Bone marrow aspirate concentrate injections can effectively improve both pain and patient reported outcomes in knee osteoarthritis (OA), but clinical superiority compared with other biologic therapies like platelet-rich plasma (PRP) and microfragmented adipose tissue (MFAT) has yet to be demonstrated. This is according to research results published in the American Journal of Sports Medicine.
Both early case series and larger prospective case studies have demonstrated “significant” improvements in patient reported outcomes after bone marrow aspirate concentrate injection for knee OA. However, current literature varies widely in terms of indications for and technical considerations of bone marrow aspirate concentrate injections. Furthermore, the clinical utility of this treatment method compared with other biologic therapies is also unclear. To address this, researchers conducted a systematic review of the current literature to evaluate the efficacy of isolated bone marrow aspirate concentrate injection for knee OA.
In total, 115 studies published through July 2020 were reviewed for inclusion. Assessed outcomes included treatment failure and patient reported outcomes, inclusive of the visual analogue scale (VAS) and the numeric rating scale (NRS) for pain, as well as data from the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, the Knee Society Score (KSS), and the Knee Injury and Osteoarthritis Outcome Score (KOOS).
A total of 8 studies met inclusion criteria, which included a total of 299 knees. Patient ages ranged between 22 and 85 years, and mean follow-up time was 12.9 months (range, 6-30 months). Forty percent of patients were men.
Studies were evaluated for bone marrow aspirate concentrate preparation and treatment methods, with the prone, lateral decubitus, and supine positions all utilized. Following anesthetization, 10,000 units/mL heparin were withdrawn into a 10 mL syringe. Heparin was injected into an introducer needle until the needle was fully rinsed, then aspirated back into the syringe. All 8 studies aspirated bone marrow from the posterior superior or anterior superior iliac spine.
Between 12 and 120 mL of bone marrow aspirate concentrate was aspirated into the medullary space. One study used a small sample of aspirate concentrate for marrow smear, flow cytometry, colony forming unit, and interleukin (IL)-1 receptor antagonist analyses.
The final volume of concentrate injected ranged from 7 to 25 mL. Six studies had patients placed in the supine position for injection and used a 20-gauge needle superolaterally or medially/laterally into the knee. Two studies utilized ultrasound guidance for injection, and 2 did not describe fully the injection technique.
Five studies were evaluated using the Risk Of Bias in Non-Randomized Studies of Interventions (ROBINS-1) tool. These studies showed a low risk of bias due to confounding. No studies excluded patients who were eligible or used variable follow-up times based on intervention. No studies deviated from the intended intervention and all clearly classified the type of treatment. The remaining 3 studies were evaluated using the Cochrane Collaboration risk of bias tool.
One study included only patients with Kellgren-Lawrence grade I to III OA (mean grade, 1.8±0.7); however, authors did not report on the number of patients per group or correlations between OA grade and outcome. Two studies only included patients with Kellgren-Lawrence grade I or II OA, and 1 included only patients with Kellgren-Lawrence grade III OA.
One study reported no study dropouts and no patients who required surgery or additional injections during the follow-up period. Another identified knees as responder or nonresponder, based on a limit of at least 25% improvement in VAS pain score at the final follow-up visit. In one study, 6 of 121 patients—5%—required a total knee arthroplasty procedure during the mean follow-up period of 11 months.
No complications of the injection were reported in any study.
Among all patient reported outcomes assessed, 94.4% demonstrated significant improvement in patients who received bone marrow aspirate concentrate therapy between baseline and the final follow-up. Three studies and 2 studies used the VAS and NRS, respectively, to report pain before and after injection. In all 5 of these studies, patients who had the injection reported significantly less pain at the last follow-up vs baseline.
Compared with other biologic therapies, bone marrow aspirate concentrate injections were associated with significant improvements in WOMAC and IKDC scores compared with PRP, but patient reported outcomes were not different between treatment groups. In another study of bone marrow aspirate concentrate vs MFAT injections saw significant improvement in KOOS, VAS, and EQUOL in both groups, but differences were nonsignificant at 1 year follow-up.
Study limitations include heterogeneity in injection technique and patient reported outcomes, a short mean follow-up time, and an inability to determine the regenerative potential of injections, which is beyond the scope of the study.
“[Bone marrow aspirate concentrate] injection is effective in improving pain and [patient reported outcomes] in patients with knee OA at short- to midterm follow-up,” researchers concluded. “Nevertheless, [bone marrow aspirate concentrate] has not demonstrated clinical superiority in relation to other biologic therapies commonly used in the treatment of OA.”
Keeling LE, Belk JW, Kraeutler MJ, et al. Bone marrow aspirate concentrate for the treatment of knee osteoarthritis: A systematic review. Am J Sports Med. Published online July 8, 2021. doi: 10.1177/03635465211018837