Combination of Intra-Articular and Intraosseous Injections of Platelet Rich Plasma for Severe Knee Osteoarthritis: A Pilot Study

Mikel Sánchez, Diego Delgado, Pello Sánchez, Emma Muiños-López, Bruno Paiva, Froilán Granero-Moltó, Felipe Prósper, Orlando Pompei, Juan Carlos Pérez, Juan Azofra, Sabino Padilla, Nicolás Fiz, Mikel Sánchez, Diego Delgado, Pello Sánchez, Emma Muiños-López, Bruno Paiva, Froilán Granero-Moltó, Felipe Prósper, Orlando Pompei, Juan Carlos Pérez, Juan Azofra, Sabino Padilla, Nicolás Fiz

Abstract

The aim of this study was to assess a novel approach to treating severe knee osteoarthritis by targeting synovial membrane, superficial articular cartilage, synovial fluid, and subchondral bone by combining intra-articular injections and intraosseous infiltrations of platelet rich plasma. We explored a new strategy consisting of intraosseous infiltrations of platelet rich plasma into the subchondral bone in combination with the conventional intra-articular injection in order to tackle several knee joint tissues simultaneously. We assessed the clinical outcomes through osteoarthritis outcome score (KOOS) and the inflammatory response by quantifying mesenchymal stem cells in synovial fluid. There was a significant pain reduction in the KOOS from baseline (61.55 ± 14.11) to week 24 (74.60 ± 19.19), after treatment (p = 0.008), in the secondary outcomes (symptoms, p = 0.004; ADL, p = 0.022; sport/rec., p = 0.017; QOL, p = 0.012), as well as VAS score (p < 0.001) and Lequesne Index (p = 0.008). The presence of mesenchymal stem cells in synovial fluid and colony-forming cells one week after treatment decreased substantially from 7.98 ± 8.21 MSC/μL to 4.04 ± 5.36 MSC/μL (p = 0.019) and from 601.75 ± 312.30 to 139.19 ± 123.61 (p = 0.012), respectively. Intra-articular injections combined with intraosseous infiltrations of platelet rich plasma reduce pain and mesenchymal stem cells in synovial fluid, besides significantly improving knee joint function in patients with severe knee osteoarthritis. This trial is registered on EudraCT with the number 2013-003982-32.

Figures

Figure 1
Figure 1
Fluoroscopic images. Intraosseous infiltration into the medial femoral condyle (a) and tibial plateau (b).
Figure 2
Figure 2
Enrolment and outcomes.
Figure 3
Figure 3
Clinical outcomes. KOOS (a), VAS (b), and Lequesne Index (c) at baseline, 8 weeks after treatment, and 24 months after treatment. ADL: function in daily living; sport/rec.: function in sport and recreation; QOL: quality of life. ∗p < 0.05 with respect to basal level.
Figure 4
Figure 4
Mechanisms of intra-articular and intraosseous injections of platelet rich plasma. Depiction of a new strategy to treat severe knee OA by targeting different knee joint structures such as synovial membrane (SM), synovial fluid (SF), articular cartilage (AC) with noncalcified cartilage (NCC) and calcified cartilage (CC), and subchondral bone (SB) with intra-articular injections (IA) and intraosseous infiltrations (IO) of platelet rich plasma (PRP) [24]. This procedure reduces pain and mesenchymal stem cells (MSC) in SF, besides significantly improving knee joint function of patients with severe OA. We suggest that various growth factors, cytokines, and chemokines trapped in the fibrin network of PRP might inhibit the NFκβ on synovial macrophages, fibroblasts as well as on chondrocytes, thereby dampening the inflammatory response of SM and AC [–18]. In addition, IO in subchondral bone, might buffer the excess of transforming growth factor β1 (TGF-β1) as well as restore hepatocyte growth factor (HGF) activity synthesized by osteoblasts, thereby leading to a new reestablished homeostatic balance between TGF-β1 and HGF [–37]. The buffer effect of PRP on TGF-β1 signalling pathway in SB might reduce the presence of nestin MSCs in SF, likely associated with the shrinking of fibroneurovascular tissue in the SB, as an antifibrotic mechanism which has already been reported on other cell phenotypes [36, 37].

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Source: PubMed

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