Comparison of clinical outcome, cartilage turnover, and inflammatory activity following either intra-articular or a combination of intra-articular with intra-osseous platelet-rich plasma injections in osteoarthritis knee: A randomized, clinical trial

Published:November 14, 2022DOI:


      • IA-PRP injections are common treatments for knee OA.
      • IA+IO-PRP injection provides better pain relief and functional improvement at 12-weeks.
      • IA-PRP and IA+IO-PRP injections reduce inflammatory markers (ESR and CRP) at 12-weeks.
      • IA-PRP and IA+IO-PRP PRP injections reduce u-CTX-II levels at 12-weeks.
      • IA+IO-PRP injection reduces u-NTX-I level at 12-weeks.



      The objective of the study was to determine the changes in clinical outcome (pain and knee activity) and assess bone/ cartilage biomarkers and inflammatory activity in persons with osteoarthritis (OA) knee following a single injection of intra-articular platelet-rich plasma (IA-PRP) and combination of intra-articular, intraosseous PRP (IA+IO-PRP).


      This prospective, randomized, single-blind clinical trial was conducted at a tertiary care teaching hospital in India. Ninety-six persons with OA knee with a Kellgren-Lawrence score of 3 were randomized into three groups- Group-I (IA-PRP), Group-II (IA+IO-PRP)], Group-III, [intra-articular normal saline (IA-NS)]. The primary outcome was a visual analog scale (VAS) for pain. The secondary outcomes were the Knee Injury and Osteoarthritis Outcome Score (KOOS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), bone/ cartilage turnover biomarkers [C-telopeptide (CTX-II), N-telopeptide (NTX-I), cartilage oligomeric matrix protein (COMP), N-terminal propeptide of collagen type-IIA (PIIANP), and hyaluronic acid (HA)], ultrasonography (USG) findings of the knee joint. The outcome measures were assessed at baseline, 6, and 12 weeks of follow-up.


      Compared to IA-NS injection, IA-PRP and IA+IO-PRP injections significantly improved VAS-pain and KOOS scores at 6 and 12 weeks. Furthermore, both PRP groups showed a significant reduction in ESR, CRP, and CTX-II at 12 weeks following PRP injections. In addition, at 12 weeks, the IA+IO-PRP group showed a significant reduction (p=0.009) in NTX-I level. Persons in the IA+IO-PRP group reported significant reductions in the synovial-effusion and infra-patellar bursitis.


      Significant clinical improvements were noticed following IA-PRP and IA-IO-PRP injections compared to IA-NS injections. Both PRP groups reported a significant reduction in ESR, CRP, and CTX-II levels at 12 weeks. Persons in the IA+IO-PRP group reported significant changes in u-NTX-I level and knee-USG findings.



      ADL (Activities of daily living), COMP (Cartilage oligomeric matrix protein), CTX-II (C-telopeptides of type-II collagen), CRP (C-reactive protein), ESR (Erythrocyte sedimentation rate), HA (Hyaluronic acid), IA-PRP (Intra-articular platelet-rich plasma), IA+IO (PRP –Intra-articular and intra-osseous platelet-rich plasma), KOOS (Knee Injury and Osteoarthritis Outcome Score), NTX-I (N-telopeptides of type-I collagen), PIIANP (N-terminal propeptide of collagen type-IIA), OA (Osteoarthritis), PRP (Platelet-rich plasma), QoL (Quality of life), RCTs (Randomized controlled trials), VAS (Visual analog scale)
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