Prevalence of and risk factors for low bone mineral density and vertebral fractures in patients with systemic lupus erythematosus.
ABSTRACT To examine the prevalence of and risk factors for low bone mineral density (BMD) and vertebral fractures in patients with systemic lupus erythematosus (SLE).
We studied 107 SLE patients. Demographic and clinical data were collected, and radiographs of the thoracic and lumbar spine and BMD measurements by dual x-ray absorptiometry were performed. Vertebral deformities were scored according to the method of Genant et al: fractures were defined as a reduction of > or = 20% of the vertebral body height. Osteoporosis was defined as a T score less than -2.5 SD and osteopenia as a T score less than -1.0 SD in at least 1 region of measurement.
Osteopenia was present in 39% of the patients and osteoporosis in 4% (93% female; mean age 41.1 years). In multiple regression analysis, low BMD in the spine was associated with a low body mass index (BMI), postmenopausal status, and 25-hydroxyvitamin D deficiency. Low BMD in the hip was associated with low BMI and postmenopausal status. At least 1 vertebral fracture was detected in 20% of the patients. Vertebral fractures were associated with ever use of intravenous methylprednisolone and male sex.
Risk factors for low BMD in SLE patients are low BMI, postmenopausal status, and vitamin D deficiency. While osteoporosis defined as a low T score was found in only 4% of the patients, osteoporotic vertebral fractures were detected in 20%. The high prevalence of low BMD and vertebral fractures implies that more attention must be paid to the prevention and treatment of osteoporosis and fractures in SLE.
- SourceAvailable from: while-science-sleeps.com[show abstract] [hide abstract]
ABSTRACT: To describe trends in systemic lupus erythematosus (SLE) incidence and mortality over the past 4 decades. Using the Rochester Epidemiology Project resources, medical records were screened to identify all Rochester, Minnesota residents with any SLE-associated diagnoses, discoid lupus, positivity for antinuclear antibodies, and/or false-positive syphilis test results determined between January 1, 1980 and December 31, 1992. Medical records were then reviewed using a pretested data collection form in order to identify cases of SLE according to the American College of Rheumatology 1982 revised criteria for SLE. Drug-induced cases were excluded. All identified SLE patients were followed up until death, migration from the county, or October 1, 1997. These data were combined with similar data from the same community obtained between 1950 and 1979, and trends in the SLE incidence and mortality over time were calculated. Of the 430 medical records reviewed, 48 newly diagnosed cases of SLE (42 women and 6 men) were identified between 1980 and 1992. The average incidence rate (age- and sex-adjusted to the 1970 US white population) was 5.56 per 100,000 (95% confidence interval [95% CI] 3.93-7.19), compared with an incidence of 1.51 (95% CI 0.85-2.17) in the 1950-1979 cohort. The age- and sex-adjusted prevalence rate as of January 1, 1993 was approximately 1.22 per 1,000 (95% CI 0.97-1.47). Survival among SLE patients was significantly worse than in the general population (P = 0.017 compared with the 1980-1992 cohort, and P < 0.0001 compared with the 1950-1979 cohort, by log-rank test). Cox proportional hazards modeling demonstrated a statistically significant improvement in the survival rate over time (P = 0.035). Over the past 4 decades, the incidence of SLE has nearly tripled, and there has been a statistically significant improvement in survival. These findings are likely due to a combination of improved recognition of mild disease and better approaches to therapy.Arthritis & Rheumatism 02/1999; 42(1):46-50. · 7.48 Impact Factor
- Rheumatology 11/2002; 41(10):1095-100. · 4.21 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: To determine the prevalence of reduced bone mineral density (BMD) in a large female cohort of systemic lupus erythematosus (SLE) and to determine the role of steroids and disease related variables. All females with SLE managed by rheumatologists affiliated with a single center were invited to undergo BMD measurement of the lumbar spine and left femoral neck by dual energy X-ray absorptiometry (DEXA), standardized examination, and medical record review. Ninety-seven females with a mean (SD) age of 44.2 (14.9) years were studied. Low bone mass [defined as BMD > 1 standard deviation (SD) below young adult mean] was present in 44.3 and 42.1% at the lumbar spine and femoral neck, respectively. Osteoporosis (defined as BMD > 2.5 SD below young adult mean) was present in 13.4 and 6.3% at the lumbar spine and femoral neck, respectively. Steroid usage showed a strong inverse relationship with BMD in the lumbar spine, but a less strong relationship in the femoral neck. The findings of high prevalence of reduced BMD and association with steroid therapy have important implications for the routine management of SLE.The Journal of Rheumatology 10/1997; 24(10):1922-9. · 3.26 Impact Factor
ARTHRITIS & RHEUMATISM
Vol. 54, No. 7, July 2005, pp 2044–2050
© 2005, American College of Rheumatology
Prevalence of and Risk Factors for Low Bone Mineral Density
and Vertebral Fractures in Patients With
Systemic Lupus Erythematosus
Irene E. M. Bultink,1Willem F. Lems,1Piet J. Kostense,2Ben A. C. Dijkmans,1
and Alexandre E. Voskuyl2
Objective. To examine the prevalence of and risk
factors for low bone mineral density (BMD) and verte-
bral fractures in patients with systemic lupus erythem-
Methods. We studied 107 SLE patients. Demo-
graphic and clinical data were collected, and radio-
graphs of the thoracic and lumbar spine and BMD
measurements by dual x-ray absorptiometry were per-
formed. Vertebral deformities were scored according to
the method of Genant et al: fractures were defined as a
reduction of >20% of the vertebral body height. Osteo-
porosis was defined as a T score less than –2.5 SD and
osteopenia as a T score less than –1.0 SD in at least 1
region of measurement.
Results. Osteopenia was present in 39% of the
patients and osteoporosis in 4% (93% female; mean age
41.1 years). In multiple regression analysis, low BMD in
the spine was associated with a low body mass index
(BMI), postmenopausal status, and 25-hydroxyvitamin
D deficiency. Low BMD in the hip was associated with
low BMI and postmenopausal status. At least 1 verte-
bral fracture was detected in 20% of the patients.
Vertebral fractures were associated with ever use of
intravenous methylprednisolone and male sex.
Conclusion. Risk factors for low BMD in SLE
patients are low BMI, postmenopausal status, and
vitamin D deficiency. While osteoporosis defined as a
low T score was found in only 4% of the patients,
osteoporotic vertebral fractures were detected in 20%.
The high prevalence of low BMD and vertebral fractures
implies that more attention must be paid to the preven-
tion and treatment of osteoporosis and fractures in
Over the last few decades, the survival of patients
with systemic lupus erythematosus (SLE) has improved
dramatically (1), and the morbidity pattern has shown a
shift toward long-term complications, including osteo-
porosis. Several studies have demonstrated a high prev-
alence of low bone mineral density (BMD) in patients
with SLE, especially female patients. For example, os-
teopenia is reported in 25–46% of SLE patients (2–4)
and osteoporosis, defined as a T score less than –2.5 SD,
is reported in 1–23% (5–7).
In contrast, little attention is paid to osteoporotic
fractures, one of the items of the Systemic Lupus
International Collaborating Clinics/American College of
Rheumatology (SLICC/ACR) damage index for SLE
(8). Studies on fractures in SLE have focused on incident
cases of symptomatic vertebral and nonvertebral frac-
tures (2,3,9,10) or on prevalent vertebral deformities,
i.e., fractures (11–17). However, the method used to
assess vertebral fractures in 6 of these studies (11,13–17)
is not clear, and vertebral fractures were scored using
dual x-ray absorptiometry (DXA) images in 1 study (12).
Moreover, in the majority of these studies, only a limited
number of patients were evaluated (11,12,14–17).
The importance of identifying prevalent vertebral
fractures in SLE patients is illustrated by the observed
association between prevalent vertebral deformities and
reduced quality of life in postmenopausal women with
osteoporosis (18) as well as increased mortality rates and
increased risk of future vertebral and nonvertebral frac-
1Irene E. M. Bultink, MD, Willem F. Lems, MD, PhD, Ben
A. C. Dijkmans, MD, PhD: VU University Medical Center, Slotervaart
Hospital, and Jan van Breemen Institute, Amsterdam, The Nether-
lands;2Piet J. Kostense, PhD, Alexandre E. Voskuyl, MD, PhD: VU
University Medical Center, Amsterdam, The Netherlands.
Address correspondence and reprint requests to Irene E. M.
Bultink, MD, Department of Rheumatology, Room 4A42, VU Uni-
versity Medical Center, Postbus 7057, 1007 MB Amsterdam, The
Netherlands. E-mail: firstname.lastname@example.org.
Submitted for publication December 6, 2004; accepted in
revised form March 16, 2005.
tures in the general population (19,20). The aim of the
present study was to investigate the prevalence of low
BMD and vertebral fractures, as determined by a stan-
dardized assessment, and to identify risk factors associ-
ated with low BMD and prevalent vertebral fractures in
a large population of SLE patients.
PATIENTS AND METHODS
Patients. One hundred seven consecutive patients with
a diagnosis of SLE were included in the study. All patients
regularly attended the outpatient rheumatology clinic of either
the VU University Medical Center, the Jan van Breemen
Institute, or the Slotervaart Hospital. These institutes provide
primary, secondary, and tertiary care for SLE patients. All
patients fulfilled the ACR revised criteria for the classification
of SLE (21) and provided informed consent for their partici-
pation. The local ethics committee approved the study.
Data collection and clinical measures. All measure-
ments were performed systematically between August 2001
and February 2003. Demographic, patient, and disease char-
acteristics were recorded by interview, self-reported question-
naire, chart review, and a clinical examination that was per-
formed by 1 rheumatologist (IEMB). Data collected at the
time of study inclusion were age, disease duration, race,
menstrual status, age at menopause, periods of amenorrhea,
family history of osteoporosis, ultraviolet (UV) light intoler-
ance, sunshine avoidance, use of sunscreens in the previous
year, calculated mean daily dietary calcium intake in the last 3
months, history of (non)vertebral fractures after the age of 25
years, comorbidity, alcohol and tobacco intake, and exercise
status. Exercise was determined as the weekly frequency of a
minimum of 40 minutes of aerobic exercise performed.
History of corticosteroid use, including intravenous
(IV) methylprednisolone use (past and current) and oral
corticosteroid use (past use, duration of use in months, maxi-
mum dosage ever taken, current use, and actual dosage), was
documented. The cumulative corticosteroid dose was not
calculated since assessment of the patients in the outpatient
clinic takes place every 3 months and some patients had, in the
past, been allowed to gradually lower their dosage of oral
corticosteroids during the time between 2 visits. As a result, the
exact dosage of oral corticosteroids used at every point in time
was not available for some patients. For this reason, we
preferred to use the available exact data on corticosteroid use
only. Past and current use of antirheumatic drugs, calcium
supplements, vitamin D supplements, multivitamin supple-
ments, hormone-replacement therapy (HRT), oral contracep-
tives, antiosteoporosis medications, antiepileptic agents, and
anticoagulants were also documented.
Body weight, height, and body mass index (BMI) were
assessed. Disease activity was scored using the Systemic Lupus
Erythematosus Disease Activity Index (SLEDAI) (22) and the
European Consensus Lupus Activity Measure (ECLAM) (23).
Accumulated organ damage was assessed with the SLICC/
ACR damage index (DI) (8). A modified DI score was derived
as the DI score excluding osteoporotic fractures as a damage
Laboratory investigations at the time of study inclusion
included routine clinical biochemistry profile, immunologic
measures (anti–double-stranded DNA antibodies, comple-
ment components, antiphospholipid antibodies), and biochem-
ical and hormonal variables related to mineral metabolism
(serum levels of calcium, phosphate, and alkaline phospha-
tase), thyroid function (thyroid-stimulating hormone), and
serum levels of 25-hydroxyvitamin D (25[OH]D). Deficiency of
25(OH)D was defined as a serum level ?25 nmoles/liter, based
on the laboratory reference value.
BMD measurements. BMD measurements of the hip
(total hip and femoral neck) and the lumbar spine (L1–4;
anteroposterior view) were performed by a trained technician
using the same DXA equipment (model 4500; Hologic,
Waltham, MA) in all patients, and the results were expressed
in grams per square centimeter. Hip measurement was not
performed in 3 patients because of bilateral hip replacements.
The BMD values were compared with lumbar spine data from
a large reference population, as supplied by the manufacturer
(Hologic) and National Health and Nutrition Examination
Survey reference database for the hip, including data for T
score and Z score estimations.
Assessment of vertebral deformities. Lateral radio-
graphs of the thoracic and lumbar spine (T5–L4) were per-
formed in the same radiology department by a trained opera-
tor and according to a standardized protocol. All radiographs
were of good quality, with good visibility and reliable identifi-
cation of all vertebrae. Spine radiographs were scored by 2
experienced observers (WFL and BACD) using a standardized
semiquantitative method described by Genant et al (24). This
method grades vertebrae on a scale of 0–3, where grade 0 ?
normal, grade 1 ? 20–25% reduction in height, grade 2 ?
?25–40% reduction in height, and grade 3 ?40% reduction in
height. For the anterior and middle heights, the posterior
height of the same vertebra was used as a reference. A
vertebral fracture was defined as a reduction of at least 20% of
the vertebral body height.
For quality assurance, blinded scoring was done after 7
months, involving 30 SLE patients, 60% of whom had at least
1 vertebral fracture, and 10 controls, 50% of whom had at least
1 vertebral fracture. The kappa value for whether an SLE
patient was classified as having any vertebral fracture was 0.62.
Statistical analysis. Variables possibly associated with
a decreased BMD or the presence of vertebral fractures were
examined first by univariate tests and subsequently by multiple
regression analysis. The following variables were examined in
relationship to BMD by univariate analyses: age, sex, race,
menopause status, BMI, disease duration, disease activity,
modified DI score, exercise, use of sunscreens, UV light
intolerance, dietary calcium intake, previous nonvertebral frac-
tures, creatinine clearance, 25(OH)D deficiency, ever use of
steroid use, current use of corticosteroids and IV methylpred-
nisolone, and past and current use of anticoagulants. Univariate
analyses of variables possibly associated with vertebral fractures
included BMD of the lumbar spine and hip as a variable.
To determine which factors were significantly associ-
ated with low BMD or with vertebral fractures, the demo-
graphic, clinical, and treatment variables showing P ? 0.2 in
the univariate analyses and variables with supposed clinical
relevance were entered into the respective multiple regression
analyses. The multiple regression models were refined by
LOW BMD AND VERTEBRAL FRACTURES IN SLE PATIENTS2045
tentatively adding to the (almost) final model single variables
that were not initially included in the model, so as to check
once more whether these variables could indeed be missed.
Confidence intervals for percentages were calculated with the
Wilson method. A P value less than or equal to 0.05 (2-sided)
was considered statistically significant. The software used was
SPSS for Windows, version 11.0 (SPSS, Chicago, IL).
Clinical, demographic, and treatment variables.
The clinical and demographic characteristics of the 107
SLE patients included in the study are shown in Table 1.
The majority of the patients were premenopausal, fe-
male, and Caucasian. At the time of study inclusion,
most patients had mild disease activity and little organ
damage. Decreased renal function was found in only a
small percentage of the patients. 25(OH)D deficiency
was detected in 8% of the patients. A history of at least
1 nonvertebral fracture following the diagnosis of lupus
was present in 11% of the patients. The majority of
patients had taken corticosteroids and hydroxychloro-
quine. Bisphosphonates and HRT were taken by a small
number of patients.
Findings of BMD measurements. The results of
the BMD measurements are shown in Table 2. The
frequency of osteoporosis (T score less than –2.5 SD at the
lumbar spine [L1–L4] and/or at the total hip) was 4.0%.
The frequency of osteopenia (T score less than –1.0 SD at
the lumbar spine [L1–L4] and/or at the total hip) was 39%.
Variables associated with BMD. Univariate ana-
lyses. There was a significant association between low
BMI and low BMD at the spine (B ? 0.0052, P ? 0.045)
and at the total hip (B ? 0.0079, P ? 0.001). Postmeno-
pausal status was significantly associated with low BMD
at the spine (B ? –0.076, P ? 0.017), but not at the hip.
There was also a significant negative association be-
tween the creatinine clearance and low BMD at the hip
(B ? 0.0011, P ? 0.027), but not at the spine. Moreover,
every use of phenprocoumon (a slow-acting coumarin
derivative) was significantly associated with low BMD at
the hip (B ? –0.19, P ? 0.01), but not at the spine. BMD
at the spine and at the total hip were not associated with
age, race, disease duration, disease activity, or measures
of corticosteroid exposure (past and current IV methyl-
prednisolone use, past use of oral corticosteroids, dura-
tion of oral corticosteroid use, maximum dosage of oral
corticosteroid ever taken, current use of oral cortico-
steroids, and actual oral corticosteroid dosage).
Multiple regression analyses. In a multiple regres-
sion analysis of the relationship between menstrual
status, BMI, age, and serum 25(OH)D deficiency as
independent variables and BMD at the spine as the
dependent variable, postmenopausal status (P ? 0.001),
Demographic, clinical, and treatment variables in the study
All study patients
(n ? 107)
Female sex, %
Caucasian race, %
Age, mean ? SD years
Body mass index, mean ? SD kg/m2
Current smoker, %
Exercise ?3 times weekly, %
Daily dietary calcium intake, mean ? SD
Disease duration, mean ? SD years
SLEDAI, mean ? SD
ECLAM score, mean ? SD
SLICC/ACR damage index, mean ? SD
SLICC/ACR damage index modified, mean
Erythrocyte sedimentation rate, mean ?
C-reactive protein, mean ? SD mg/liter
Creatinine clearance ?70 ml/minute, %
Ever had lupus nephritis, %
25-hydroxyvitamin D deficiency, %
Ultraviolet light intolerance, %
Use of sunscreen, %
Previous nonvertebral fracture, %
Previous symptomatic vertebral fracture, %
Ever use, %
Current use, %
Treatment duration in ever users, mean
? SD months
Actual prednisone dosage, mean ? SD
Current users only
Ever use of other medications, %
Phenprocoumon (slow-acting coumarin
Current use of other medications, %
Vitamin D supplements
41 ? 13
25 ? 6
775 ? 317
6.9 ? 6.7
4.9 ? 4.0
3.1 ? 1.6
1.4 ? 1.9
1.3 ? 1.9
26 ? 25
11 ? 16
62 ? 69
7 ? 11
13 ? 12
* SLEDAI ? Systemic Lupus Erythematosus Disease Activity Index
(range 0–105); ECLAM ? European Consensus Lupus Activity Mea-
sure (range 0–10); SLICC/ACR ? Systemic Lupus International
Collaborating Clinics/American College of Rheumatology (modified
damage index excludes osteoporotic fractures as a damage item).
2046BULTINK ET AL
low BMI (P ? 0.025), and serum 25(OH)D deficiency
(P ? 0.047) were significantly associated with low BMD
at the spine. In a multiple regression analysis of the
relationship between menstrual status, sex, and BMI as
independent variables and BMD at the hip as the
dependent variable, low BMI (P ? 0.0001) and post-
menopausal status (P ? 0.037) were significantly asso-
ciated with low BMD at the hip (Table 3). None of the
other variables investigated demonstrated a significant
contribution to the model for spine or hip BMD. The
final models explained 40% of the variation for spine
BMD and 43% of the variation for hip BMD.
Vertebral deformities. Lateral spine radiographs
were available in 90 patients. Osteopenia was present in
39% of these patients and osteoporosis in 3%. The
results of the assessment of vertebral deformities are
shown in Table 2. The total number of vertebral frac-
tures, defined according to Genant et al as a reduction of
the vertebral body height by at least 20%, was 26. Of all
vertebral fractures, 89% were located in the thoracic
spine and 11% in the lumbar region. At least 1 vertebral
fracture was observed in 18 patients (20%; 95% confi-
dence interval 13–29) and at least 2 vertebral fractures in
6 patients (7%; 95% confidence interval 3–14). Twenty-
seven percent of vertebral fractures were grade 2 (at
least 25% reduction of vertebral body height) or higher.
Variables associated with vertebral deformities.
Univariate analyses. There was a significant association
between male sex (B ? 0.47, P ? 0.001) and age (B ?
0.0075, P ? 0.024) and fractures in the thoracic and/or
lumbar spine. Furthermore, there was a trend toward
previous nonvertebral fractures (B ? 0.27, P ? 0.054),
ever use of IV methylprednisolone (B ? 0.21, P ?
0.054), and non-Caucasian race (B ? –0.19, P ? 0.058).
Multivariate analyses. In a multivariate analysis of
the relationship between vertebral fractures as the de-
pendent variable and sex, age, race, modified DI, previ-
ous nonvertebral factures, and ever use of IV methyl-
prednisolone as the independent variables, ever use of
IV methylprednisolone (P ? 0.01) and male sex (P ?
0.002) were significantly associated with fractures in the
thoracic and/or lumbar spine (Table 3).
This is the first study on the estimation of prev-
alent vertebral fractures in a large group of SLE pa-
tients, using a standardized semiquantitative method of
scoring vertebral deformities. Associations between clin-
ical data and low BMD and vertebral fractures were also
evaluated in this large group of SLE patients. The main
conclusion from our study is that low BMD and verte-
bral fractures are observed frequently in SLE patients,
which emphasizes that osteoporosis is a common feature
in SLE. In addition, we found a significant association
between the prevalence of vertebral fractures and ever
use of methylprednisolone and male sex.
The frequency of osteopenia found in our popu-
lation (39%) is consistent with previous studies showing
osteopenia in 25–46% of SLE patients (2–4). The
prevalence of osteoporosis in our patients (4%) was in
the lower range seen in previous studies of patients with
SLE (1.4–23%) (5–7). The association between post-
menopausal status and low BMD found in 2 previous
studies in female patients with SLE (5,25) and the
association between low BMI and low BMD demon-
strated in other studies in SLE patients (5,6,26–28) were
confirmed in the present study.
Deficiency of serum 25(OH)D was significantly
associated with low BMD in the lumbar spine in our
patients. Low serum levels of 25(OH)D in SLE patients
have been previously described and are usually ascribed
BMD variables and assessment of vertebral deformities*
All study patients
(n ? 107)
BMD, mean ? SD gm/cm2
T score, mean ? SD
Z score, mean ? SD
Lumbar spine and/or total hip
Lumbar spine and/or total hip
Vertebral deformities in 90 SLE
At least 1 vertebral deformity
At least 2 vertebral deformities
Severity of 26 vertebral deformities in 90
SLE patients, %
Grade 1 (20–25% reduction of height)
Grade 2 (25–40% reduction of height)
Grade 3 (?40% reduction of height)
1.02 ? 0.15
0.91 ? 0.13
?0.23 ? 1.32
?0.27 ? 1.06
0.24 ? 1.35
0.49 ? 1.11
* Osteopenia is defined as a T score less than ?1.0 SD. Osteoporosis
is defined as a T score less than ?2.5 SD in at least 1 region of
measurement. Vertebral deformities are defined as at least a grade 1
deformity (?20% reduction of vertebral body height) according to the
method of Genant et al (24). BMD ? bone mineral density; SLE ?
systemic lupus erythematosus.
LOW BMD AND VERTEBRAL FRACTURES IN SLE PATIENTS2047
to conscious avoidance of exposure to the sun and/or the
use of sunscreens by these patients (29–32).
Surprisingly, a relationship between cortico-
steroid use and low BMD could not be demonstrated in
our study. This observation is supported by various
studies in SLE patients (12–15,28–30,33–35) but is in
conflict with other studies in SLE patients in which an
association between corticosteroid use and low BMD in
the lumbar spine and/or the hip was demonstrated
(2,3,5–7,11,16,17,25,26). The reasons for this discrep-
ancy are unclear but may be related to differences
between patient populations in, for example, size, mean
age, disease duration, and menstrual status, as well as
differences between centers in treatment strategies for
osteoporosis, use of corticosteroids, and differences in
assessments of corticosteroid use.
Subanalyses of variables associated with low
BMD at the lumbar spine and at the hip in patients who
had never been treated with bisphosphonates and/or
HRT (n ? 77) confirmed the importance of low BMI
and postmenopausal status as major risk factors for low
BMD at lumbar spine and at the hip, both in univariate
and multiple regression analyses (data not shown). In
these subanalyses, 25(OH)D deficiency was not signifi-
cantly associated with low BMD, a finding that might be
explained by the small number of patients with
25(OH)D deficiency in the subgroup.
The most striking finding of the present study was
the high prevalence of vertebral fractures in our patients
(20%), who had a mean age of 41 years, compared with
a prevalence of 12% in the general population of Europe
ages 65–69 years (36). One would expect a lower prev-
alence of vertebral fractures in a younger population
Only a few studies on fractures in SLE have been
published, and these were focused on incident symptom-
atic vertebral and nonvertebral fractures. In 4 studies,
symptomatic vertebral and nonvertebral fractures occur-
ring since the onset of lupus were documented in
9–16.5% of patients (2,3,5,9). However, studies focusing
on symptomatic fractures have a disadvantage in that
only one-third of all vertebral fractures come to clinical
attention (37). In the present study, only 2 of 18 patients
with 1 or more prevalent vertebral fractures had a
documented previous symptomatic vertebral fracture,
which illustrates the possibility of underestimating ver-
tebral fractures in patients with SLE if only symptomatic
fractures are considered in the scoring.
The association between ever use of IV methyl-
prednisolone and the prevalence of vertebral fractures in
this study is consistent with 2 studies documenting an
association between corticosteroid use and symptomatic
fractures in SLE (9,10). The association between male
sex and prevalent vertebral fractures in our study is not
surprising, since in the general population, the preva-
lence of vertebral fractures at ages younger than 65 years
is higher in men than in women (36).
A subanalysis of factors associated with grade 1
vertebral fractures (according to the method of Genant
et al) demonstrated the same significant association
deformities (dependent variables) and demographic, clinical, and treatment variables (independent
Multiple regression analyses of BMD at the lumbar spine, BMD at the total hip, and vertebral
BMD at the lumbar spine in 107 SLE patients
Body mass index
25-hydroxyvitamin D deficiency
BMD at the total hip in 107 SLE patients
Body mass index
Vertebral deformities in 90 SLE patients
Ever use of IV methylprednisolone
SLICC/ACR damage index modified
* BMD ? bone mineral density; SLE ? systemic lupus erythematosus; IV ? intravenous; SLICC/ACR ?
Systemic Lupus International Collaborating Clinics/American College of Rheumatology; B ? regression
coefficient (when considered in the multiple regression model); SE ? standard error of B.
2048BULTINK ET AL
between ever use of IV methylprednisolone and preva-
lent vertebral fractures, both in univariate and multiple
regression analyses (data not shown). These results
demonstrate that ever use of IV methylprednisolone is
also a strong risk factor for prevalent vertebral fractures
after the 26% more severe fractures were excluded from
the analyses. The subanalysis of factors associated with
Genant grade 1 vertebral fractures did not show an
association with male sex (data not shown). This finding
can be explained by the small number of male patients in
the study and the fact that 3 of the 5 male patients with
at least 1 vertebral fracture had a fracture that was a
Genant grade 2 or more.
Limitations of the present study are the racial
background of the study population and the method
used to assess corticosteroid use. As a consequence of
the rather high percentage of Caucasians in the study
population (79%), the associations found in the present
study may not be generalized to lupus cohorts with a
significantly different racial background. Second, since
the cumulative oral corticosteroid dose was not calcu-
lated, associations between the cumulative cortico-
steroid dose and BMD and prevalent vertebral fractures
could not be assessed. However, all other measures of
oral corticosteroid use we assessed were not associated
with BMD or vertebral fractures.
The results of this study suggest that attention
must be paid to the prevention and treatment of osteo-
porosis and fractures as an important disease complica-
tion. Prevention strategies directed toward SLE patients
who are at risk of osteoporosis include advice for
maintaining a normal body weight and performing
weight-bearing physical activity, calcium and vitamin D
supplementation in cases of deficiency, and treatment
with appropriate antiosteoporosis medication in cases of
osteoporosis and/or a vertebral fracture. When con-
sidering osteoporosis, osteopenia in combination with
corticosteroid use and/or the prevalence of 1 or more
porosis drugs, 40% of the patients in our study should
have been treated with antiosteoporosis drugs. At the
time of the study, only 16% of the patients were taking
bisphosphonates and 5% were taking HRT.
The high prevalence of vertebral fractures in our
study indicates that the assessment of fracture risk in
SLE patients should include assessment of vertebral
fractures, since these are often asymptomatic and are
clinically important in terms of morbidity, mortality, and
future fracture risk. Therefore, we recommend that in
the assessment of osteoporosis and future fracture risk
in SLE patients, spine radiographs (analyzed using a
standardized method for scoring vertebral deformities)
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