Rheumatol Int (2005) 26: 2129
DOI 10.1007/s00296-004-0496-3
O R I GI N A L A R T IC L E
Funda Tascioglu Omer Colak Onur Armagan
Ozkan Alatas Cengiz Oner
The treatment of osteoporosis in patients with rheumatoid arthritis
receiving glucocorticoids: a comparison of alendronate and intranasal
salmon calcitonin
Received: 7 January 2004 / Accepted: 28 May 2004 / Published online: 2 February 2005
Springer-Verlag 2005
Abstract Objective: The purpose of this study was to assess
the eects of alendronate and intranasal salmon calcito-
nin (sCT) treatments on bone mineral density and bone
turnover in postmenopausal osteoporotic women with
rheumatoid arthritis (RA) receiving low-dose glucocor-
ticoids. Methods: Fifty osteoporotic postmenopausal
women with RA, who had been treated with low-dose
corticosteroids for at least 6 months, were randomized to
receive alendronate 10 mg/day or sCT 200 IU/day for a
period of 24 months. All patients received calcium sup-
plementation 1,000 mg and vitamin D 400 IU daily.
Bone mineral density (BMD) of the lumbar spine, fem-
oral neck, and trochanter was measured annually using
dual-energy X-ray absorptiometry. Bone metabolism
measurements included urinary deoxypyridinoline
(DPD), serum bone alkaline phosphatase (BAP), and
serum osteocalcin (OC). Results: Over 2 years, the lum-
bar spine (4.34%, P <0.001), femoral neck (2.52%, P
<0.05), and trochanteric (1.29%, P <0.05) BMD in the
alendronate group increased signicantly. The sCT
treatment increased lumbar spine BMD (1.75%, P
<0.05), whereas a signicant bone loss occurred at the
femoral neck at month 24 ( 3.76%, P <0.01). A non-
signicant decrease in the trochanteric region was ob-
served in the sCT group ( 0.81%). The dierence
between the groups with respect to the femoral neck
and trochanteric BMD was statistically signicant (P
<0.001and P <0.05, respectively). The decreases in
urinary DPD ( 21.87%, P <0.001), serum BAP
( 10.60%, P <0.01), and OC ( 19.59%, P <0.05)
F. Tascioglu (&) O. Armagan C. Oner
Department of Physical Therapy and Rehabilitation,
Osmangazi University Faculty of Medicine,
26480 Eskisehir, Turkey
E-mail: fbatmaz@superonline.com
Tel.: +90-222-2392979
Fax: +90-222-2393774
O. Colak O. Alatas
Department of Biochemistery,
Osmangazi University Faculty of Medicine,
Eskisehir, Turkey
values were statistically signicant in the alendronate
group, whereas nonsignicant decreases were observed in
the sCT group ( 5.77%, 1.96%, and 4.31%, respec-
tively). A signicant dierence was found in the DPD and
BAP levels between the two treatment groups in favor of
the alendronate group at all time points ( P =0.001 and P
<0.05, respectively). Conclusion: The results of this study
demonstrated that alendronate treatment produced sig-
nicantly greater increases in the femoral neck BMD and
greater decreases in bone turnover than intranasal sCT in
RA patients receiving low dose glucocorticoids.
Keywords Glucocorticoids Osteoporosis
Rheumatoid arthritis
Introduction
Rheumatoid arthritis (RA) is a chronic inammatory
disease characterized by symmetrical polyarthritis [1].
Generalized osteoporosis is a common complication of
RA [2, 3]. Although the pathogenesis of this osteopo-
rosis is not completely understood, it is thought to be
multifactorial [4]. The factors shown to play an impor-
tant role in osteoporosis in patients with RA are long
disease duration [5, 6], decreased physical activity [7, 8],
persistently active disease [9, 10], bone resorbing cyto-
kines such as interleukin 1[IL-1], interleukin 6 [IL-6],
and tumor necrosis factor alpha (TNF-a) [11, 12], and
glucocorticoid treatment [13].
Glucocorticoids are widely used in the treatment of
RA and are the most common cause of drug-related
osteoporosis [14]. Bone loss is greatest early in the course
of treatment [15]. Consequently, the risk of fractures also
increases. In various studies the incidence of vertebral and
femur fractures was found to be signicantly higher in
patients with RA treated with glucocorticoids compared
to RA patients without glucocorticoid treatment [16, 17].
Therefore, optimal management strategies are needed
in the treatment of glucocorticoid-induced osteoporosis.
22
Bisphosphonates are strong inhibitors of osteoclast-med-
iated bone resorption. In several clinical trials conducted in
RA patients with established osteoporosis, it has been
shown that bisphosphonates such as etidronate [18, 19,
20], risedronate [21], and pamidronate [22] produced sig-
nicant and progressive increases in bone mineral density
(BMD) at the lumbar spine and the hip. Alendronate is
another potent bisphosphonate that is widely used in the
treatment of postmenopausal osteoporosis. More recently,
alendronate has been reported to increase BMD in pa-
tients with RA receiving glucocorticoids [23, 24].
Salmon calcitonin (sCT) is also a potent inhibitor of
bone resorption, and in a few studies, it has been shown
to be eective in the treatment of glucocorticoid-induced
osteoporosis in patients with RA [25, 26]. However, the
number of studies on bone-sparing eects of intranasal
sCT in patients receiving low-dose glucocorticoids is
limited, and the results of these studies are contradictory.
In the present study, we therefore aimed to investi-
gate the eects of alendronate and salmon calcitonin on
bone mineral density and bone turnover in patients with
RA receiving low-dose glucocorticoid therapy.
Patients and methods
Fifty patients with RA who lled the diagnostic criteria
of the American Collage of Rheumatology were enrolled
in this study [27]. All patients were on long-term glu-
cocorticoid therapy with established osteoporosis as
shown with t scores of the lumbar spine below 2.5 SD
of the mean peak value in young adults. The mean
duration of glucocorticoid therapy was 4.28 years. All
patients were postmenopausal and had been receiving
corticosteroid equivalent to 510 mg prednisolone per
day for more than 6 months.
Exclusion criteria included: serious hepatic, renal,
hematologic, pulmonary or cardiovascular disease,
underlying malignancy, active peptic ulcer, metabolic
bone disease known to aect the bone metabolism such
as hyperthyroidism, any medication known to aect bone
turnover other than glucocorticoids, and the presence of
abnormalities on spinal and femoral radiographs that
could eect precise densitometric measurement. Patients
who had been treated with estrogen, calcitonin, vitamin
D, or active metabolites, and bisphosphonates within the
past 12 months were also excluded.
Patients continued to receive their disease modifying
antirheumatic drugs for RA. At study entry, 27 patients
were taking methotrexate (15 patients in the alendronate
group and 12 patients in the sCT group), 12 were taking
sulfasalazine (5 patients in the alendronate group and 7
patients in the sCT group), 5 patients were taking a
combination of methotrexate and sulfasalazine (2 patients
in the alendronate group and 3 patients in the sCT group),
and 6 were taking antimalarial (3 patients in each group)
drugs. All patients provided informed consent, and the
study protocol was approved by the local ethics committee
of the Osmangazi University Faculty of Medicine.
The study was designed as a randomized and open
study conducted at the Osmangazi University Hospital,
Department of Physical Therapy and Rehabilitation.
Fifty patients were randomly assigned to receive daily
10 mg of alendronate sodium or 200 IU intranasal sal-
mon calcitonin for 24 months. All patients received
calcium supplementation 1,000 mg and vitamin D 400 IU
daily. The patients were instructed to take alendronate in
the morning as the rst drug with at least a glass of water
and to avoid eating anything or lying down during the
next 1 h.
Disease activity was assessed by using the European
League Against Rheumatism Modied Disease Activity
Score based on the unweighted 28 joint count [28], and
the functional impairment was estimated by the Health
Assessment Questionnaire [29].
Bone mineral density of the lumbar spine (L1L4),
femoral neck, and trochanteric region was measured by dual
X-ray absorptiometry (DXA) (Hologic QDR 4,500 W) and
was taken at baseline and every year thereafter.
Laboratory investigations included the erythrocyte
sedimentation rate (ESR), white blood cell count, hemo-
globulin, hematocrit, and platelets, C-reactive protein
(CRP), serum calcium, phosphorus, alkaline phosphotase,
aspartate transaminase, alanine transaminase, gamma
glutamyl transaminase, creatinine, glucose, total protein,
albumin, bilirubin, 25-hydroxyvitamin D3, and parathy-
roid hormone. Creatinine and calcium levels were also
estimated on 24-h urine collections.
Bone metabolism measurements included urinary
deoxypyridinoline (DPD), serum bone alkaline phos-
phatase (BAP), and serum osteoalcin (OC). Urinary DPD
(adjusted for creatinine excretion) as a marker of bone
resorption was measured using the chemiluminescence
method with an automatic hormone analyzer (DPC-Im-
mulite). Serum OC and BAP levels and markers of bone
formation were measured with commercially available
ELISA kits (Trinity Biotech and Metra Biosystems Inc.,
respectively). These measurements were performed at
baseline and at 6, 12, and 24 months. At each visit, patients
were questioned about adverse events, and the adverse
events related to the treatments were recorded.
For statistical analysis, the ecacy parameters were
statistically analyzed using the values measured at base-
line and at months 6, 12, and 24. The two-tailed t test and
Fishers exact tests were used to compare the demo-
graphic data. Analysis of variance (ANOVA) was used to
test for percentage changes in the BMD of the lumbar
spine, femoral neck, trochanter, BAP, OC, and DPD
from baseline within and between the treatment groups at
6, 12, and 18 months. The changes in the daily dose of
glucocorticoids and disease activity parameters within
and between the treatment groups were analyzed by using
ANOVA. Fishers exact test was used to compare the
number of adverse events between the groups.
Data were expressed as the mean standard devia-
tion (SD). Dierences were considered signicant if the
P values were less or equal to a level of 5%, and all
results are expressed with a 95% condence interval.
 23

BMD of the patients increased signicantly in the

Results
Although 50 postmenopausal women with RA and
osteoporosis were included in this study, 2 in the
alendronate and 1 in the sCT group withdrew from the
study because of the side eects. In addition, one patient
in the alendronate group failed to complete the study
because of an active are up of RA. Thus, a total of 46
patients completed the follow-up period of 24 months.
The treatment groups were comparable at baseline
with regard to demographic ndings, and there were no
statistically signicant dierences between the groups
(Table 1).
The mean daily dose of glucocorticoid and a sum-
mary of disease activity parameters are given in Table 2.
The mean daily dose of glucocorticoid was similar be-
tween groups throughout the study period. Comparison
of disease activity parameters showed no signicant
dierences within and between the groups.
Bone mineral density measurements
alendronate (+2.60%, P <0.001) and sCT (+1.54%, P
<0.05) treated groups. At the lumbar spine, BMD in-
creased signicantly at the 24th month in both the
alendronate (+4.34%, P <0.001) and sCT groups
(+1.75%, P <0.05). The changes in lumbar spine BMD
with time were signicant between the two groups at the
24th month ( P <0.05) (Fig. 1). The alendronate treat-
ment increased femoral neck BMD (+2.52%, P <0.05),
whereas a signicant bone loss relative to baseline values
occurred at the femoral neck in the sCT-treated group
( 3.76%, P <0.01) at month 24 (Fig. 2). The dierence
between the groups with respect to the femoral neck
BMD was statistically signicant ( P =0.001) at that
time point. Relative to baseline, the trochanteric BMD
increased in the alendronate-treated group at months 12
(+1.39%, P <0.05) and 24 (+1.29%, P <0.05). A
nonsignicant decrease in trochanteric BMD was ob-
served in the sCT group at the 12th and 24th months
( 0.48% and 0.81%, respectively) (Fig. 3). The changes
in BMD at the trochanter were signicantly dierent
between the groups at both time points ( P <0.05).

Table 3 shows the changes in BMD at the lumbar spine,

femoral neck, and trochanteric region throughout the Biochemical markers of bone turnover
study. At the end of the 12 months, the lumbar spine
At months 6, 12, and 24, alendronate treatment decreased
the excretion of urinary DPD, a specic marker for bone
Table 1 Baseline demographic characteristics of the patients resorption ( 17.17%, 19.37%, and 21.82%, respec-
Alendronate Calcitonin tively, P <0.001), whereas no signicant changes relative
n =22 n =24 to baseline were seen in the sCT group ( 1.13%,
4.33%, and 5.77%, respectively) (Fig. 4). The dier-
Age (years) 55.676.67 58.136.51 ences in DPD excretion over time between the two groups
Disease duration (years) 8.372.71 9.204.29
Weight (kg) 64.509.57 61.838.42
were signicant at all time points ( P <0.001, P <0.001,
Height (cm) 157.534.71 158.604.41 and P =0.001, respectively). Alendronate treatment also
Body mass index 25.973.49 24.432.63 decreased serum BAP and OC, two markers of bone
Duration of menopause (years) 7.104.82 8.975.31 formation, relative to baseline at month 6 ( 10.30%, P
Duration of corticosteroid 4.001.76 4.572.28 <0.01 and 21.27%, P <0.05, respectively), month 12
use (years)
Romatoid factor positivity (%) 90% 86.6% ( 10.50%, P <0.01 and 22.58%, P <0.05), and month
24 ( 10.60, P <0.01 and 19.59%, P <0.05). In the

Table 2 Glucocorticoid dose and parameters of disease activity in the alendronate- and calcitonin-treated rheumatoid arthritis patients
during the study period

Baseline Month 6 Month 12 Month 24

Glucocorticoid dose
Alendronat ( n =22) 8.001.77 7.851.55 7.701.98 7.891.80
Calcitonin ( n =24) 7.582.04 8.171.17 7.831.95 7.752.59
Disease activity score
Alendronat ( n =22) 3.881.45 3.721.28 3,831.56 3.911.72
Calcitonin ( n =24) 4.221.18 4.171.53 4.201.62 4.161.64
Health assessment questionnaire
Alendronat ( n =22) 1.310.62 1.330.98 1.340.85 1.320.71
Calcitonin ( n =24) 1.340.58 1.350.89 1.361.01 1.350.93
Erythroyte sedimentation rate (mm/h)
Alendronat ( n =22) 28.5514.64 30.828.16 31.739.87 32.779.11
Calcitonin ( n =24) 32.6311.48 34.2510.90 35.4611.72 34.799.88
C-reactive protein (mg/dl)
Alendronat 1.431.29 1.581.56 1.360.96 1.821.04
Calcitonin 1.831.30 1.801.19 1.880.87 2.230.95
24

Table 3 Bone mineral density ( BMD) values (g/cm2) at the lumbar spine, femoral neck and trochanteric region of the patients measured
at baseline and at months 12 and 24 (mean annual % changes were given in parenthesis)

Baseline Month 12 Month 24

Lumbar BMD
Alendronate ( n =22) 0.690.07 0.710.06* (2.60) 0.720.06* (4.34)
Calcitonin ( n =24) 0.680.07 0.690.07
(1.54) 0.690.07
(1.75)
P <0.05
Femoral neck BMD
Alendronate ( n =22) 0.570.05 0.580.06 (0.80) 0.590.07 (2.52)
Calcitonin ( n =24) 0.550.05 0.540.06 ( 1.05) 0.530.06 ( 3.76)
P =0.001
Trochanteric region BMD
Alendronate ( n =22) 0.640.05 0.650.07
(1.39)
0.650.07
(1.29)
Calcitonin ( n =24) 0.630.08 0.620.06 ( 0.48) 0.620.06 ( 0.81)
P <0.05 P <0.05

* P <0.001 (one way ANOVA; baseline versus month 12 and month 24),
P <0.05 (one way ANOVA; baseline versus month 12 and
month 24),  P <0.05 (one way ANOVA; baseline versus month 24)

sCT-treated group, small but nonsignicant decreases in Adverse events

BALP and OC levels were observed at months 6 ( 0.81%
and 0.24%), 12 (2.14% and 3.30%), and 24 (1.96% and
4.31%; Figs. 5 and 6). A signicant dierence was
found in the BALP level between the two treatment
groups in favor of the alendronate group, and the dif-
ferences between the alendronate and sCT groups were
maintained throughout the study ( P <0.05). The chan-
ges in the OC levels with time were not statistically sig-
nicant between the two groups during the entire period
of study (Table 4).
The mean serum calcium, phosphorus, parathyroid
hormone, 25-hydroxyvitamin D3,, and 24-h urinary
calcium levels were similar between the treatment groups
during the study and remained comparable to pretreat-
ment levels (data not shown).
The percentage of the withdrawals because of the
drug-related side eects was found to be nonsignicant
between the groups (9.1% in the ALN group and 4.2%
in the sCT group). There was a variety of adverse events
reported in each group. Six patients in the alendronate
group (27%) and two patients in the sCT group (8.3%)
had adverse eects during the study period. In the
alendronate-treated group, four patients reported abdom-
inal pain. Other adverse events in this group were nausea,
vomiting, and myalgia. In the sCT-treated group, one
patient reported facial ushing, and the other patient
reported intranasal dryness. Most of these adverse
events were mild, and no other patient was excluded
from the study. There was no signicant dierence

Fig. 1 Mean percentage change

in the bone mineral density of
the lumbar spine (values are the
mean SEM)
 25

Fig. 2 Mean percentage change

in the bone mineral density of
the femoral neck (values are the
mean SEM)

between groups with respect to the frequency of adverse
events.
Discussion
Glucocorticoid-induced osteoporosis is a common and
disabling clinical condition for patients with rheumatoid
arthritis. Since RA patients have additional risk factors
such as persistently active disease and decreased physical
and weight-bearing activity, specic bone antiresorptive
drugs may be required [9].
In the present study, we found that daily 10 mg
alendronate treatment increased bone mineral density at
the lumbar spine (4.34%), femoral neck (2.52%), and
trochanter (1.29%) relative to baseline values at the end
of the 24 months. Our ndings are consistent with pre-
vious studies showing that alendronate prevents bone
loss and increases bone mass in patients receiving long-
term glucocorticoid therapy [23, 30, 31]. In a recent

Fig. 3 Mean percentage change

in the bone mineral density of
the trochanteric region (values
are the mean SEM)
26

Fig. 4 Mean percentage

changes in the urinary levels of
deoxypridinoline (values are the
mean SEM)

study, Sambrook et al. showed bone-sparing eects of
alendronate in a group of patients treated with gluco-
corticoids [30]. In this randomized, multi-center, open-
label trial, the author also showed that alendronate was
superior to simple vitamin D or calcitriol. The preven-
tion of bone loss with alendronate was shown in a 12-
month, prospective, randomized, double-blind, and
placebo-controlled clinical trial by Saag et al. [23]. They
found that the alendronate group had a mean increase in
spinal mass of 2.9%, while the femoral neck BMD
(1.0%) was maintained at the end of the 12 months. In
the 2nd year follow-up of this study, Adachi et al.
showed that bone density of the lumbar spine continued
to increase (3.85%) and was maintained at the femoral
neck (0.61%) with daily 10-mg alendronate treatment
[31]. These results for BMD are in accordance with our
results, showing an increase of bone density in the spine
and femoral neck.
On the other hand, we found that a 2-year daily
200 IU sCT administration prevents bone loss only in

Fig. 5 Mean percentage

changes in the levels of bone
specic alkaline phosphotase
(values are the mean SEM)
 27

Fig. 6 Mean percentage

changes in the levels of
osteocalcin (values are the mean
SEM)

the lumbar spine (1.75%), not in the femoral neck
( 3.76%). The number of studies on bone-sparing ef-
fects of sCT in RA is limited, and the results have varied
between studies with regard to the ecacy of sCT. For
instance, in a 2-year, double-blind, randomized, con-
trolled trial, Healey et al. showed that salmon calcitonin
with calcium and vitamin D3 provided no greater bone
preservation than that observed with calcium and vita-
min D3 alone in patients receiving long-term corticos-
teroids [32]. In another study, Sambrook et al. could not
nd any additional eect of intranasal sCT in RA pa-
tients treated with calcitriol and calcium [33].
In contrast, some of these studies have shown that
sCT leads to signicant bone gain, especially in the
lumbar spine [25, 26]. In a randomized, open-label
study, Kotaniemi et al. found statistically signicant
increases at the lumbar spine (4.6%) and femoral neck
(2.6%) BMD of RA patients receiving low-dose gluco-
corticoid treatment [34]. In this study, we failed to show
an increase at the femoral neck BMD in our patients. In
Kotaniemis trial, the study group consisted of both
premenopausal and postmenopausal women, and the
sCT dose was lower than in our study. For these rea-
sons, the results of Koteniemi et al. are not directly
comparable with the results of our study.
In a meta-analysis, Cranney et al. reviewed the e-
cacy of calcitonin for the treatment and prevention of
glucucorticoid-induced osteoporosis [35]. The authors
concluded that calcitonin treatment appeared to pre-
serve bone mass at the lumbar spine by about 3% as
compared to a placebo, but not at the femoral neck.
Considering the results that we obtained in this study,

Table 4 Serum bone alkaline phosphatase ( BAP), osteocalcin ( OC) and urinary deoxypyridinoline ( DPD) levels (corrected for creat-
inine) of the patients measured at baseline and months 6, 12 and 24 (mean % changes were given in parenthesis)

Baseline Month 6 Month 12 Month 24

DPD (nM/mMCr)
Alendronate (n =22)
Calcitonin ( n =24)
BAP (U/l)
Alendronate (n =22)
Calcitonin ( n =24)
OC (ng/ml)
Alendronate (n =22)
Calcitonin ( n =24)
7.822.13 6.471.53* ( 17.17) 6.271.82* ( 19.37) 6.111.73* ( 21.87)
7.982.65 7.772.53 ( 1.13) 7.562.39 ( 4.33) 7.442.44 ( 5.77)
<0.001 <0.001 =0.001
19.194.41 16.964.42
( 10.30) 16.694.65
( 10.50) 16.534.08
( 10.60)
20.817.27 ( 0.81) 20.987.27 (2.14) 20.896.97 (1.96)
21.026.60
<0.05 <0.05 <0.05
9.295.94 7.675.17 ( 21.27) 7.214.08 ( 22.58) 7.693.94 ( 19.59)
8.985.95 8.546.12 (0.24) 8.395.48 ( 3.30) 8.155.39 ( 4.31)

* P <0.001 (one way ANOVA, baseline versus months 6, 12, and 24),
P <0.01(one way ANOVA; baseline versus months 6, 12, and 24),
P <0.05 (one way ANOVA, baseline versus months 6, 12, and 24)
28
we agree with the author and suggest that the protective
eect of calcitonin is greater in the lumbar spine.
Biochemical markers of bone turnover were found to
be an exiting eld, which may emerge as useful in risk
prediction, choice of therapy, and monitoring the time
course of bone loss and the ecacy of therapy [36]. Few
studies have focused on the biochemical markers of
generalized bone loss in RA [37]. In the present study,
the urinary excretion of DPD, a marker of bone
resorption, decreased signicantly in the alendronate
groups during the course of the study. Similarly, in the
group that received alendronate, serum BAP and OC,
bone formation markers, decreased signicantly,
whereas no signicant decrease was seen in the sCT
group. The reduction in bone turnover in our study is
consistent with the ndings of other alendronate trials
[23, 31]. In this study, the decrease in DPD was more
pronounced than the decrease in bone formation
markers. Bone formation and resorption both increased
and coupled in postmenopausal osteoporosis [36]. On
the other hand, bone metabolism may be uncoupled in
chronic RA. Bone formation appears to be reduced,
partly reecting disease activity, whereas bone resorp-
tion is increased in RA patients compared to healthy
controls [38].
Our study is the rst prospective study to compare
the eects of alendronate and sCT on BMD and bone
turnover in RA patients receiving low-dose glucocor-
ticoids. The main limitation in this study was the rela-
tively small sample size. Since other factors such as
menopausal status and sex could have an eect on bone
mass and bone turnover, only postmenopausal women
with RA were included in this study. The open-label
protocol was another limitation of our study. Because of
the dierences in the administration of the study drugs,
we had to use this protocol.
In conclusion, this randomized trial comparing the
ecacy of alendronate and intranasal salmon calcitonin
in postmenopausal RA patients receiving low-dose glu-
cucorticoids demonstrated that patients treated with
alendronate had signicantly greater increases in BMD
at the femoral neck than did those treated with sCT.
Moreover, alendronate was more eective in suppressing
bone turnover. These results showed that alendronate is
an eective and well-tolerated therapy for the treatment
of glucocorticoid-induced osteoporosis in patients with
RA.
References
1. Van Jaarsveld CHM, Jacobs JWG, Van Der Veen MJ, Blaauw
AAM, Kruize AA, Hofman DM, Brus HLM (2000) Aggressive
treatment in early rheumatoid arthritis: a randomised con-
trolled trial. Ann Rheum Dis 59:468477
2. DequekerJ, Maenaut K, Verwilghen J, Westhowens R (1995)
Osteoporosis in rheumatoid arthritis. Clin Exp Rheumatol
12:S16
3. Suzuki Y, Mizushima Y (1997) Osteoporosis in rheumatoid
arthritis. Osteoporos Int 7 [Suppl 3]:S217222
4. Celiker R, Gokce-Kutsal Y, Cindas A, Ariyurek M, Renda N,
Koray Z, Basgoze O (1995) Osteoporosis in rheumatoid
arthritis: eect of disease activity. Clin Rheumatol 14:429433
5. Laan RFJM, van Riel PLCM, van de Putte LBA (1992) Bone
mass in patients with rheumatoid arthritis. Ann Rheum Dis
51:826832
6. Haugeberg G, Uhlig T, Flach JA, Halse JI, Kvien TK (2000)
Bone mineral density and frequency of osteoporosis in female
patients with rheumatoid arthritis. Results from 394 patients in
the Oslo country rheumatoid arthritis register. Arthritis Rheum
43:522530
7. Kroger H, Honkanen R, Saarikoski S, Alhave E (1994) De-
creased axial bone mineral density in perimenopausal women
with rheumatoid arthritisa population based study. Ann
Rheum Dis 53:1823
8. Iwamoto J, Takeda T, Ichimura S (2002) Forearm bone min-
eral density in postmenopausal women with rheumatoid
arthritis. Calcif Tissue Int 70:18.
9. Cortet B, Guyot MH, Solau E, Pigny P, Dumoulin F, Flipo
RM (2000) Factors inuencing bone loss in rheumatoid
arthritis: a longitudinal study. Clin Exp Rheumatol 18:683690
10. Eastgate JA, Wood NC, Di Giovine FS, Symons JA, Grinlin-
ton FM, Du GW (1988) Correlation of plasma interleukin-1
levels with disease activity in rheumatoid arthritis. Lancet
340:706709
11. Deodhar AA, Woolf AD (1996) Bone mass measurement
and bone metabolism in rheumatoid arthritis: a review. Br
J Rheumatol 35:309322
12. Buckley LM, Leib ES, Cartularo KS, Vacek PM, Cooper SM
(1995) Eects of low dose corticosteroids on the bone mineral den-
sity of patients with rheumatoid arthritis. J Rheumatol 22:10551059
13. Saario R, Sonninen P, Mottonen T, Viikari J, Toivanen A
(1999) Bone mineral density of the lumbar spine in patients
with advanced rheumatoid arthritis: inuence of functional
capacity and corticosteroid use. Scand J Rheumatol 28:363367
14. Saag K, Koehnke R, Cadwell J, Brasington R, Burmeister LD,
Zimmerman B, et al (1994) Low dose long-term corticosteroid
therapy in RA: an analyis of serious adverse events. Am J Med
96:115123
15. LoCasvio V, Bonucci E, Imbimbo B, Ballanti P, Adami S,
Milani S, et al (1990) Bone loss in response to long-term glu-
cocorticoid therapy. Bone Miner 8:3951
16. Peel NF, Moore DJ, Barrington NA, Bax DE, Eastell R (1995)
Risk of vertebral fracture and relationship to bone mineral density
in steroid treated rheumatoid arthritis. Ann Rheum Dis 54:801806
17. Cooper C, Coupland C, Mitchell M (1995) Rheumatoid arthritis,
corticosteroid therapy, and hip fractures Ann Rheum Dis 54:4952
18. Hasegawa J, Nagashima M, Yamamoto M, Nishijima T, Ka-
tsumata S, Yoshino S (2003) Bone resorption and inamma-
tory inhibition of intermittent cyclical etidronate therapy in
rheumatoid arthritis. J Rheumatol 30:474479
19. Jenkins EA, Walker-Bone KA, Wood A, McCrae FC, Cooper
C, Calwey MID (1999) The prevention of corticosteroid-in-
duced bone loss with intermittent cyclical editronate. Scand J
Rheumatol 28:152156
20. >Geusens P, Dequeker J, Vanhoof J, Stalmans R, Boonen S,
Joly J, et al (1998) Cyclical editronate increases bone density in
the spine and hip of postmenopausal women receiving long
term corticosteroid treatment. A double blind, randomised,
placebo controlled study. Ann Rheum Dis 57:724727
21. Eastell R, Devogelaer JP, Peel NFA, Chines AA, Bax DE, et al
(2000) Prevention of bone loss with risedronate in glucocorticoid-
treated rheumatoid arthritis patients. Osteoporos Int 11:331337
22. Eggelmeijer F, Papapoulos SE, vanPaessen H, Dijkmans BEC,
Valkema R, Westedt ML (1996) Increased bone mass with
pamidronate treatment in rheumatoid arthritis. Arthrits
Rheum 39:396402
23. Saag KG, Emkey R, Schnitzer TJ, Brown JP, Hawkins F,
Goemaere S, et al (1998) Alendronate for the prevention and
treatment of glucocorticoid-induced osteoporosis. Glucocorti-
coid Induced Osteoporosis Intervention Study Group. N Engl
J Med 339:292299

24. Yilmaz L, Ozoran K, Gunduz OH, Ucan H, Yucel M (2001)
Alendronate in rheumatoid arthritis patients treated with
methotrexate and glucocorticoids. Rheumatol Int 20:6569
25. Sileghem A, Geusens P, Dequeker J (1992) Intranasal calcito-
nin for the prevention of bone erosion and bone loss in rheu-
matoid arthritis. Ann Rheum Dis 51:761764
26. Adachi JD, Bensen WG, Bell MJ, Bianchi FA, Cividino AA,
Craig GL, et al (1997) Salmon calcitonin nasal spray in the
prevention of corticosteroid-induced osteoporosis. Br J Rheu-
matol 36:255259
27. Arnett FC, Edworthy SM, Bloch DA, et al (1988) The American
Rheumatism Association 1987 revised criteria for the classica-
tion of rheumatoid arthritis. Arthritis Rheum 31:315324
28. Prevoo MLL, vant Hof MA, Kuper HH, van Leeuwen MA,
van de Putte LBA, van Riel PLCM (1995) Modied disease
activity scores that include 28-joint counts: development and
validation in a prospective longitudinal study of patients with
rheumatoid arthritis. Arthritis Rheum 38:4448
29. Kirwan JR, Reeback JS (1986) Stanford health assessment
questionnaire modied to assess disability in British patients
with rheumatoid arthritis. Br J Rheumatol 25:206209
30. Sambrook PN, Kotowicz M, Nash P, Styles CB, Naganathan V,
Henderson-Bria KN (2003) Prevention and treatment of glu-
cocorticoid-induced osteoporosis: a comparison of calcitriol,
vitamin D plus calcium, and alendronate plus calcium. J Bone
Miner Res 18:919924
31. Adachi JD, Saag KG, Delmas PD, Liberman UA, Emkey RD,
Seeman E, et al (2001) Two-year eects of alendronate on bone
mineral density and vertebral fracture in patients receiving
glucucorticoids. Arthritis Rheum 44:202211
29
32. Healey JH, Paget SA, Williams-Russo P, Szatrowski TP,
Schneider R, Spiera H (1996) A randomized controlled trial of
salmon calcitonin to prevent bone loss in corticosteroid-treated
temporal arteritis and polymyalgia rheumatica. Calcif Tissue
Int 58:7380
33. Sambrook P, Birmingham J, Kelly P, Kempler S, Nuguyen T,
Pocock N, et al (1993) Prevention of corticosteroid osteopo-
rosis. A comparison of calcium, calcitriol, and calcitonin. N
Engl J Med 17:17471752
34. Kotaniemi A, Piirainen H, Paimela L, Leirisalo-Repo M, Uoti-
Reilama K, Lahdentausta P, et al (1996) Is continuous intra-
nasal salmon calitonin eective in treating axial bone loss in
patients with active rheumatoid arthritis receiving low dose
glucocorticoid therapy? J Rheumatol 23:18751879
35. Cranney A, Welch V, Adachi JD, Homik J, Shea B, Suarez-
Almazor ME, et al (2000) Calcitonin for the treatment and
prevention of corticosteroid-induced osteoporosis. Cochrane
Database Syst Rev 2:CD001983
36. Takahashi M, Kushida H, Hoshino H, Ohishi T, Inoue T
(1997) Evaluation of bone turnover in postmenopausal, verte-
bral fracture, and hip fracture using biochemical markers
for bone formation and resorption. J Endocrinol Invest
20:112117
37. Seriolo B, Ferretti V, Sulli A, Caratto E, Fasciolo D, Cutolo M
(2002) Serum osteocalcin levels in premenopausal rheumatoid
arthritis patients. Ann N Y Acad Sci 966:502507
38. Hall GM, Spector TD, Delmas PD (1995) Markers of bone
metabolism in postmenopausal women with rheumatoid
arthritis: eects of corticosteroids and hormone replacement
therapy. Arthritis Rheum 38:902906