ARTHRITIS & RHEUMATISM
Vol. 48, No. 1, January 2003, pp 64–71
© 2003, American College of Rheumatology
Elucidation of the Relationship Between Synovitis
and Bone Damage
A Randomized Magnetic Resonance Imaging Study of Individual Joints
in Patients With Early Rheumatoid Arthritis
Philip G. Conaghan,1Philip O’Connor,2Dennis McGonagle,1Paul Astin,1
Richard J. Wakefield,1Wayne W. Gibbon,2Mark Quinn,1Zunaid Karim,1Michael J. Green,1
Susanna Proudman,1John Isaacs,1and Paul Emery1
Objective. To simultaneously image bone and
synovium in the individual joints characteristically in-
volved in early rheumatoid arthritis (RA).
Methods. Forty patients with early, untreated RA
underwent gadolinium-enhanced magnetic resonance
imaging (MRI) of the second through fifth metacarpo-
phalangeal joints of the dominant hand at presentation,
3 months, and 12 months. In the first phase (0–3
months), patients were randomized to receive either
methotrexate alone (MTX) or MTX and intraarticular
corticosteroids (MTX ? IAST) into all joints with
clinically active RA. The MTX-alone group received no
further corticosteroids until the second phase (3–12
months), when both groups received standard therapy.
Results. In the first phase, MTX ? IAST reduced
synovitis scores more than MTX alone. There were signif-
icantly fewer joints with new erosions on MRI in the
former group compared with the latter. During the second
phase, the synovitis scores were equivalent and a similar
number of joints in each group showed new erosions on
the degree of synovitis and the number of new erosions,
with the area under the curve for MRI synovitis the only
significant predictor of bone damage progression. In indi-
vidual joints, there was a threshold effect on new bone
damage related to the level of synovitis; no erosions
occurred in joints without synovitis.
Conclusion. In early RA, synovitis appears to be
the primary abnormality, and bone damage occurs in
proportion to the level of synovitis but not in its absence.
In the treatment of patients with RA, outcome measures
and therapies should focus on synovitis.
Rheumatoid arthritis (RA) is a chronic inflam-
matory polyarthritis characterized by widespread syno-
vitis and joint destruction (1). However, the relationship
between synovitis and joint damage (conventionally de-
scribed by radiographic erosions) remains controversial.
Some studies have shown progression of joint destruc-
tion despite suppression of synovitis (2–6). Other studies
have indicated that despite no change in clinical synovi-
tis measures, certain therapies retard bone damage (7).
More recently, it has been demonstrated that the sup-
pression of disease activity slows or even halts progres-
sion of bone damage, although there was a poor corre-
lation between clinical response and radiographic
change (8,9). Such clinical and radiographic observa-
tions, where synovitis and bone damage are seemingly
independent processes, have been supported by experi-
mental models of RA, where joint damage may be
uncoupled from synovitis (10). All these studies used
Supported by a grant from the Arthritis Research Campaign.
1Philip G. Conaghan, MBBS, FRACP, Dennis McGonagle,
MBBCh, Paul Astin, PhD, Richard J. Wakefield, BM, MRCP, Mark
Quinn, MBChB, MRCP, Zunaid Karim, MBBS, MRCPI, Michael J.
Green, MBChB, MRCP, Susanna Proudman, MBBS, FRACP, John
Isaacs, MB, PhD, FRCP, Paul Emery, MA, MD, FRCP: University of
Leeds and Leeds General Infirmary, Leeds, UK;2Philip O’Connor,
MBBS, MRCP, FRCR, Wayne W. Gibbon, MBBCh, FRCS, FRCR:
Leeds General Infirmary, Leeds, UK.
Address correspondence and reprint requests to Paul Emery,
MA, MD, FRCP, ARC Professor of Rheumatology, Academic Unit of
Musculoskeletal & Rehabilitation Medicine, Leeds General Infirmary,
Great George Street, Leeds LS1 3EX, UK. E-mail: p.emery@
Submitted for publication April 24, 2002; accepted in revised
form October 3, 2002.
either indirect or insensitive measures or imaged com-
plex joints such as the wrist, with consequent difficulty in
interpretation. However, a recent analysis of hand joints
in an early RA cohort (using tender and swollen joint
counts as surrogate measures of synovitis) did demon-
strate a close relationship between suppression of clini-
cal synovitis and reduction of erosion progression (11).
An understanding of the interrelationship be-
tween synovitis and bone damage is critical for the
optimal management of RA, especially in determining a
logical approach for drug treatment, and provides the
model for all diseases in which chronic inflammation is a
dominant feature. Magnetic resonance imaging (MRI)
offers advantages over clinical examination and radio-
graphic techniques in its ability to simultaneously assess
both synovitis and bone changes (12–19). We have
previously used MRI of the metacarpophalangeal
(MCP) joints as a model system for measuring damage
(20) because these are the characteristically affected
joints of early rheumatoid disease. Furthermore, their
anatomy permits the most reproducible and interpret-
able documentation of the interrelationship between
synovitis and bone damage at the individual joint level.
Patients were studied at the onset of disease to minimize
the confounding effects of drugs, disability, and disease
Our previous cross-sectional study of early dis-
ease had suggested a close association between synovitis
and bone damage (20). In the current prospective lon-
gitudinal study, undertaken with previously untreated
patients, the same approach was used to assess individ-
ual joint disease and in particular the relationship be-
tween synovitis and bone damage over time. This was
done in a model 2-stage system with 2 standard therapies
known to produce differential rates of synovitis reduc-
tion. Patients were randomized to receive either metho-
trexate (MTX) alone, a relatively slow-acting agent, or
MTX and an intraarticular corticosteroid (MTX ?
IAST), the latter drug being well known for its rapid
reduction of synovitis.
PATIENTS AND METHODS
Patients. Between December 1, 1997, and November
30, 1998, we recruited a total of 42 consecutive patients from
an early arthritis clinic, all of whom fulfilled the American
College of Rheumatology (formerly, the American Rheuma-
tism Association) criteria for RA (21). Entry criteria included
disease duration of less than 12 months and the presence of
clinical MCP joint disease. Patients who had previously been
treated with any disease-modifying antirheumatic drugs
(DMARDs) or who were taking oral or intramuscular (IM)
corticosteroids were excluded. All patients gave their consent
to the study, and the protocol was approved by the local
research ethics committee of Leeds Teaching Hospital Trust.
Patients were evaluated at baseline for age and known
severity factors, such as sex, disease duration, rheumatoid
factor (RF) positivity, shared epitope positivity (previously
known as HLA–DR1 or DR4, performed using molecular
typing for HLA alleles DRB1*0101, *0102, *0401, *0404,
*0405, *0408, and *1001), and the presence of radiographic
erosions (based on standard hand and foot radiographs). The
following were recorded at each visit (baseline and 1, 2, 3, 6, 9,
and 12 months): early morning stiffness, patient assessment of
disease activity on a visual analog scale, tender and swollen
joint counts, modified Health Assessment Questionnaire (22)
raw scores, and C-reactive protein levels. All patients had
repeat radiographs performed at 12 months.
Treatment and MRI protocol. All patients had MRI
scans performed on the day of their entry into the study and were
then randomized, using a computer-generated list kept by an
independent research nurse, to receive either IAST (methylpred-
nisolone) into all joints with clinically active RA (defined as both
on oral MTX, beginning at a dosage of 7.5 mg once weekly, and
increasing over time by titration against disease activity. All
patients also received 5 mg of oral folic acid twice weekly. Simple
analgesics and nonsteroidal antiinflammatory drugs (NSAIDs)
were allowed, but with no change in the NSAID dosage for 1
week prior to MRI scans. No more corticosteroids were given to
the MTX-alone group until after the month-3 MRI scan. After
the month-3 scan, patients in both groups received the same
standard care, with continuing MTX dosage escalation and IA
and IM corticosteroids as routinely indicated. All patients had
repeat MRI scans after 12 months of therapy, although the time
of the third scan could be moved up if disease control was
considered unsatisfactory after attaining the maximum dosage of
MTX for at least 6 weeks. No MRI scans were performed within
4 weeks after administration of corticosteroid therapy.
MRI evaluation. Scans of the second through fifth
MCP joints of the dominant hand were performed using a
commercially available 1.5T Gyroscan ACS NT whole-body
MRI system with image acquisition (Philips, Best, The Neth-
erlands). A linear circular 11-cm surface coil (Philips) was
placed on the dorsum of the hand when the patient was prone
with an extended arm. All patients had 5 sequences performed:
T1-weighted spin-echo (SE) coronal and axial pulse sequences
(T1 SE), T2-weighted turbo spin-echo fat-suppressed (T2 TSE
FS) coronal pulse sequences, T1 SE post–gadolinium–
diethylenetriaminepentaacetic acid (Gd-DTPA) axial se-
quences, and T1 FS post–Gd-DTPA coronal sequences.
The imaging parameters for the T1-weighted axial
images were repetition time (TR) 485 msec, echo time (TE) 20
msec, matrix 256 ? 256, field of view (FOV) 10 ? 5 cm, slice
thickness 1.5 mm, slice gap 0.15 mm, number of signals
averaged (NSA) 2, and total acquisition time 201 seconds. The
T1 coronal SE parameters were similar, but the FOV was 10 ?
10 cm, and the acquisition time was 250 seconds. The T1
coronal FS post–Gd-DTPA parameters were TR 450 msec, TE
20 msec, matrix 256 ? 256, FOV 10 ? 10 cm, and total
acquisition time 524 seconds. The T2 TSE FS acquisition
parameters were TR 2,000 msec, TE 100 msec, matrix 256 ?
256, FOV 10 ? 10 cm, slice thickness 2.0 mm, slice gap 0.2 mm,
NSA 4, and acquisition time 224 seconds. The images were
SYNOVITIS AND BONE DAMAGE IN EARLY RA65
printed on radiographic acetate film and stored. Contrast-
enhanced and non–contrast-enhanced MRI films were scored
by 2 experienced readers (PGC, PO’C) who were blinded to
clinical details and radiographic findings.
Synovitis was scored from those areas demonstrating
increased enhancement on the T1 axial post–Gd-DTPA scans
compared with the corresponding sequence on the pre–Gd-
DTPA sequences, in accordance with recent expert recommen-
dations (23). To avoid the recognized problems with Gd-
DTPA leakage into the joint fluid, post–Gd-DTPA sequences
were performed within 5 minutes of injection (24). The
individual slice demonstrating maximum inflammation was
chosen and then the maximum enhancing thickness of syno-
vium per MCP joint was measured in millimeters (Figure 1A).
Maximum thickness was chosen to represent the “ceiling”
measure of synovitis, the measure that would be most respon-
sive to change.
Bone erosions were defined as bone defects with sharp
margins visible in 2 planes with a cortical break seen in at least
1 plane on T1 sequences (23). Each bone erosion was recorded
according to its site within a given joint. Bone edema was
defined as an area with ill-defined margins and high signal
intensity on FS sequences (Figure 2A) and was only recorded
when present without an associated erosion; bone edema was
scored as present or absent in the metacarpal head or proximal
end of the phalanx for each joint. To reduce artifactual count
changes resulting from partial voluming (sectioning) effects,
after the initial scoring each bone lesion was accounted for
with random-time readings of a patient’s films and with the
readers still blinded to time sequence and treatment group.
Interobserver disagreements were settled by consensus.
Statistical analysis. Our primary analysis grouped all
MCP joints from patients who received IAST at baseline, even
though not all the MCP joints had been injected. We thought
this was a cautious interpretation, given the possible effects of
IAST on adjacent joints and the known difficulty with place-
ment of small joint injections. Parametric and nonparametric
tests were applied to baseline demographic and clinical para-
meters as appropriate. A repeated-measures general linear
model approach assuming linearity was used to analyze the
changes in MRI synovial thickness. Bone erosion data were
analyzed using Fisher’s exact test. The repeatability index was
calculated to determine whether the “within-patient” changes
over time were greater than the measurement error. Area
under the curve (AUC) values for all MRI and clinical values
were calculated using the trapezium rule. Statistical correlation
tests were performed using sum scores for an individual patient
(rather than individual joints) and using Spearman’s rank
correlation. Statistical analysis was performed using SPSS
version 8.0 (SPSS, Chicago, IL).
Demographic baseline characteristics and medi-
cation use. Forty-two patients fulfilled entry criteria,
underwent baseline MRIs, and were randomized to
Figure 1. Axial T1-weighted post-gadolinium sequences of the second through fifth metacarpophalangeal (MCP) joints. A, Before methotrexate and
intraarticular corticosteroid (MTX ? IAST) therapy. Marked MCP joint synovitis and tenosynovitis are visible, as demonstrated by high signal
intensity. Arrow indicates the dimension measured for maximum synovial thickness. Arrowhead shows an erosion that becomes clearly visible in B
after suppression of synovitis. B, After MTX ? IAST therapy. (A defect in the cortex, fulfilling the definition of an erosion, was visible on the
equivalent coronal film.)
66CONAGHAN ET AL
either MTX alone (n ? 20) or MTX ? IAST (n ? 22).
One patient from each group did not have subsequent
MRI scans (one due to malignancy and another due to
claustrophobia) and were not included. The demo-
graphic data for age, sex, disease duration, serology, and
radiographic erosions are presented in Table 1, with the
baseline disease characteristics presented in Table 2.
The only significant difference between the 2 groups was
the presence of RF (P ? 0.01).
As the protocol had dictated, no patient in the
MTX-alone group had any corticosteroid before the
month-3 scan and no patient in either group received a
DMARD other than MTX. The mean (range) weekly
dosages of MTX were as follows: 3 months, MTX alone
12.5 mg (10.0–12.5), MTX ? IAST 10.0 mg (10.0–15.0);
12 months, MTX alone 17.5 mg (12.5–20.0), MTX ?
IAST 16.25 mg (10.0–20.0). All patients continued to
take MTX. According to protocol, all patients in the
MTX ? IAST group received IAST at baseline. The
mean (range) number of injections per patient was 9
(3–16). The mean (range) number of the second through
fifth MCP joints injected of the dominant hand was 1.8
(1–4). In the first phase of the study, the mean (range)
total methylprednisolone dose was 181.9 mg (30–300),
while in the second phase (3–12 months) the mean
(range) total corticosteroid doses were MTX alone 117.8
mg (0–800) and MTX ? IAST 141.6 mg (0–540). The
clinical and laboratory outcomes related to the imaging
time points are presented in Table 2. The imaging
findings are presented in Table 3.
MRI: synovitis and erosions. Baseline. Since
there was unequal distribution of seropositive patients,
with a greater number in the MTX-alone group, the
outcome was analyzed according to RF status. There
Figure 2. Coronal T1 fat-suppressed sequences of the second through fifth metacarpophalangeal (MCP) joints. A, Before methotrexate and
intraarticular corticosteroid (MTX ? IAST) therapy. Bone edema is seen as areas of high signal intensity in both the proximal and distal subchondral
bones of the third and fourth MCP joints. This edema has characteristic ill-defined margins (arrow). B, After MTX ? IAST therapy. The bone
edema has disappeared.
MTX ? IAST
No. of patients (no. of women)
Mean age, years (range)
Median disease duration, months (range)
No. with family history of RA
No. rheumatoid factor positive
No. shared epitope positive
No. with radiographic erosions
* MTX ? methotrexate; IAST ? intraarticular corticosteroid; RA ?
SYNOVITIS AND BONE DAMAGE IN EARLY RA 67
was no difference in baseline synovitis scores between
seropositive and seronegative patients. When the pres-
ence of the shared epitope was analyzed, there was a
trend toward higher synovitis scores in the patients who
possessed the shared epitope compared with those who
were negative for this epitope (mean ? SEM 2.8 ? 0.2
mm versus 2.2 ? 0.3 mm; P ? 0.07).
For MRI synovitis scores, the repeatability index
(the smallest detectable difference, twice the SD of the
difference in scores) was calculated using 20 scans
assessed twice (with a 12-week interval) in a blinded
manner. The repeatability index was 1.6 and this was
incorporated on a Bland-Altman plot (data not shown),
together with the change in synovitis scores seen from
baseline to 3 months in the MTX ? IAST group. The
plot showed that many of the changes seen were greater
than the repeatability index, indicating that the observed
differences were beyond measurement error and there-
fore most likely real.
Phase 1. During the first 3 months, there was a
significant difference in synovitis reduction between the
2 groups. The synovitis scores (mean ? SEM) per joint
for MTX alone were baseline 2.5 ? 0.17 mm, 3 months
2.7 ? 0.19 mm; for MTX ? IAST, baseline 2.7 ? 0.17
mm, 3 months 1.6 ? 0.16 mm (difference in change
between groups, P ? 0.001). During the same period, in
the MTX-alone group 7 joints developed new erosions
compared with 1 joint in the MTX ? IAST group (P ?
Outcome Baseline 3 months12 months
Early morning stiffness, minutes
MTX ? IAST
Disease activity, visual analog score
MTX ? IAST
Tender joint count
MTX ? IAST
Swollen joint count
MTX ? IAST
MTX ? IAST
C-reactive protein, mg/liter
MTX ? IAST
101.0 ? 21.0
94.0 ? 21.7
64.2 ? 23.5
31.4 ? 10.4
38.6 ? 14.2
36.4 ? 55.6
52.6 ? 6.5
46.4 ? 4.4
41.3 ? 6.9
30.8 ? 5.3
27.3 ? 5.6
31.2 ? 5.7
18.0 ? 3.2
26.2 ? 3.1
15.8 ? 3.3
17.9 ? 3.6
13.3 ? 3.4
18.6 ? 3.8
11.7 ? 1.6
12.2 ? 1.4
7.4 ? 1.4
4.9 ? 1.3
5.5 ? 1.4
7.6 ? 1.7
35.8 ? 8.2
18.5 ? 4.2
18.4 ? 5.0
17.9 ? 5.5
15.8 ? 4.9
16.7 ? 5.3
* Except for modified Health Assessment Questionnaire (M-HAQ; see ref. 22) raw scores, which are
presented as medians (with ranges), values are the mean ? SEM. MTX ? methotrexate; IAST ?
Imaging outcomes for the second through fifth metacarpophalangeal joints
Outcome*Baseline3 months12 months
Synovitis, mean ? SEM mm per joint
MTX ? IAST
Bone edema sites, total no.†
MTX ? IAST
New MRI erosions, no. of joints†
MTX ? IAST
New radiographic erosions, no. of joints†
MTX ? IAST
2.5 ? 0.17
2.7 ? 0.17
2.7 ? 0.19
1.6 ? 0.16
1.9 ? 0.13
1.6 ? 0.12
* MTX ? methotrexate; IAST ? intraarticular corticosteroid; MRI ? magnetic resonance imaging.
† Total numbers of metacarpophalangeal joints imaged for erosions ? 76 in the MTX group and 84 in the
MTX ? IAST group. Bone edema was imaged at 2 sites per joint.
68 CONAGHAN ET AL
0.03). Furthermore, for the patient group as a whole,
there was a close correlation between the level of
synovitis and the likelihood of developing erosions dur-
ing this period (Figure 3A), with no new bony erosions in
the joints without synovitis.
Phase 2. For the period between 3 and 12 months,
there was no significant difference between the treat-
ment groups in either the synovitis scores (at 12 months,
MTX alone 1.9 ? 0.13 mm versus MTX ? IAST 1.6 ?
0.12 mm) or the progression of erosion scores (MTX
alone 5 versus MTX ? IAST 7). Thus, at the end of 12
months the total erosion rate was 12 for MTX versus 8
for MTX ? IAST (P not significant). Again, there were
no new erosions seen in any joints without synovitis, and
the likelihood of bony erosions was directly related to
the level of synovitis (Figure 3B).
Correlation analysis. The increase in MRI bone
erosion score was significantly correlated with the AUC
for MRI synovitis (? ? 0.420, P ? 0.007). No other
variables (including baseline synovitis, RF, HLA status,
and all clinical parameters) were correlated with in-
crease in bone erosions.
MRI: synovitis and bone edema. In phase 1, there
was a significant reduction in the number of sites with
bone edema, similar to the pattern for reduction in
synovitis (number of bone edema sites for MTX alone,
baseline 10, 3 months 14; for MTX ? IAST, baseline 18,
3 months 6; P ? 0.01). By 12 months, there was no
difference between the groups for number of sites
involved (MTX 5 versus MTX ? IAST 3).
The synovial thickness in all joints with bone
edema was much greater than in those without edema
(mean ? SEM 3.6 ? 0.3 versus 2.4 ? 0.1 mm; P ? 0.01).
The level of synovitis reduction in joints without persis-
tent edema was significantly greater than in those joints
with persistent edema (phase 1 1.4 ? 0.5 versus 0.5 ? 0.1
mm, phase 2 1.9 ? 0.4 versus 0.3 ? 0.1; P ? 0.001). Bone
edema preceded a subsequent MRI erosion in 9 of 22
new erosions (41%).
Radiography. In the MTX-alone group, only 2
erosions were seen radiographically in the study MCP
joints at baseline, with no increase over time. In the
MTX ? IAST group, only 6 erosions were seen at
baseline and again this number did not increase over
time. These radiographic erosions correlated by site with
MRI erosions. Based on hand and foot radiographs, in
the MTX-alone group 10 patients had erosions at base-
line and 12 had erosions at 12 months, while in the
MTX ? IAST group, 8 patients had erosions at baseline
and 9 patients had erosions at 12 months.
The results of this study strongly suggest the
primacy of synovitis in patients with RA and demon-
strate that effective suppression of synovitis prevents
bone damage. There was no evidence for a dichotomy
between synovitis and bone damage in those patients
with early RA. In fact, there was a close parallel between
the level of synovitis and the rate of appearance of new
erosions in patients independent of whether they re-
ceived slow- or fast-acting therapies. An important find-
ing was that without synovitis, no erosions occurred and
there was a threshold level of synovitis below which
there was no association with new bony damage. The
findings have major implications for pathogenic con-
cepts and the development of therapies for RA.
In the last decade, the view has emerged that
there are 2 independent processes in RA, a phase
characterized by synovial inflammation and a phase
Figure 3. Percentage of all joints with new erosions versus mean level
of synovitis, during phase 1 (A) and phase 2 (B). Level of synovitis is
rounded to the nearest whole number. Data are based on individual
SYNOVITIS AND BONE DAMAGE IN EARLY RA69
characterized by autonomous joint destruction (25).
These concepts have culminated in the idea that strate-
gies specifically aimed at inhibiting bone damage are
necessary in addition to the control of synovitis (26). In
contrast, previous MRI studies in RA have demon-
strated that persistence of synovitis is associated with
ongoing joint damage (5,27,28). However, these studies
often focused on the wrist (a complex structure with
multiple separate joints), used a variety of DMARDs,
and included patients with RA of differing durations.
We used a sensitive validated imaging system to study
individual joints over time, and the patient group was
selected to be homogeneous in terms of being newly
presenting patients with RA of short disease duration
with no prior exposure to DMARDs. Two DMARDs
selected for their differing times until onset of action
were used. Our data suggest that any proposed dichot-
omy between synovitis and bone damage has arisen from
previous inappropriate analyses of the clinical and ra-
diologic outcome measures used in those studies. Also,
the addition of biologic agents to the treatment regimen
in patients whose disease has been only partially respon-
sive to MTX is more effective in preventing damage,
because additional therapy with biologic agents results
in more effective synovitis suppression.
This study, using a novel synovial outcome mea-
sure, confirms previous findings obtained by traditional
methods (11). Synovitis, as detected by Gd-DTPA–
enhanced MRI, has been correlated with microscopic
features of inflammation (29). Also, the MRI sequences
used fall within the recommendations of the Outcome
Measures in Rheumatology Clinical Trials MRI working
party for synovitis measurement (23). There is strong
face value for the synovial measure used, in that cortico-
steroids produced a reduction in MRI synovitis within
the expected time period, as previously demonstrated
(28,30–32). Similarly, in the second phase, after 12
months of similar DMARD therapy, both groups had
comparable synovial thickness scores.
Unfortunately, the MRI sequences used and the
current scoring system preclude the measurement of any
effects on cartilage. With respect to bone abnormalities,
MRI erosions have been shown to be equivalent to
radiographic erosions in a validation study (33). The
insensitivity of radiography is due to its inability to
detect small cortical defects that can be imaged by other
modalities (33). They are specific for RA (20), correlate
with radiographic erosions, and are predictive of long-
term joint destruction (5,27). Although the difference in
MRI erosions between treatment groups at 12 months
was not significant, this study was not designed to detect
such a change. Care was taken to distinguish these
structural lesions from areas of bone marrow edema
seen on fat-suppressed MRI sequences only.
This study provides the strongest evidence to date
that bone edema is related to the degree of synovitis and
is the forerunner of erosions on MRI. Furthermore,
effective suppression of synovitis can reverse these pre-
erosive changes and subsequent structural damage. Fi-
nally, this study demonstrates that synovitis is primary
for the pathogenesis of bone disease in early RA and
does not support the concept of independent destruction
of bone. Future management of RA is likely to focus on
controlling synovitis and, by doing so, may obviate the
need for separate monitoring of bone damage progres-
sion. This may be particularly relevant with regard to
expensive therapies not limited by toxicity. Therefore,
titration of therapy to optimize the reduction of synovitis
may become the preferred method of monitoring dis-
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