Bone marrow lesions in osteoarthritis: Characterising genetic and histological changes to understand disease pathophysiology

Osteoarthritis (OA) is a chronic debilitating condition that affects the whole joint. There are several sources of pain in OA that include the synovium, bone, including osteophytes and more recently bone marrow lesions (BML) that correlate with pain. Recent studies have shown that the bone compartment contributes to pain in OA through the development of OA-BMLs which are richly innervated and demonstrate angiogenesis. The synovium is also innervated in OA tissue and is another distinct source of pain, with imaging and genetic studies supporting the observation that synovitis is an important component of pain in OA. Previous studies using magnetic resonance imaging (MRI) have shown that bone marrow lesions (BMLs), observed as high intensity signal on T2 fat-suppressed imaging sequences, are commonly found in OA and are associated with progression of pain symptoms. Recent studies have described the genetic signature of BMLs and the characteristic histological changes of BML tissue. In this narrative review we describe the recent developments in the discovery of the gene expression profiles identified from BMLs. We also review the recently characterised histological changes from BMLs in large weight-bearing joints including the knee and hip. Finally, we discuss the implications of new genetic and histological findings in BML in the context of new developments for pharmacological therapies in OA.