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.
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ABSTRACT: Whole vertebrae areal and volumetric bone mineral density (BMD) measurements are not ideal predictors of vertebral fractures. We introduce a technique which enables quantification of bone microstructural parameters at precisely defined anatomical locations. Results show that local assessment of bone volume fraction at the optimal location can substantially improve the prediction of vertebral strength. Whole vertebrae areal and volumetric BMD measurements are not ideal predictors of vertebral osteoporotic fractures. Recent studies have shown that sampling bone microstructural parameters in smaller regions may permit better predictions. In such studies, however, the sampling location is described only in general anatomical terms. Here, we introduce a technique that enables the quantification of bone volume fraction and microstructural parameters at precisely defined anatomical locations. Specific goals of this study were to investigate at what anatomical location within the vertebrae local bone volume fraction best predicts vertebral-body strength, whether this prediction can be improved by adding microstructural parameters and to explore if this approach could better predict vertebral-body strength than whole bone volume fraction and finite element (FE) analyses. Eighteen T12 vertebrae were scanned in a micro-computed tomography (CT) system and FE meshes were made using a mesh-morphing tool. For each element, bone microstructural parameters were measured and correlated with vertebral compressive strength as measured experimentally. Whole bone volume fraction and FE-predicted vertebral strength were also compared to the experimental measurements. A significant association between local bone volume fraction measured at a specific central region and vertebral-body strength was found that could explain up to 90 % of the variation. When including all microstructural parameters in the regression, the predictive value of local measurements could be increased to 98 %. Whole bone volume fraction could explain only 64 % and FE analyses 76 % of the variation in bone strength. A local assessment of volume fraction at the optimal location can substantially improve the prediction of bone strength. Local assessment of other microstructural parameters may further improve this prediction but is not clinically feasible using current technology.Osteoporosis International 12/2013; · 4.04 Impact Factor
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ABSTRACT: Systemic lupus erythematosus (SLE) is a multi-systemic immune-complex mediated autoimmune condition which chiefly affects women during their prime year. While the management of the condition falls into the specialty of internal medicine, patients with SLE often present with signs and symptoms pertaining to the territory of orthopedic surgery such as tendon rupture, carpal tunnel syndrome, osteonecrosis, osteoporotic fracture and infection including septic arthritis, osteomyelitis and spondylodiscitis. While these orthopedic-related conditions are often debilitating in patients with SLE which necessitate management by orthopedic specialists, a high index of suspicion is necessary in diagnosing these conditions early because lupus patients with potentially severe orthopedic conditions such as osteomyelitis frequently present with mild symptoms and subtle signs such as low grade fever, mild hip pain and back tenderness. Additionally, even if these orthopedic conditions can be recognized, complications as a result of surgical procedures are indeed not uncommon. SLE per se and its various associated pharmacological treatments may pose lupus patients to certain surgical risks if they are not properly attended to and managed prior to, during and after surgery. Concerted effort of management and effective communication among orthopedic specialists and rheumatologists play an integral part in enhancing favorable outcome and reduction in postoperative complications for patients with SLE through thorough pre-operative evaluation, careful peri-operative monitoring and treatment, as well as judicious postoperative care.World journal of orthopedics. 01/2014; 5(1):38-44.
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ABSTRACT: Prior studies showed that loss of TNFα signaling delayed fracture healing by delaying chondrocyte apoptosis and cartilage resorption. Mechanistic studies showed that TNF-α induced Fas expression within chondrocytes; however, the degree to which chondrocyte apoptosis is mediated by TNFα alone or dependent on the induction of Fas is unclear. This question was addressed by assessing fracture healing in Fas deficient B6.MRL/Fas(lpr) /J mice. Loss of Fas delayed cartilage resorption but also lowered bone fraction in the calluses. The reduced bone fraction was related to elevated rates of coupled bone turnover in the B6.MRL/Fas(lpr) /J callues, as evidenced by higher osteoclast numbers, and increased osteogenesis. Analysis of the apoptotic marker caspase 3 showed fewer positive chondrocytes and osteoclasts in calluses of B6.MRL/Fas(lpr) /J mice. To determine if an active autoimmune state contributed to increased bone turnover, the levels of activated T cells and Treg cells were assessed. B6.MRL/Fas(lpr) /J mice had elevated Treg cells in both spleens and bones of B6.MRL/Fas(lpr) /J but decreased percentage of activated T cells in bone tissues. Fracture lead to ∼30-60% systemic increased in Treg cells in both wild type and B6.MRL/Fas(lpr) /J bone tissues during the period of cartilage formation and resorption but either decreased (wild type) or left unchanged (B6.MRL/Fas(lpr) /J) the numbers of activated T-cells in bone. These results show that an active autoimmune state is inhibited during the period cartilage resorption and suggests that iTreg cells play a functional role in this process. These data show that loss of Fas activity specifically in chondrocytes: a) prolonged the life span of chondrocytes; and b) synergized with TNFα signaling to mediate chondrocyte apoptosis. Conversely loss of Fas systemically lead to: a) increased osteoclast numbers during later periods of fracture healing; and b) increased osteogenesis. These findings suggest that retention of viable chondrocytes locally inhibits osteoclast activity or matrix proteolysis during cartilage resorption. © 2014 American Society for Bone and Mineral Research.Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 02/2014; · 6.04 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: email@example.com.
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)
and measurements of spine and hip BMD be performed.
1. Uramoto KM, Michet CJ Jr, Thumboo J, Sunku J, O’Fallon WM,
Gabriel SE. Trends in the incidence and mortality of systemic
lupus erythematosus, 1950–1992. Arthritis Rheum 1999;42:46–50.
2. Gordon C. Long-term complications of systemic lupus erythema-
tosus. Rheumatology (Oxford) 2002;41:1095–100.
3. Kipen Y, Buchbinder R, Forbes A, Strauss B, Littlejohn G,
Morand E. Prevalence of reduced bone mineral density in systemic
lupus erythematosus and the role of steroids. J Rheumatol 1997;
4. Redlich K, Ziegler S, Kiener HP, Spitzauer S, Stohlawetz P,
Bernecker P, et al. Bone mineral density and biochemical para-
meters of bone metabolism in female patients with systemic lupus
erythematosus. Ann Rheum Dis 2000;59:308–10.
5. Bhattoa HP, Bettembuk P, Balogh A, Szegedi G, Kiss E. Bone
mineral density in women with systemic lupus erythematosus. Clin
6. Sinigaglia L, Varenna M, Binelli L, Zucchi F, Ghiringhella D,
Gallazzi M, et al. Determinants of bone mass in systemic lupus
erythematosus: a cross sectional study on premenopausal women.
J Rheumatol 1999;26:1280–4.
7. Uaratanawong S, Deesomchoke U, Lertmaharit S, Uaratanawong
S. Bone mineral density in premenopausal women with systemic
lupus erythematosus. J Rheumatol 2003;30:2365–8.
8. Gladman D, Ginzler E, Goldsmith C, Fortin P, Liang M, Urowitz
M, et al. The development and initial validation of the Systemic
Lupus International Collaborating Clinics/American College of
Rheumatology damage index for systemic lupus erythematosus.
Arthritis Rheum 1996;39:363–9.
9. Ramsey-Goldman R, Dunn JE, Huang CF, Dunlop D, Rairie JE,
Fitzgerald S, et al. Frequency of fractures in women with systemic
lupus erythematosus: comparison with United States population
data. Arthritis Rheum 1999;42:882–90.
10. Zonana-Nacach A, Barr SG, Magder LS, Petri M. Damage in
systemic lupus erythematosus and its association with cortico-
steroids. Arthritis Rheum 2000;43:1801–8.
11. Boyanov M, Robeva R, Popivanov P. Bone mineral density
changes in women with systemic lupus erythematosus. Clin Rheu-
12. Dhillon VB, Davies MC, Hall ML, Round JM, Ell PJ, Jacobs HS,
et al. Assessment of the effect of oral corticosteroids on bone
mineral density in systemic lupus erythematosus: a preliminary
study with dual energy x ray absorptiometry. Ann Rheum Dis
13. Formiga F, Moga I, Nolla JM, Pac M, Mitjavila F, Roig-Escofet D.
Loss of bone mineral density in premenopausal women with
systemic lupus erythematosus. Ann Rheum Dis 1995;54:274–6.
14. Formiga F, Nolla JM, Mitjavila F, Bonnin R, Navarro MA, Moga
I. Bone mineral density and hormonal status in men with systemic
lupus erythematosus. Lupus 1996;5:623–6.
15. Formiga F, Moga I, Nolla JM, Navarro MA, Bonnin R, Roig-
Escofet D. The association of dehydroepiandrosterone sulphate
levels with bone mineral density in systemic lupus erythematosus.
Clin Exp Rheumatol 1997;15:387–92.
16. Houssiau FA, Lefebvre C, Depresseux G, Lambert M, Devogelaer
JP, Nagant DD. Trabecular and cortical bone loss in systemic
lupus erythematosus. Br J Rheumatol 1996;35:244–7.
17. Pons F, Peris P, Guanabens N, Font J, Huguet M, Espinosa G, et
al. The effect of systemic lupus erythematosus and long-term
steroid therapy on bone mass in pre-menopausal women. Br J
18. Oleksik A, Lips P, Dawson A, Minshall ME, Shen W, Cooper C,
LOW BMD AND VERTEBRAL FRACTURES IN SLE PATIENTS2049
et al. Health-related quality of life in postmenopausal women with
low BMD with or without prevalent vertebral fractures. J Bone
Miner Res 2000;15:1384–92.
19. Black DM, Arden NK, Palermo L, Pearson J, Cummings SR, and
the Study of Osteoporotic Fractures Research Group. Prevalent
vertebral deformities predict hip fractures and new vertebral
deformities but not wrist fractures. J Bone Miner Res 1999;14:
20. Hasserius R, Karlsson MK, Nilsson BE, Redlund-Johnell I,
Johnell O. Prevalent vertebral deformities predict increased mor-
tality and increased fracture rate in both men and women: a
10-year population-based study of 598 individuals from the Swed-
ish cohort in the European Vertebral Osteoporosis Study. Osteo-
poros Int 2003;14:61–8.
21. Hochberg MC. Updating the American College of Rheumatology
revised criteria for the classification of systemic lupus erythema-
tosus [letter]. Arthritis Rheum 1997;40:1725.
22. Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH,
and the Committee on Prognosis Studies in SLE. Derivation of the
SLEDAI: a disease activity index for lupus patients. Arthritis
23. Vitali C, Bencivelli W, Isenberg DA, Smolen JS, Snaith ML, Sciuto
M, et al, and the European Consensus Study Group for Disease
Activity in SLE. Disease activity in systemic lupus erythematosus:
report of the Consensus Study Group of the European Workshop
for Rheumatology Research. II. Identification of the variables
indicative of disease activity and their use in the development of an
activity score. Clin Exp Rheumatol 1992;10:541–7.
24. Genant HK, Wu CY, van Kuijk C, Nevitt MC. Vertebral fracture
assessment using a semiquantitative technique. J Bone Miner Res
25. Lakshminarayanan S, Walsh S, Mohanraj M, Rothfield N. Factors
associated with low bone mineral density in female patients with
systemic lupus erythematosus. J Rheumatol 2001;28:102–8.
26. Gilboe IM, Kvien TK, Haugeberg G, Husby G. Bone mineral
density in systemic lupus erythematosus: comparison with rheu-
matoid arthritis and healthy controls. Ann Rheum Dis 2000;59:
27. Kipen Y, Briganti E, Strauss B, Will R, Littlejohn G, Morand E.
Three year followup of bone mineral density change in premeno-
pausal women with systemic lupus erythematosus. J Rheumatol
28. Li EK, Tam LS, Young RP, Ko GT, Li M, Lau EM. Loss of bone
mineral density in Chinese pre-menopausal women with systemic
lupus erythematosus treated with corticosteroids. Br J Rheumatol
29. Becker A, Fischer R, Scherbaum WA, Schneider M. Osteoporosis
screening in systemic lupus erythematosus: impact of disease
duration and organ damage. Lupus 2001;10:809–14.
30. Bhattoa HP, Kiss E, Bettembuk P, Balogh A. Bone mineral
density, biochemical markers of bone turnover, and hormonal
status in men with systemic lupus erythematosus. Rheumatol Int
31. Muller K, Kriegbaum NJ, Baslund B, Sorensen OH, Thymann M,
Bentzen K. Vitamin D3 metabolism in patients with rheumatic
diseases: low serum levels of 25-hydroxyvitamin D3 in patients
with systemic lupus erythematosus. Clin Rheumatol 1995;14:
32. Teichmann J, Lange U, Stracke H, Federlin K, Bretzel RG. Bone
metabolism and bone mineral density of systemic lupus erythem-
atosus at the time of diagnosis. Rheumatol Int 1999;18:137–40.
33. Hansen M, Halberg P, Kollerup G, Pedersen-Zbinden B, Horslev-
Petersen K, Hyldstrup L, et al. Bone metabolism in patients with
systemic lupus erythematosus: effect of disease activity and glu-
cocorticoid treatment. Scand J Rheumatol 1998;27:197–206.
34. Kalla AA, Fataar AB, Jessop SJ, Bewerunge L. Loss of trabecular
bone mineral density in systemic lupus erythematosus. Arthritis
35. Pineau CA, Urowitz MB, Fortin PJ, Ibanez D, Gladman DD.
Osteoporosis in systemic lupus erythematosus: factors associated
with referral for bone mineral density studies, prevalence of
osteoporosis and factors associated with reduced bone density.
36. Lips P. Epidemiology and predictors of fractures associated with
osteoporosis. Am J Med 1997;103:3S–8S.
37. Cooper C, Atkinson EJ, O’Fallon WM, Melton LJ III. Incidence
of clinically diagnosed vertebral fractures: a population-based
study in Rochester, Minnesota, 1985–1989. J Bone Miner Res
2050BULTINK ET AL