title: Combination of Intra-Articular and Intraosseous Injections of Platelet Rich Plasma for Severe Knee Osteoarthritis: A Pilot Study.
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.
authors.affiliation: Arthroscopic Surgery Unit, Hospital Vithas San Jose, C/Beato Tomás de Zumarraga 10, 01008 Vitoria-Gasteiz, Spain.
authors.forename: Mikel
authors.identifier: 0000-0001-9992-6927
authors.initials: M
authors.lastname: Sánchez
authors.affiliation: Arthroscopic Surgery Unit Research, Hospital Vithas San Jose, C/Beato Tomás de Zumarraga 10, 01008 Vitoria-Gasteiz, Spain.
authors.forename: Diego
authors.identifier: 0000-0002-0494-0804
authors.initials: D
authors.lastname: Delgado
authors.affiliation: Arthroscopic Surgery Unit Research, Hospital Vithas San Jose, C/Beato Tomás de Zumarraga 10, 01008 Vitoria-Gasteiz, Spain.
authors.forename: Pello
authors.initials: P
authors.lastname: Sánchez
authors.affiliation: Cell Therapy Area, Clínica Universidad de Navarra, Avenida de Pío XII 36, 31008 Pamplona, Spain.
authors.forename: Emma
authors.initials: E
authors.lastname: Muiños-López
authors.affiliation: Center for Applied Medical Research, Avenida de Pío XII 55, 31008 Pamplona, Spain.
authors.forename: Bruno
authors.identifier: 0000-0003-1977-3815
authors.initials: B
authors.lastname: Paiva
authors.affiliation: Cell Therapy Area, Clínica Universidad de Navarra, Avenida de Pío XII 36, 31008 Pamplona, Spain; Orthopaedic Surgery and Traumatology Department, Clínica Universidad de Navarra, Avenida de Pío XII 36, 31008 Pamplona, Spain.
authors.forename: Froilán
authors.identifier: 0000-0003-4817-5232
authors.initials: F
authors.lastname: Granero-Moltó
authors.affiliation: Cell Therapy Area, Clínica Universidad de Navarra, Avenida de Pío XII 36, 31008 Pamplona, Spain; Hematology Department, Clínica Universidad de Navarra, Avenida de Pío XII 36, 31008 Pamplona, Spain.
authors.forename: Felipe
authors.initials: F
authors.lastname: Prósper
authors.affiliation: Arthroscopic Surgery Unit, Hospital Vithas San Jose, C/Beato Tomás de Zumarraga 10, 01008 Vitoria-Gasteiz, Spain.
authors.forename: Orlando
authors.initials: O
authors.lastname: Pompei
authors.affiliation: Arthroscopic Surgery Unit, Hospital Vithas San Jose, C/Beato Tomás de Zumarraga 10, 01008 Vitoria-Gasteiz, Spain.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Pérez
authors.affiliation: Arthroscopic Surgery Unit, Hospital Vithas San Jose, C/Beato Tomás de Zumarraga 10, 01008 Vitoria-Gasteiz, Spain.
authors.forename: Juan
authors.identifier: 0000-0002-6864-9258
authors.initials: J
authors.lastname: Azofra
authors.affiliation: Fundacion Eduardo Anitua, C/Jose María Cagigal 19, 01007 Vitoria-Gasteiz, Spain.
authors.forename: Sabino
authors.initials: S
authors.lastname: Padilla
authors.affiliation: Arthroscopic Surgery Unit, Hospital Vithas San Jose, C/Beato Tomás de Zumarraga 10, 01008 Vitoria-Gasteiz, Spain.
authors.forename: Nicolás
authors.initials: N
authors.lastname: Fiz
mesh_terms: D000328:Adult; D000368:Aged; D001842:Bone and Bones / Q000473:pathology*; D003710:Demography; D005260:Female; D005471:Fluoroscopy; D006801:Humans; D007270:Injections, Intra-Articular; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging / Q000628:therapy*; D010865:Pilot Projects; D053657:Platelet-Rich Plasma / Q000378:metabolism*; D016896:Treatment Outcome