Release Date: December 13, 2007  
Expiration Date: December 13, 2008 
Estimated Time to Complete: 15 Minutes

Supported by: Genentech Inc and Biogen Idec and Bristol-Myers Squibb 
Sponsored by: The Foundation for Better Health Care   

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 Author: Janis Kelly
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 Independent Reviewer: Mark Fisher, MD, MPH
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AUCKLAND, New Zealand—Edema in the subchondral bone, uniquely detectable by magnetic resonance imaging (MRI), provides important prognostic information in rheumatoid arthritis (RA) and probably explains what causes pain in osteoarthritis (OA) knees. Fiona M. McQueen, MD, and colleagues from the faculty of medicine and health sciences at the University of Auckland in New Zealand report their research on MRI edema in both types of arthritis in Annals of the Rheumatic Diseases.1,2

"Clearly, the subchondral bone is not ‘inert' in OA any more than it is in RA, and while bone edema may be a different lesion histologically in these conditions, it is a red flag in both for progressive bone damage and potentially an important biomarker for use in clinical trials."— Fiona M. McQueen, MD.
"Traditionally, it has been assumed that pain [in RA] derives from synovitis, bone erosion, or secondary osteoarthritis. Our findings challenge this assumption. While we found synovitis and erosion within the surgical field as expected, the new and surprising observation was that bone edema was so common. Moreover, the bone edema score was associated with the pain score as well as the CRP (C-reactive protein)," Dr. McQueen said.

Surprising degree of MRI bone edema in RA patients opting for joint replacement

Dr. McQueen and colleagues compared contrast-enhanced MRI scans with pathology findings in 11 RA patients scheduled for orthopaedic surgery to the hand, wrists, or feet. In four patients, 7 bone samples were examined for a cellular infiltrate and the histopathology findings were compared with MRI bone edema, scored for spatial extent and intensity.

Their main findings were
  • bone edema in 60% of surgical sites versus 38% of bone in nonsurgical sites
  • high-grade bone edema most likely to be found in the surgical field
  • a strong correlation of bone edema scores and pain
  • a strong correlation of bone edema scores and CRP
  • concordance between bone edema and subchondral osteitis in four of 7 bone samples examined
"High-grade MRI bone edema was common within the field of intended surgery and associated with pain. There was concordance between the presence and severity of MRI bone edema and osteitis on histology...," the researchers concluded.

Dr. McQueen said, "Our findings confirmed first that there was an association between the presence of bone edema and the site of intended surgery. High-grade bone edema was nine times more likely to be scored within the surgical field than outside it, and was more strongly associated with the site of surgery than MRI bone erosion." MRI bone-marrow edema, defined as "an MRI appearance resulting from replacement of bone-marrow fat by material containing H+ ions, in the form of water," is unique to MRI and cannot be visualized by X-ray, CT scanning, or ultrasound.

MRI bone marrow edema linked to pain in OA

In OA, MRI bone edema has been described as "hemispheric" and referred to as bone-marrow lesions (BML). Dr. McQueen said that enlargement of these BMLs is three times more common in OA knees that develop pain than in OA control knees that do not develop pain. "[T]here is a dose-effect relationship in that more pain tends to go with larger lesions," she said.

OA BMLs are also associated with progressive joint damage. However, unlike the situation in RA, OA bone edema is probably not primarily an inflammatory lesion but is likely the result of bone trauma, damage, deformity of subchondral bone, and collagen breakdown.

Translating research into practice

Dr. McQueen suggested that rheumatologists treating RA patients "consider the presence of MRI bone edema as an indicator of active bone disease and a reason to intensify medical management with disease-modifying drugs (DMARDs) or biological therapies, as recent studies have confirmed that bone edema can be reduced by anti-TNF agents, coinciding with clinical improvement."

"Clearly, the subchondral bone is not ‘inert' in OA any more than it is in RA, and while bone edema may be a different lesion histologically in these conditions, it is a red flag in both for progressive bone damage and potentially an important biomarker for use in clinical trials," Dr. McQueen concluded.

Bone Edema in Rheumatoid Arthritis
  • Bone edema was present in 60% of surgical sites versus 38% of bone in nonsurgical sites
  • High-grade bone edema most likely to be found in the surgical field in patients undergoing orthopedic surgery for RA (OR 9.3, P <.0001)
  • MRI bone edema scores correlate strongly with pain. (P = .048)
  • MRI bone edema scores correlate strong with CRP levels (P = .01)
  • There was concordance between bone edema scores and subchondral osteitis in four of 7 bone samples examined, but not in those with only mild osteitis.
Source: Adapted from Ann Rheum Dis. 2007;66:1581-1587.1

MRI Bone Edema/Bone Marrow Lesions and Osteoarthritis
  • Observed in 57% to 62% of OA knees
  • Predict radiographic progression
  • Associated with pain
  • Associated with malalignment
  • Histology of subchondral bone shows fibrosis, necrosis, and trabecular remodeling
Source: Adapted from Ann Rheum Dis. 2007;66:1549-1552.2


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References
1. McQueen FM, Gao A, Ostergaard M, et al. High-grade MRI bone edema is common within the surgical field in rheumatoid arthritis patients undergoing joint replacement and is associated with osteitis in subchondral bone. Ann Rheum Dis. 2007;66:1581-1587.
2. McQueen FM. A vital clue to deciphering bone pathology: MRI bone oedema in rheumatoid arthritis and osteoarthritis. Ann Rheum Dis. 2007;66:1549-1552.