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Increased bone mass with pamidronate treatment in rheumatoid arthritis. Results of a three-year randomized double-blind trial

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ARTHRITIS & RHEUMATISM
Vol. 39, No. 3, March I%, pp 396-402
8 1996, American College of Rheumatology
396
INCREASED BONE MASS WITH PAMIDRONATE TREATMENT IN
RHEUMATOID ARTHRITIS
Results of a Three-Year Randomized, Double-Blind Trial
FRANK EGGELMEUER, SOCRATES E. PAPAPOULOS, HENK C. V A N PAASSEN,
BEN A. C. DIJKMANS, ROELF VALKEMA, MARIE LOUISE WESTEDT, JAN-OTTO LANDMAN,
ERNEST K. J. PAUWELS, and FERDINAND C. BREEDVELD
Objective. Osteoporosis is a frequent complication of rheumatoid arthritis (RA). We therefore investigated the effect of oral pamidronate therapy as a
specific bone-sparing agent in RA.
Methods. The study design was a 3-year randomized, double-blind trial of 300 mg oral pamidronate/day
compared with placebo in 105 RA patients. Bone mineral density (BMD) measured at 12-month intervals was
the primary efficacy parameter.
Results. In 3 years, lumbar spine and forearm
BMD increased significantly in the pamidronate-treated
group (by 8.4 f 6.9% [mean f SEMI [P< 0.00011 and
5.2 f 6.5% [P< 0.0051, respectively), compared,with
nonsignificant changes in the placebo-treated patients
(increase of 0.6 f 5.2% and decrease of 1.2 f 5.8%,
respectively). Femoral neck BMD increased in the
pamidronate-treated group (by 2.6 f 8.6%) and decreased significantly in the placebo-treated group (by
4.0
1.3% [P < 0.005l). The changes in BMD with
time at all 3 measurement sites were significantly different between the treatment groups (P < 0.0001).
Changes in radiographic signs of joint damage and in
disease activity were similar in the 2 groups.
Conclusion. The present study provides the first
evidence that long-term treatment with an orally admin-
*
Supported by “Het Nationaal Reumafonds.”
Frank Eggelmewer, MD, Socrates E. Papapoulos, MD, Ben
A. C. Dijkmans, MD, Roelf Valkema, MD, Jan-Otto Landman, MD,
Ernest K. J. Pauwels, PhD, Ferdinand C. Breedveld, MD: University Hospital, Leiden, The Netherlands; Henk C. van Paassen, MD:
St. Franciscus Hospital, Rotterdam, The Netherlands; Marie Louise
Westedt, MD: Bronovo Hospital, The Hague, The Netherlands.
Address reprint requests to Ferdinand C. Breedveld, MD,
University Hospital, Department of Rheumatology, Building 1,
CCR, P. 0. Box 9600, 2300 RC Leiden, The Netherlands.
Submitted for publication March 1, 1995; accepted in revised form September 29, 1995.
istered bisphosphonate overcomes bone loss and increases bone mass when compared with placebo. This
finding may have significance with regard to the treatment of patients with RA.
Generalized osteoporosis is recognized as a
common complication of rheumatoid arthritis (RA) (1).
A reduction in mean bone mass in both the appendicular and axial skeletons has been found with different
techniques, including radiography, single- and dualphoton absorptiometry, computed tomography, and
dual x-ray absorptiometry (DXA), in RA patients who
were not treated with corticosteroids (2,3). An increased risk of pelvic and femoral fractures in these
patients has been reported (4,5), and the relative risk
of vertebral fractures was estimated to be 2.0 in a
study of a large group of postmenopausal RA patients
(age 45-65 years) (6).
Factors that were found to contribute to demineralization are persistently active disease and immobility (7). Since control of these risk factors is frequently incomplete, specific bone-sparing agents may
be required (7,8). The effects of such therapies in RA
have not been studied on a large scale. Bisphosphonates, synthetic analogs of natural pyrophosphate, are
taken up preferentially by the skeleton and suppress
osteoclast-mediated bone resorption. The presence of
a nitrogen molecule in their secondary structure increases their antiresorptive potency. consequently,
nitrogen-containingbisphosphonates (either registered
or in clinical development), such as, for example,
pamidronate, alendronate, risedronate, and olpadronate, are much more potent and have a higher activityto-toxicity ratio than etidronate, the first bisphosphonate developed for clinical use.
PAMIDRONATE IN RA
Bisphosphonates are currently the treatment of
choice in disorders characterized by increased bone
resorption, such as malignancy-associated hypercalcemia and Paget’s disease of bone (9,lO). More recently, these compounds have been shown in open as
well as in controlled studies to prevent bone loss and
even to increase bone mass in patients with osteoporosis (1 1-14), the preferred mode of treatment with
nitrogen-containing bisphosphonates being the continuous oral administration of the drug (15). Pamidronate,
in particular, has been shown to be effective in the
treatment of all of the above-mentioned conditions
(9-1 1, 13-15). In addition, in a recent short-term study
of patients with RA, intravenous pamidronate was
reported to possess antiarthritic properties (16). In the
present randomized, double-blind, placebo-controlled
study, we therefore investigated the effect of 3-year
treatment with pamidronate on bone mass in ambulatory, non-steroid-treated RA patients.
PATIENTS AND METHODS
Patients. One hundred five patients who fulfilled the
American College of Rheumatology (formerly, the American
Rheumatism Association) criteria for RA (17) were enrolled
in a randomized, double-blind, placebo-controlled study
between July 1989 and February 1990. Patients were assessed by a single investigator (FE) at 3 centers after
approval of the protocol by the local Medical Ethical Committees. Informed consent was obtained from all patients.
Patients with physical incapacity (Steinbrocker class
111 or IV) (18) were excluded from the study. Other exclusion criteria were previous or present treatment with corticosteroids, other treatments known to affect bone metabolism,
or a concurrent disease known to affect bone metabolism.
The use of slow-acting antirheumatic drugs (SAARDs) was
permitted. At study entry, 48 patients were taking antimalarial drugs, 23 were taking sulfasalazine, 17 were taking gold
salts, 7 were taking D-penicillamine, and 6 were taking
cytostatic drugs.
Patients were assigned to 1 of 2 treatment groups by
block randomization at each center. Patients were allocated
to receive oral daily doses of either pamidronate 300 mg/day
(n = 54) or placebo (n = 51), in addition to conventional
antirheumatic treatment. Parnidronate was administered as
enteric-coated 150-mg tablets to be taken twice daily, 30
minutes before meals, with water only. The tablets were
manufactured at the pharmacy of Leiden University Hospital. Dosage reductions were not allowed during the study.
Assessments. Bone mass of the lumbar spine, hip, and
forearm was measured at baseline and every year thereafter.
Bone mineral density (BMD) of the lumbar spine (L2-L4)
and left femoral neck was measured by DXA (Hologic
QDR-1000). BMD of the nondominant forearm proximally
from the site where the gap between the radius and ulna is 8
mrn was measured by single-photon absorptiometry (Nucle-
397
Table 1. Clinical and demographic features of the 2 treatment
groups at study entry*
Parameter
Age, years
No. femaleho. male
No. premenopausaY
no. postmenopausal
women
RA duration, years
No. of swollen joints
Placebo group
(n = 51)
Pamidronate group
(n = 54)
*
51.1 2 1.5
49.0 1.9
( 19-69)
36/15
23/ 13
3.7
13.5
* 0.5
* 0.9
(0.3-14)
Ritchie articular index
CRP (mgiliter)
No. RF positive
HAQ score
BMD, gm HA/cm2
Lumbar spine
Femoral neck
Forearm
Urinary
hydroxyprolinel
creatinine excretion
(ynoles/mmole)
Erosion score
Joint space narrowing
score
10.8 2 1.0
18.8 2 3.6
46
1.1 2 0.1
(0-2.62)
0.82 -I- 0.02
(0.60-1.02)
0.79 ? 0.03
(0.61-1 .00)
1.34 f 0.04
(O.Sk1.75)
20 1
*
(4-5)
9.6
6.5
2
k
1.9
1.3
(24-69)
35/19
14/21
3.8 f 0.5
13.8 f 0.7
(0.2-22)
9.8 f 0.8
23.0 f 5.5
43
1.0 f 0.1
(0-2.62)
0.77
2
0.02
(0.46-1.00)
0.75 5 0.02
(0.604%)
1.36 f 0.05
(0.73-2.06)
23 f 1
(W7)
10.2 f 1.5
7.8 k 1.0
* Except where otherwise indicated, values are the mean f SEM
(range). RA = rheumatoid arthritis; CRP = C-reactive protein; RF
= rheumatoid factor; HAQ = Health Assessment Questionnaire;
BMD = bone mineral density; HA = hydroxyapatite.
ar Data 1100 A). Femoral neck BMD was not evaluated in 1
patient because of a hip prosthesis.
Radiographs of the hands, wrists, and feet obtained
at baseline and every year thereafter were assessed according to the criteria of Kellgren et a1 (19), by 2 observers who
were unaware of treatment assignment. Erosions and joint
space narrowing were scored on a 5-point scale (maximum
score 200). The total number of affected joints was established by counting the joints with erosions and/orjoint space
narrowing.
Disease activity was assessed at 3-month intervals by
the Ritchie articular index (20) and the number of swollen
joints (maximum count 44). Functional status was assessed
by the modified and validated Stanford Health Assessment
Questionnaire (21). Erythrocyte sedimentation rate (ESR),
serum C-reactive protein (CRP), and serum rheumatoid
factor levels were assessed at the same time points. Active
disease was defined based on the presence of an ESR that
was persistently 220 mdhour. Urinary hydroxyproline
(second morning urination I2-hour sample] after an overnight
fast), a biochemical parameter of bone resorption, was
measured by established methods at 6-month intervals (22).
Urinary hydroxyproline excretion was corrected for creatinine excretion (pmoles/mmole). Iliac crest bone biopsy
EGGELMEIJER ET AL
398
110
h
(d
108
In
(d
106
0
s?
*
v
104
7J
cu
-I
102
n
H
m
100
*"
I
1
1
2
3
I
I
1
2
3
I
0
106
h
(d
v)
2
104
c
0
$
v
102
Y
0
100
5
96
m
-
I
I
0
Time (years)
Figure 1. Changes in lumbar spine and femoral neck bone mineral
density (BMD)in pamidronate (APD)- or placebo-treated rheumatoid arthritis patients who completed the 3 years of study. Values
are the mean f SEM.
significant differences between the pamidronatetreated and placebo-treated groups. The groups were
similar in terms of years since menopause in female
subjects, body mass index, and number and type of
SAARDs ever used or used at present (data not
shown). The trial was completed by 44 of the 51
placebo-treated patients and by 34 of the 54
pamidronate-treated patients. Baseline characteristics
of the patients who completed the study did not differ
from those of the patients who withdrew.
Changes in bone mass. During the 3 years of the
trial, the mean lumbar spine BMD of the patients who
completed the study increased significantly (P <
0.O0Ol) in the pamidronate group (8.4%; 95% confidence interval [95% CI] 6.1, 10.8), while there was a
slight but nonsignificant increase in the placebo group
(0.6%; 95% CI -0.9, 2.1) (Figure 1). The changes in
lumbar spine BMD with time were significantly (P <
0.0001) different between the 2 groups throughout the
whole period of study ( p = -1.24, 95% CI -1.57,
-0.92).
The BMD of the femoral neck decreased significantly (P< 0.005) in the placebo group (-4.0%; 95%
CI -1.7, -6.3), while there was a nonsignificant
increase in the pamidronate group (2.6%; 95% CI
-0.3, 5.6) (Figure 1). The changes in femoral neck
BMD with time were significantly (P< 0.0001) different between the 2 groups during the entire period of
study ( p = -1.1, 95% CI -1.6, -0.7).
BMD of the forearm increased significantly
(P < 0.005) in the pamidronate group (5.2%; 95% CI
2.5, 7.8), while there was a nonsignificant decrease in
the placebo group (-1.2%; 95% CI -3.4, 1.0). The
changes in forearm BMD with time were significantly
(P< 0.0001) different between the 2 groups during the
whole period of study ( p = -0.92, 95% CI -1.3,
-0.5).
specimens obtained at the end of the study after doublelabeling with tetracycline were investigated by a pathologist
who was unaware of treatment assignment.
Statistical analysis. A sample size of 45 patients per
arm was estimated to be sufficient to detect a 5% difference
in bone mass with a statistical power of 0.9 and an alpha
level of 0.05. Two-tailed r-tests and chi-square tests, where
appropriate, were used to compare group data. For repeated
measurements, the changes over time within and between
groups were analyzed by analysis of variance. The SPSSPC
statistical package was used.
RESULTS
Baseline characteristics of the treatment groups
are shown in Table 1. There were no statistically
The results of an intent-to-treat analysis corroborated those of the analysis of patients who completed
the 3 years of treatment. An intent-to-treat analysis for
forearm BMD was not available since the patients who
discontinued the study were assessed only for lumbar
spine and femoral neck BMD 3 years after study entry.
In the entire group of patients enrolled and assigned to
receive pamidronate treatment, BMD of the lumbar
spine and the femoral neck increased by a mean f
SEM of 5.9 7.1% and 2.7 ? 8.4%, respectively. The
statistical significance of the difference between the 2
treatment groups in the changes in BMD measured at
these 2 sites over time was similar in both the intentto-treat and the completer analyses.
*
399
PAMIDRONATE IN RA
Table 2. Percentage change in bone mineral density at 3 sites in the pamidronate- and placebotreated RA patients who completed the study, grouped according to the presence or absence of specific
risk factors for bone loss, i.e., postmenopausal status, persistent disease activity (ESR >20/mm/hour),
and reduced mobility (HAQ score > 1.25)*
Treatment, risk factor (n)
Pamidronate
Premenopausal (9)
Postmenopausal (12)
Placebo
Premenopausal (19)
Postmenopausal (12)
Pamidronate
ESR 520 mm/hour (10)
ESR >20 mm/hour (24)
Placebo
ESR 520 mm/hour (20)
ESR >20 d o u r (23)
Pamidronate
HAQ score <1.25 (23)
HA0 score 21.25 (11)
Placebo
HAQ score <1.25 (32)
HA0 score 21.25 (11)
Spine BMD
Femoral neck BMD
Forearm BMD
8.5 f 2.7
8.8 t 1.5
6.5 f 3.4
0.3 ? 2.4
8.6 f 5.5
1.9 f l.lt
-0.1 t 1.1
-0.7 ? 1.7
-3.3 2 1.8
-8.1 t 2.5t
7.4 ? 1.3
8.9 t 1.6
2.0 t 2.1
2.9 2 2.0
1.4 t 1.0
0.0 f 1.2
-1.4 f 1.2
-6.3 f 1.9$
6.7 t 1.2
12.1 t 2.3$
3.5 f 1.8
0.4 t 2.9
1.6 f 0.9
-2.1 t 1.2-4
-3.0
-6.6
?
f
1.2 ? 1.2
-5.1 t 2.2$
4.2
5.6
?
f
0.9
1.9
1.6 t 1.2
-3.7 ? 1.6$
6.5
3.0
f
2
1.9
1.7
0.7 2 1.0
-.6.4 f 2 . 3
1.2
3.0t
* Values are the mean 2 SEM. RA = rheumatoid arthritis; BMD = bone mineral density; ESR =
erythrocyte sedimentation rate; HAQ = Health Assessment Questionnaire.
t P < 0.05 versus patients in the same treatment group without the risk factor.
$ P < 0.01 versus patients in the same treatment group without the risk factor.
RA patients with persistently active disease,
reduced mobility, and postmenopausal status are presumed to be at higher risk for increased bone loss.
Comparison of the changes in BMD between the
placebo-treated patients with versus those without one
of these risk factors confirmed these findings (Table 2).
Appendicular bone loss was higher in postmenopausal
patients, patients with active disease, and patients
with low functional status. Similar comparisons for the
130
60
1
!
0
Table 3. Radiographic scores in the placebo-treated (n = 44)and
pamidronate-treated (n = 34) rheumatoid arthritis patients who
completed the study*
T
1
1
6
12
pamidronate-treated patients showed that significant
differences between patients with and those without
risk factors occurred less frequently, which indicates
that patients at risk for bone loss benefited from the
treatment (Table 2).
Biochemical parameters of bone metabolism.
Urinary hydroxyproline excretion was suppressed by
pamidronate to -70% of initial values during the entire
treatment period, but did not change significantly in
18
24
30
36
Time (months)
Figure 2. Urinary hydroxyproline (OHP) excretion (corrected for
creatinine [Cr] excretion) in pamidronate (APDbtreated or placebotreated rheumatoid arthritis patients who completed the 3 years of
study. Values are the mean f SEM.
Erosion score
Placebo
Pamidronate
Joint space
narrowing
score
Placebo
Pamidronate
Total no. of
affected
joints
Placebo
Pamidronate
Study
entry
12 months
24 months
36 months
9.7 t 2.1
10.1 f 1.8
12.3 2 2.3
14.6 5 2.4
14.5 f 2.5
17.2 2 2.8
16.4
19.0
6.8 t 1.4
7.2 t 1.3
6.9
7.4
* 1.1
5
1.1
11.1 t 1.9 16.7 t 2.6
10.2 2 1.5 18.3 t 2.4
*
2
2
2.7
3.0
18.3 t 2.7
19.0 t 2.8
9.1 t 1.2 10.9 1.2 11.6 t 1.3
9.4 f 1.2 12.3 f 1.4 12.3 1.6
* Values are the mean 5 SEM.
*
EGGELMEIJER ET AL
400
Table 4.
Parameters of disease activity in the placebo- and pamidronate-treated rheumatoid arthritis patients who completed the study*
Months after study entry
6
12
18
f 0.1
f 0.8
7.3 f 0.8
6.8 ? 0.8
5.6 2 0.8
5.3 ? 0.7
4.9 f 0.8
4.1 2 0.5
4.4
4.1
14.0k0.9
12.9T0.9
10.6f0.8
10.9f1.0
9.320.8
9.221.1
7.6k0.7
7.621.0
6.820.7
6.820.9
22.4
27.7
2
f
2.7
3.8
21.6
27.1
k 2.4
f 3.8
23.3 5 2.9
26.2 2 3.6
22.6
27.5
3.0
3.6
15.3
26.3
f
2
3.0
5.5
16.5 ? 3.1
21.1 f 5.0
17.3 2 3.3
19.3 2 5.2
18.3 k 3.4
19.4 f 4.2
1
Ritchie articular index
Placebo
Pamidronate
No. of swollen joints
Placebo
Pamidronate
Erythrocyte
sedimentation rate
Placebo
Pamidronate
C-reactive protein
Placebo
Pamidronate
3
10.4 f 0.9
9.5 f 0.8
7.5
7.5
f
k
24
30
36
2 0.7
f 0.7
5.0 f 0.6
4.9 f 0.7
5.5&0.6
5.320.7
5.120.7
5.820.7
5.1f0.7
4.850.8
21.2 2 2.8
31.0 2 3.9
25.6 2 2.9
32.9 ? 4.4
29.5 2 3.9
33.6 2 4.2
30.4
32.7
23.0 2 5.2
32.2 2 6.5
22.3
28.3
22.7 2 4.6
26.6 f 4.8
18.9 f 3.1
18.8 f 3.3
2
2
?
2
5.1
5.2
0.6
0.6
4.3
6.1
2
2
3.6
3.9
* Values are the mean -t SEM.
the placebo-treated group (Figure 2). The differences
in hydroxyproline excretion over time between patients in the 2 treatment groups who completed the
study was highly significant (P < 0.OOOl). There were
no significant changes in serum calcium concentrations, and no differences between the 2 groups. All
patients remained normocalcemic.
Course of RA. In both treatment groups, there
was a gradual increase in all 3 mean radiologic scores
in the patients who completed the study (Table 3). The
changes over time did not differ between patients in
the 2 groups.
Clinical and laboratory parameters of disease
activity in the patients who completed the trial are
shown in Table 4. The Ritchie articular index and the
number of swollen joints improved significantly (P <
0.001 and P < 0.0005, respectively) in both groups,
while there were no apparent changes in the ESR or
the serum CRP level. Changes in SAARD treatment
were considered necessary because of failure to control disease activity in 20 patients in the placebo group
and 6 patients in the pamidronate group (P = 0.01, by
chi-square analysis).
Pamidronate toxicity. Twenty-seven of the 105
patients enrolled withdrew from the study before
completion; 19 withdrew because of gastrointestinal
symptoms consisting of nausea and vomiting (4
placebo-treated, I5 pamidronate-treated), 1 because of
mouth ulcers (placebo-treated), 1 died of myocardial
infarction (pamidronate-treated), and 6 lost interest in
participating (2 placebo-treated, 4 pamidronatetreated). The total number of withdrawals was significantly higher in the pamidronate group (P < 0.001, by
chi-square analysis). Fractures occurred in 5 patients
(3 placebo-treated, 2 pamidronate-treated). No evidence of osteomalacia was detected qualitatively in
bone biopsies from 15 randomly selected patients (8
pamidronate-treated, 7 placebo-treated) after 3 years
of treatment.
DISCUSSION
The results of this trial show that continuous
oral pamidronate therapy is highly effective in preserving and increasing bone mass in RA. The increase in
bone mass is not confined to the first year of treatment,
but continues thereafter. In the patient population
studied, baseline BMD of the axial and appendicular
skeletons was within the range of that in age-matched
healthy controls. The rate of bone loss in the appendicular skeleton during followup of the placebo-treated
patients, particularly in subgroups with persistently
active disease, low functional status, or postmenopausal status, is consistent with the results of previous
longitudinal studies of RA patients with relatively
short disease duration (7,23,24). The stable lumbar
BMD in the placebo-treated group is also in accordance with the results of some previous studies
(25,26), but contrasts with others (7,23,24). The vanations in study results can probably be attributed to
differences in patient selection with respect to corticosteroid use, body composition, disease duration, and
disease activity.
The findings of our study support the conclusion that pamidronate effectively prevents bone loss in
the appendicular skeleton and increases bone mass in
PAMIDRONATE IN RA
the axial skeleton. First, relatively large and highly
significant differences in response between the
pamidronate- and placebo-treated groups were seen,
the effect being particularly notable in the subgroups
of patients who had risk factors for bone loss. Second,
urinary hydroxyproline excretion was directly suppressed by pamidronate, which is indicative of decreased bone resorption. The results were very similar
to those obtained in osteoporosis patients treated with
nitrogen-containing bisphosphonates ( 1 9 , although
our study is the first to investigate the continuous
administration of a bisphosphonate for 3 years in a
controlled study.
The catabolic effect of RA on bone has been
previously demonstrated with biochemical measures
of bone metabolism (27,28). Cytokines such as
interleukin-1 and interleukin-6, abundantly produced
at sites of rheumatoid inflammation, are known to
stimulate osteoclastic bone resorption and are likely to
be the mediators of bone loss in RA. Bisphosphonates
are potent inhibitors of osteoclast-mediated bone resorption and represent the treatment of choice in
disorders associated with accelerated bone loss; more
recently, they have been shown to be effective in the
treatment of osteoporosis (15). The findings of the
present controlled study in RA patients are consistent
with these results.
The potency of the pamidronate dosage studied, 300 mg/day (equivalent to 3 mg intravenously), is
in the lowest part of the dose-response curve (29).
This dosage was chosen because of concern for gastrointestinal intolerance and overall suppression of
bone turnover to a degree that may reduce the ability
of bone to remodel. Indeed, the 28% rate of study
withdrawal due to toxicity was mainly due to nausea
and vomiting in the first months after enrollment,
which is consistent with our previous experience with
this dosage of oral pamidronate in patients with breast
cancer and bone metastases (30). Histologic studies of
bone biopsies showed no evidence of pamidronateinduced osteomalacia, and followup of urinary hydroxyproline as a parameter of bone metabolism revealed stable decreased excretion, strongly suggesting
that continuous pamidronate therapy was not accompanied by a cumulative effect on bone turnover.
Several lines of evidence suggest that bisphosphonates may have antiarthritic properties. These
compounds have been shown to decrease inflammatory activity and joint destruction in animal models of
arthritis (31,32), whereas small open as well as controlled studies in RA patients have suggested that they
401
decrease clinical signs of arthritis activity (16,33-35).
In the present study, an effect of pamidronate on
disease activity or the progression of radiologic signs
of joint destruction could not be substantiated. Only
the higher number of SAARDs prescribed because of
arthritis activity in the placebo group compared with
the pamidronate group suggests an antiarthritic effect
of pamidronate. The use of higher oral or intravenous
dosages in studies in which an antiarthritic effect was
shown is the most obvious explanation for the discrepancy. Since tolerability hampers the use of pamidronate in dosages >300 mg/day, further information on
antiarthritic effects must await the results of studies
with long-term parenteral pamidronate treatment in
RA or with other more potent and less toxic bisphosphonates.
This study supports the suggestion that RA
patients with persistent disease activity, low functional status, andor postmenopausal status are at
increased risk for bone loss and may benefit from
measures to maintain bone mass. Furthermore, the
data indicate that pamidronate may be a suitable
bone-sparing treatment in these patient populations.
Whether long-term treatment with oral pamidronate
leads to a decreased rate of complications associated
with bone loss, such as fractures or complications of
joint surgery, requires further study. In conclusion, it
was shown that long-term therapy with a specific
bone-sparing agent increases bone mass in RA patients, when compared with treatment. This finding
suggests a treatment option that may prove to be
useful in the management of RA.
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