Bone marrow aspirate concentrate (BMAC)

Bone marrow is aspirated from the iliac crest, spun down, and reinjected into the knee. The concentrate carries platelets, growth factors, IL-1 receptor antagonist — and mesenchymal stromal cells at very low frequency, typically less than 0.01% of nucleated cells. The claimed mechanism is trophic and anti-inflammatory signaling, not engraftment, and no human trial has shown a structural cartilage effect from a BMAC injection.

The placebo test

Only one trial has put BMAC against saline: Shapiro 2017, in 25 patients with bilateral knee OA — BMAC in one knee, saline in the other. Pain dropped dramatically in both knees at 1 week, 3 months, and 6 months, with no significant difference between them. That pattern is what a large placebo and natural-history effect looks like, not a BMAC-specific one. No adequately powered BMAC-versus-saline trial has read out since.

The comparative trials

Against active comparators, the story repeats. Anz 2022 randomized 90 patients to a single BMAC or a single leukocyte-rich PRP injection: both groups improved through 24 months with no difference at any time point — BMAC's extra cost and harvest morbidity bought nothing over PRP. Dulic 2021 (175 patients across BMAC, PRP, and HA arms) found improvement everywhere; at 12 months BMAC separated from hyaluronic acid on every score and from PRP on none. That one advantage carries a caveat the paper's own methods supply — patients were not randomized into the BMAC arm, which was treated sequentially through 2016 before randomization began the following year between the HA and PRP arms — and two of the scores BMAC won on already favored it before treatment.

Mautner 2023 is the largest of them: a 480-patient phase 3 trial in Nature Medicine, the largest US orthobiologics RCT to date. BMAC, adipose stromal vascular fraction, and umbilical-cord-tissue MSCs were each compared with a single corticosteroid injection. At 12 months, no cell product was superior to the steroid shot, or to each other.

A systematic review of 8 studies (299 knees) captures the field: 94% of reported outcome measures improved from baseline, and not one comparative study showed superiority over PRP, microfragmented fat, or placebo. Improvement-from-baseline is exactly what saline delivers too.

The cell content of the concentrate

BMAC is not a stem-cell-dose product — the MSC content of point-of-care concentrate is orders of magnitude below the defined doses used in culture-expanded-cell trials (see the cultured MSC entry). Preparation systems vary widely, cell counts are rarely reported or standardized, and the field's own systematic review flags cost without demonstrated superiority.

Practical notes

Trials used a single injection of concentrate from roughly 30–120 mL of aspirate. The procedure adds a bone-marrow harvest — local pain, rare donor-site complications — and typically costs thousands of dollars out-of-pocket. Nothing in the comparative literature justifies choosing BMAC over cheaper injections.

Safety

No procedure-related serious adverse events in the cited RCTs, including the 480-patient trial, which did record post-procedural contusion in 12.2% of its BMAC arm and none in the steroid arm. Expect aspiration-site soreness and a transient injection flare. The main risks are financial, plus forgoing options with better-characterized benefit.

What would change the tier

An adequately powered BMAC-versus-saline trial; standardized reporting of cell counts per injection; and evidence that any subgroup — younger patients, earlier disease — actually benefits. None of the trials run so far was designed to answer these.