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Bone marrow aspirate concentrate injections provide similar results versus viscosupplementation up to 24 months of follow-up in patients with symptomatic knee osteoarthritis. A randomized controlled trial

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Knee Surgery, Sports Traumatology, Arthroscopy Aims and scope

Abstract

Purpose

The purpose of this double-blind randomized controlled trial (RCT) was to compare clinical improvement and radiographic findings up to 2 years of follow-up of a single intra-articular injection of bone marrow aspirate concentrate (BMAC) versus hyaluronic acid (HA) for the treatment of knee osteoarthritis (OA). The hypothesis was that BMAC injection could lead to better clinical and radiographic results compared to viscosupplementation.

Methods

Patients with bilateral knee OA were randomized to one intra-articular injection of tibial-derived BMAC in one knee and one HA injection in the contralateral knee. Sixty patients were enrolled, and 56 were studied up to the final follow-up (35 men, 21 women, mean age 57.8 ± 8.9 years), for a total of 112 knees. Patients were evaluated before the injection and at 1, 3, 6, 12, and 24 months with the IKDC subjective score, VAS for pain, and the KOOS score. Minimal clinically important difference (MCID), patient treatment judgement, and adverse events were documented, as well as bilateral X-Rays (Rosenberg view) before and after treatment.

Results

No severe adverse events nor differences were reported in terms of mild adverse events (7.1% vs 5.4%, p = ns) and treatment failures (10.7% vs 12.5%, p = ns) in BMAC and HA groups, respectively. The IKDC subjective score improved from baseline to all follow-ups for BMAC (p < 0.0005), while it improved up to 12 months (p < 0.0005) and then decreased at 24 months (p = 0.030) for HA. Compared to HA, BMAC showed a higher improvement for VAS pain at 12 (2.2 ± 2.6 vs 1.7 ± 2.5, p = 0.041) and 24 months (2.2 ± 2.6 vs 1.4 ± 2.8, p = 0.002). The analysis based on OA severity confirmed this difference only in Kellgren–Lawrence 1–2 knees, while comparable results were observed in moderate/severe OA. Radiographic evaluation did not show knee OA deterioration for both treatment groups, without intergroup differences.

Conclusion

BMAC did not demonstrate a clinically significant superiority at short-term compared to viscosupplementation, reporting overall comparable results in terms of clinical scores, failures, adverse events, radiographic evaluation, MCID achievement, and patient treatment judgment. However, while HA results decreased over time, BMAC presented more durable results in mild OA knees.

Level of evidence

Level I.

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Acknowledgements

The authors would like to acknowledge Elettra Pignotti for the statistical analysis and Biologic Therapies for providing kits and centrifuge.

Funding

This study received no external funding.

Author information

Authors and Affiliations

  1. Clinica Ortopedica e Traumatologica 2, IRCCS Istituto Ortopedico Rizzoli, Via Di Barbiano, 1/10, 40136, Bologna, Italy

    Angelo Boffa, Alessandro Di Martino, Luca Andriolo, Alberto Poggi & Stefano Zaffagnini

  2. Clinica Mediterranea, Via Orazio 2, 80122, Napoli, Italy

    Roberto De Filippis

  3. Humanitas Clinical and Research Center – IRCCS, via Manzoni 56, 20089, Rozzano, MI, Italy

    Elizaveta Kon

  4. Humanitas University, Department of Biomedical Sciences, Via Rita Levi Montalcini 4, 20090, Pieve Emanuele, MI, Italy

    Elizaveta Kon

  5. Department of Traumatology, Orthopedics and Disaster Surgery, Sechenov First Moscow State Medical University (Sechenov University), 2-4 Bolshaya Pirogovskaya st., 119991, Moscow, Russia

    Elizaveta Kon

  6. Applied and Translational Research (ATR) Center, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy

    Giuseppe Filardo

Authors
  1. Angelo Boffa
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Contributions

Conceptualization, S.Z. and G.F.; methodology, L.A. and E.K..; data curation, R.D.F.; writing—original draft preparation, A.B. and A.P..; writing—review and editing, G.F.; supervision, A.D.M., E.K., G.F., and S.Z. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Alberto Poggi.

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Conflict of interest

EK reports consulting for Carihealldt, Green Bone, Geistlich, and Bioveex, and speaking for Zimmer Biomet and Fidia Farmaceutici SPA. SZ reports non-financial support from personal fees from I + SRL, grants from Grants from FidiaFarmaceutici SPA, Cartihealltd, IGEA clinical biophysics, BIOMET, and Kensey Nash, outside the submitted work. The funders had no role in the design of the study, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results. The other authors declare no conflict of interest.

Ethical approval

This prospective double-blind RCT was approved by the Hospital Ethics Committee of the Rizzoli Orthopaedic Institute, Bologna, Italy (prot. n. 0001181). The trial was registered at clinicaltrials.gov (registration number NCT03110679) and was entirely conducted in a highly specialized referral center for orthopaedic pathologies.

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Boffa, A., Di Martino, A., Andriolo, L. et al. Bone marrow aspirate concentrate injections provide similar results versus viscosupplementation up to 24 months of follow-up in patients with symptomatic knee osteoarthritis. A randomized controlled trial. Knee Surg Sports Traumatol Arthrosc 30, 3958–3967 (2022). https://doi.org/10.1007/s00167-021-06793-4

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