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- PATIENTS AND METHODS
Several studies have demonstrated an increased frequency of osteoporosis in female patients with rheumatoid arthritis (RA) (1–3). However, fractures represent the clinically important aspect of osteoporosis. Vertebral deformities are associated with increased morbidity and mortality and an augmented risk of developing additional osteoporotic fractures (4, 5). Inconsistent data have been published regarding associations between clinical variables and vertebral deformities in RA, especially the relative contribution of reduced bone mineral density (BMD), corticosteroid use, immobilization, and disease activity (6–8). No studies regarding vertebral deformities have been performed in cohorts suggested to be representative of the total population with underlying RA.
The aim of this study was to describe the occurrence of vertebral deformities in a fairly representative cohort of female patients with RA, and the association between vertebral deformities and BMD and clinical and demographic variables.
- Top of page
- PATIENTS AND METHODS
This is, to our knowledge, the largest, single-center study on vertebral deformities in female patients with RA, examining their association with clinical and demographic variables as well as BMD measurements. We found that the presence of vertebral deformities was independently associated with age, long-term corticosteroid use, and previous nonvertebral fractures. The results also imply that reduced bone mass is weakly but independently associated with vertebral deformities in patients with RA.
We chose a standardized, semiquantitative method for identifying vertebral deformities (12). There is no consistence regarding which grade of change should be defined as a deformity, and the number of deformities found will differ according to the method and cut-off chosen (13, 14). For the statistical analyses, we chose to define clinically relevant vertebral deformities as at least 2 mild or 1 moderate/severe deformity, an approach that has also been used in a previous study of vertebral deformities in RA (4). A semiquantitative method will detect more deformities than does quantitative morphometry if a reduction of 3 SD is chosen for the latter method, and it may be questioned if some of these deformities may be considered clinically important (15). However, several studies have demonstrated that mild deformities are also associated with morbidity and increased risk of future additional fractures (8, 9).
Some preliminary analyses were done before deciding on the models used for logistic regression analysis. Especially, we explored the significance of adding weight, height, or BMI, because these factors have been shown to relate to both BMD and fracture risk. As shown in Table 1, there was no significant relationship between vertebral deformities and either weight or BMI. The strong negative association between height and vertebral deformities remained when examined by logistic regression but had no influence on the significance of the other variables in the equation (data not shown). We thereby decided to exclude this value, because height reduction may be a consequence of deformities by themselves.
A few earlier studies have described possible predictors of vertebral deformities in RA, and especially the relationship to use of corticosteroids (6–8). In 2 of 3 studies, there was no significant relationship between vertebral deformities and various measurements of corticosteroid use (6, 8). However, in a recent Italian multicenter study, Sinigaglia et al (7) found a significant relationship between cumulative corticosteroid dose and vertebral deformities. Furthermore, several larger epidemiologic studies on patients receiving corticosteroids for various reasons recently demonstrated an increased, dose-dependent risk of both vertebral and nonvertebral fractures (16, 17).
Of all the parameters tested in our study, except for age, long-term use of corticosteroids showed the strongest association with vertebral deformities. We chose long-term use as the variable of interest because reliable data on cumulative dose were not available. Because vertebral deformities are to be regarded as an irreversible event, long-term use will also include patients with a history of previous treatment that could have contributed to deformities, even though the corticosteroid-induced effect on BMD has been shown to be partly reversible (18). Exchanging long-term use with prednisolone (doses >7.5 mg for longer than 6 months) did not significantly change the results. The dose of 7.5 mg is considered by many clinicians and researchers to be the threshold for deleterious effects on bone metabolism and is used as a cut-off for recommending therapeutic interventions to prevent corticosteroid-induced bone loss (19). In our study, however, a much smaller number of patients had used corticosteroids in such high doses, compared with the number of long-time users (33 versus 124 patients), reflecting that low doses of corticosteroids over long periods of time are frequently used by patients with RA. Our data support that there is no “safety threshold” for steroid dose, but that the risk of fractures increases over the whole range of doses.
Exposure to corticosteroids could reflect long-term disease severity and activity rather than being a risk factor in itself. We explored this by adding various disease variables to the multivariate analyses. Unfortunately, radiographic damage scores for our sample of patients are not available. The deformed joint count is considered an alternative damage variable that could reflect the suggested common disease mechanisms for osteoporosis and joint destruction (20, 21). However, neither disease activity variables nor the presence of deformed joints was independently associated with vertebral deformities.
We observed a strong and independent association between a history of previous nonvertebral fracture and vertebral deformities. Previous fractures were self-reported, and no attempt was made to verify this information. This method has, however, been proven to be reliable in at least 2 previous studies (22, 23).
Our data, suggesting that BMD measurements are independently, but weakly, associated with vertebral deformities, is consistent with other data from samples of patients with RA or corticosteroid-treated patients (6, 7, 24). The fact that BMD values of the total hip showed a relationship to vertebral deformities that was an equal to or stronger than that of BMD of the spine (L2–4) might be due to degenerative or arthritic changes in the spine of patients with RA. This observation is supported by an earlier study in patients from the Oslo RA register showing no reduction of BMD values in the spine compared with controls (3). A possible limitation to this part of our study was that we did not exclude fractured vertebrae from the BMD analysis. However, such adjustments are rarely done in a clinical setting.
In conclusion, the clear and consistent relationship between the use of corticosteroids and vertebral deformities demonstrated in this study should alert physicians to be especially aware of this complication in patients with RA. This is important, taking into account that corticosteroids are effective both as symptom-modifying and disease-modifying agents in RA. A history of earlier nonvertebral fractures is also relevant when considering the risk of having vertebral deformities, as well as reduced BMD. Our study was, however, unable to show any consistent relationship between various clinical variables and vertebral deformities in RA. Studies with a longitudinal design are required to examine whether the associations identified in this cross-sectional study also can serve as risk factors for future fractures and vertebral deformities.