LEEDS, UK—Heberden's nodes [Figure 1], first described by William Heberden in 1802, may offer important clues to an unresolved question in rheumatology: how osteoarthritis (OA) develops in the untraumatized joint. Dennis McGonagle, FRCP, PhD, says that ligaments play a key role in the pathogenesis of early nodal OA.1

“Joint inflammation in a 'periarthritis' pattern is well recognized in generalized OA, and histological studies have shown that the ligament and capsule could represent the epicentre of such inflammatory changes.”—Dennis McGonagle, FRCP, PhD
“The earliest structural abnormalities in [generalized] OA 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 generalized OA, and histological studies have shown that the ligament and capsule could represent the epicentre of such inflammatory changes.”

Figure 1: Heberden's node. High-res MRI points to ligaments in hand OA

Much of the new understanding of OA pathology, particularly in the hand, is the result of high-resolution magnetic resonance imaging studies that have revealed previously unappreciated elements associated with joint inflammation and joint erosion, especially in joints that appeared uninvolved on routine X-ray.

“[I]t was established that chronic symptomatic OA was a disease that affected virtually every joint tissue and in which there was florid joint degeneration, inflammation, or both. In chronic disease, the most striking abnormality was disruption of the collateral ligements of the PIP [proximal interphalangeal] and DIP [distal interphalangeal]  joints,” Dr. McGonagle said.

Furthermore, since ligament position predicted adjacent weakness in the joint capsules, there was clearly a relationship between Heberden's nodes and the collateral ligaments. “It was at these sites that acute Heberden's node tissue could be seen to bulge out in a manner reminiscent of Baker's cyst formation in the arthritis knee,” Dr. McGonagle said.

These areas were also associated with osteophyte formation and with bony spurs or enthesophytes. Finally, the position of the ligaments was a good indicator of MRI-determined bone erosions.

The importance of collateral ligaments in the hand
Because nodal OA is often asymmetric at presentation but eventually involves DIP and PIP joints in both hands, the researchers imaged asymptomatic joints that were radiographically normal at presentation, on the theory that these joints represented preclinical OA. They found that most of the joint structures were normal but that there was characteristic thickening of the joint collateral ligaments [Figure 2].


Figure 2. Source: Rheumatology. 2008;47:1281.1

In the hand, the collateral ligaments are large relative to the size of the joint and to the articular cartilage due to the need to prevent abduction and adduction of the IP joints. This permits the hand both to grip fairly large objects and to act as a fine “precision” tool. However, these ligaments are not just reinforcing cables for joint capsules. “Unlike articular cartilage, ligaments are vascularized, and when they are injured, there is a typical inflammatory reaction with remodeling and repair,” Dr. McGonagle explained. In early OA, this might explain inflammation that can be extensive and involve the periarticular tissues even when the cartilage looks normal.

“[A]n epicentre of inflammation in the ligament or capsule, rather than the synovium, could explain the 'periarthritis' or extracapsular pattern of hand inflammation in [generalized] OA.” A similar sequence might partly explain why anterior cruciate ligament (ACL) injury is associated with progress OA of the knee. Dr. McGonagle suggested that ligament involvement might also be the cause of degenerative disease of the lumbar spine.

“This perspective argues for a pivotal role for joint ligaments in the phenotypic expression of [generalized] OA, but many of the arguments herein are equally relevant to tendon insertions and immediately adjacent tissues, since these are functionally linked with ligaments,” he added.

In an accompanying editorial, Fraser Birrell, MD, and N. K. Arden, MD, comment, “The hypothesis is provocative and should stimulate others to reproduce their findings and to explore them further using longitudinal cohort studies in order to establish a robust temporal frame for these changes. In the meantime, we should factor the ligaments into our theoretical frameworks of the pathogenesis of hand OA.”

References

1. McGonagle D, Tan AL, Grainger AJ, Benjamin M. Heberden's nodes and what Heberden could not see: the pivotal role of ligaments in the pathogenesis of early nodal osteoarthritis and beyond. Rheumatology. 2008;47:1278-1285.
2. Birrell F, Arden NK. A view on the pathogenesis of osteoarthritis from the shoulders of giants. Rheumatology. 2008;47:1263-1264.