Self reported non-vertebral fractures in rheumatoid arthritis and population based controls: incidence and relationship with bone mineral density and clinical variables.

Abstract

To compare the incidence of self reported non-vertebral fractures after RA diagnosis between female patients with RA and control subjects, and to explore possible associations between non-vertebral fractures and bone mineral density (BMD), disease, and demographic factors.
249 women (mean age 63.0 years) recruited from a county register of patients with RA and population controls (n = 249) randomly selected after matching for age, sex, and residential area were studied. Data on previous non-vertebral fractures were obtained from a detailed questionnaire, and BMD was measured at the hip and spine.
53 (21.3%) patients with RA had had 67 fractures after RA diagnosis, the corresponding numbers for controls were 50 (20.1%) and 60 (odds ratio (OR) for paired variables for overall fracture history 1.09, 95% CI 0.67 to 1.77). The overall fracture rates per 100 patient-years were 1.62 and 1.45, respectively, but self reported hip fractures were increased in RA (10 v 2, OR 9.0, 95% CI 1.2 to 394.5). Patients with a positive fracture history had longer disease duration, were more likely to have at least one deformed joint, and had lower age and weight adjusted BMD than those with no fracture history. In logistic regression analysis, fracture history was independently related to BMD only.
With the probable exception of hip fractures, non-vertebral fractures do not seem to be a substantial burden in RA. Similar independent relationships between levels of BMD and fracture history were found in patients with RA and in population based controls.

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EXTENDED REPORT
Self reported non-vertebral fractures in rheumatoid arthritis
and population based controls: incidence and relationship
with bone mineral density and clinical variables
R E Ørstavik, G Haugeberg, T Uhlig, P Mowinckel, J A Falch, J I Halse, T K Kvien
.............................................................................................................................. .
See end of article for
authors’ affiliations
.......................
Correspondence to:
Dr R Ørstavik, Department
of Rheumatology,
Diakonhjemmet Hospital,
Box 23, Vinderen, N-0319
Oslo, Norway;
ragnhild.orstavik@
ioks.uio.no
Accepted 28 April 2003
.......................
Ann Rheum Dis 2004;63:177–182. doi: 10.1136/ard.2003.005850
Objective: To compare the incidence of self reported non-vertebral fractures after RA diagnosis between
female patients with RA and control subjects, and to explore possible associations between non-vertebral
fractures and bone mineral density (BMD), disease, and demographic factors.
Methods: 249 women (mean age 63.0 years) recruited from a county register of patients with RA and
population controls (n=249) randomly selected after matching for age, sex, and residential area were
studied. Data on previous non-vertebral fractures were obtained from a detailed questionnaire, and BMD
was measured at the hip and spine.
Results: 53 (21.3%) patients with RA had had 67 fractures after RA diagnosis, the corresponding numbers
for controls were 50 (20.1%) and 60 (odds ratio (OR) for paired variables for overall fracture history 1.09,
95% CI 0.67 to 1.77). The overall fracture rates per 100 patient-years were 1.62 and 1.45, respectively,
but self reported hip fractures were increased in RA (10 v 2, OR 9.0, 95% CI 1.2 to 394.5). Patients with a
positive fracture history had longer disease duration, were more likely to have at least one deformed joint,
and had lower age and weight adjusted BMD than those with no fracture history. In logistic regression
analysis, fracture history was independently related to BMD only.
Conclusions: With the probable exception of hip fractures, non-vertebral fractures do not seem to be a
substantial burden in RA. Similar independent relationships between levels of BMD and fracture history
were found in patients with RA and in population based controls.
P
corticosteroid treatment, which has been shown to increase
the risk of both vertebral and non-vertebral fractures.2–6
However, rather few studies have explored the rates of
fractures in patients with RA. It has been demonstrated that
patients with RA have a higher risk of vertebral deformi-
ties5 7 8and hip fractures9 10than control subjects. Two
previous studies have suggested that aging, impaired
ambulation and, perhaps, corticosteroid use are indepen-
dently associated with non-vertebral fractures in RA.11 12Only
one of these studies compared the incidence of non-vertebral
fractures in patients with RA with that in control subjects,
finding an overall increased risk of about 50%.11This study
was performed as far back as in 1984, without the currently
applied methods of defining RA, disease activity, or severity.
No previous studies on non-vertebral fractures in RA
included bone mineral density (BMD) measurements.
This study aimed at comparing the incidence of self
reported non-vertebral fractures in a representative cohort
of female patients with RA aged 50–72 years with the
incidence in individually matched control subjects. Secondly,
we wanted to examine possible relationships between a
positive fracture history and BMD, corticosteroid use,
markers of disease activity, and other possible risk factors
for non-vertebral fractures.
atients with rheumatoid arthritis (RA) have an increased
risk of osteoporosis and osteopenia.1Furthermore, a
substantial proportion of patients with RA receive
MATERIALS AND METHODS
Patients and controls
The Oslo RA register consists of patients fulfilling the
American College of Rheumatology 1987 revised classifica-
tion criteria for RA,13and who have a residential address in
the county of Oslo. The completeness of the register is 85%,
and details of the register have been extensively described
previously.14 15The inclusion criteria of this study were
enrolment in the Oslo RA register, female sex, Caucasian
race, disease duration of at least 2 years, and year of birth
between 1926 and 1948 (age at least 50 at study onset).
Patients were recruited from a representative subgroup of
the RA register who had been part of an epidemiological
study including BMD measurements 2 years previously.1A
single control for each patient was randomly selected from
the population register of Oslo, after matching for age, sex,
and residential area. Possible controls were asked by letter,
and a reminder was sent if no answer was received within a
month. If one declined, a second subject was identified.
Evaluation of non-vertebral fractures
While attending the clinical examination, all patients
received a detailed questionnaire, including questions on
non-vertebral fractures obtained after the age of 25.
Participants were specifically asked for fractures at the wrist,
humerus, ankle, tibia, and hip, and the year in which the
fracture occurred. They were then asked to mark whether the
fracture was due to a traffic accident, skiing accident,
occurred during other sports activities, was work related, or
if they fell while walking or standing. A separate column was
left for additional remarks. In the statistical analyses,
fractures were stratified as to whether they had occurred
before or after the time of RA diagnosis (by at least one year).
All fractures due to traffic accidents were excluded.
... ............ ............. ............ ............. ...........
Abbreviations: BMD, bone mineral density; DAS, Disease Activity
Score; RA, rheumatoid arthritis; RF, rheumatoid factor
177
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For verification of this recording, we performed a
‘‘blinded’’ telephone interview with 129 subjects (87 patients
with RA and 42 controls), of whom 60 (47%) had reported
any previous fracture. The interviews were performed about
2–3 years after the first investigation. The patients were asked
the same questions as in the original questionnaire and, in
addition, more detailed questions about diagnosis and
treatment.
BMD analysis
BMD measurements of the hip (total hip and femoral neck)
and the lumbar spine (L2–4, anterior-posterior) were
performed using the same dual energy x ray absorptiometry
equipment (Lunar Expert, Madison, Wisconsin). T and Z
score estimations were computed from a pooled European/
American reference database. Detailed descriptions of the
reference database, equations for computing age and weight
adjusted Z score estimations, and quality control procedures
have been published previously.1 16
Collection of clinical and demographic variables
All measurementswere
Demographic, patient and disease characteristics, including
performedduring 1998–2001.
conventional RA disease core measurements (table 1), were
recorded partly by self reported questionnaires and partly by
interview and clinical examination. A specially trained
research nurse (patients with RA) or medical student
(control group) performed the latter in cooperation with a
rheumatologist (REØ or GH). Joint assessment included 28
swollen joint count; 28 tender joint count; and 18 deformed
joint count (patients with RA). The Disease Activity Score
(DAS) was computed using the 28 joint counts.17Patients
with a rheumatoid factor (RF) titre >64 measured on at least
one occasion were classified as RF positive.
Statistical analyses
Differences between patients and controls were analysed by
applying paired t tests (continuous data) or by McNemar’s
test for counts. Odds ratios and 95% confidence intervals for
paired variables were computed if allowed by the distribution
of data sets. Patients with and without a history of any
peripheral fracture were compared for their demographic and
clinical variables and BMD, using t tests (continuous
variables) and x2tests (counts). Kaplan-Meier survival
analysis was applied to compare time to event between
patient and controls. A dummy year of disease onset was set
Table 1
for continuous variables, % for counts)
Demographic and disease characteristics for patients and controls (mean (SD)
Clinical and demographic variables NoPatientsControls p Value
Age (years)
Height (cm)
Weight (kg)
BMI (kg/m2)
Disease duration (years)
RF positive (%)
DAS28
MHAQ
18 Deformed joints count
Smoking status
Current smoker (%)
Previous smoker (%)
Current DMARD use (%)
Corticosteroid use
Current users (%)
Ever users (%)
Long term users* (%)
249
249
249
249
249
239
230
248
249
239
63.0 (6.8)
164.2 (6.0)
66.1 (12.5)
24.5 (4.4)
16.6 (10.4)
51.9
4.7 (1.2)
1.7 (0.6)
4.5 (1.1)
63.4 (6.7)
163.7 (5.9)
69.5 (11.9)
25.9 (4.2)
,0.001
0.36
0.002
,0.001
1.1 (0.2)
,0.001
33.1
66.1
55.4
30.1
58.2
0.56
0.08
249
47.8
69.5
53.0
2.4
11.1
2.4
,0.001
,0.001
,0.001
Bone protecting agents
Oestrogens
Current users (%)
Ever users (%)
Bisphosphonates
Current users (%)
Ever users (%)
Calcitonin
Current users (%)
Ever users (%)
Calcium supplement
Current users (%)
Ever users (%)
Vitamin D supplement
Current users (%)
Ever users (%)
249
43.4
57.8
29.3
48.0
0.002
0.04
249
12.0
16.0
1.2
1.6
,0.001
,0.001
249
0.8
4.3
0.8
1.3
1.00
0.09
249
61.8
73.1
20.9
26.9
,0.001
,0.001
249
72.5
80.4
57.3
66.3
,0.001
,0.001
BMD variables
BMD femoral neck (g/cm2)
BMD total hip (g/cm2)
BMD L2–4 (g/cm2)
Z score femoral neck
Z score total hip
Z score of the spine
226
226
245
226
226
245
0.80
0.83
1.06
20.26
20.42
0.25
0.87
0.91
1.11
0.24
0.16
0.58
,0.001
,0.001
0.005
,0.001
,0.001
0.02
No, complete pairs, numbers differ because of missing data.
When variables appear in both pairs, significance of difference is tested with paired t test for continuous variables
and McNemar’s tests for dichotomous variables.
BMI, body mass index; MHAQ, modified Health Assessment Questionnaire; DAS, Disease Activity Score; DMARD,
disease modifying antirheumatic drug
*Ever users for 12 months or more.
178Ørstavik, Haugeberg, Uhlig, et al
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for the matched controls, corresponding to the time of
disease onset of the paired patient. Possible independent
predictors of non-vertebral fractures were subsequently
entered into a logistic regression analysis, applying a posi-
tive history of any non-vertebral peripheral fracture as
dependent variable. Factors were included in the first model
if there was a significance level below p=0.20 in the
bivariate analysis, and then removed one by one until all
variables had a statistically significant contribution in the
final model. Patients and controls were also pooled together
in logistic regression analysis to test whether a diagnosis of
RA was independently related to a previous non-vertebral
fracture.
All tests were two sided, and the level of significance was
set to p=0.05.
RESULTS
Demographic and disease characteristics of patients
and controls
Table 1 shows the demographic and disease characteristics of
the 249 patients and 249 controls. Group differences of
importance were found for body weight, body mass index,
disability level, use of corticosteroids, and osteoporosis drug
treatment. Patients with RA had significantly lower BMD and
Z scores at all measurement sites than controls. Hypertension
was recorded in 16.5% of the patients with RA compared with
24.2% of the controls (p=0.04); occurrence of other
concomitant diseases was similar. Fifty five (22.1%) controls
self reported a rheumatic disease other than RA, most
commonly chronic musculoskeletal pain syndromes or
osteoarthritis.
Representivity of the patient cohort
The total number of patients with RA fulfilling the entry
criteria was 528, and the final participant rate in this study
was 249 (47.2%). The non-attending patients (n=279,
52.8%) comprised 154 patients not meeting for the initial
clinical examination, 75 patients not attending the initial
BMD examination, and 41 patients not attending the follow
up. In nine cases we were not able to identify suitable
controls. The patients finally included in the analyses were
slightly younger than the RA register patients who fulfilled
the entry criteria and did not participate (mean difference
(CI) 1.67 (0.51 to 2.79) years). There were no statistically
significant differences in disease duration or presence of RF.
Among patients who met for clinical examination two years
previously (n=358), no statistically significant differences
were found between those included in the present study
(n=249) and those who declined to attend (n=109) for
measurement of the following clinical variables: disability
score from the modified Health Assessment Questionnaire,
DAS, prednisolone use, or ever use of disease modifying
antirheumatic drugs. Thus, it is considered that the patients
included are fairly representative of the entire underlying
patient population in the county of Oslo born between 1926
and 1948.
In addition to the included controls, letters were sent to
168 who either declined (n=69) or who did not respond
(n=99). Thus, the final attendance rate was 59.8%.
History of non-vertebral fractures
One or more non-vertebral fractures after the age of 25 were
reported by 71 patients (28.5%). Fifty three (21.3%) patients
had had a total of 67 non-vertebral fractures after onset of RA
(fig 1), corresponding with a rate of 1.62 fractures per 100
patient-years. In the control group, 71 subjects (28.5%)
reported having had one or more non-vertebral fractures after
the age of 25, and 50 (20.1%) had had a total of 60 fractures
after the dummy time of disease onset (corresponding to the
onset of RA in the paired patient) (rate 1.45 non-vertebral
fractures per 100 person-years). Figure 1 shows that the
difference between patients with RA and controls for overall
fracture history was not significant (odds ratio (OR) for
paired variables 1.09, 95% CI 0.67 to 1.77). The difference for
hip fractures was statistically significant (10 patients v 2
controls, OR 9.0, 95% CI 1.2 to 394.5). Twice as many
humerus fractures occurred in the RA groups than in
controls, and more wrist and ankle fractures in the control
group, but these differences did not reach statistical
significance.
Survival analysis with time from RA diagnosis to first non-
vertebral fracture showed an equal distribution between time
and event in patients and controls (fig 2, log rank test
p=0.73).
In the RA group, 3/67 (4.5%) non-vertebral fractures (all
radius) reported after diagnosis occurred during skiing or
other sports activities, compared with 13/60 (21.7%) in
controls (seven radius, four ankle, one humerus and one
leg) (difference 17.2%, 95% CI 5.6% to 29.5%). If these
fractures were excluded from analysis, the odds ratio for any
fracture in the RA group was 1.56 (95% CI 0.91 to 2.68).
Verification of non-vertebral fractures
One hundred and twenty one (94%) of the 129 partici-
pants gave the same answer(s) in the telephone interview as
they self reported in the questionnaire. Eight participants
(6%) gave a different answer. One of these (a patient with
RA) had previously reported a wrist fracture, which was not
reported in the telephone interview. The remaining seven
subjects all reported a positive fracture history on both
occasions, but the number or type of fracture(s) was
different. In all cases, the diagnosis and treatment reported
seemed likely for the current type of fracture. However, there
was a larger difference in time span: in 17/59 (29%) cases
with a positive fracture history, the year of fracture did not
Figure 1
patients and 249 matched controls.
Non-vertebral fractures (%) after RA diagnosis in 249 female
Figure 2
matched controls. 0 = time of RA onset. A dummy time was set for
controls, corresponding with the year of disease onset for the matched
patient with RA. Kaplan-Meier survival plot.
Proportion without fracture in 249 patients with RA and 249
Self reported non-vertebral fractures179
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agree with that previously reported (median 2 years, range
1–15 years).
Comparison of patients and controls with and without
a previous fracture
Table 2 presents bivariate comparisons of demographic and
clinical variables between patients and controls with and
without at least one non-vertebral fracture after RA
diagnosis. Patients with a positive fracture history had
significantly longer disease duration, and were more likely
to be current bisphosphonate users and to have at least one
deformed joint than patients with a negative fracture history.
Older age and a history of long term corticosteroid use were
close to being significantly associated with a positive fracture
history. BMD, both as raw values and as age and weight
adjusted Z scores, was significantly reduced at all measure-
ment sites in patients with a history of at least one fracture
after RA diagnosis. In the controls, age, height, ‘‘disease
duration’’ (time since dummy year of diagnosis, see section
on ‘‘Statistical analyses’’ under ‘‘Materials and methods’’)
and lower BMD were significantly associated with a positive
fracture history.
Multivariate analysis
Table 3 shows the results of logistic regression analysis in 249
patients with RA, with a history of any non-vertebral fracture
as dependent variable. In the original model, we included
age, disease duration, any fracture before RA diagnosis, the
presence of any deformed joint, a history of long term
corticosteroid use, and BMD. We also controlled for present
use of oestrogens or bisphosphonates. An interaction test was
performed for age and disease duration, but removed, as it
was not significant. Separate analyses were performed for the
three sites of BMD measurements. A history of any non-
vertebral fracture after RA diagnosis was independently
associated with disease duration and with BMD levels, at
all three measurement sites. Adjusted for disease duration,
the odds ratio for having had any peripheral fracture after RA
diagnosis was 1.52 (95% CI 1.10 to 2.12) for each SD
reduction in Z score of the total hip (table 3). The
corresponding numbers for Z score at the femoral neck and
lumbar spine (L2–4) were 1.52 (1.08 to 2.13) and 1.27 (1.03
to 1.94), respectively. The same models were repeated in the
control group, where disease duration corresponded with the
time since the dummy year of diagnosis (see section on
Table 2
variables, % for counts)
Comparisons of patients and controls with and without a previous non-vertebral fracture (mean (SD) for continuous
Patients with RA Controls
Any fracture (53) No fracture (196)p Value Any fracture (50)No fracture (199)p Value
Demographic variables
Age (years)
Height
Weight
BMI (kg/m2)
Age at menopause (years)
Current smoker
64.5 (6.2)
163.0 (6.7)
67.7 (16.5)
25.4 (5.8)
47.6 (8.0)
35.8
62.6 (6.8)
164.0 (5.8)
65.6 (11.2)
24.2 (3.9)
48.8 (4.8)
32.3
0.06
0.28
0.09
0.08
0.16
0.65
65.1 (6.4)
165.1 (6.1)
71.9 (11.2)
26.4 (4.4)
49.8 (5.3)
22.0
63.0 (6.7)
163.4 (5.7)
69.0 (12.0)
25.8 (4.1)
49.4 (4.8)
31.6
0.04
0.002
0.06
0.13
0.38
0.20
Clinical variables
Disease duration*
Rheumatoid factor positive
MHAQ
DAS
Any deformed joint
Fracture before RA diagnosis
Long term CS use (>12 months)
Current oestrogen use
Current bisphosphonate use
20.1 (10.8)
62.0
1.8 (0.6)
4.79 (1.33)
77.4
13.2
64.2
45.1
21.6
15.6 (10.0)
49.2
1.7 (0.5)
4.68 (1.22)
59.2
9.2
50.0
37.7
9.7
0.004
0.12
0.19
0.57
0.02
0.38
0.07
0.37
0.03
20.7 (11.2)15.6 (10.0)0.002
1.1 (0.2) 1.1 (0.3)0.60
14.0
0.0
18.0
0
8.6
3.0
32.1
1.5
0.30
0.23
0.05
0.40
BMD variables
BMD femoral neck (g/cm2)
BMD total hip (g/cm2)
BMD L2–4 (g/cm2)
Z score femoral neck
Z score total hip
Z score of the spine
0.76 (0.20)
0.78 (0.19)
1.00 (0.24)
20.63 (1.00)
20.82 (1.24)
20.11 (1.90)
0.82 (0.13)
0.85 (0.14)
1.07 (0.19)
20.17 (1.35)
20.31 (1.05)
0.36 (1.44)
0.02
0.01
0.03
0.01
0.01
0.05
0.88 (0.11)
0.87 (0.13)
1.05 (0.19)
20.19 (0.87)
20.10 (0.97)
0.16 (1.48)
0.84 (0.13)
0.92 (0.13)
1.12 (0.19)
0.32 (0.98)
0.25 (0.98)
0.68 (1.53)
0.03
0.03
0.03
0.03
0.03
0.03
For abbreviations, see table 1.
*For controls, disease duration = number of years since dummy time of disease onset, corresponding with the time of disease onset of the matched patient with RA.
p value, t tests for continuous and x2tests for dichotomous variables.
Table 3
and controls. Logistic regression analysis for patients with RA and controls
Possible independent risk factors for non-vertebral fractures in patients with RA
b
SE OR95% CI
Patients with RA
Disease duration
Z score total hip (21 SD)
Constant
Controls
Disease duration*
Z score total hip (21 SD)
Constant
0.04
0.42
22.32
0.02
0.12
0.42
1.04
1.52
1.01 to 1.07
1.10 to 2.12
0.05
0.46
22.16
0.02
0.18
0.34
1.05
1.55
1.01 to 1.08
1.07 to 2.20
*For controls, disease duration = number of years since dummy time of disease onset, corresponding with the time
of disease onset of the matched patient with RA.
180Ørstavik, Haugeberg, Uhlig, et al
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‘‘Statistical analyses’’ under ‘‘Materials and methods’’). The
relationships between Z score and non-vertebral fractures
were similar to those in the patient group (table 3).
To explore whether there was any relationship between a
history of non-vertebral fracture and a diagnosis of RA, a
pooled logistic regression analysis was performed. When
controlling for BMD at the total hip, disease duration
(number of observed years after dummy time of RA diagnosis
in controls), and current use of oestrogens or bisphos-
phonates, there was no significant relationship between a
diagnosis of RA and a history of any non-vertebral fracture
(OR 0.77, 95% CI 0.45 to 1.30). If the three versus 13 fractures
that occurred during skiing or other sports activities were
excluded, the odds ratio for any fracture was 1.03 (95% CI
0.59 to 1.80).
DISCUSSION
In this cross sectional case-control study we found that a
history of non-vertebral fractures in RA was independently
associated with lower BMD. We did not find significant
associations between past fractures and long term cortico-
steroid use, or markers of longstanding disease activity, and
our study does not support the view that patients with RA are
generally more prone to non-vertebral fractures than the
background population.
The similarity between the two groups in the number of
subjects who reported a previous fracture (53 patients with
RA and 50 control subjects, fig 1), and in the time to event
analysis (fig 2) was striking. Owing to small numbers, it is
not possible to draw any strong conclusions about individual
fracture types, except hip fractures. Twice as many humerus
fractures occurred in the patients with RA as in the controls,
but this difference was not statistically significant. There was,
however, no tendency towards a higher incidence of wrist
fractures in patients with RA compared with controls (23 v
28, p=0.55).
To our knowledge, this study is the first to present data on
BMD along with information on non-vertebral fractures in
patients with RA. Several studies on postmenopausal
osteoporosis have established the relationship between
fractures and BMD.18 19Although conflicting evidence exists,
some authors have argued that patients with RA, or patients
receiving long term corticosteroid treatment, may fracture on
a higher BMD threshold than controls.4 5 20–22These conclu-
sions are drawn mainly from studies focusing on vertebral
fractures. In our study, both patients and controls with a
history of prior fracture had lower age adjusted BMD than
those without, and the odds ratios for non-vertebral fracture
in logistic regression analysis for each SD Z score unit were
similar (tables 1 and 3).
Two previous studies have examined possible risk factors
for non-vertebral fractures in RA, suggesting that aging,
impaired ambulation and, perhaps, corticosteroid use are
independently associated with non-vertebral fractures.11 12In
388 female patients with RA, the authors found that the
relative risk of non-vertebral fractures was increased by about
50% compared with the incidence in the general population.
By retrospectively examining the patient charts, the authors
found that only thinness, aging, and impaired ambulation
were independently associated with fracture incidence. In a
larger study, Michel et al additionally found an independent
relationship between fractures and corticosteroid use, as well
as a previous diagnosis of osteoporosis.12
We did not find any independent relationship between
fracture history and markers of disease severity, disability, or
corticosteroid use. Neither could we find any relationship
with the number of deformed joints—our best measurement
of longstanding disease activity. There are several possible
explanations for our findings, and the discrepancy between
these and previously published results from other studies.
The numbers may be too small and the patients too young to
gain statistical power. Most fracture rates increase with age.23
Thus, a study focusing on elderly patients might reveal
differences between patients and controls not seen in our
study. The Oslo Rheumatoid Arthritis Register reflects the
entire RA population. Different results might have been
reached in a hospital based setting including patients with
more severe disease only.
The only previous study comparing overall fracture history
between patients and controls was published nearly 20 years
ago.11The diagnosis and treatment of RA have changed
substantially during the past years, and there are reasons to
believe that the total burden of the disease has diminished.24
Better awareness and treatment of osteoporosis have been
reached during the same period,16as reflected by the
relatively large proportion of patients and controls currently
taking bone protecting agents (table 1). Bisphosphonates
have been shown to reduce the risk of clinical fractures by
30–50% in women with osteoporosis.25–27A higher proportion
of patients with RA than controls were current users of
bisphosphonates or oestrogens (table 1). Thus, there is a
possibility that the apparently low incidence of fractures in
our study is masked partly by the use of bone protecting
agents, even if the use of these drugs was controlled for in the
multivariate analyses.
The effect of disease activity, disability, and reduced BMD
might be opposed by a less physically active lifestyle in
patients with RA than in the general population. There was a
significant difference in the proportions of subjects who
obtained their fractures during skiing or other sports
activities. However, excluding these fractures from the
analyses did not alter the significance of the overall fracture
history between the groups, the differences for individual
fracture types, or the results of the pooled multivariate
analysis. Still, a more active lifestyle probably partly explains
the lack of difference between patients and controls. Patients
with an increased risk of osteoporosis should, however, not
be discouraged from taking part in physical activity, as this is
known to have a protective effect against later fractures by
moderately increasing BMD and muscle strength.28
There are several limitations to our study. It is cross
sectional, so possible risk factors for non-vertebral fractures
might have been obtained after the time of the event. Factors
such as reduced BMD or impaired ambulation might be
consequences of, rather than causes of, any previous fracture.
Secondly, all fracture data are self reported. For practical and
ethical reasons, it would be impossible to verify the fractures
radiographically, or by gaining access to the patient’s charts
to confirm the time of the fractures. Self reporting has been
proved to be fairly reliable in previous publications, especially
in postmenopausal women and when considering major
fractures and fractures of the upper limbs.29 30Our quality
control procedure supports the findings from these studies.
Longitudinal studies and studies better powered to
examine individual fracture types are needed to draw strong
conclusions about non-vertebral fractures in patients with
RA. However, our study suggests that BMD is a reliable tool
for assessing fracture risk in patients with RA, and to the
same extent as that seen in postmenopausal women. It seems
that non-vertebral fractures, other than hip and perhaps
humerus fractures, are not a substantial medical burden on
patients with RA aged less than 72 years. Clinical practice
should focus on the prevention of hip and vertebral fractures
in this patient group.
ACKNOWLEDGEMENTS
We gratefully appreciate the expert technical assistance of our
research nurses Margareth Sveinsson, Ingerid Mu ¨ller, Sidsel
Self reported non-vertebral fractures 181
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