Randomized Controlled Trial
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Exp Med. Sep 20, 2025; 15(3): 106020
Published online Sep 20, 2025. doi: 10.5493/wjem.v15.i3.106020
Comparative outcome analyses of subchondral vs intra-articular bone marrow aspirate concentrate in primary osteoarthritis knee: A double-blinded randomized controlled trial protocol
Arulkumar Nallakumarasamy, Sandeep Shrivastava, Ravi Velamoor Rangarajan, Naveen Jeyaraman, Swaminathan Ramasubramanian, Sathish Muthu, Madhan Jeyaraman
Arulkumar Nallakumarasamy, Sandeep Shrivastava, Naveen Jeyaraman, Department of Orthopaedics, Datta Meghe Institute of Higher Education and Research, Wardha 442004, Maharashtra, India
Arulkumar Nallakumarasamy, Naveen Jeyaraman, Swaminathan Ramasubramanian, Sathish Muthu, Madhan Jeyaraman, Department of Regenerative Medicine, Agathisha Institute of Stemcell and Regenerative Medicine, Chennai 600030, Tamil Nadu, India
Arulkumar Nallakumarasamy, Ravi Velamoor Rangarajan, Naveen Jeyaraman, Swaminathan Ramasubramanian, Madhan Jeyaraman, Department of Regenerative Medicine, Mother Cell Regenerative Centre, Tiruchirappalli 620017, Tamil Nadu, India
Naveen Jeyaraman, Sathish Muthu, Madhan Jeyaraman, Department of Orthopaedics, Orthopaedic Research Group, Coimbatore 641045, Tamil Nadu, India
Sathish Muthu, Central Research Laboratory, Meenakshi Medical College Hospital and Research Institute, Meenakshi Academy of Higher Education and Research, Kanchipuram 631552, Tamil Nadu, India
Madhan Jeyaraman, Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai 600077, Tamil Nadu, India
Co-corresponding authors: Sathish Muthu and Madhan Jeyaraman.
Author contributions: Nallakumarasamy A designed the research; Nallakumarasamy A and Jeyaraman N analyzed the articles for performing review and wrote the manuscript; Shrivastava S, Rangarajan VR, Ramasubramanian S, Muthu S, and Jeyaraman M finalized the manuscript; Data analysis and interpretation for the trial will be performed by Nallakumarasamy A and Jeyaraman N.
Institutional review board statement: Institutional review board No. PR23AKS0 L5 dated 28.10.2023.
Clinical trial registration statement: Clinical trial registry of India/2024/04/065284 dated 05.04.2024.
Informed consent statement: Everyone signs the informed consent.
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript
CONSORT 2010 statement: The authors have read the CONSORT 2010 statement, and the manuscript was prepared and revised according to the CONSORT 2010 statement.
Data sharing statement: Data is contained within the manuscript.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Madhan Jeyaraman, Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, Velappanchavadi, Chennai 600077, Tamil Nadu, India. madhanjeyaraman@gmail.com
Received: February 14, 2025
Revised: April 9, 2025
Accepted: May 18, 2025
Published online: September 20, 2025
Processing time: 180 Days and 2.4 Hours
Abstract
BACKGROUND

Knee osteoarthritis (OA) imposes a substantial burden through pain, functional limitation, and progressive cartilage loss. Bone marrow aspirate concentrate (BMAC) has emerged as a promising regenerative therapy for OA due to its rich composition of mesenchymal stromal cells (MSCs) and bioactive factors. While intra-articular BMAC injections provide short-term symptomatic relief, recent literature suggests that targeting the subchondral bone—an area crucial to OA progression—may offer superior and longer-lasting clinical benefits.

AIM

To compares the outcomes of subchondral vs intra-articular BMAC injections in patients with primary knee OA.

METHODS

In this unicentric, double-blinded, randomized controlled trial, 30 patients with radiologically confirmed primary knee OA (Kellgren-Lawrence grades II and III) will be equally randomized to receive either subchondral (Group A) or intra-articular (Group B) BMAC injections. BMAC will be harvested from the posterior iliac crest, processed using a standardized centrifugation protocol to yield a product with > 85% cell viability, and administered under image guidance. The primary outcome is the change in pain intensity at 12 months as measured by the Visual Analog Scale (VAS). Secondary outcomes include functional improvement assessed by Knee Injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC), and Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores, structural changes evaluated through advanced magnetic resonance imaging using (MRI) the whole-organ MRI Score, and safety as determined by the incidence of adverse events.

RESULTS

This study aims to evaluate pain reduction at 12 months post-injection, using the VAS as the primary outcome. Secondary outcomes include functional improvement (KOOS, WOMAC, IKDC), cartilage regeneration (T2 cartigram), adverse event incidence, patient satisfaction (standardized questionnaires, Likert scale), and quality of life (EQ-5D). Ethical considerations follow the Declaration of Helsinki and Good Clinical Practice, with institutional review board approval and participant informed consent ensured. Confidentiality and data security comply with regulations, and a data safety monitoring board oversees trial safety. Results will be shared via peer-reviewed journals, presentations at international orthopedic conferences, and detailed summaries for stakeholders and participants. The trial is registered under clinical trial registry of India/2024/04/065284. Findings emphasize patient-centered advancements in knee osteoarthritis management.

CONCLUSION

This trial aims to refine regenerative strategies for knee OA by comparing subchondral vs intra-articular BMAC injections, addressing long-term efficacy, safety, and treatment standardization to guide targeted interventions. This trial will provide critical insights into the comparative efficacy and safety of subchondral vs intra-articular BMAC injections in treating primary knee OA.

Keywords: Osteoarthritis; Bone marrow aspirate concentrate; Subchondral injection; Intra-articular injection; Regenerative therapy; Randomized controlled trial

Core Tip: In this double-blinded, randomized controlled trial, 30 patients with primary knee osteoarthritis will receive either subchondral or intra-articular Bone marrow aspirate concentrate (BMAC) injections. The study aims to compare pain relief (measured by Visual Analog Scale) at 12 months. Secondary outcomes include functional improvement (Knee Injury and Osteoarthritis Outcome Score, International Knee Documentation Committee, and Western Ontario and McMaster Universities Arthritis Index scores), structural changes [magnetic resonance imaging (MRI) using the whole-organ MRI Score], and safety (adverse events). BMAC is harvested from the posterior iliac crest, processed, and administered under image guidance.