Knee injections


 Marine DELCROS, MD.

The 4 grades of gonarthrosis according to Kellgren & Lawrence


Interest in autologous platelet-rich plasma (PRP) emerged in the 1970s with the discovery that platelets release growth factors [1].

  • This new autologous treatment option has opened up a whole new field of possibilities for musculoskeletal pathologies (mainly cartilage and tendinopathy).
  • Today, the efficacy of platelet-rich plasma is well established, but its use is the subject of much debate, in terms of variability of preparation, indications and application protocols.
  • The practice of using this biological product needs to be protocolized, with high levels of evidence, as clinical experience alone is not sufficient [...2].

Osteoarthritis is the most common chronic joint disease, the "disease of the century" affecting millions of people worldwide [?3]. His study of the knee is the most widely reported.

  • How does platelet-rich plasma fit into the therapeutic arsenal for symptomatic gonarthrosis?
  • The aim of this article is to summarize the recommendations of international learned societies, which are striving to draw up guidelines that are as standardized and objective as possible, as part of an Evidence Based Practice approach.
    • ESSKA (The European Society of Sports Traumatology, Knee Surgery and Arthroscopy) [4]
    • GRIIP (Groupe de Recherche Internationale sur les Injections de Plaquettes) [5]
    • SIOT (Italian Society of Orthopaedics and Traumatology) [6]
    • GOTS (German Society of Orthopaedics and Traumatology) [7]
    • NICE (National Institute for Health and Care Excellence) [2]

The clinical efficacy of PRP in gonarthrosis has been evaluated in numerous controlled studies, against placebo (saline solution), and against the infiltrative therapies generally used (hyaluronic acid, corticosteroids), basing the results on criteria :

  • pain,
  • function,
  • quality of life,
    • with VAS (Visual Analogic Scale) indices,
    • WOMAC (Western Ontario and McMaster Universities Arthritis Index),
    • IKDC (The International Knee Documentation Committee)
    • and KOOS (Knee Injury and Osteoarthritis Outcome Score).

Indications for PRP infiltration focus on minimal to moderate gonarthrosis (≤ stages III), according to the Kellgren & Lawrence classification.

Although expected results remain low, PRP is still indicated in severe stage IV gonarthrosis for patients with co-morbidities that contraindicate surgery or who wish to postpone surgery as long as possible.

All the experts agree that conservative treatments are the way to go:

  • physical activity,
  • weight loss,
  • rehabilitation,
  • associated with treatment per os :
    • chondroitin or glucosamine taken chronically,
    • nonsteroidal anti-inflammatory drugs (NSAIDs) on an ad hoc basis in case of
    • According to these recommendations, PRP is used as a second-line treatment when viscosupplementation fails.
    • Corticosteroids (CTS), limited to 3 injections per year, are reserved for severe acute attacks.

Indeed, the chondral toxicity of corticosteroids, combined with accelerated cartilage degradation and their time-limited effect, mean that CTS are reserved for recurrent congestive episodes and painful crises.

  • PRP shows a beneficial effect over the longer term, with fewer associated side effects.

At the same time, a number of meta-analyses have demonstrated a clinical improvement with PRP, associated with a longer-term effect, compared with hyaluronic acid (HA) infiltration.

Particular attention must then be paid to the HA formulas involved:

  • low molecular weight formulas being reserved for the light stages of
  • while high molecular weight formulas are more effective on advanced stages.

The combination of PRP and AH would be of great benefit, as it potentiates the effects of each.

Cellular Matrix tubes® for the preparation of autologous platelet-rich plasma (RegenPRP®) combined with non-crosslinked Hyaluronic Acid (HA) in a closed-loop system.

All scientific societies agree that PRP should not be used in conjunction with anaesthetics or CTS, to avoid potential negative interactions due to in vitro platelet toxicity. [8].

Standardization of PRP application protocols is essential: regarding the number of infiltrations recommended, the majority of articles report a superiority of multiple injections (2 to 3 times) rather than a single injection [...].9], with the lowest grades of gonarthrosis reporting more response with few infiltrations [ ].4].

An interval of 3 weeks between 2 gestures must be respected [...4This is the main period of activity and release of growth factors.

It seems obvious that the infiltrative procedure should be carried out under ultrasound or fluoroscopic control. [6]. Without echo-guidance, intra-articular infiltration via the lateral approach is the most recommended.

The pathophysiological mechanisms of PRP are complex and multifactorial. They involve several biological players :

  • enzymes,

  • proteins :

    • albumins, globulins,

    • coagulation factors,

    • fibrinogen,

  • pro- and anti-inflammatory cytokines involved in platelet activation,

  • growth factors in different numbers and types, inducing cell migration, proliferation and differentiation processes.

  • Plasma fibrinogen, once converted to fibrin, serves as a support for this cell migration and tissue reconstruction.

There is no consensus on the exact formulation of PRP.

  • Inter-individual variability in PRP composition is difficult to control. Platelets are central to the pathophysiological process and play a definite role in therapeutic effects, but no clear correlation has been established between their numbers and clinical results.
  • There is no need to focus on a minimum platelet count, as long as the patient's blood count is within the normal range.
  • The main focus is on how to produce the PRP [...2] :
    • standardize centrifugation procedures,
    • product handling...
    • in order to ensure a product with live platelets and

Similarly, the current trend is for large volumes of PRP to be injected: this is still of interest in the context of multiple infiltrations during the same consultation.

Nevertheless, from a quantitative point of view, the interest seems limited, since the binding of a growth factor to its receptor on the cell membrane triggers one and only one cellular response at a time (migration, proliferation, differentiation, protein production...).

However, increasing the concentration of platelets or growth factors has no greater effect [...10]. What's more, once secreted, growth factors have a short half-life: the surplus is superfluous.

From a qualitative point of view, PRP differs from purified growth factor solutions in that platelets secrete growth factors in a controlled and orchestrated manner throughout the regenerative process [...].11].

What about leukocyte concentration?

Osteoarthritis is characterized by progressive degradation of the extracellular matrix of cartilage and low-intensity inflammation of the synovial membrane.

The correlation between the effect of PRP and leukocyte count alone is overestimated, since other factors are also involved.

None of the options is predominant, each bringing benefits according to the indications :

  • LR-PRP (leukocyte-rich PRP) is useful for tendinopathy [?12],
  • while LP-PRP (leukocyte-poor PRP) is preferred for gonarthrosis [ ].13].

We're not at the end of our discoveries: a team of researchers from Créteil recently demonstrated that PRP contains glycosaminoglycans (GAGs), the latter showing significant differences in terms of concentration, structural and functional properties, between PRP from a healthy patient and PRP from a patient suffering from gonarthrosis.

The therapeutic effect of PRP may be mediated by its glycosaminoglycan composition and their interactions with growth factors, most of which are heparin-binding proteins (HBPs), implying repercussions on the phenotype of chondrocytes and synoviocytes [14]. A clinical study also demonstrated that 3 injections of LP-PRP positively modified thent the composition of synovial fluid [15].

Medicine is constantly evolving, bringing with it its share of questions and challenges.

The aim is to improve these recommendations so that the recognized use of PRP becomes increasingly standardized and harmonized, focusing on preparation methods and application protocols.

Plasma rich in platelets. Rich in possibilities and promise, certainly.


  1. Ross R, Glomset J, Kariya B, Harker L. A platelet-dependent serum factor that stimulates the proliferation of arterial smooth muscle cells in vitro. Proc Natl Acad Sci U S A. 1974;71(4):1207-10.
  2. Platelet-rich plasma injections for knee osteoarthritis; Interventional procedures guidance [IPG637]. 2019.
  3. Fusco M, Skaper SD, Coaccioli S, Varrassi G, Paladini A. Degenerative Joint Diseases and Neuroinflammation. Pain practice: the official journal of World Institute of Pain. 2017;17(4):522-32.
  4. Use of injectable orthobiologics for the treatment of knee osteoarthritis Part 1: blood-derived products (aka PRP). 2022.
  5. Eymard F, Ornetti P, Maillet J, Noel E, Adam P, Legre-Boyer V, et al. Intra-articular injections of platelet-rich plasma in symptomatic knee osteoarthritis: a consensus statement from French-speaking experts. Knee Surg Sports Traumatol 2021;29(10):3195-210.
  6. Pesare E, Vicenti G, Kon E, Berruto M, Caporali R, Moretti B, Randelli Italian Orthopaedic and Traumatology Society (SIOT) position statement on the non-surgical management of knee osteoarthritis. Journal of orthopaedics and traumatology : official journal of the Italian Society of Orthopaedics and Traumatology. 2023;24(1):47.
  7. Tischer T, Bode G, Buhs M, Marquass B, Nehrer S, Vogt S, et al. Platelet-rich plasma (PRP) as therapy for cartilage, tendon and muscle damage - German working group position statement. J Exp Orthop. 2020;7(1):64.
  8. Carofino B, Chowaniec DM, McCarthy MB, Bradley JP, Delaronde S, Beitzel K, and Corticosteroids and local anesthetics decrease positive effects of platelet-rich plasma: an in vitro study on human tendon cells. Arthroscopy. 2012;28(5):711-9.
  9. Huang PH, Wang CJ, Chou WY, Wang JW, Ko JY. Short-term clinical results of intra- articular PRP injections for early osteoarthritis of the knee. Int J Surg. 2017;42:117-22.
  10. Filardo G, Kon E, Pereira Ruiz MT, Vaccaro F, Guitaldi R, Di Martino A, and Platelet-rich plasma intra-articular injections for cartilage degeneration and osteoarthritis: single- versus double-spinning approach. Knee Surg Sports Traumatol Arthrosc. 2012;20(10):2082-91.
  11. Golebiewska EM, Poole Secrets of platelet exocytosis - what do we really know about platelet secretion mechanisms? Br J Haematol. 2013.
  12. Fitzpatrick J, Bulsara M, Zheng The Effectiveness of Platelet-Rich Plasma in the Treatment of Tendinopathy: A Meta- analysis of Randomized Controlled Clinical Trials. The American journal of sports medicine. 2017;45(1):226-33.
  13. Riboh JC, Saltzman BM, Yanke AB, Fortier L, Cole Effect of Leukocyte Concentration on the Efficacy of Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis. The American journal of sports medicine. 2016;44(3):792-800.
  14. Saadan C, C F, Cachen L, Lammari Y, Boezennec B, Eymard F, Albanese Structural and functional characterization of the glycan component of platelet-rich plasma. Revue du Rhumatisme. 2023;90:A87.
  15. Chen CPC, Cheng CH, Hsu CC, Lin HC, Tsai YR, Chen The influence of platelet rich plasma on synovial fluid volumes, protein concentrations, and severity of pain in patients with knee osteoarthritis. Experimental gerontology. 2017;93:68-72.



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