What can we learn about osteoarthritis by studying a healthy person against a person with early onset of disease?

Purpose of review The structural changes of osteoarthritis are usually age-related and have long been regarded as irreversible. Using sensitive tools such as MRI in populations with relatively good knee health, including participants with a spectrum of knee structural changes from the healthy to those with the early changes of osteoarthritis, may help us to understand the trajectory of this disease from the earliest stages. Understanding pathogenic relationships at different stages of disease will help development of strategies for the prevention and treatment of osteoarthritis. This review aims to examine the recent epidemiological and clinical evidences of early knee structural changes in the younger populations with relatively healthy knees. Recent findings Knee structural changes assessed by MRI are far more common than radiographic changes. A cascade of changes in joint structure start from subchondral bone expansion, bone marrow lesions (BMLs), meniscal tears and extrusion, to cartilage defects, and ultimately, but not inevitably, lead to cartilage loss and radiographic osteoarthritis at late stage. BMLs and cartilage defects both have significant potential to reverse especially at a younger age. Furthermore, novel risk factors such as smoking, lipids, leptin, vitamin D deficiency, and inflammation have been associated with early knee structural changes. Summary Studying people from the healthy to those with early disease with new MRI techniques has enabled us understand the natural history of osteoarthritis and the effects of early risk factors. The changes in joint structure and risk factors identified in this population are potential targets for future interventions.