Bone Marrow Lesions: Are They the Canary in the Osteoarthritis and Disc Degeneration Coal Mine?

Key Takeaways

* Nomenclature Shift: BMLs are not "edema" (fluid); they are active lesions of fibrosis, microfracture, and necrosis. 

* Predictive Power: Progressive BMLs carry a threefold higher risk of rapid radiographic OA onset (Moradi et al., 2024). 

* The Spine Connection: In the vertebral column, these lesions are clinically recognized as Modic Changes, sharing the same inflammatory pathology as knee BMLs. 

* Therapeutic Target: Long-term data suggest subchondral biologic delivery may outperform intra-articular injection for preventing arthroplasty, provided mechanical alignment is preserved.

Introduction: Osteoarthritis Beyond Cartilage

Osteoarthritis (OA) has traditionally been framed as a disease of cartilage wear—a gradual erosion of a tissue with limited intrinsic healing capacity. Yet, this cartilage-centric view has long struggled to explain a fundamental clinical reality: symptoms, imaging findings, and disease progression frequently do not align. Patients with minimal radiographic cartilage loss may experience severe pain, while others with advanced cartilage thinning remain relatively asymptomatic.

Over the past two decades, advances in MRI have exposed a more complex picture. Among the most consequential findings is the identification of bone marrow lesions (BMLs) within the subchondral bone. Once dismissed as incidental “edema,” BMLs are now viewed as biologically active lesions that may precede and predict cartilage degeneration. They function as an early warning signal within the osteochondral unit.

What Are Bone Marrow Lesions—And What Are They Not?

Historically labeled “bone marrow edema,” this terminology implies fluid accumulation. However, histologic correlation studies challenge that assumption. Pathologic analyses demonstrate that BMLs are not simple fluid cysts; they are composite biological responses to mechanical overload containing:

• Trabecular microfractures 

• Fibrosis and necrosis 

• Increased vascularity and venous congestion 

True interstitial edema is often minimal. As a result, “bone marrow lesion” is a more accurate descriptor than “edema”. This distinction matters: it reframes BMLs not as passive imaging artifacts, but as markers of active subchondral pathology requiring biologic stabilization.

The Predictive Value: The "Threefold Risk"

Longitudinal imaging studies consistently demonstrate that BMLs are not static. Their trajectory correlates directly with clinical outcomes. Data from the Osteoarthritis Initiative show that increases in BML volume are associated with accelerated cartilage loss and a higher risk of symptomatic OA.

Most notably, the 2024 Moradi et al. analysis demonstrated that knees with progressive BML volume had a threefold higher risk of developing radiographic OA compared with BML-free knees, even after adjusting for confounders. It is not merely the presence of a BML that matters—but its trajectory over time.

The "Treatment Gap": Why This Matters for Industry & Practice

For medical executives and innovators, BMLs represent the "missing link" in the care continuum. If OA is a whole-joint disease, treatments confined to the joint space (intra-articular) may miss key drivers of progression. Intra-articular therapies can modulate synovitis, but they often have limited impact on subchondral pathology.

This creates a massive "Treatment Gap": millions of patients who fail NSAIDs and physical therapy but are considered "too young" or "not severe enough" for total joint arthroplasty. Targeting the subchondral bone offers an intraosseous (IO) approach designed to modify abnormal remodeling and restore a favorable mechanical environment. Conceptually, this mirrors fracture biology more than cartilage repair.

The Clinical Evidence: Promise and "Failure Criteria"

Several clinical studies have explored intraosseous delivery of bone marrow–derived biologics to target these lesions. The most pertinent data comes from Hernigou and colleagues, who compared intra-articular versus subchondral bone delivery of bone marrow concentrate (BMC) in knee OA.

At long-term follow-up (mean 15 years), knees treated at the subchondral level demonstrated better clinical scores and lower rates of progression to arthroplasty. The authors hypothesized that targeting areas of low native progenitor cell density within subchondral bone may offer advantages over intra-articular delivery alone.

However, biology cannot overcome physics. It is critical to note that subchondral injection is not a "silver bullet" for all comers. The literature suggests that IO therapies are less effective where significant mechanical malalignment (varus/valgus deformity) remains uncorrected. The ideal target appears to be the patient with active metabolic subchondral pathology but a preserved mechanical axis.

Beyond the Knee: The Spine Connection (Modic Changes)

While most data focuses on the knee, the osteochondral unit concept is not joint-specific.

• Hip: Subchondral changes are evident in the femoral head.

• Spine: In the vertebral column, these BMLs are clinically recognized as Modic Changes (specifically Type 1). Just as in the knee, these inflammatory vertebral endplate changes correlate strongly with pain, often independently of disc height loss.

Recognizing that "Modic Changes" and "BMLs" are essentially the same pathologic entity allows spine and sports medicine specialists to share therapeutic insights.

Closing Thoughts: Listening to the Canary

Bone marrow lesions may not be the sole cause of osteoarthritis—but the literature increasingly suggests they are among its earliest and most informative signals. They sit at the intersection of mechanics, biology, and symptoms.

For the clinician, BMLs offer a window into disease activity before irreversible cartilage loss occurs. For the industry, they represent a distinct, treatable target that addresses the massive patient population stuck in the treatment gap.

The canary does not stop the collapse—but it tells us something important is happening. And for the first time, we may have the tools to intervene.