Advancing Regenerative Medicine: The Superior Potential of Subchondral Intraosseous Injections for Osteoarthritis and Spinal Conditions

In the evolving field of regenerative medicine, innovative approaches are transforming how we address chronic conditions like osteoarthritis (OA) in the knees, shoulders, and even spinal issues. Traditional treatments often focus on symptom management, but regenerative therapies aim to promote healing at the cellular level. Among these, platelet-rich plasma (PRP) and bone marrow concentrate (BMC) injections have gained prominence for their ability to harness the body's natural repair mechanisms. However, not all injection methods are created equal. While intra-articular injections—delivered directly into the joint space—are common and effective for many, emerging evidence highlights the advantages of subchondral intraosseous injections, which target the bone beneath the cartilage. This blog explores the science behind these techniques, dives into key studies comparing them, and discusses why advanced targeting can lead to better outcomes, particularly at specialized clinics like HyperCharge Health and the Institute for Regenerative Medicine.

Understanding the Basics: Intra-Articular vs. Subchondral Intraosseous Injections

Osteoarthritis isn't just a cartilage problem; it affects the entire joint, including the subchondral bone—the layer of bone just below the cartilage. This bone provides the primary blood supply to the cartilage, making it a critical area for regeneration. Intra-articular injections involve delivering PRP or other biologics directly into the joint fluid, where they can reduce inflammation, stimulate repair, and improve lubrication. These are straightforward procedures requiring standard ultrasound or fluoroscopic guidance and are widely available.

In contrast, subchondral intraosseous injections deliver the therapeutic agents directly into the subchondral bone. This method requires greater precision, often using advanced imaging like fluoroscopy or MRI guidance to navigate bone structures safely. By targeting the subchondral region, these injections can enhance vascularity (blood flow) in the bone, which in turn supports cartilage healing more effectively. Studies suggest this approach addresses underlying bone marrow lesions (BMLs)—areas of damaged bone associated with pain and progression in OA—leading to potentially superior long-term results. The increased technical demand means not every clinic offers it, but for patients with moderate to severe OA, it represents a step forward in personalized care.

Diving into the Literature: Comparing Outcomes for Knee Osteoarthritis

Knee OA is one of the most studied applications for regenerative injections, with compelling data favoring subchondral approaches over intra-articular alone, especially when using PRP or BMC.

A landmark randomized study by French orthopedic surgeon Dr. Philippe Hernigou and colleagues examined 60 patients with bilateral knee OA of similar severity. During a single procedure, bone marrow concentrate (containing mesenchymal stem cells) was injected subchondrally into one knee and intra-articularly into the other. At a 15-year follow-up, the subchondral group showed dramatically better results: only 20% of these knees required total knee arthroplasty (TKA), compared to 70% in the intra-articular group. Clinical scores (Knee Society score) and MRI improvements were also superior in the subchondral knees, with patients unanimously preferring that side if no further surgery was needed. The yearly TKA incidence was 1.3% for subchondral injections versus 4.6% for intra-articular, highlighting how targeting the bone can postpone or avoid invasive surgery more effectively.

In another Hernigou study involving 140 patients scheduled for bilateral TKA, one knee received subchondral BMC while the other underwent TKA. Over 15 years, the BMC-treated knees had an 18% rate of eventual TKA (at an average of 10 years post-injection), with an annual incidence of 1.19%—comparable to the revision rate for the TKAs on the contralateral side (1.00%). Notably, the regenerative side often required fewer additional procedures long-term, and regression of BMLs on MRI predicted better outcomes. Persistent large BMLs (>3 cm³) increased the risk of needing TKA fourfold, underscoring the importance of addressing subchondral pathology.

Other research supports these findings. A review of orthobiologic injections concluded that subchondral delivery may outperform intra-articular for OA management, as it better targets the osteochondral unit. Combined intra-articular and intraosseous PRP has been shown to reduce pain more effectively and decrease mesenchymal stem cells in synovial fluid, indicating improved joint homeostasis. In a study of severe knee OA, patients receiving both approaches experienced significant functional improvements, with intraosseous adding benefits by stimulating subchondral healing. While some trials found no added benefit from intraosseous PRP alone, the overall body of evidence points to enhanced efficacy, safety, and potential disease modification when the subchondral bone is targeted.

• Target Area:

  • Intra-Articular Injections (e.g., PRP): Joint space and synovial fluid

  • Subchondral Intraosseous Injections (e.g., PRP/BMC): Bone beneath cartilage (subchondral region)

• Technical Complexity:

  • Intra-Articular Injections (e.g., PRP): Moderate; standard guidance

  • Subchondral Intraosseous Injections (e.g., PRP/BMC): High; requires precise bone navigation

• Key Benefits:

  • Intra-Articular Injections (e.g., PRP): Reduces inflammation, improves function

  • Subchondral Intraosseous Injections (e.g., PRP/BMC): Enhances vascularity, addresses BMLs, better long-term regeneration

• Literature Support:

  • Intra-Articular Injections (e.g., PRP): Effective for mild-moderate OA; short-term pain relief

  • Subchondral Intraosseous Injections (e.g., PRP/BMC): Superior for severe OA; postpones TKA (e.g., 20% vs. 70% at 15 years)

• Risks / Safety:

  • Intra-Articular Injections (e.g., PRP): Low; minimal invasiveness

  • Subchondral Intraosseous Injections (e.g., PRP/BMC): Low; safe with imaging guidance, but demands expertise

• Outcomes Example:

  • Intra-Articular Injections (e.g., PRP): Pain reduction in 70-80% of cases

  • Subchondral Intraosseous Injections (e.g., PRP/BMC): 80% avoidance of surgery at 15 years in some studies

Extending to Shoulder Osteoarthritis and Spinal Conditions

The principles of subchondral intraosseous injections extend beyond knees. For shoulder OA, where cartilage degeneration affects the glenoid or humeral head, intraosseous delivery can target subchondral bone to improve blood supply and promote repair. While shoulder-specific studies are emerging, general joint research shows intraosseous PRP enhances cartilage and bone healing more than intra-articular alone, with longer-lasting effects. This is particularly valuable for active individuals seeking to avoid shoulder arthroplasty.

For spinal conditions like discogenic low back pain or vertebral OA, vertebral intraosseous injections of PRP (often combined with intradiscal) have shown promise. A study on plasma rich in growth factors (PRGF-Endoret) injected into vertebrae and discs reported significant pain relief, functional improvement, and structural regeneration on imaging, with no adverse events. By stimulating bone and disc healing, this approach offers a minimally invasive alternative to surgery for conditions like facet OA or vertebral compression.

Expert Insights on Subchondral Injections

Leading experts in stem cell and regenerative medicine underscore the advantages of subchondral intraosseous injections, particularly when used in addition to intra-articular approaches. Dr. Philippe Hernigou, a pioneering French orthopedic surgeon, emphasizes: "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."

A systematic review highlights the promise of this method: "Considering the involvement of subchondral pathology in OA and the limitations of IA injections, intraosseous (IO) treatment modalities such as IO injections of platelet-rich plasma (PRP) and subchondroplasty (SCP) are promising, as they are thought to provide a supportive environment for cartilage repair by targeting proinflammatory mediators and improving structural integrity in the subchondral bone."

Dr. Mikel Sánchez and colleagues note the broader benefits: "The importance of treating KOA as a whole-organ disease has recently been demonstrated by the finding that the microchannel network of the subchondral bone is already modified and shows collective structural deterioration in the early stages of KOA." These insights reinforce how targeting the subchondral bone can enhance overall joint regeneration beyond what intra-articular injections achieve alone.

Why Expertise Matters: Differentiating Advanced Care

While intra-articular injections are a solid foundation in regenerative medicine and accessible at many clinics, subchondral intraosseous procedures require specialized skills to ensure safety and efficacy. This precision allows for more comprehensive healing by directly addressing the subchondral bone's role in cartilage nutrition and joint stability. Clinics equipped to perform these—often under fluoroscopic guidance in an outpatient setting—can offer patients a distinct advantage, potentially leading to better regeneration and fewer interventions down the line.

At HyperCharge Health and the Institute for Regenerative Medicine in Edina, Minnesota, led by board-certified anesthesiologist and pain medicine specialist Dr. Louis Saeger, patients benefit from this cutting-edge approach. As the only clinic in Minnesota currently offering subchondral intraosseous injections for extremities and spine, they stand out by providing personalized, advanced regenerative options that go beyond routine intra-articular treatments. Dr. Saeger's expertise in interventional pain and regenerative medicine ensures procedures are tailored to maximize healing, drawing on the latest evidence to help patients reclaim mobility without unnecessary surgery.

Embracing Innovation for Better Healing

Regenerative medicine is about empowering the body to heal itself, and subchondral intraosseous injections represent a powerful evolution in this field. By targeting the source of cartilage's blood supply, these techniques offer superior results compared to intra-articular PRP alone, as evidenced by long-term studies like those from Dr. Hernigou. For those dealing with knee, shoulder, or spinal OA, exploring these options could mean less pain, improved function, and delayed progression. Whether you're in Minnesota, the Midwest, or anywhere in the United States, Dr. Saeger and the team at HyperCharge Health are happy to provide in-person discovery consultations or discovery calls to discuss whether these techniques may be right for you. Always discuss with a qualified provider to weigh benefits based on your unique condition.

Bibliography

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2. Hernigou, P., et al. (2020). Human bone marrow mesenchymal stem cell injection in subchondral lesions of knee osteoarthritis: what better postpone or avoid total knee arthroplasty? Randomized study of two protocols with 5 year follow-up. International Orthopaedics. Available at: https://pubmed.ncbi.nlm.nih.gov/32322943/

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