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 osteoporosis. Several studies have demonstrated a high prevalence of low bone mineral density (BMD) in patients with SLE, especially female patients. For example, osteopenia 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 fractures (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 fractures 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 standardized assessment, and to identify risk factors associated with low BMD and prevalent vertebral fractures in a large population of SLE patients.
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- PATIENTS AND METHODS
This is the first study on the estimation of prevalent vertebral fractures in a large group of SLE patients, using a standardized semiquantitative method of scoring vertebral deformities. Associations between clinical 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 vertebral 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 population (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 postmenopausal 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 demonstrated 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 to conscious avoidance of exposure to the sun and/or the use of sunscreens by these patients (29–32).
Surprisingly, a relationship between corticosteroid 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 discrepancy 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 significantly 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 prevalence of vertebral fractures in a younger population (36).
Only a few studies on fractures in SLE have been published, and these were focused on incident symptomatic vertebral and nonvertebral fractures. In 4 studies, symptomatic vertebral and nonvertebral fractures occurring 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 vertebral fractures in patients with SLE if only symptomatic fractures are considered in the scoring.
The association between ever use of IV methylprednisolone 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 prevalence 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 between ever use of IV methylprednisolone and prevalent 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 calculated, associations between the cumulative corticosteroid 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 osteoporosis and fractures as an important disease complication. 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 considering osteoporosis, osteopenia in combination with corticosteroid use and/or the prevalence of 1 or more vertebral fractures as a reason for treatment with antiosteoporosis 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.