Cross-Sectional Retrospective Study of Serum Vitamin D Level and Its Impact on Activity of Rheumatoid Arthritis

Cross-Sectional Retrospective Study of Serum Vitamin D Level and Its Impact on Activity of Rheumatoid Arthritis

Masoumi M1*,2, Alibeik P1, Parham M1

  1. Qom University Of Medical Sciences(QUMS)- Shahid Beheshti Hospital- Qom-Iran
  2. Behcet’s Disease Unit,Rheumatology Research Center(RRC)- Tehran University of Medical Science- Shariati Hospital- Tehran- Iran

*Corresponding author: Dr. Maryam Masoumi, Qom University of Medical Sciences, Qom, Iran
Rheumatology Research Center, Tehran, Iran. Tel; +98 919 012 3098; Email: masoumiy@gmail.com

Abstract

Vitamin D plays an important role in bone metabolism and regulation of the immunity system. The purpose of this study was to survey the serum level of vitamin D in patients suffering from rheumatoid arthritis and its relationship with the activity  of the disease.

Methods

This cross-sectional retrospective study was done on 216 patients attending rheumatology clinics in Qom Province meeting the criteria of American Rheumatology Association. The activity of the disease was calculated based on the DAS28 (Disease activity score in 28 joints) using the related software. The cut-off points of DAS28 of 2.6, 3.2 and 5.1 have been suggested to be indications of remission, low disease activity and high disease activity, respectively. Patients in the active disease group were further classified into four subgroups, including intensive Disease Activity Subgroup (DAS 28 exceeding 5.1), average disease activity subgroup (DAS 28 3.2-5.1), mild disease activity subgroup (DAS 28 3.2-2.6), and inactive disease subgroup (DAS 28 below 2.6).

Results

The results showed that the activity of rheumatoid arthritis disease was increased as serum levels of vitamin D decreased. In other words, the prevalence of vitamin D deficiency among patients suffering from severe rheumatoid arthritis activity was high. A significant difference was also observed between the serum level of vitamin D and erythrocyte sedimentation rate (ESR) , C-reactive protein (CPR), platelet count, and visual analogue scale (VAS) (P<0.001), but no significant relationship was found between serum levels of vitamin D and the number of affected joints and WBS.

Conclusion

There is a significant relationship between vitamin D deficiency in patients suffering from rheumatoid arthritis and the activity of the disease.

Keywords

Rheumatoid arthritis; DAS 28; Vitamin D; Disease activity

Abbreviations

DAS 28: Disease activity score in 28 joints

ESR: Erythrocyte sedimentation rate

CRP: C-reactive protein

VAS: Visual analogue scale

ACR: American Rheumatology Association

RA: Rheumatoid arthritis

Introduction

Epidemiological studies have showed that vitamin D deficiency may be a risk factor for development of autoimmune diseases such as diabetes mellitus type 1, multiple sclerosis [1], and other chronic diseases [2,3]. Recent studies have also revealed that the prevalence of vitamin D deficiency is increasing in men and women living in Iran [4]. Vitamin D may be inversely related with the occurrence, progression, and activity of rheumatoid arthritis (RA) [5-7]. Studies have shown the anti-inflammatory and autoimmune modulating role of vitamin D [8]. The activity of arthritis is assessed by a combination of objective and non-objective measurements, the sum of which provides the score of disease activity in 28 joints (DAS 28). There is evidence that the activity of RA can be affected by vitamin D [9]. However, these findings, though provable in the initial RA evaluation, disappear after three years from onset of the diseases [10]. The principle studied in this index is inflammation and tenderness of 28 major joints of body along with ESR and VAS factors [10]. CRF is another index used for determination of the degree of disease activity [11].

The purpose of this study was to determine the relationship between the serum level of vitamin D and activity of rheumatoid arthritis in Qom Province. We hypothesized that low levels of vitamin D were common in RA patients and that it was inversely related with the activity of the disease and disability of the patients.

Materials and Methods

This cross-sectional retrospective study was conducted by surveying the medical records of rheumatoid arthritis patients attending a number of rheumatology clinics in Qom Province. The statistical population consisted of all patients suffering from rheumatoid arthritis presenting to rheumatology clinics in Qom Province, with a confirmed diagnosis of RA based on the ACR 2010 criteria. The inclusion criterion was confirmation of rheumatoid arthritis diagnosis based on the ACR criteria. The exclusion criteria were hepatic and renal diseases; receiving diuretics, antispasmodics, heparin, calcium, and vitamin D and its derivatives; malignancy; malabsorption syndromes; history of digestive system surgery; and receiving blood transfusion within the recent six months. Among  276 patients,  216 patients were chosen that had inclusion criterion (table 1).

Demographic characteristics, height, weight, medicines taken by the patient, number of tender joints, vitamin D serum level, kind of extension of the involvement joints, and kind of involvement joints were recorded in a checklist. The degree of disease activity was determined based on the DAS 28 in each case. To determine the DAS 28, factors such as the number of tender and swollen joints, ESR, CRP, and the patient’s self-assessment of his/ her global health (VAS) are taken into consideration using the related software [12]. The active disease group was divided into three subgroups including those with severe disease activity (DAS 28: over 5.1), those with medium disease activity (DAS 28: 3.2-5.1), and those with mild disease activity (DAS 28: 3.2 to 2.6). The inactive disease group was divided based on DAS 28 equal or below 2.6. The vitamin D level was determined in each group. A serum level of vitamin D below 30 ng/ml was considered deficiency. The data were analyzed with Pearson’s correlation coefficient, chi – square, and T-test using the SPSS statistical software version 22. P values <0.05 were considered significant.

Results

A total of 216 subjects, including 184 women (85.2%) and 32 men (14.8%), with a mean age of 49.86 years participated in our study. The patients included in the study received an average daily dose of 5 mg prednisolone, 200-400 mg hydroxychloroquine, and 7.5-15 mg methotrexate per week in case of disease activity on the first examination. The mean number of involved joints was 20.31±9. The duration of the disease ranged from 2 months to 49 years. The mean serum level of vitamin D was 34.56±28 ng/ml (range: 3-150 ng/ml). Of 216 subjects studied in our research, 136 (63%) had vitamin D levels below normal (<30 ng/ml) of whom 25 subjects (11.6%) suffered from severe vitamin D deficiency and 111 (31.4%) had insufficient vitamin D levels. There was significant relationship between serum levels of vitamin D and activity of RA (P<0.001). The activity of RA disease was increased as the serum levels of vitamin D decreased. In other words, the prevalence of vitamin D deficiency among patients suffered from severe RA activity, was high (table 2).

An inverse correlation was found between the serum level of vitamin D and ADS28 in a way that the score of DAS28 decreased with an increase in the serum level of vitamin D (p <0.001). An inverse correlation was also observed between the serum level of vitamin D and ESR in a way that ESR decreased with an increase in the serum level of vitamin D (P<0.001). Moreover, we found a significant inverse correlation between the serum level of vitamin D and CRP (P<0.0001). However, there was no significant correlation between the serum level of vitamin D and WBC, but a significant correlation was observed between the serum level of vitamin D and the number of involved joints (P<0.001).

Chi-square test of independence showed no correlation between vitamin D deficiency and the type of joint involvement (monoarticular, oligoarticular and polyarticular).

The results of ANOVA showed a significant relationship between the serum level of vitamin D and the number of tender joints (p<0.001), number of swollen joints (p<0.001), DAS 28 (p<0.001), DAS 28/crp (p<0.001), VAS (p<0.001), ESR (p<0.001) and blood platelet count (p<0.005). However, no significant relationship was observed between the number of involved joints and WBC count (Table 3).

The results of the subsequent tests showed a significant difference in the number of tender joints between subjects suffering from severe vitamin D deficiency and the subjects with normal levels of vitamin D (p<0.001) (Table 4). However, there was no significant difference in the insufficient vitamin D level group (P < 0.387).Also, no significant differences in the number of swollen joints were seen between subjects with severe vitamin D deficiency and the patients who had insufficient levels of vitamin D (P<0.362). A significant difference was observed in other variables (DAS 28, VSR, ESR and Platelet) among patients with severe vitamin D deficiency and insufficient vitamin D level and the group of subjects with normal vitamin D levels.

Discussion

Studies investigating the relationship between the serum level of vitamin D and the activity  of rheumatoid arthritis have shown contradictory results, indicating the need for further research in this area. In this study, we assessed the relationship between the serum level of vitamin D and the activity  of rheumatoid arthritis in the hospitals of Qom Province. Some studies have shown a correlation between the level of vitamin D and the activity and recurrence of the disease [13-18], while other studies have found no correlations [19,20,5 ,21,18]. In a study done by Abourazzak et al [13] in 170 patients from Morocco, the results showed that the vitamin D level was inversely correlated with DAS-28, disease activity , and HAQ scores. Another study revealed an inverse relationship with DAS-28 [21]. A study on 499 RA patients showed no correlation between the vitamin D level and disease activity, van der Heijde-Sharp score, and inflammatory markers [21]. A double-blind randomized controlled study on 80 RA patients showed that the level of vitamin D had no relationship with disease activity and recurrence (5).

In general, the contradiction in the results of studies about serum vitamin D levels and the activity  of the activity of arthritis rheumatoid can be attributed to reasons such as the differences in sampling period, the duration of rheumatoid arthritis, and the difference in the amount and type of medications used by patients.

Conclusion

We found a significant correlation between vitamin D deficiency and disease activity in patients suffering from rheumatoid arthritis. This relationship was significant in spite of controlling factors such as age, gender and the other confounding variables.

References

 

Table 1. The number of patients that were excluded from study by each exclusion criterion.

exclusion criteria A B C D E F G H I J
number of patients 9 7 3 4 12 17 1 3 3 1

Patients that had A: hepatic and renal diseases; or consumed B: diuretics; C: antispasmodics; D: heparin; E: calcium; F: vitamin D and its derivatives; or had G: malabsorption syndromes; H: malignancy; I: history of digestive system surgery; J: receiving blood transfusion.

 

 

 

Table 2. Comparison of disease activity between patients with or without vitamin D deficiency according to DAS-28 based on Pearson Chi-Square test

Vitamin D sreum level Based on Das 28 Significance

 

silent mild moderate severe
Below normal (136) 4 3 22 107  

 

0.001

Normal (80) 55 3 11 11
Total 59 6 33 118

 

 

Table 3. ANOVA for the main studied characteristics based on the level of serum vitamin D

Variable Normal   Insufficiency   Deficiency   P-value
95% C.I Mean 95% C.I Mean 95% C.I Mean
The number of involved joints 19.6-23.42 21.51 18.3-21.51 19.77 15.5-22.7 18.88 0.294
The number of Tender Joints 0.9-2.86 1.88 8.5-11 9.75 8.7-14.2 11.48 p <0.001
The number of swollen joints 0.78-2.16 1.57 7.74-10.16 8.95 7.86-13.41 10.64 p <0.001
DAS28 2.43-3.73 3.08 5.66-6.28 5.97 5.75-6.68 6.21 p <0.001
CRP/DAS28 1.68-2.47 2.08 5.04-5.66 5.35 5.27-6.16 5.72 p <0.001
VAS 13.33-27.16 19.75 73.61-83.67 78.64 76.77-88.02 82.40 p <0.001
ESR 16.76-24.88 20.82 39.95-50.74 45.35 25.96-47.63 36.8 p <0.001
WBC 6443-11927 9185 7938-12221 10080 7170-8792 7981.16 0.660
PLT 265312-294587 279950 302574-347551 325063 259447-311112 285280 p <0.001
CRP 1.31-6.30 3.81 7.05-15.99 11.52 12.76-19.82 16.29 p <0.001

 

 

Table 4. The results of post hoc test of the traits examined based on serum vitamin D level using Tukey test

Variables Group Vit D level Difference mean sig
 

The number of tender joints

Dificiency Insufficiency 1.72 0.387
Normal 9.59 <0.001
Insufficiency Dificiency -1.72 0.387
Normal 7.86 <0.001
Normal Deficiency -9.59 <0.001
Insufficiency -7.86 <0.001
 

The number of swollen joints

Deficiency Insufficiency 1.68 0.362
Normal 9.06 <0.001
Insufficiency Deficiency -1.68 0.362
Normal 7.38 <0.001
Normal Deficiency -9.06 <0.001
Insufficiency -7.38 <0.001
 

 

 

DAS 28

Deficiency Insufficiency 0.245 0.572
Normal 3.64 <0.001
Insufficiency Deficiency -0.245 0572
Normal 3.27 <0.001
Normal Deficiency -3.64 <0.001
Insufficiency -3.27 <0.001
 

 

VAS

Deficiency Insufficiency -3.75 0.821
Normal 62.65 <0.001
Insufficiency Deficiency -3.75 0.821
Normal 58.89 <0.001
Normal Deficiency -62.65 <0.001
Insufficiency -58.89 <0.001
 

 

 

ESR

Deficiency Insufficiency -8.55 0.372
Normal 15.97 0.016
Insufficiency Deficiency 8.55 0.272
Normal 24.52 <0.001
Normal Deficiency -15.97 0.016
Insufficiency -24.52 <0.001
 

 

 

PLT

Deficiency Insufficiency -39783 -0.159
Normal 5330 0.969
Insufficiency Deficiency 39783 0.159
Normal 45113 0.005
Normal Deficiency 5330 0.969
Insufficiency 45113 0.005
 

 

CRP

Deficiency Insufficiency -4.77 0.350
Normal 7.71 0.080
Insufficiency Deficiency 4.77 0.350
Normal 12.48 <0.001
Normal Deficiency -7.71 0.080
Insufficiency -12.48 <0.001

 

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