Bone marrow lesions in osteoarthritis: What lies beneath

Abstract

Osteoarthritis (OA) is the most common joint disease in the United States, affecting more than 30 million people, and is characterized by cartilage degeneration in articulating joints. OA can be viewed as a group of overlapping disorders, which result in functional joint failure. However, the precise cellular and molecular events within which lead to these clinically observable changes are neither well understood nor easily measurable. It is now clear that multiple factors, in multiple joint tissues, contribute to degeneration. Changes in subchondral bone are recognized as a hallmark of OA, but are normally associated with late-stage disease when degeneration is well established. However, early changes such as Bone Marrow Lesions (BMLs) in OA are a relatively recent discovery. BMLs are patterns from magnetic resonance images (MRI) that have been linked with pain and cartilage degeneration. Their potential utility in predicting progression, or as a target for therapy, is not yet fully understood. Here, we will review the current state-of-the-art in this field under three broad headings: (i) BMLs in symptomatic OA: malalignment, joint pain, and disease progression; (ii) biological considerations for bone-cartilage crosstalk in joint disease; and (iii) mechanical factors that may underlie BMLs and drive their communication with other joint tissues. Thus, this review will provide insights on this topic from a clinical, biological, and mechanical perspective. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1818-1825, 2018.

Keywords: Pain; TGF-β; bone-cartilage crosstalk; microdamage; subchondral.

Figure 1:

MR images in the sagittal plane of a knee joint with Bone Marrow Lesions (BMLs) in the subchondral compartments of the distal femur and proximal tibia. These are the regions of diffuse white signal within the bone compartment, denoted by arrows.

Figure 2:

The image shows articular cartilage overlaying sequentially the calcified cartilage layer, the subchondral bone plate and the subchondral trabecular bone. Potential treatments that might address the cartilage compartment, or the bone compartment, respectively, may also be protective of the other compartment, due to communication between the two. Thus, surgical distraction of the knee joint and HA treatment have been claimed to have efficacy for the cartilage clinically, and lubricin and TGF–β in animal models. Treatment of the bone compartment with anti-resorptives and anti-TGF-β at specific early time-points has been shown to have chondroprotective effects in animal models.

Figure 3:

Cyclic loading causes the initiation (orange) and propagation (green) of tissue microdamage in cancellous bone. Tissue material properties were associated with damage propagation. Microdamage and associated bone remodeling within a BML may therefore be influenced not only by applied mechanical loads but also by tissue material properties. From Torres et al. 2016 used with permission.