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Editorial Commentary: Injections for Knee Osteoarthritis: Doc, You Gotta Help Me!

      Abstract

      Injections for the pain caused by knee osteoarthritis have been the focus of significant research for the last few decades. Systematic reviews and meta-analyses suggest that platelet-rich plasma (PRP) can provide up to 12 months of pain relief in these patients, superior to both cortisone and hyaluronic acid. There is also some evidence for a synergistic effect when combining both PRP and hyaluronic acid. Bone marrow aspirate concentrate (BMAC) has significantly greater levels of interleukin-1ra than PRP, as well as a small concentration of mesenchymal stromal cells. However, BMAC is yet unproven in its efficacy, and obtaining BMAC is not as simple as taking blood. Research into the use of expanded autologous and allogenic mesenchymal stem cells continues and shows future promise. For today, PRP remains the gold standard for the treatment of pain associated with knee osteoarthritis.
      It has been our experience that the majority of people with painful knee osteoarthritis (OA) will choose to try an injection before taking on the much more significant intervention of joint replacement. While there have been considerable advancements in this area of medicine over the last few decades, we are far from end game, and the search for a long-lasting, symptom- and disease-modifying injection continues.
      Cortisone, long the sole weapon in the knee surgeon’s arsenal, only provides relief for very short periods in the majority of patients.
      • Hepper C.T.
      • Halvorson J.J.
      • Duncan S.T.
      • et al.
      The efficacy and duration of intra-articular corticosteroid injection for knee osteoarthritis: A systematic review of level I studies.
      In the late 1990s, hyaluronic acid (HA) was an important development, providing many patients with a viable option to cortisone. Over time, we have learned that the average time HA provides relief for is probably in the region of 3 to 6 months.
      • Campbell K.A.
      • Erickson B.J.
      • Saltzman B.M.
      • et al.
      Is local viscosupplementation injection clinically superior to other therapies in the treatment of osteoarthritis of the knee: A systematic review of overlapping meta-analyses.
      The introduction of platelet-rich plasma (PRP) was a game changer. A relatively simple, office-based solution based on the centrifugation of a patient’s own blood, PRP can provide pain relief for up to 12 months, with demonstrated superiority over HA.
      • Meheux C.J.
      • McCulloch P.C.
      • Lintner D.M.
      • et al.
      Efficacy of intra-articular platelet-rich plasma injections in knee osteoarthritis: A systematic review.
      • Dai W.L.
      • Zhou A.G.
      • Zhang H.
      • et al.
      Efficacy of platelet-rich plasma in the treatment of knee osteoarthritis: A meta-analysis of randomized controlled trials.
      • Tang J.Z.
      • Nie M.J.
      • Zhao J.Z.
      • et al.
      Platelet-rich plasma versus hyaluronic acid in the treatment of knee osteoarthritis: A meta-analysis.
      Unfortunately, in practice PRP does not work for everyone, nor does it always last 12 months. Whether autologous interleukin-1ra blood-derived products prove to be superior to PRP remains to be seen.
      • Ajrawat P.
      • Dwyer T.
      • Chahal J.
      Autologous interleukin 1 receptor antagonist blood-derived products for knee osteoarthritis: A systematic review.
      Bone marrow aspirate concentrate (BMAC) has exploded onto the scene relatively recently. Shown to have significantly greater levels of interleukin-1ra than PRP, as well as a small concentration of mesenchymal stromal cells,
      • Cassano J.M.
      • Kennedy J.G.
      • Ross K.A.
      • et al.
      Bone marrow concentrate and platelet-rich plasma differ in cell distribution and interleukin 1 receptor antagonist protein concentration.
      BMAC is yet unproven in its efficacy.
      • Shapiro S.A.
      • Kazmerchak S.E.
      • Heckman M.G.
      • et al.
      A prospective, single-blind, placebo-controlled trial of bone marrow aspirate concentrate for knee osteoarthritis.
      ,
      • Chahla J.
      • Dean C.S.
      • Moatshe G.
      • et al.
      Concentrated bone marrow aspirate for the treatment of chondral injuries and osteoarthritis of the knee: A systematic review of outcomes.
      Unfortunately, obtaining BMAC is not as simple as taking blood, and is certainly not something we personally would be too eager to sign up for! Although research into the use of expanded autologous and allogenic mesenchymal stem cells continues,
      • Vega A.
      • Martin-Ferrero M.A.
      • Del Canto F.
      • et al.
      Treatment of knee osteoarthritis with allogeneic bone marrow mesenchymal stem cells: A randomized controlled trial.
      • Kim S.H.
      • Djaja Y.P.
      • Park Y.B.
      • et al.
      Intra-articular injection of culture-expanded mesenchymal stem cells without adjuvant surgery in knee osteoarthritis: A systematic review and meta-analysis.
      • Ha C.W.
      • Park Y.B.
      • Kim S.H.
      • et al.
      Intra-articular mesenchymal stem cells in osteoarthritis of the knee: A systematic review of clinical outcomes and evidence of cartilage repair.
      it would seem that in 2021 PRP remains the gold standard for the treatment of pain associated with knee OA.
      Clinicians continue to search for ways of improving outcomes after injections. To their credit, Karasavvidis, Totilis, Gilat, and Cole investigate this issue in an article entitled “Platelet-Rich Plasma Combined With Hyaluronic Acid Improves Pain and Function Compared With Hyaluronic Acid Alone in Knee Osteoarthritis: A Systematic Review and Meta-analysis.”
      • Karasavvidis T.
      • Totlis T.
      • Gilat R.
      • et al.
      Platelet-rich plasma combined with hyaluronic acid improves pain and function compared with hyaluronic acid alone in knee osteoarthritis: A systematic review and meta-analysis.
      The authors determine that the combination of PRP and HA provides superior patient outcomes in terms of pain and function compared to HA alone at up to 12 months. As the authors note in their discussion, there is already evidence of the superiority of PRP over HA.
      • Dai W.L.
      • Zhou A.G.
      • Zhang H.
      • et al.
      Efficacy of platelet-rich plasma in the treatment of knee osteoarthritis: A meta-analysis of randomized controlled trials.
      Interestingly, they reference a systematic review by Zhao et al.
      • Zhao J.
      • Huang H.
      • Liang G.
      • et al.
      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.
      published in 2020 demonstrating that the combination of PRP and HA improved knee pain scores more than PRP alone at 12 months’ postinjection.
      Combination therapy is food for thought. It may be that to maximize outcomes for our patients, we should consider the potentially synergistic effects of PRP and HA. The exact products and protocols remain unclear, nor is it clear whether combination therapy is cost-effective. However, costs aside, our patients are in pain and want the best treatment based on the best evidence available. Although biological injectable therapies have a role to play in the treatment of knee OA, combination therapy will be a further area of focus in 2021 and beyond.

      Supplementary Data

      References

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