Heberden's nodes and what Heberden could not see: the pivotal role of ligaments in the pathogenesis of early nodal osteoarthritis and beyond.

Despite its relatively high prevalence, polyarticular nature, limited treatment options and recognized genetic contribution, the study of generalized OA (GOA) has lagged behind that of isolated knee OA. Whilst the pathogenesis of OA has been viewed in relation to either articular cartilage or bone disease, this article offers a viewpoint on why GOA may, in fact, be primarily a disorder of ligaments, and to a lesser extent tendon and joint capsule dysfunction. A relatively fast presentation of GOA, typically in the perimenopausal period, and its recognition on clinical grounds alone makes this type of OA potentially useful for pathogenic studies in OA, in general. The recent high-resolution MRI studies, microanatomical studies and animal models, in addition to established clinical and radiographic data that support this ligament-centric perspective of disease, are reviewed. The earliest structural abnormalities in GOA may be evident in ligaments and the ligament-associated 'enthesis organ', where degenerative changes are evident. Ligaments also influence the expression of joint damage including Heberden's node and joint erosion formation. Joint inflammation in a 'periarthritis' pattern is well recognized in GOA, and histological studies have shown that the ligament and capsule could represent the epicentre of such inflammatory changes. A perspective is also offered on how ligaments could play a pivotal role in OA in general; for example, the loss of joint space in knee OA due to meniscal extrusion could ultimately be related to derangement of the medial collateral ligament to which the meniscus is anchored.