(Rochester, NY) - Researchers have unraveled some of the mechanisms by which psoriatic arthritis (PsA) causes such extensive and characteristic bone damage, which is quite different from that seen in rheumatoid arthritis. The new information helps explain the success of anti-TNF medication in PsA, and may also open doors for new approaches to its treatment.

Dr. Christopher Ritchlin (University of Rochester Medical Center, NY) and colleagues reported their work in the March 2003 issue of the Journal of Clinical Investigation. They studied 30 patients with PsA and 12 healthy volunteers.

One of the main findings was that compared to the healthy volunteers, the people with PsA had much higher numbers of circulating osteoclast precursors (OCPs). These are cells that progress into mature osteoclasts, the principal cells for bone resorption. Bone resorption is the process in which bone is removed from the body. This finding was most striking in those who had bone erosions visible on a plan x-ray - they had much higher circulating OCP levels than patients without such erosions.

Their transformation into mature osteoclasts is also distorted in PsA patients. Normally, this process requires the presence of two different signals, but in people with PsA, the precursor cells transform into mature osteoclasts without either signal.

The researchers also found that osteoclasts were attacking the bone in two different regions (within the bone as had been expected, but also deep within the bone). "We've found nests of osteoclasts deep within the bone, just perched and ready to attack. These are big monster cells - giant compared with other nearby cells. They appear to migrate toward the joint, where they do their damage," says Ritchlin.

This new information may help in developing new ways of tracking and predicting the course of PsA, and opening up new drug strategies.

Another key finding from this study explained the success of anti-TNF therapy in PsA. Previous studies have shown that TNF is involved in creating the greater number of osteoclast precursors seen in PsA. Now Ritchlin and colleagues have shown that anti-TNF therapy produced a significant decline in the number of osteoclast precursor cells - and this is unparalleled clinical improvement. They predict that anti-TNF medications "may prove to be an effective strategy for inhibiting bone destruction in PsA."

Etanercept (Enbrel) is the only drug approved specifically for use in psoriatic arthritis.