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

Abstract

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.

Keywords: Bone marrow lesions; Genetics; Osteoarthritis; Osteoarthritis bone score.

Fig. 1

Modified Prisma Flow Diagram for study identification. *Duplicate studies, or not in English language.

Fig. 2

Presence of OA-BML in knee and hand OA. Results from imaging and tissue analysis in knee and hand osteoarthritis from the Pain Perception in Osteoarthritis study (the study was conducted with full Ethical Approval, Research Ethics Committee approval number 12/LO/1970). A. Magnetic Resonance Imaging (MRI) scan of knee of participant with osteoarthritis demonstrating osteophytes, synovitis, cartilage degradation and bone marrow lesions. B. Magnetic Resonance Imaging (MRI) scan of hand participant with osteoarthritis demonstrating cartilage degradation and bone marrow lesions. C. Histological section of medial tibial subchondral knee tissue from participant with OA-BML. D. Trapezium bone from participant with hand OA undergoing trapeziectomy. The 7 typical features showing OA-BML changes include Cysts (C), Fibrosis (F), blood vessels (BV), Thickened trabeculae (T), cartilage (Ca), tidemark integrity (TM), inflammation (I) which comprise the Osteoarthritis Bone Score (OABS).

Fig. 3

Bone marrow lesions caused by alternative pathologies to OA. A. BML caused by trauma: Coronal fat-suppressed intermediate-weighted MRI shows hyperintensity of the posterior lateral tibial plateau, but there is no fracture line (arrows). There is also a smaller hyperintense lesion is visible at the posterior medial tibia (arrowhead). There is also a traumatic anterior cruciate ligament tear (asterisk) and the bone marrow changes are consistent with bone contusions found in association with the cruciate ligament tear. B. BML caused by Subchondral Insufficiency Fracture (SIF). Coronal fat-suppressed MRI shows a subchondral linear hypo-intensity zone directly adjacent to the normal subchondral plate (short arrow) at the medial femoral condyle. There is also extensive bone marrow hyperintensity of the femoral condyle (‘bone marrow oedema’, asterisk) and soft tissue hyperintensity (‘inflammation’) at the medial joint line (arrowheads). Subchondral linear hypo-intensity is pathognomonic for SIF. There is also full-thickness cartilage loss at the central medial femur (long arrow) and meniscal extrusion due to a posterior medial meniscus root tear, which are commonly found with SIF.