ERLANGEN, Germany—Inflammatory infiltrates into the bone marrow are responsible for the bone erosions and bone marrow edema seen with magnetic resonance imaging (MRI) in many rheumatoid arthritis (RA) patients, according to a histopathology study reported by Esther Jimenez-Boj, MD, and colleagues in Arthritis & Rheumatism.1

"The present results show that MRI bone erosions as well as MRI bone marrow edema/osteitis reflect bone marrow inflammation. This indicates that, in addition to the synovial membrane, juxta-articular parts of the bone marrow are inflamed in RA, suggesting active involvement of this compartment in the inflammatory process. These findings reveal a previously uncharacterized component of the pathophysiology of RA," Dr. Jimenez-Boj, at the Medical University of Vienna, in Austria, writes.

Preop MRI linked to extensive histologic examination of excised joints

The researchers analyzed 12 different joints from three RA patients who were having total joint replacement of the proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints. The patients were all female, ages 43, 56, and 61 years, with RA duration of 8, 14, and 24 years. All were taking methotrexate (15 mg/week) and low-dose glucocorticoids (5 mg/day). The joints' affected metacarpal or proximal phalangeal heads were resected and replaced with silicone spacers.

All joints were scanned by MRI on the day before surgery, and 3-dimensional orientation of the excised joints was carefully documented to permit correct orientation with the MRI images. About 70 serial sections of each joint were stained with hematoxylin and eosin and analyzed for degree of bone marrow alteration.

MRI lesions were defined as erosions if they were localized close to cortical bone and associated with synovitis, and defined as edema/osteitis if the lesions were more diffuse in the bone marrow. Both types of lesions reflect increased water content and decreased fat content in the marrow, either because bone marrow fat is replaced by water or because it is replaced by structures containing more water and less fat than normal bone marrow.

In all 12 joints examined, the MRI lesions corresponded to histologic signs of bone marrow inflammation.

Analysis of histologic sections corresponding with areas of MRI bone erosion showed that erosion was due to "localized replacement of bone marrow fat by accumulated inflammatory cells adjacent to a broken cortical bone barrier," the researchers report. The accumulated inflammatory tissue was either "synovial inflammatory tissue or lymphocytic B-cell-rich aggregates within the marrow space."

Analysis of sections corresponding with areas of MRI bone marrow edema, a more diffuse signal, also showed infiltration of the bone marrow by inflammatory tissue. "This lends more credence to the term ‘osteitis' rather than ‘bone marrow edema'," the authors comment.

First demonstration in which parts of marrow near joint are inflamed in RA

"The fact that MR techniques have revealed profound changes in a previously uncharacterized compartment of the rheumatoid joint, beneath the inflamed surface, is of particular interest," the investigators note. The study demonstrates that parts of the bone marrow near the affected joint are inflamed in RA patients with late-stage disease.

"MRI bone erosions and . . . bone marrow edema are due to the formation of inflammatory infiltrates in the bone marrow of patients with RA. This emphasizes the value of MRI in sensitively detecting inflammatory tissue in the bone marrow and demonstrates that the inflammatory process extends to the bone marrow cavity, which is an additional target structure for anti-inflammatory therapy," Dr. Jimenez-Boj concludes.

James F. Fries, MD, professor of immunology and rheumatology at Stanford University School of Medicine, in California, told CIAOMed that he finds this study suggestive rather than convincing. "I doubt if it has clinical utility; certainly not now. It would have to predict response to particular treatment rather than to just serve as one of many measures of severity, Dr. Fries said.

Reference

1. Jimenez-Boj E, Nöbauer-Huhmann I, Hanslik-Schnabel B, et al. Bone erosions and bone marrow edema as defined by magnetic resonance imaging reflect true bone marrow inflammation in rheumatoid arthritis. Arthritis Rheum. 2007;56:1118-1124.