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Bone Marrow Injections in Orthopedics

(Bone Marrow Aspirate / Bone Marrow Aspirate Concentrate - BMA/BMAC)

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1. Introduction and Background

• Mesenchymal Stem Cells (MSCs) - the key regenerative cells, comprising 0.001-0.01% of the bone marrow
• Hematopoietic progenitor cells
• Endothelial progenitor cells
• Growth factors: PDGF, TGF-β, BMP-2, BMP-7, VEGF, IGF-1
• Anti-inflammatory cytokines: IL-1ra, IL-10, IL-4

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2. Biological Basis and Mechanism of Action

2.1 Why Bone Marrow?

• Osteoblasts - for bone repair
• Chondrocytes - for cartilage regeneration
• Tenocytes - for tendon healing
• Fibroblasts - for soft tissue repair

2.2 Mechanisms

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3. Harvest Sites

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4. Methodology - Step-by-Step Procedure

4.1 Pre-Procedure

• Baseline blood tests: CBC, coagulation profile
• Patient counseling and informed consent
• Cessation of NSAIDs 5-7 days before procedure (reduces platelet function interference)
• Positioning: Prone (posterior iliac approach) or supine (anterior iliac approach)
• Sterile field preparation
• Anesthesia: Monitored anesthesia care (conscious sedation) or local anesthetic infiltration (1% lidocaine to skin, periosteum)

4.2 Bone Marrow Aspiration

• Bone marrow aspiration needle/cannula (e.g., Jamshidi needle, 11G or 8G)
• Anticoagulant-lined syringes (ACD-A - Acid Citrate Dextrose Solution A to prevent clotting)
• 10-60 mL syringes

1. Palpate and mark the posterior superior iliac spine (PSIS)
2. Make a 5-7 mm stab incision through skin and subcutaneous tissue
3. Insert the trocar cannula through the incision down to the iliac cortex
4. Advance through the outer cortex into the cancellous bone with a rotational motion under controlled force
5. Remove the trocar; confirm position - the cannula should be seated in cancellous bone
6. Attach an ACD-A-primed syringe and aspirate 5-10 mL per site
7. To obtain additional marrow, withdraw the needle slightly and redirect at a new angle (do NOT aspirate >10-15 mL per insertion - excessive volume dilutes with peripheral blood, reducing MSC concentration)
8. Repeat at 2-4 separate insertion sites within the same skin incision to collect 60-120 mL total aspirate

Key technical point: Each syringe should contain only 5-10 mL per position to maintain MSC concentration. Large-volume aspiration from a single site dilutes with sinusoidal blood and reduces cell yield significantly.

4.3 Processing - Centrifugation (BMAC Preparation)

• Single-spin systems (e.g., Arthrex Angel, Harvest SmartPrep, Zimmer BioCUE)
• Double-spin / density gradient systems (Ficoll or similar)

1. Transfer aspirate to centrifuge tubes containing anticoagulant
2. Centrifuge at 1,500-3,200 rpm for 7-15 minutes (system dependent)
3. Results in 3 layers:
   • Bottom: Red blood cells and granulocytes (discarded)
   • Middle (buffy coat): MSCs, platelets, mononuclear cells - the target layer
   • Top: Platelet-poor plasma
4. Carefully extract the buffy coat layer (approximately 3-7 mL from 60 mL aspirate)
5. The final BMAC product is ~6x concentrated compared to raw aspirate

From Rockwood and Green (2025): A typical 300 cm³ aspirate concentrates to approximately 50 cm³ with an average of 2,579 ± 1,121 MSCs/cm³.

4.4 Injection of BMAC

• Injection is performed image-guided (ultrasound or fluoroscopy) for intra-articular/precise delivery
• Volume injected: typically 3-7 mL
• For intra-articular (knee, hip, shoulder): single or combined with hyaluronic acid
• For nonunion/fracture: percutaneous injection directly into fracture gap under fluoroscopy
• For osteochondral defects: arthroscopic delivery onto defect site, often mixed with scaffold material
• For spinal fusion: mixed with allograft or osteoconductive matrix

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5. Indications

5.1 Established / Widely Used

5.2 Regenerative / Biologics Applications

5.3 Open Fractures

• Bone healing rate: 87.4% (vs 50.7% in controls)
• Significantly lower infection risk

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6. Contraindications

6.1 Absolute Contraindications

6.2 Relative Contraindications

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7. Advantages

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8. Disadvantages and Limitations

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9. Complications

Harvest Site (Iliac Crest)

• Donor site pain (most common, 3-7 days)
• Hematoma at harvest site
• Injury to lateral femoral cutaneous nerve (LFCN) - paresthesia/meralgia paresthetica
• Superior gluteal artery injury (rare)
• Iliac wing fracture (very rare, usually with osteoporotic bone)
• Infection at harvest site

Injection Site

• Transient pain and swelling (most common)
• Infection (rare due to autologous nature)
• Hematoma
• Neurovascular injury (ultrasound guidance reduces this risk)
• Theoretical tumor promotion (in undetected malignancy)

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10. Comparison with Other Biologics

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11. From the Operative Orthopaedics Textbook

"When mixed with autogenous bone or perhaps even host bone marrow aspirate (BMA) or bone marrow aspirate concentrate (BMAC), cancellous allograft can be used in nonstructural applications... High-quality evidence comparing autogenous autograft with allograft combined with BMA or BMAC is lacking."

"Satisfactory patient-reported outcomes and superior MRI results have been noted with micronized allogenic cartilage ECM with bone marrow concentrate (BMAC) compared with microfracture alone in arthroscopic repair of osteochondral talar lesions."

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12. Special Considerations by Condition

12.1 Fracture Nonunion

• Best results in atrophic nonunions with adequate bone stock
• Percutaneous injection under fluoroscopy directly into fracture gap
• BMAC can be loaded onto scaffolds (bioactive glass, calcium phosphate)
• Evidence supports use in septic nonunion where BMAC reduced reinfection rate

12.2 Knee Osteoarthritis

• Most studied BMAC application
• Typical injection volume: 5-7 mL intra-articular
• Can be combined with HA for synergistic effect
• 4-year follow-up data (Pabinger et al., Sci Reports 2024) shows sustained benefit even in KL Grade III-IV
• Obese patients (high BMI) show significantly less benefit

12.3 Avascular Necrosis (AVN) of Femoral Head

• Standard approach: core decompression + BMAC injection into necrotic zone
• Best results in Steinberg Stage I-III (pre-collapse)
• BMAC promotes revascularization through VEGF and angiogenic factors

12.4 Osteochondral Defects

• Delivered arthroscopically in combination with cartilage ECM scaffolds
• BMAC provides MSCs that differentiate into chondrocyte-like cells within the scaffold
• Superior MRI and patient-reported outcomes vs microfracture alone

12.5 Spinal Fusion

• BMAC mixed with allograft in interbody or posterolateral fusion
• Augments osteogenic potential of allograft, which has limited intrinsic osteogenesis

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13. Post-Procedure Care

• Activity restriction for 24-48 hours
• Ice and elevation of treated joint
• Avoid NSAIDs for 2-4 weeks post-injection (may impair MSC activity)
• Physical therapy can begin at 2-4 weeks
• Pain and swelling at injection site typically resolve within 3-7 days
• Clinical improvement often noted at 4-8 weeks, with maximum benefit at 3-6 months
• Full procedure time: approximately 2 hours (harvest + processing + injection)

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14. Current Evidence Summary and Future Directions

• BMAC is superior to hyaluronic acid for knee OA at 6+ months (Level I-II)
• BMAC is safe with minimal adverse events across all orthopedic applications
• BMAC combined with scaffolds improves osteochondral repair vs microfracture alone
• Early BMAC injection in open fractures significantly reduces infection risk and improves healing

• Lack of large RCTs with long-term follow-up
• No standardized centrifugation protocols
• Variability in MSC content between patients and centers
• Reimbursement challenges limit widespread adoption
• Multiple clinical trials ongoing (NCT05517434 ABLE OA trial completing 2026)

• BMAC combined with 3D bioprinted scaffolds
• Ex vivo expansion of MSCs (regulatory pathway under FDA IND)
• Combined BMAC + gene-activated matrices (BMP gene therapy)
• Point-of-care MSC quantification to predict responders

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Key References

• Campbell's Operative Orthopaedics, 15th Ed. 2026 (Elsevier)
• Rockwood and Green's Fractures in Adults, 10th Ed. 2025 (Wolters Kluwer)
• Belk JW et al. Arthroscopy 2023 [PMID 36913992] - Meta-analysis: BMAC/PRP > HA for knee OA
• Jawanda H et al. Arthroscopy 2024 [PMID 38331363] - Network meta-analysis: BMAC/PRP/HA > Corticosteroids
• Moyal AJ et al. Eur J Orthop Surg Traumatol 2024 [PMID 39060552] - BMAC in long-bone nonunion
• Pabinger C et al. Sci Reports 2024 - 4-year results of BMAC for KL III-IV knee OA
• Zimmer Biomet Bone Marrow Aspiration Surgical Technique Guide
• Cleveland Clinic BMAC Procedure Overview