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Subchondral bone or intra-articular injection of bone marrow concentrate mesenchymal stem cells in bilateral knee osteoarthritis: what better postpone knee arthroplasty at fifteen years? A randomized study
Philippe Hernigou 1 , Charlie Bouthors 2 , Claire Bastard 3 , Charles Henri Flouzat Lachaniette 3 , Helene Rouard 4 , Arnaud Dubory 3
Int Orthop 2021 Feb;45(2):391-399. RCT Abstract
Purpose: There is an increasing number of reports on the treatment of knee osteoarthritis (OA) using mesenchymal stem cells (MSCs). However, it is not known what would better drive osteoarthritis stabilization to postpone total knee arthroplasty (TKA) targeting the synovial fluid by injection or targeting on the subchondral bone with MSCs implantation.
Methods: A prospective randomized controlled clinical trial was carried out between 2000 and 2005 in 120 knees of 60 patients with painful bilateral knee osteoarthritis with a similar osteoarthritis grade. During the same anaesthesia, a bone marrow concentrate of 40 mL containing an average 5727 MSCs/mL (range 2740 to 7540) was divided in two equal parts: after randomization, one part (20 mL) was delivered to the subchondral bone of femur and tibia of one knee (subchondral group) and the other part was injected in the joint for the contralateral knee (intra-articular group). MSCs were counted as CFU-F (colony fibroblastic unit forming). Clinical outcomes of the patient (Knee Society score) were obtained along with radiological imaging outcomes (including MRIs) at two year follow-up. Subsequent revision surgeries were identified until the most recent follow-up (average of 15 years, range 13 to 18 years).
Results: At two year follow-up, clinical and imaging (MRI) improvement was higher on the side that received cells in the subchondral bone. At the most recent follow-up (15 years), among the 60 knees treated with subchondral cell therapy, the yearly arthroplasty incidence was 1.3% per knee-year; for the 60 knees with intra-articular cell therapy, the yearly arthroplasty incidence was higher (p = 0.01) with an incidence of 4.6% per knee-year. For the side with subchondral cell therapy, 12 (20%) of 60 knees underwent TKA, while 42 (70%) of 60 knees underwent TKA on the side with intra-articular cell therapy. Among the 18 patients who had no subsequent surgery on both sides, all preferred the knee with subchondral cell therapy.
Conclusions: Implantation of MSCs in the subchondral bone of an osteoarthritic knee is more effective to postpone TKA than injection of the same intra-articular dose in the contralateral knee with the same grade of osteoarthritis.
This paper is a welcome follow-up to Hernigou’s earlier studies that seemed to indicate that BMC/MSC (used interchangeably here) may outperform knee arthroplasty for pain relief as well as longevity in selected patients. It also defines a typical patient population, painful arthritis of both knees.
The keys to this study:
- specific to osteoarthritis (as opposed to osteonecrosis in some previous series)
-“perfect” matched controls; same patient & arthritis grade, different knees
- long-term (15-year) follow-up
Obviously, additional studies are needed to confirm the superiority of sub-chondral vs. joint BMC therapy, both of which may be effective in relieving arthritic joint pain.
So what is the baseline progression to knee replacement at 15 yrs with no BMC (the"true control group", based on osteoarthritis grade)?
Perhaps the literature has the answer...
Kelly Cunningham MD
Austin OrthoBiologics austinorthobio.com
Board-certified Orthopedic & Regenerative Sports Medicine Specialist
Cellular "stem cell" & PRP therapy, with & without surgery of the knee, shoulder, elbow & hip