secondary outcomes (each WOMAC component score) showed sustained improvement in PRP group and were significantly better than MPA group at 12 and 24 weeks. At 24 weeks, compared to baseline, mean total WOMAC and pain VAS scores decreased by an average of 41% versus 9%–16% for PRP versus MPA group, respectively. There were no adverse events in either of the group.

There have been multiple meta-analyses studying the effects of PRP in KOA. A recent systematic review and meta-analysis inferred that though the overall clinical outcomes were not superior in patients receiving PRP injections, PRP may have a significant beneficial effect on pain for 6–12 months, compared to IHA.[7] Chen et al. summarised evidence from four previous meta-analyses recently.[8] Three meta-analyses indicated PRP showed more benefit in pain relief and functional improvement than the control group, and the other one suggested no difference (in overall scores) between these groups. However, even the latter meta-analysis showed that PRP may have a sustained effect on pain relied in KOA. Hegazy et al., demonstrated that many of these PRP trials achieved meaningful outcomes above minimal clinical important difference thresholds.[9] Most PRP trials in KOA have been performed with IHA or sometimes placebo as a comparator arm and meta-analyses results do reflect the same. There are published randomised studies comparing PRP versus IACS[10],[11] with meaningful outcomes similar to current study by Arjun et al.[4] PRP injections have been found to be consistently safe in all these reported studies.

With regards to intra-articular corticosteroids, an individual patient data meta-analysis gave evidence that patients with more severe pain responded much better to IACS.[12] The recent most Cochrane review (2015) on IACS use in KOA concluded that clinically important benefits of these injections beyond 1–6 weeks remain unclarified due to low quality of studies under review.[12] Similarly, in the current study,[4] MPA (IACS) group did have benefits at 6 weeks, but unlike PRP group, even after second injection at 12 weeks, the effects in MPA group were not sustained at 24 weeks. A randomised trial also raised concerns regarding slightly more deterioration of cartilage thickness over a period of 2 years, with 3 monthly IACS compared to placebo, the clinical significance of which remains unclear.[12] The evidence on use of visco-supplementation (IHA) in KOA is more controversial, with small effect size and benefits restricted to trials with higher risk of bias.[13]

In spite of the issues with evidence on efficacy of IACS and IHA in KOA, recent Osteoarthritis research society international (OARSI) guidelines (2019) “conditionally recommend” IACS and IHA use in KOA.[14] American College of Rheumatology-Arthritis Foundation (ACR-AF) guidelines (2019) “strongly recommend” IACS and “conditionally (not strongly) recommend against” IHA use in KOA.[13] In contrast, despite meta-analyses suggesting its beneficial effect on pain, OARSI and ACR-AF guidelines “do not recommend” or “strongly recommend against” use of PRP in KOA, respectively. This is due to the fact that most positive PRP studies in KOA have extreme heterogeneity in PRP preparation technique and vary widely in frequency and total number of injections. Most of these studies also have quality issues viz being single centre, are nonblinded, have small numbers, lack a placebo arm (most have IHA as comparator) and carry a high risk of bias in many other domains. The current study by Arjun et al. has some similar limitations and authors have duly acknowledged the same.[4]

Nevertheless, this study adds to growing evidence that PRP therapy may at least have a significant sustained analgesic effect lasting for 6–12 months and may also improve physical function in patients with KOA. There is no conclusive evidence that PRP therapy has any benefits in stabilising or improving structural changes in KOA patients. The fact remains that most therapies in osteoarthritis may have contextual (placebo) benefits, more so with intra-articular therapy and this might be exaggerated when a patient is given an autologous blood derived product like PRP.[15] However, that alone should not preclude use of PRP in KOA patients. We need large, high quality, randomised double-blind trials (having placebo arms), with standardized technique, and uniform frequency of PRP injections, supported by evaluation of objective parameters (e.g.: Imaging), to settle the verdict on use of PRP in patients with KOA.



 
  References Top

1.
Neogi T. The epidemiology and impact of pain in osteoarthritis. Osteoarthritis Cartilage 2013;21:1145-53.  Back to cited text no. 1
    
2.
Wehling P, Evans C, Wehling J, Maixner W. Effectiveness of intra-articular therapies in osteoarthritis: a literature review. Ther Adv Musculoskelet Dis 2017;9:183-96.  Back to cited text no. 2
    
3.
Gato-Calvo L, Magalhaes J, Ruiz-Romero C, Blanco FJ, Burguera EF. Platelet-rich plasma in osteoarthritis treatment: review of current evidence. Ther Adv Chronic Dis 2019;10:2040622319825567.  Back to cited text no. 3
    
4.
Xie X, Zhang C, Tuan RS. Biology of platelet-rich plasma and its clinical application in cartilage repair. Arthritis Res Ther 2014;16:204.  Back to cited text no. 4
    
5.
Raeissadat SA, Ghorbani E, Sanei Taheri M, Soleimani R, Rayegani SM, Babaee M, et al. MRI Changes After Platelet Rich Plasma Injection in Knee Osteoarthritis (Randomized Clinical Trial). J Pain Res 2020;13:65-73.  Back to cited text no. 5
    
6.
Arjun MN, Vasdev V, Kishore K, Hegde A, Shanmuganandan K, Kumar A, et al. Comparison of intra articular autologous platelet-rich plasma with steroids in osteoarthritis knee: Experience from a North Indian tertiary care center. Indian J Rheumatol. Available from: http://www.indianjrheumatol.com/preprintarticle.asp? id=287293. [Last accessed on 2020 Jul 13].  Back to cited text no. 6
    
7.
Hohmann E, Tetsworth K, Glatt V. Is platelet-rich plasma effective for the treatment of knee osteoarthritis? A systematic review and meta-analysis of level 1 and 2 randomized controlled trials. Eur J Orthop Surg Traumatol 2020;30:955-67.  Back to cited text no. 7
    
8.
Chen P, Huang L, Ma Y, Zhang D, Zhang X, Zhou J, et al. Intra-articular platelet-rich plasma injection for knee osteoarthritis: a summary of meta-analyses. J Orthop Surg Res 2019;14:385.  Back to cited text no. 8
    
9.
Hegazy A, Karabelas P, Selim A. Meaningful effectiveness of platelet-rich plasma in treating patients with osteoarthritis of the knee: Meta-analysis and review. J Int Soc Phys Rehabil Med 2019;2:159-67.  Back to cited text no. 9
  [Full text]  
10.
Joshi Jubert N, Rodríguez L, Reverté-Vinaixa MM, Navarro A. Platelet-Rich Plasma Injections for Advanced Knee Osteoarthritis: A Prospective, Randomized, Double-Blinded Clinical Trial. Orthop J Sports Med 2017;5:2325967116689386.  Back to cited text no. 10
    
11.
Ismaiel AH. Comparison between the effect of intra-articular injections of platelet-rich plasma and corticosteroids in advanced knee osteoarthritis. J Med Sci Res 2018;1:278-84  Back to cited text no. 11
    
12.
Hunter DJ, Bierma-Zeinstra S. Osteoarthritis. Lancet 2019;393:1745-59.  Back to cited text no. 12
    
13.
Kolasinski SL, Neogi T, Hochberg MC, Oatis C, Guyatt G, Block J, et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the management of osteoarthritis of the hand, hip, and knee. Arthritis Care Res (Hoboken) 2020;72:149-62.  Back to cited text no. 13
    
14.
Bannuru RR, Osani MC, Vaysbrot EE, Arden NK, Bennell K, Bierma-Zeinstra SMA, et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage 2019;27:1578-89.  Back to cited text no. 14
    
15.
Zou K, Wong J, Abdullah N, Chen X, Smith T, Doherty M, et al. Examination of overall treatment effect and the proportion attributable to contextual effect in osteoarthritis: meta-analysis of randomised controlled trials. Ann Rheum Dis 2016;75:1964-70.  Back to cited text no. 15
    



 
 
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