Abstract

Osteoarthritis (OA) is the most prevalent form of arthritis worldwide and affects the whole joint. Changes in cartilage integrity, subchondral bone, and synovitis are recognised during OA progression. Although advances have been made in our understanding of OA pathophysiology, there are no current treatments that halt the progression of the disease. Treatments are largely based on physical therapies to improve joint function, anti-inflammatory agents to manage pain, and joint replacement surgery for late-stage disease in large weight-bearing joints. There is, therefore, an urgent need to better understand OA pathophysiology, which could help in the development of new treatments. The aim of this article is to review the evidence for structural correlates of pain and reduced joint function in OA; the data available for different joint compartments, including cartilage, bone, and the synovium, and their association with symptoms of OA are summarised and the use of imaging tools in assisting the understanding of OA pathophysiology is discussed. In recent years, more advanced imaging techniques, including MRI, have led to an improved understanding of changes at the bone–cartilage interface in OA, with a recognition that loss of integrity at this junction and development of bone marrow lesions (BML) in the subchondral bone are associated with OA pain in large epidemiological studies. One of the main challenges in OA BML research has been identifying the structural characteristics and patterns of gene and protein expression. Gene analyses of BML have demonstrated that they are highly metabolically active structures, providing evidence of angiogenesis, new bone and cartilage formation, and expression of neurotrophic factors. Findings from genomic and proteomic studies of BML, which are discussed in this review, have contributed to the identification of new molecular targets and an increase in our understanding of OA pathophysiology.