Rheumatology 2009;48:1530–1532
Advance Access publication 22 September 2009
doi:10.1093/rheumatology/kep283
Concise Report
Bone erosions at the distal ulna detected by ultrasonography
are associated with structural damage assessed by conventional
radiography and MRI: a study of patients with recent onset
rheumatoid arthritis
Hilde B. Hammer1, Espen A. Haavardsholm1, Pernille Bøyesen1 and Tore K. Kvien1
Objectives. Ultrasonography (US) is a sensitive tool for detecting erosions in patients with RA. The wrist is usually involved in the RA
process, where the distal ulna with its superficial localization is easily accessible for US examination. In this longitudinal study, we wanted to
examine the presence, localization and development of erosions at the distal ulna by US in patients with recent onset RA, and to analyse
whether erosions at this localization are associated with joint damage in hands assessed by conventional radiography (CR) and MRI.
Methods. Seventy patients with recent onset RA (median disease duration 106 days) were examined by US of the distal ulna, in addition to
hand radiography [assessed by van der Heijde-modified Sharp score (vdHSS)] and MRI of the wrist [assessed by RA MRI scoring (RAMRIS)
erosion score]. Twelve months later 58 patients were re-assessed.
Results. US detected erosions at the distal ulna in 11% of the patients at baseline and 24% at follow-up (the majority of erosions were at the
ulnar side). Logistic regression analyses showed the presence of erosions at baseline to be associated with baseline RAMRIS erosion score
(P < 0.001), and at follow-up to RAMRIS erosion score (P ¼ 0.02) and vdHSS (P ¼ 0.008).
Conclusions. A significant number of patients had US erosions at the distal ulna at baseline, with increased prevalence after 1 year. The
US-detected erosions were associated with structural joint damage in hands assessed by both MRI and CR. US of the distal ulna could
thus give useful clinical information.
KEY
WORDS:
Ultrasonography, Early rheumatoid arthritis, Erosions, Distal ulna, MRI, Radiography.
Introduction
Patients and methods
The presence of bone erosions in patients with early RA indicates
a severe disease course. Ultrasonography (US) is an imaging technique that is able to detect erosions [1] with a higher sensitivity
and specificity than conventional radiography (CR) [2, 3]. The
sensitivity and specificity are comparable with MRI for joint
surfaces assessable by US [2–4], and high interobserver agreement
on US erosions has been found [3, 5]. In addition, the US-detected
erosions have been shown to be true erosions when CT was used
as the reference method [6].
The wrist joint is commonly affected in RA. In a longitudinal
study of wrist involvement in RA patients, radiographic erosions
of the styloid ulna were seen as a relatively early isolated finding in
25% of the patients [7]. Further, the distal radioulnar joint showed
a rapid increase of erosions and was involved in 78% of the
patients with established disease [7]. The distal ulna may be examined by US to assess erosions in the superficial part of the bone.
Erosions on the dorsal part may be caused by inflammation of the
radioulnar joint, with synovitis extending over the dorsal area of
the distal ulna, whereas erosions at the ulnar side may be caused
by tenosynovitis of the extensor carpi ulnaris (ECU) tendon.
The two main objectives of the present study were to assess, in
patients with recent onset RA, the presence, size and location of
erosions at the distal ulna by the use of US, and to examine
whether US erosions were associated with overall joint damage
in hands assessed by CR or wrist MRI.
From a cohort of 84 patients with recent onset RA [8], 70 patients
{53 (76%) women, median [interquartile range (IQR)] disease
duration 106 (62–184) days, age 58 (48–66) years} were eligible
for participation in the present study, which focused on US examination of the distal ulna in the dominant hand. A total of
53 patients (76%) used DMARDs including MTX (n ¼ 43), antiTNF drugs (n ¼ 1) and prednisolone (n ¼ 43). Fifty-eight patients
were available for follow-up and were re-assessed after 12 months
(not including the patient using anti-TNF medication).
All US examinations were performed by H.B.H. with the use
of an 8–12-MHz linear array transducer on a Diasus machine
(Dynamic Imaging Ltd, Livingston, UK) that did not have
Doppler function. The patients were sitting with their dominant
hand resting on a small table. The diameter of the largest US
erosion on the dorsal as well as the ulnar part of the distal ulna
(Fig. 1) was measured in two perpendicular planes and graded
as follows: no erosion, 0; erosions with diameter 42 mm, 1;
with 2–4 mm, 2; and >4 mm, 3.
Bilateral digital CR of hands and wrists in the posterio-anterior
view was scored by a trained observer (P.B.) for erosions and joint
space narrowing according to the van der Heijde-modified Sharp
score (vdHSS) with a possible maximum score of 280 U [9, 10].
MRI of the dominant wrist was performed using a 1.5-T scanner
with a dedicated high-resolution wrist phased array coil. The
images were scored by E.A.H. according to the semiquantitative
RA MRI scoring (RAMRIS) erosion score [11, 12] with a
maximum score of 10 for each assessed joint: 0, no erosion; 1,
1–10% of the bone eroded; 2, 11–20%, etc., and with a possible
maximum total erosion score of 150 U.
Clinical examinations included visual analogue scale (VAS)
pain, VAS patient global assessment of disease activity, modified
health assessment questionnaire (MHAQ) (range 0–3) and VAS
1
Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway.
Submitted 8 March 2009; revised version accepted 4 August 2009.
Correspondence to: Hilde B. Hammer, Department of Rheumatology,
Diakonhjemmet Hospital, Box 23, Vinderen, N-0319 Oslo, Norway.
E-mail: [email protected]
1530
ß The Author 2009. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: [email protected]
US of the distal ulna in RA patients
1531
TABLE 1. Comparison of baseline levels of imaging and laboratory assessments
between patients with and without US-detected erosions of the distal ulna
Erosion, n ¼ 8
vdHSS
RAMRIS erosion score
CRP, mg/l
ESR, mm/h
Anti-CCP, U/ml
IgA RF, U/ml
IgM RF, U/ml
3
13
17
26
251
35
98
(2–8)
(9–26)
(8–50)
(11–51)
(66–251)
(16–64)
(23–245)
No erosion, n ¼ 62
2
8
4
15
36
9
10
(0–5)
(5–11)
(2–8)
(8–22)
(4–211)
(1–38)
(3–81)
P-value
0.23
0.006*
0.005*
0.11
0.041*
0.045*
0.057
The values are given as median (IQR). *P < 0.05.
FIG. 1. US (longitudinal scan) of the distal ulna showing Grade 2 erosion.
assessor’s evaluation of disease activity. ESR was performed as
part of the laboratory routine tests, and serum was frozen at
708C for later analysis of CRP (high-sensitive nephelometry),
anticyclic citrullinated peptide (anti-CCP) (second-generation
ELISA with levels from 1 to 251 U/ml, cut-off at 25) as well as
IgA and IgM rheumatoid factor (RF) (‘in-house’ ELISA, range of
2–300 U/ml, cut-off at 25). The local ethics committee [The
Regional Committee for Medical and Health Research Ethics
(REK), Southeast] approved the study, and the patients signed
informed consent according to the Declaration of Helsinki.
Statistical methods
The variables were not normally distributed and therefore nonparametric tests were used. Group comparisons were performed
by using Mann–Whitney U-test, and binary logistic regression
analyses were applied to investigate for associations. A P-value
<0.05 was considered as statistically significant.
Results
Erosions at the distal ulna were detected by US in 8 of the
70 patients (11.4%) at baseline (Grade 1, n ¼ 5; Grade 2, n ¼ 3).
At follow-up, 14 (24%) of the 58 patients had US erosions
(Grade 1, n ¼ 9; Grade 2, n ¼ 3; Grade 3, n ¼ 2). Eleven patients
with no US erosions at baseline developed erosions after 1 year
(Grade 1, n ¼ 9; Grade 2, n ¼ 2). Two patients had an increase in
erosion size from Grade 1 to 3, and one patient had an unchanged
Grade 2 erosion. At baseline, the erosion at the distal ulna having
the largest diameter was found at the ulnar side in five patients
and at the dorsal side in three patients. At follow-up, the
corresponding numbers of patients were 12 and 2.
MRI of the distal ulna showed erosions in 49 (71%) of the
69 patients at baseline (Score 1, n ¼ 47; Score 2, n ¼ 1; Score 3,
n ¼ 1), and in 46 (74.2%) of the 62 patients at 12 months examination (Score 1, n ¼ 39; Score 2, n ¼ 6; Score 3, n ¼ 1), including
one new patient with erosion. Except for one, all patients with
erosions detected by US had erosions assessed by MRI both at
baseline and follow-up.
CR of the distal ulna showed erosion in only 2 (2.8%) of the
69 patients at baseline. Two (3.2%) out of 63 patients had erosions
at the 12-month follow-up, including one patient who had
developed erosion on CR during the study. Of the 8 patients
with US-detected erosions at baseline, only 1 patient had
radiographic erosion, and of the 14 patients with erosion on US
at follow-up, only 2 had erosion seen on radiography.
The median (IQR) vdHSS levels at baseline/follow-up was 2
(0–5)/3 (1–8) and the RAMRIS erosions levels were 8 (5–11)/9
(6–13), respectively. At baseline/follow-up, the median (IQR)
of the laboratory and clinical assessments were as follows: CRP,
5 (2–10)/4 (2–7) mg/l; ESR, 15 (10–22)/12 (7–17) mm/h; anti-CCP,
41 (4–251)/37 (3–244) U/ml; IgA RF, 11 (1–39)/6 (1–27) U/ml;
IgM RF, 14 (3–92)/10 (1–54) U/ml; VAS pain, 20 (9–37)/22 (9–41)
mm; VAS patient global assessment of disease activity, 23 (10–38)/
22 (12–44) mm; VAS assessor’s evaluation of disease activity,
11 (9–18)/9 (6–15) mm; and MHAQ 0.1 (0–0.6)/0.1 (0–0.5).
Patients with US erosions at baseline had higher RAMRIS
erosion scores as well as higher levels of CRP, anti-CCP and
IgA RF than non-erosive patients (Table 1). The two patients
with US erosion scores increasing from Grade 1 to 3 during the
study had baseline RAMRIS erosion scores of 28 and 29 vs
median (IQR) 8 (5–11) in the other patients (P ¼ 0.001). The
11 patients developing US erosions during the study had significantly higher baseline levels of VAS pain (P ¼ 0.03), VAS patient
global assessment of disease activity (P ¼ 0.03), VAS assessor’s
evaluation of disease activity (P ¼ 0.002) and MHAQ (P ¼ 0.03)
as well as follow-up total vdHSS score (P ¼ 0.05) than patients not
developing erosions. However, neither baseline vdHSS nor
RAMRIS erosion levels were significantly different between
the groups. The patients developing erosions were all on antirheumatic medication (MTX, n ¼ 7; low-dose prednisolone, n ¼ 4).
Logistic regression analyses with the presence of US erosions at
baseline as the dependent variable showed significant associations
with baseline RAMRIS erosion score (P < 0.001) when adjusted
for sex, age and disease duration. Similar analyses with the
presence of US erosions at follow-up as the dependent variable
and follow-up RAMRIS erosion score or vdHSS values in the
equation (adjusted for sex, age and disease duration) showed
significant associations with both RAMRIS and vdHSS
(P ¼ 0.02 and 0.008, respectively).
Discussion
Imaging techniques such as US and MRI have increased the
sensitivity for detecting erosions in early RA [13–15]. Most US
studies have been performed on MCP or MTP joints, since these
joints are frequently affected in RA patients and are simple to
examine by US. However, the distal ulna is also easily accessible
for US examinations, and the radioulnar joint and the ECU tendon
sheath are both frequently inflamed in RA patients. The present
study is, to our knowledge, the first to assess US erosions of the
distal ulna in RA patients with very short disease duration. US
erosions were found in about one-tenth of the patients at baseline,
with a significant increase after 1 year. Erosions detected by US
were also seen on MRI, but only in one and two patients on CR at
baseline and follow-up, respectively.
The presence of US erosions at the distal ulna was found to be
associated with joint damage assessed by CR and MRI of hand
joints. A limitation of the present study was focus on erosions
only, without assessing the synovitis surrounding the distal ulna.
However, the present finding indicates that this simple US assessment may be useful in the evaluation of disease severity in early
RA patients. Another potential limitation is that US is operator
dependent. However, all assessments were performed by a single
experienced assessor (H.B.H.). A reliability study should ideally
Hilde B. Hammer et al.
1532
have been performed. As a proxy for reliability assessments, 59 of
the patients were reassessed 3 months after baseline examinations.
Seven of these patients had erosions both at baseline and after
3 months, no patient had US-detected erosions at baseline not
seen at the 3-month assessment, whereas six new patients had
developed erosions.
Most of the US erosions were found at the ulnar side of
the distal ulna, which is located under the ECU tendon. Thus,
inflammation in the tendon sheath may cause bone erosions.
MRI studies have shown that tenosynovitis in the ECU tendon
is a frequent finding [16, 17]. US erosions were also found at the
dorsal part of the distal ulna, and these erosions were located
under the ulnar area of the synovitis extending from the radioulnar joint. Future study should assess both the radioulnar joint
and the ECU tendon by the use of greyscale and power/colour
Doppler US, to explore the possible associations between active
inflammation and development of erosions.
Even though the patients received standard medical treatment,
several developed US erosions of the distal ulna during the 1-year
follow-up, and these patients had a more active disease. There are
few prospective studies of US-detected erosions, but the present
finding supports previous US studies that showed increased
number of erosions in finger joints after 2 or 7 years [18, 19].
The presence of US erosions at the distal ulna was, in this
study, associated with increased structural joint damage in hand
joints assessed by radiography and MRI. This is a small study,
and larger studies should be performed to explore the current
topic further. However, the present study suggests that US of
the distal ulna, which is an easily performed examination, could
be performed on patients with early RA, and the presence of
erosions would indicate a more severe disease course.
Rheumatology key messages
A significant number of patients with early RA have US erosions at
the distal ulna.
Presence of US erosions was associated with structural joint
damage in hands assessed by CR and MRI.
Disclosure statement: The authors have declared no conflicts of
interest.
References
1 Wakefield RJ, Balint P, Szkudlarek M et al. Musculoskeletal ultrasound including
definitions for ultrasonographic pathology. J Rheumatol 2005;32:2485–7.
2 Szkudlarek M, Klarlund M, Narvestad E et al. Ultrasonography of the metacarpophalangeal and proximal interphalangeal joints in rheumatoid arthritis: a comparison with
magnetic resonance imaging, conventional radiography and clinical examination.
Arthritis Res Ther 2006;8:R52.
3 Wiell C, Szkudlarek M, Hasselquist M et al. Ultrasonography, magnetic resonance
imaging, radiography, and clinical assessment of inflammatory and destructive
changes in fingers and toes of patients with psoriatic arthritis. Arthritis Res Ther
2007;9:R119.
4 Magnani M, Salizzoni E, Mulè R, Fusconi M, Meliconi R, Galletti S. Ultrasonography
detection of early bone erosions in the metacarpophalangeal joints of patients with
rheumatoid arthritis. Clin Exp Rheumatol 2004;22:743–8.
5 Szkudlarek M, Court-Payen M, Jacobsen S, Klarlund M, Thomsen HS,
Østergaard M. Interobserver agreement in ultrasonography of the finger and toe
joints in rheumatoid arthritis. Arthritis Rheum 2003;48:955–62.
6 Døhn UM, Ejbjerg BJ, Court-Payen M et al. Are bone erosions detected by magnetic
resonance imaging and ultrasonography true erosions? A comparison with computed
tomography in rheumatoid arthritis metacarpophalangeal joints. Arthritis Res Ther
2006;8:R110.
7 Leak RS, Rayan GM, Arthur RE. Longitudinal radiographic analysis of rheumatoid
arthritis in the hand and wrist. J Hand Surg 2003;28A:427–34.
8 Haavardsholm EA, Bøyesen P, Østergaard M, Schildvold A, Kvien TK.
Magnetic resonance imaging findings in 84 patients with early rheumatoid arthritis:
bone marrow oedema predicts erosive progression. Ann Rheum Dis 2008;67:
794–800.
9 Van der Heijde DM, van Riel PL, Nuver-Zwart IH, Gribnau FW, van de Putte LB.
Effects of hydroxychloroquine and sulphasalazine on progression of joint damage in
rheumatoid arthritis. Lancet 1989;I:1036–8.
10 van der Heijde D. How to read radiographs according to the Sharp/van der Heijde
Method. J Rheumatol 2000;27:261–3.
11 Østergaard M, Peterfy C, Conaghan P et al. OMERACT Rheumatoid Arthritis
Magnetic Resonance Imaging Studies. Core set of MRI acquisitions, joint pathology
definitions, and the OMERACT RA-MRI scoring system. J Rheumatol 2003;30:
1385–6.
12 Haavardsholm EA, Østergaard M, Ejbjerg BJ et al. Reliability and sensitivity
to change of the OMERACT rheumatoid arthritis magnetic resonance
imaging score in a multireader, longitudinal setting. Arthritis Rheum 2005;52:
3860–7.
13 Wakefield RJ, Gibbon WW, Conaghan PG et al. The value of sonography in the
detection of bone erosions in patients with rheumatoid arthritis. A comparison with
conventional radiography. Arthritis Rheum 2000;43:2762–70.
14 Bajaj S, Lopez-Ben R, Oster R, Alarcón GS. Ultrasound detects rapid progression of
erosive disease in early rheumatoid arthritis: a prospective longitudinal study.
Skeletal Radiol 2007;36:123–8.
15 Hoving JL, Buchbinder R, Hall S et al. A comparison of magnetic resonance imaging,
sonography, and radiography of the hand in patients with early rheumatoid arthritis.
J Rheumatol 2004;31:663–75.
16 McQueen FM, Stewart N, Crabbe J et al. Magnetic resonance imaging of the wrist in
early rheumatoid arthritis reveals a high prevalence of erosions at four months after
symptom onset. Ann Rheum Dis 1998;57:350–6.
17 Stewart NR, McQueen FM, Crabbe JP. Magnetic resonance imaging of
the wrist in early rheumatoid arthritis: a pictorial essay. Australas Radiol 2001;45:
268–73.
18 Backhaus M, Burmester GR, Sandrock D et al. Prospective two year follow up study
comparing novel and conventional imaging procedures in patients with arthritic finger
joints. Ann Rheum Dis 2002;61:895–904.
19 Scheel AK, Hermann K-GA, Ohrndorf S et al. Prospective 7 year follow up imaging
study comparing radiography, ultrasonography, and magnetic resonance imaging in
rheumatoid arthritis finger joints. Ann Rheum Dis 2006;65:595–600.