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Rheumatology 2001; 40: 1375-1383
© 2001 British Society for Rheumatology

Original Papers

Prevalence of vertebral deformities and symptomatic vertebral fractures in corticosteroid treated patients with rheumatoid arthritis

R. N. J. de Nijs, J. W. G. Jacobs, J. W. J. Bijlsma, W. F. Lems1, R. F. J. M. Laan2, H. H. M. Houben3, E. J. ter Borg4, A. M. Huisman5, G. A. W. Bruyn6, P. L. M. van Oijen7, A. A. A. Westgeest8, A. Algra9 and D. M. Hofman10 on behalf of the Osteoporosis Working Group of the Dutch Society for Rheumatology

Department of Rheumatology and Clinical Immunology, F02.127, University Medical Center, PO Box 85500, 3508 GA Utrecht,
1 Department of Rheumatology, Free University Hospital, PO Box 7057, 1007 MB Amsterdam,
2 Department of Rheumatology, University Medical Center, PO Box 9101, 6500 HB Nijmegen,
3 Department of Rheumatology, Atrium Medical Center, PO Box 4446, 6401 CX Heerlen,
4 Department of Rheumatology, Sint Antonius Hospital, PO Box 2500, 3430 EM Nieuwegein,
5 Department of Rheumatology, Sint Franciscus Gasthuis, Kleiweg 500, 3045 PM Rotterdam,
6 Department of Rheumatology, Hospital Medisch Centrum Leeuwarden, Henri Dunantweg 2, 8934 AD, Leeuwarden,
7 Department of Rheumatology, Hospital Bosch Medicentrum, Nieuwstraat 34, 5211 NL's-Hertogenbosch,
8 Department of Rheumatology, Hospital Diaconessenhuis, PO Box 90052, 5600 PD Eindhoven,
9 Julius Center for General Practice and Patient Oriented Research, University Medical Center, PO Box 85500, 3508 GA Utrecht and
10 Department of Rheumatology, Hospital Hilversum, PO Box 10016, 1201 DA Hilversum, The Netherlands


   Abstract
Top
 Abstract
Introduction
 Patients and methods
 Results
 Discussion
 References
 
Objective. This study was designed to determine whether the prevalence of vertebral deformities in patients with rheumatoid arthritis (RA) treated with corticosteroids (Cs) is higher than in RA patients not receiving Cs therapy.

Patients and methods. This multicentre cross-sectional study included 205 patients with RA who were receiving Cs orally on a daily basis and 205 patients with RA who did not receive Cs, matched for sex and age. Vertebral deformities were scored according to the Kleerekoper method.

Results. Vertebral deformities were found in 52 (25%) patients on Cs and in 26 (13%) patients not on Cs. Sixteen (8%) patients in the group on Cs had experienced clinical manifestations of an acute vertebral fracture in the past vs only three patients (1.5%) among those not on Cs. The use of Cs tended to increase the risk of developing a vertebral deformity [adjusted odds ratio (OR) 1.56, 95% confidence interval (CI) 0.81–2.99] and symptomatic vertebral fracture (adjusted OR 1.42, 95% CI 0.24–8.32). Each 1-mg increase in the current daily Cs dose increased the risk of a vertebral deformity (adjusted OR 1.05, 95% CI 0.98–1.13) and of a symptomatic vertebral fracture (adjusted OR 1.05, 95% CI 0.89–1.24).

Conclusion. There is a higher prevalence of vertebral deformities and clinical manifestations of vertebral fractures in patients on Cs than in those not on Cs. Our data indicate that the use of Cs and each 1-mg increase in the current daily Cs dose may increase the risk of development of a vertebral deformity and symptomatic vertebral fracture in patients with RA.

KEY WORDS: Corticosteroids, Prevalence, Rheumatoid arthritis, Symptomatic vertebral fractures, Vertebral deformities.


   Introduction
Top
 Abstract
 Introduction
Patients and methods
 Results
 Discussion
 References
 
Patients with rheumatoid arthritis (RA) are at risk of generalized osteoporosis. This is due to a combination of factors, in particular disease activity, immobility and medication. Corticosteroids (Cs) are often prescribed for patients with severe RA who respond poorly to anti-rheumatic drugs. Cs are known to uncouple bone formation and resorption, thus inducing osteoporosis [1, 2]. Cs decrease the intestinal absorption and increase the renal excretion of calcium [3, 4]. This may lead to secondary hyperparathyroidism [5]. In addition, Cs inhibit osteoblast proliferation and matrix attachment [6]. The effects of Cs occur mainly in regions of the skeleton with a high content of trabecular bone, in particular the ribs and spine, and seem to depend on the duration and dose of therapy [7, 8]. Prednisone doses exceeding 7.5 mg daily result in increased risks of fractures and bone loss [9, 10], but there are also negative effects of lower prednisone doses on bone mineral density [11].

Disease activity in patients with active RA is associated with increased generalized loss of bone mass, probably because of increased release of bone-resorbing cytokines, such as interleukins 1 and 6, tumour necrosis factor {alpha} and interferon-{gamma} [12, 13]. The incidence of vertebral deformities in women with RA was over twice that in healthy controls [14]. In patients with early RA without Cs therapy, bone loss at the hips exceeded that in the control group [15]. The occurrence of osteoporosis is correlated with both disease activity and immobilization in patients with RA [16, 17].

A peripheral osteoporotic fracture is nearly always accompanied by symptoms and is often associated with trauma, whereas vertebral osteoporotic fractures often do not give rise to symptoms [18] and the association with trauma is less evident. The prevalence of vertebral deformities reported in the literature varies from 3 [19] to 27% [20] for post-menopausal women aged 65 yr and older. This wide range in prevalence is probably due to differences between centres in both the scoring method and the definition of vertebral deformities [21]. This is illustrated by a study of the prevalence of vertebral deformities in patients with RA treated with Cs, which varied from 35 to 79% depending upon the scoring method. The incidence of clinical manifestations of vertebral fractures was also higher in Cs-treated RA patients than in a group of patients with RA who were not taking Cs [22].

The influence of Cs on bone mineral density and vertebral deformities has been the subject of numerous studies. Most of these studies, however, had a relatively small patient population and the patients had heterogeneous diseases. We report the results of a large cross-sectional study of a group of RA patients. We investigated whether the prevalence of vertebral deformities and symptomatic vertebral fractures was higher in RA patients treated with Cs than in RA patients who did not receive Cs.


   Patients and methods
Top
 Abstract
 Introduction
 Patients and methods
Results
 Discussion
 References
 
Patients
Patients were recruited by members of the Osteoporosis Working Group of the Dutch Society for Rheumatology at 10 hospitals in The Netherlands, university and non-university centres. Two hundred and five patients with RA [1987 American Rheumatism Association (ARA) criteria] [35] had been using Cs orally on a daily basis for at least 1 month. Another 205 patients with RA who were currently not receiving Cs, were matched one-to-one for sex and age (the greatest difference was 5 yr) to form a comparison group. Informed consent was obtained from all patients. The ethics committees of the participating hospitals approved of the study.

Clinical evaluation
In this cross-sectional study, the following data were obtained from the medical records of the patients: duration of RA; cumulative oral prednisone dose (or prednisone equivalent dose); duration of Cs treatment; other medications that might affect bone (use of calcium, vitamin D, fluoride, bisphosphonates, oestrogens, thiazide diuretics and methotrexate at the time of inclusion); and laboratory data [mean and cumulative (since the diagnosis of RA) erythrocyte sedimentation rate (ESR) and rheumatoid factor test status]. Data on the patients were obtained from a form filled in by a rheumatologist at each of the participating centres, and included age, sex, height, weight, ARA functional class (Steinbrocker) [23], daily dietary calcium intake and current daily oral prednisone dose or prednisone equivalent dose. The Dutch version of the Health Assessment Questionnaire (HAQ) (Vragenlijst Dagelijks Functioneren) [24] was filled in by the patients. The range of the HAQ is 0–3; 0 represents optimal and 3 poor functional capacity. Symptomatic vertebral fractures were identified from reports in the medical records of vertebral deformities after a period of back pain that led to prescription of analgesics or bed rest [25].

Vertebral deformities
Lateral X-rays of the thoracic and lumbar spine were made of all patients of both RA groups, as part of this study. All X-rays were scored twice, once by a regular observer and once by one of three alternating observers. The X-rays were scored blind following the method of Kleerekoper et al. [26]. This method consists of naked-eye inspection of vertebrae Th4–L5, comparing each vertebra with the vertebrae below and above it. If an abnormally shaped vertebra was found, the anterior, middle and posterior heights of this vertebra were measured with a ruler. Measurement of the height of an abnormally shaped vertebra was repeated if the interobserver difference in the measurement exceeded 15%. If the difference in the measurement again exceeded 15%, the height was discarded. This occurred in 0.4% of the measurements, which implies that 0.4% of the vertebrae could not be scored according to the Kleerekoper method. The mean of the heights measured by the regular observer and one other observer was used. The scoring system was as follows: 0=normal shape and dimensions; 1=only endplate deformity, middle height<85%; 2=anterior wedge deformity, anterior height<85%; 3=compression deformity, all three heights<85%. The Vertebral Deformation Score (VDS) is the total score for the part of the vertebral spine that is assessed, and ranges from 0 to 42 (fourteen vertebrae, the score for each ranging from 0 to 3); the higher the VDS score, the greater the degree of spine deformity.

Statistical analysis
Univariate odds ratios (ORs) were calculated to describe the crude relationship between Cs use (yes or no), current daily Cs dose, cumulative Cs dose and the prevalence of vertebral deformities. For this purpose, logistic regression was used. Cs use, the current daily Cs dose and the cumulative Cs dose were used as independent variables. The OR of the current daily Cs dose is given per 1-mg increase in prednisone or prednisone equivalent dose. The OR of the cumulative Cs dose is given per 1-g increase in prednisone or equivalent prednisone dose. Bivariate logistic models were used to adjust for incomparability between the RA patients on Cs and those not on Cs. The following variables were taken into account: sex, age, weight, height, duration of RA, mean ESR, ARA functional class, HAQ score, rheumatoid factor test status, daily dietary calcium intake and the use (yes or no) of calcium supplementation, vitamin D, oestrogens, bisphosphonates, fluoride, methotrexate or chlorthalidone. Variables that changed the crude OR importantly in bivariate analyses were taken together for multivariate adjustment. At this level we distinguished between additional adjustment with and without concomitant medication prescribed for the treatment or prevention of osteoporosis. A similar approach was used for the analysis of symptomatic vertebral fractures. P<0.05 was considered to be statistically significant.


   Results
Top
 Abstract
 Introduction
 Patients and methods
 Results
Discussion
 References
 
During the 10-month period, 205 pairs of patients were assessed (Table 1Go). RA patients on Cs were, on average, 2 cm shorter and 3 kg lighter than the patients not on Cs. The mean ESR in the group of patients on Cs was 40 (S.D. 18) mm/h compared with 30 (S.D. 26) in the group not on Cs, indicating more active RA in the patients on Cs. Impairment of functional capacity, according to the Steinbrocker classification and the HAQ score, was greater for the patients on Cs than for the patients not on Cs. Compared with the group of RA patients not on Cs, the group on Cs included significantly more patients who were positive for rheumatoid factor, and who currently received methotrexate. The numbers of patients taking calcium, vitamin D or bisphosphonates were also significantly higher in the group of patients on Cs.


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  		TABLE 1. Patient characteristics

 
Prevalence of vertebral deformities
Vertebral deformities were found in 52 patients taking Cs (25%) and in 26 patients not taking Cs (13%) [OR 2.34, 95% confidence interval (CI) 1.39–3.93]. Biconcave, wedge and crush vertebral deformities all occurred more frequently in patients with RA on Cs. In both groups, wedge deformities were the most frequently observed type of deformity (68 in the group of patients on Cs, 26 in the group not on Cs). The most common location of vertebral deformity in patients using Cs was L2 (14%); in the patients not on Cs, L1 (18%) was affected more often. The mean VDS for the RA group on Cs was 1.0 (S.D. 2.4) vs 0.3 (1.0) for the RA group not using Cs, indicating a more severely affected spine in RA patients receiving Cs (mean difference 0.70, 95% CI 0.34–1.06).

The crude and adjusted ORs for the association between the prevalence of vertebral deformities and Cs use in the total group (patients with RA on Cs and not on Cs) are shown in Table 2Go. Bivariate analysis revealed HAQ score, Steinbrocker functional class, bisphosphonate use, calcium and vitamin D supplementation as confounders. These variables were included in a final multivariate logistic model. The adjusted OR of Cs use without concomitant medication [variables included in the model were Steinbrocker functional class and functional capacity (HAQ)] was 2.00 (95% CI 1.17–3.41). The adjusted OR of Cs use with concomitant medication [variables included in the model were Steinbrocker functional class, functional capacity (HAQ), bisphosphonate use (yes/no), vitamin D and calcium supplementation (yes/no)] was 1.56 (95% CI 0.81–2.99). The crude OR of current daily Cs dose in the total group was 1.10 (95% CI 1.04–1.16). After adjustment for functional capacity (HAQ) the OR was 1.08 (95% CI 1.02–1.15) and after adjustment for functional capacity and calcium supplementation (yes/no) the OR was 1.05 (95% CI 0.98–1.13). The crude OR of current daily Cs dose in the patients on Cs without their matched controls was 1.04 (95% CI 0.95–1.15). Adjustment for age and weight revealed an OR of 1.09 (95% CI 0.98–1.21) and did not change after bisphosphonate use was added to the model. The crude OR of cumulative Cs dose was 1.00; in bivariate analyses no confounding was found by any of the variables. To examine the effect of the various cumulative Cs doses on the prevalence of vertebral deformities, we divided the RA patients who were using Cs into subgroups according to their cumulative Cs dose. There were no statistically significantly differences between subgroups in the prevalence of vertebral deformities (Table 3Go).


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  		TABLE 2. Crude and adjusted ORs for the association between the prevalence of vertebral deformities and Cs use in the total group of patients with RA (n=410), and the current daily Cs dose (per 1-mg increase in prednisone or prednisone equivalent dose) in the total group and in the group of patients with RA on Cs (n=205)

 

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  		TABLE 3. Number of patients on Cs (n=205) with at least one vertebral deformity or symptomatic vertebral fracture grouped according to cumulative Cs dose

 

Prevalence of symptomatic vertebral fractures
More patients using Cs [16 (8%)] than those not on Cs [3 (1.5%)] had experienced at least one symptomatic vertebral fracture in the past.

The crude OR of the use of Cs (yes/no) in the total group vs prevalence of symptomatic vertebral fractures was 5.70 (95% CI 1.63–19.87). After adjustment without concomitant medication [variables included in the model were rheumatoid factor (positive/negative), methotrexate use (yes/no), mean ESR, age, height, weight, Steinbrocker functional class and functional capacity (HAQ)], the OR was 4.31 (95% CI 1.13–16.47). When the model included concomitant medication [bisphosphonate use (yes/no), vitamin D and calcum supplementation (yes/no)], the adjusted OR was 1.42 (95% CI 0.24–8.32) (Table 4Go). The crude OR of current daily Cs dose in the total group vs prevalence of symptomatic vertebral fractures was 1.16 (95% CI 1.05–1.28). The OR after adjustment for height, sex, weight, age and functional capacity was 1.19 (95% CI 1.04–1.35); when vitamin D and calcium supplementation (yes/no) were included in the model, the adjusted OR was 1.05 (95% CI 0.89–1.24). When the group of RA patients on Cs was analysed separately, the crude OR of current daily Cs dose vs prevalence of symptomatic vertebral fractures was 1.07 (95% CI 0.92–1.24). Adjusting for height, weight, age and sex gave an OR of 1.17 (95% CI 0.97–1.42) and the OR did not change when bisphosphonate use (yes/no) was included in the model. The crude OR of cumulative Cs dose vs prevalence of symptomatic vertebral fractures was 1.00. This OR did not change after adjustment. We divided the RA patients using Cs into subgroups according to the cumulative Cs dose. There were no statistically significantly differences between these subgroups in the prevalence of symptomatic vertebral fractures (Table 3Go).


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  		TABLE 4. Crude and adjusted ORs for the association between the prevalence of symptomatic vertebral fractures and the use of Cs in the total group of patients with RA (n=410), and the current daily Cs dose (per 1-mg increase in prednisone or prednisone equivalent dose) in the total group and in the group of patients with RA who were on Cs (n=205)

 


   Discussion
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
References
 
This cross-sectional study of 410 patients with RA was designed to evaluate the influence of Cs on the prevalence of vertebral deformities in patients with RA on Cs therapy. Little is known about the prevalence of vertebral deformities in patients with RA treated with Cs. Lems et al. [22] studied a group of 52 Cs-treated patients with RA and 55 RA patients not receiving Cs. There was a higher prevalence of vertebral deformities (Kleerekoper method) in the Cs group (58 vs 25% of the group not on Cs). We also used the Kleerekoper method to investigate the occurrence of vertebral deformities. Our data revealed a prevalence of vertebral deformities of 25% in the patients with RA who were using Cs. Only 26 (13%) of the 205 patients with RA not on Cs had a vertebral deformity. However, there are differences between our study and the study of Lems et al.; in the latter there were fewer patients and the study was performed in a tertiary care centre, where the RA patient group probably had greater disease activity. The RA patients on Cs in that study had a higher mean ESR, disease duration and age in comparison with our study. This could explain the higher prevalence of vertebral deformities in their study [22].

In our study, the crude OR of prevalence of vertebral deformities in the total group of RA patients was 2.34 (95% CI 1.39–3.93), indicating an increased risk of developing a vertebral deformity in patients treated with Cs. This is in agreement with the relative risk of 2.31 (95% CI 1.36–3.90) calculated in the study of Lems et al. [22]. In our study, we performed bivariate and final multivariate logistic analyses to correct for confounding. The adjusted OR was 1.56. This demonstrates that, even after correction for confounding, the risk of development of vertebral deformities in patients with RA treated with Cs was 1.5 times greater than in RA patients not treated with Cs; however, this increase in risk was not statistically significant. Because the crude OR of prevalence of vertebral deformities in RA patients receiving Cs is influenced by the concomitant medication (bisphosphonates, vitamin D and calcium) given to these patients to treat or prevent osteoporosis, which might influence the prevalence of vertebral deformities, we also performed multivariate logistic analysis with and without this medication to see if there was any change in the adjusted OR. When the influence of current daily dose of Cs on the prevalence of vertebral deformities in the total group was analysed, we found a crude OR of 1.10 (95% CI 1.04–1.16). The adjusted OR with concomitant medication taken into account [functional capacity (HAQ) and calcium supplementation (yes/no) were included in the multivariate model] was 1.05 (95% CI 0.98–1.13). The adjusted OR without calcium supplementation (yes/no) was 1.08 (95% CI 1.02–1.15). This means that, with an increase in the current prednisone (or equivalent) dose of 1 mg/day in RA patients, the risk of a vertebral deformity will increase by a factor of 1.08. We would like to stress, however, that even after correction by means of logistic regression analysis, there may be residual confounding due to unknown risk factors.

Dykman et al. [7] showed that long-term therapy with various prednisone regimens resulted in glucocorticoid-induced osteopenia and fractures. This effect was cumulative and occurred in all patient groups. Julian et al. [27], however, could not demonstrate a correlation between the degree of bone loss and the cumulative dose of glucocorticoids. Lems et al. [25] could not find a correlation between cumulative prednisone dose and the prevalence of vertebral deformities. In our study, the OR of cumulative Cs dose vs the prevalence of vertebral deformities was 1.00, demonstrating that there was no effect of the cumulative Cs dose on the prevalence of vertebral deformities. When we divided the RA patients on Cs into subgroups according to cumulative Cs dose, there were no statistically significant differences in the prevalence of vertebral deformities between the subgroups. We have no plausible explanation for the fact that, in our study, the prevalence of vertebral deformities was not related to the cumulative Cs dose. There are, however, differences between our study and the study of Dykman. We had the larger patient population, matched for age and sex, which consisted only of patients with RA; furthermore, we used a validated method to score vertebral deformities.

Vertebral deformities are frequently asymptomatic and sometimes occur during normal physical activities. A vertebral deformity detected on an X-ray might be the result of a symptomatic fracture or an asymptomatic deformity that occurred earlier. Symptomatic vertebral fractures are defined here as acute vertebral deformities leading to the prescription of a therapy. Lems et al. [25] found that 13% of the patients treated with Cs had a symptomatic vertebral fracture, and the occurrence of vertebral deformities in their study was 35–79% depending upon the method used to score the vertebral deformities. In their study, only 2% of the RA patients not taking Cs had a manifest vertebral fracture, whereas the prevalence of vertebral deformities in this group varied from 25 to 67% [22]. According to our data, 8% of the RA patients in the group taking Cs suffered from a manifest vertebral fracture vs 1.5% of the group of RA patients not receiving Cs. Some degree of surveillance bias cannot be excluded, however. RA patients on Cs who have back pain may have more X-ray investigations of the spine. To identify symptomatic vertebral fractures, we used reports in the medical records on vertebral deformities after a period of back pain that led to the prescription of analgesics or bed rest. This method may result in underestimation of the number of symptomatic vertebral fractures because some patients with an episode of back pain may not be treated by their rheumatologist but by their general practitioner, and this information may not be passed on to their rheumatologist. The prevalence of vertebral deformities in the RA group taking Cs was 25% vs 13 for the RA group not on Cs. A discrepancy between the prevalence of vertebral deformities and the prevalence of symptomatic vertebral fractures has also been reported by Cooper et al. [28]. Kleerekoper hypothesized that vertebral fractures lead to vertebral deformities but that not all vertebral deformities are the consequence of a vertebral fracture [18]. Because of the use of the Kleerekoper method, the prevalence of vertebral deformities might have been overestimated slightly in our study as this semiquantitative method does not take into account the normal shape of the vertebrae. The thoracic and lumbar vertebrae are to some degree wedge-shaped and inversely wedge-shaped respectively. Another reason for overestimation of the prevalence of vertebral deformities by the Kleerekoper method is the low threshold (height reduction of 15% or more) for diagnosing vertebral deformities. Some investigators take a cut-off point of 20% for vertebral deformity [29]. However, the Kleerekoper method is one of the most feasible approaches in the clinical setting. It is easy to perform and complex calculations are not necessary. Experienced assessors are highly reliable in the identification of vertebral deformities [30]. In our study, we showed that the use of Cs in patients with RA increases the risk of development of a symptomatic vertebral fracture (crude OR 5.70, 95% CI 1.63–19.87). The multivariate adjusted OR was 1.42 (95% CI 0.24–8.32) with and 4.31 (95% CI 1.13–16.47) without concomitant medication [bisphosphonate use (yes/no), vitamin D and calcium supplementation (yes/no)]. This means that calcium supplementation, bisphosphonate use, vitamin D supplementation, functional capacity and Steinbrocker functional class had a considerable influence. The adjusted OR, with concomitant medication taken into account, of the influence of the current daily Cs dose on the development of symptomatic vertebral fractures was 1.05 (95% CI 0.89–1.24), demonstrating that an increase of 1 mg in the daily Cs dose (prednisone or equivalent) was associated with an increase of 1.05 in the risk of a symptomatic vertebral fracture and an increase of 1.19 after adjustment when the model multivariate did not include vitamin D and calcium supplementation (yes/no).

The prevalence of Cs therapy in combination with preventive therapy of osteoporosis was assessed in two studies in the UK. The study by Walsh et al. [31] in a community (in Nottinghamshire) showed that only 14% of the patients on oral Cs received medication to prevent secondary osteoporosis. Only 6% of the Cs-treated patients studied by Peat et al. [32] received calcium supplementation. These figures do not meet the recommendations published by the American College of Rheumatology Task Force on Osteoporosis, which stress the need for preventive treatment of patients receiving Cs [33]. In our study, more RA patients on Cs received calcium, vitamin D and bisphosphonate medication than RA patients not using Cs. Despite our statistical adjustment, this treatment, although used only in a small number of patients, might have obscured the effect of Cs on the number of vertebral deformities, because this medication may have been prescribed more frequently to patients with a history of deformities. An important question is what kind of prevention should RA patients treated with Cs receive? There is a need for studies to determine which strategy should be used for the preventive treatment of patients receiving Cs [34].

In summary, we demonstrated in a large cross-sectional study in patients with RA, designed to evaluate the final outcome measure of Cs on bone, namely fracture, that vertebral deformities and symptomatic vertebral fractures occurred more often in patients with RA who were treated with Cs than in patients with RA who were not receiving Cs (matched for age and sex). We performed multivariate logistic analyses to adjust for confounding and showed that the use of Cs in patients with RA, even after correction for confounding, carries a substantial risk of the development of a vertebral deformity and symptomatic vertebral fracture.


   Acknowledgments
 
We wish to thank E. Buskens, clinical epidemiologist, for help with the statistical analysis. This work was supported by grant VR/713 from the Dutch League against Rheumatism (Het Nationaal Reumafonds).


   Notes
 
Correspondence to: R. N. J. de Nijs, Department of Rheumatology and Clinical Immunology, F02.127, University Medical Center, PO Box 85500, 3508 GA Utrecht, The Netherlands. Back


   References
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 

  1. Lukert BP, Raisz LG. Glucocorticoid-induced osteoporosis: pathogenesis and management. Ann Intern Med1990;112:352–64.
  2. Adachi JD, Bensen WJ, Hodsman AB. Corticosteroid-induced osteoporosis. Semin Arthritis Rheum1993;22:375–84.[Medline]
  3. Klein RG, Arnaud SB, Gallagher JC, DeLuca HF, Riggs BL. Intestinal calcium absorption in exogenous hypercortisonism. Role of 25-hydroxyvitamin D and corticosteroid dose. J Clin Invest1977;60:253–9.
  4. Hahn TJ, Halstead LR, Bran DT. Effects of short term glucocorticoid administration on intestinal calcium absorption and circulating vitamin D metabolite concentrations in man. J Clin Endocrinol Metab1981;52:111–5.[Abstract]
  5. Suzuki Y, Ichikawa Y, Saito E, Homma M. Importance of increased urinary calcium excretion in the development of secondary hyperparathyroidism of patients under glucocorticoid therapy. Metabolism1983;32:151–6.[ISI][Medline]
  6. Gronowicz G, McCarthy MB. Glucocorticoids inhibit the attachment of osteoblasts to bone extracellular matrix proteins and decrease ß-1 integrin levels. Endocrinology1995;136:598–608.[Abstract]
  7. Dykman TR, Gluck OS, Murphy WA, Hahn TJ, Hahn BH. Evaluation of factors associated with glucocorticoid-induced osteopenia in patients with rheumatic diseases. Arthritis Rheum1985;28:361–8.[ISI][Medline]
  8. Reid IR, Heap SW. Determinants of vertebral mineral density in patients receiving longterm glucocorticoid therapy. Arch Intern Med1990;150:2545–8.[Abstract]
  9. Verstraeten A, Dequeker J. Vertebral and peripheral bone mineral content and fracture incidence in postmenopausal patients with rheumatoid arthritis: effect of low dose corticosteroids. Ann Rheum Dis1986;45:852–7.[Abstract/Free Full Text]
  10. Michel BA, Bloch DA, Wolf F, Fries JF. Fractures in rheumatoid arthritis: an evaluation of associated risk factors. J Rheumatol1993;20:1666–9.[ISI][Medline]
  11. Laan RF, van Riel PL, van Erning LJ, Lemmens JA, Ruijs SH, van de Putte LB. Vertebral osteoporosis in rheumatoid arthritis patients: effect of low dose prednisone therapy. Br J Rheumatol1992;31:91–6.[Abstract/Free Full Text]
  12. Eastgate JA, Wood NC, Di Giovine FS, Symons JA, Grinlinton FM, Duff GW. Correlation of plasma interleukin 1 levels with disease activity in rheumatoid arthritis. Lancet1988;ii:706–9.
  13. Arend WP, Dayer J-M. Cytokines and cytokine inhibitors or antagonists in rheumatoid arthritis. Arthritis Rheum1990;33:305–15.[ISI][Medline]
  14. Spector TD, Hall GM, McCloskey EV, Kanis JA. Risk of vertebral fracture in women with rheumatoid arthritis. Br Med J1993;306:58.
  15. Gough AK, Lilley J, Eyre S, Holder RL, Emery P. Generalised bone loss in patients with early rheumatoid arthritis. Lancet1994;344:23–7.[ISI][Medline]
  16. Laan RF, Buijs WC, Verbeek AL et al. Bone mineral density in patients with recent onset rheumatoid arthritis: influence of disease activity and functional capacity. Ann Rheum Dis1993;52:21–6.[Abstract/Free Full Text]
  17. Hooyman JR, Melton LJ, Nelson AM, O'Fallon WM, Riggs BL. Fractures after rheumatoid arthritis. Arthritis Rheum1984;27:1353–61.[Medline]
  18. Kleerekoper M. Vertebral fracture or vertebral deformity. Calcif Tissue Int1992;50:5–6.[ISI][Medline]
  19. Härmä M, Heliovaara M, Aromaa A, Knekt P. Thoracic spine compression fractures in Finland. Clin Orthop1986;205:188–94.
  20. Melton LJ III, Kan SH, Frye MA, Wahner HW, O'Fallon MO, Riggs BL. Epidemiology of vertebral fractures in women. Am J Epidem1989;129:1000–10.[Abstract/Free Full Text]
  21. O'Neill TW, Varlow J, Felsenbeng D et al. Variation in vertebral height ratios in population studies. European Vertebral Osteoporosis study. J Bone Miner Res1994;9:1895–907.[Medline]
  22. Lems WF, Jahangier ZN, Jacobs JWG, Bijlsma JWJ. Methods to score vertebral deformities in patients with rheumatoid arthritis. Br J Rheumatol1997;36:220–4.[Abstract/Free Full Text]
  23. Hochberg MC, Chang WR, Dwosh I, Lindsey S, Pincus T, Wolfe F. The American College of Rheumatology 1991 revised criteria for the classification of global functional status in rheumatoid arthritis. Arthritis Rheum1992;35:498–502.[ISI][Medline]
  24. Bijlsma JWJ, Oude Heuvel CHB, Zaalberg A. Development and validation of the Dutch questionnaire capacities of daily life (VDF) for patients with rheumatoid arthritis. J Rehabil Sci1990;3:71–4.
  25. Lems WF, Jahangier ZN, Jacobs JWG, Bijlsma JWJ. Vertebral fractures in patients with rheumatoid arthritis treated with corticosteroids. Clin Exp Rheumatol1995;13:293–7.[ISI][Medline]
  26. Kleerekoper M, Parfitt AM, Ellis BI. Measurement of vertebral fracture rates in osteoporosis. In: Christiansen C, Arnaud CD, Nordin BEC, Parfitt AM, Peck WA, Riggs BL, eds. Proceedings of the Copenhagen International Symposium on Osteoporosis 1984. Copenhagen: Aalberg Stiftsbogtrykkeri, 1984:103–9.
  27. Julian BA, Laskow DA, Dubovsky J, Dubovsky EV, Curtis JJ, Quarles LD. Rapid loss of vertebral mineral density after renal transplantation. N Engl J Med1991;325:544–50.[Abstract]
  28. Cooper C, O'Neill T, Silman A. The epidemiology of vertebral fractures. Bone1993;14:S89–97.
  29. Genant HK, Wu CY, van Kuijk C, Nevitt MC. Vertbral fracture assessment using a semiquantitative technique. J Bone Miner Res1993;8:1137–48.[ISI][Medline]
  30. Wu CY, Li J, Jergas M, Genant HK. Comparison of semiquantitative and quantitative techniques for the assessment of prevalent and incident vertebral fractures. Osteoporosis Int1995;5:354–70.[ISI][Medline]
  31. Walsh LJ, Wong CA, Pringle M, Tattersfield AE. Use of oral corticosteroids in the community and the prevention of secondary osteoporosis: a cross sectional study. Br Med J1996;313:344–6.[Abstract/Free Full Text]
  32. Peat ID, Healy S, Reid DM, Ralston SH. Steroid induced osteoporosis: an opportunity for prevention. Ann Rheum Dis1995;54:66–8.[Abstract/Free Full Text]
  33. American College of Rheumatology Task Force on Osteoporosis Guidelines. Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Rheum1996;39:1791–801.[ISI][Medline]
  34. Bijlsma JWJ. Prevention of glucocorticoid induced osteoporosis. Ann Rheum Dis1997;56:507–9.[Free Full Text]
  35. Arnett FC, Edworthy SM, Bloch DA et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum1998;31:315–24.
Submitted 1 November 2000; Accepted 4 June 2001


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H A Capell, R Madhok, J A Hunter, D Porter, E Morrison, J Larkin, E A Thomson, R Hampson, and F W Poon
Lack of radiological and clinical benefit over two years of low dose prednisolone for rheumatoid arthritis: results of a randomised controlled trial
Ann Rheum Dis, July 1, 2004; 63(7): 797 - 803.
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