Ankylosing spondylitis and low vitamin D – several studies

Ankylosing Spondylitis patients should increase Vitamin D levels - meta-analysis Nov 2022

Ankylosing spondylitis disease activity and serum vitamin D levels: A systematic review and meta-analysis
Medicine (Baltimore) . 2022 Nov 18;101(46):e31764. doi: 10.1097/MD.0000000000031764.
Menglu Chen 1 , Wen Li, Lailai Li, Yihui Chai, Yuqi Yang, Xiang Pu

Background: To prove that serum vitamin D (VD) levels are strongly associated with ankylosing spondylitis (AS) disease activity, the association between serum VD levels and key monitoring indicators of AS disease activity has been analyzed, such as the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP).

Methods: Studies published in PubMed, Cochrane Library, EMBASE, and China National Knowledge Infrastructure by August 30, 2022 were searched, and 6 studies finally met the selection criteria. Serum 25-hydroxyvitamin D (25(OH)D), ESR, CRP levels, and correlation coefficients between serum VD and BASDAI, ESR, CRP in AS, and control in these studies were extracted for the meta-analysis.

Results: When compared to controls, patients with AS had considerably lower blood 25(OH)D levels (MD = -7.53 ng/mL, 95% CI, -9.78 to -5.28, P < .001) and significantly higher ESR and CRP levels (ESR: MD = 11.75 mm/h, 95% CI, 4.20 to 19.31, P = .002; CRP: MD = 15.36 mg/L, 95% CI, 4.95 to 25.77, P = .004). Additionally, a negative correlation was discovered between serum VD levels and BASDAI, ESR, and CRP (Fisher' Z = -0.34, -0.38, -0.35, respectively).

Conclusion: The findings of our meta-analysis demonstrated a negative correlation between serum VD levels and the main monitoring indices of disease activity in patients with AS and verified that the differences in the continent and ethnicity may be one of the major contributors to this finding.
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__Conclusion in PDF))
In conclusion, our findings revealed a negative correlation
between serum VD levels and the primary monitoring markers
of disease activity in AS patients, including BASDAI, ESR, and
CRP levels. This finding suggests that higher serum VD levels
are strongly linked to both disease control and an improved
quality of life for AS patients. Additionally, we confirmed that
the total serum 25(OH)D levels and the inverse relationship
between serum VD levels and BASDAI in AS patients may be
significantly influenced by continental and ethnic variations.
Therefore, patients with AS are advised to supplement VD by sun exposure or supplements in order to lessen clinical symptoms and enhance quality of life. ESR and CRP levels were examined in our meta-analysis in relation to the occurrence of
AS, but their correlation with serum VD levels was based on less
conclusive evidence. Therefore, more clinical high-quality studies in these areas should be conducted in the future to further
validate our results.

Ankylosing Spondylitis is still associated with low Vitamin D - meta-analysis Sept 2022

Peripheral vitamin D levels in ankylosing spondylitis: A systematic review and meta-analysis
Front Med (Lausanne) . 2022 Aug 26;9:972586. doi: 10.3389/fmed.2022.972586
Maohui Diao 1 , Jun Peng 1 , Daidong Wang 1 , Hongbo Wang 1

Image
Conclusion: In conclusion, the study showed an inverse association between 25OHD and AS, which suggests that vitamin D may have a protective effect on AS. ESR and C-reactive protein (CRP) are important biomarkers for AS.
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Considering testing all AS patients for low Vitamin D - Jan 2017

Are Systematic Screening for Vitamin D Deficiency and Vitamin D Supplementation Currently Feasible for Ankylosing Spondylitis Patients?
Int J Inflam. 2017;2017:7840150. doi: 10.1155/2017/7840150. Epub 2017 Jan 1.
Essouma M1, Noubiap JJ2.
1 Department of Internal Medicine and Specialties, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon.
2 Department of Medicine, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa.
Every AS pathway is associated with Vitamin D
Image

Beyond its role in calcium and phosphorus metabolism for healthy bone mineralization, there is increasing awareness for vitamin D contribution in modulation of immune reactions. Given that ankylosing spondylitis (AS) is a chronic inflammatory disease involving excess immune/inflammatory activity and posing great therapeutic challenges, it is conceivable to claim that vitamin D treatment may be a safe and effective treatment to influence or modify the primary disease and its related comorbidities. Nevertheless, consistent body of research supporting this hypothesis is still lacking. In this paper, we examine whether systematic screening and treatment for vitamin D deficiency are feasible at present. We will review the immunomodulatory role of vitamin D and its contribution in initiation and progression of AS, as well as how they would determine the occurrence of comorbid conditions. Our conclusion is that despite the overwhelmed interest about vitamin D treatment in AS patients, systematic screening and treatment for vitamin D deficiency of all AS patients are not feasible as yet. This stresses the need for further extensive well-designed research to prove vitamin D efficacy in AS beyond bone protection. And if utility is proven, personalized treatment regimes, duration of treatment, and threshold values for vitamin D should be provided.
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Patients with Ankylosing Spondylitis continue to have low Vitamin D - March 2021

Hypovitaminosis D in Patients with Ankylosing Spondylitis: Frequency and Consequences
Curr Rheumatol Rev. 2021 Mar 8. doi: 10.2174/1573397117666210308122515
Gehan Elolemy 1, Waleed Hassan 1, Mohamed Nasr 2, Eman Baraka 1

Objectives: Was to assess the frequency of hypovitaminosis D in patients with ankylosing spondylitis (AS) compared to healthy controls and to evaluate its association with disease activity, structural damage and bone mineral density (BMD).

Methods: Serum 25(OH) D in 30 AS male patients was compared to 30 matched healthy controls. AS disease activity was assessed using AS Disease Activity Score and C - reactive protein (ASDAS-CRP). Bath AS Functional Index (BASFI) and Bath AS Metrology Index (BASMI) were used to assess the functional impairment and the spinal mobility respectively. Radiological damage was scored according to modified Stoke AS Spine Score (mSASSS) and BMD was measured in the lumbar spine and femoral neck.

Results: The mean serum 25(OH)D levels in AS patients were significantly lower compared to healthy controls
(27.73 ± 14.27 vs. 38.46 ± 8.11ng/ml, P <0.001).
Among the patients, 60% exhibited hypovitaminosis D. AS patients with hypovitaminosis D had significantly higher ASDAS-CRP (p<0.001), BASFAI (p=0.0003) and mSASSS (p=0.04) scores. Additionally, BMD and Z scores at lumbar and femoral sites were significantly reduced in the patients with hypovitaminosis D (P < 0.05). Serum 25(OH)D was positively correlated with BMD (lumbar and femoral; p=0.002 and p=0.01 respectively) and Z scores (lumbar and femoral; p<0.001and p=0.01 respectively), whereas, negatively correlated with ASDAS-CRP (p<0.001), BASFI (p<0.001), mSASSS (p=0.003). ASDAS -CRP was the only significant predictor of hypovitaminosis D in AS patients.

Conclusions: hypovitaminosis D is prevalent among AS patients and is associated with increased risk of active disease, impaired function, radiographic severity and bone mineral loss. Future studies with larger sample size are recommended to assess the impact of vitamin D deficiency on radiological progression in AS and to address whether or not vitamin D supplementation will help control active disease.

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Males with Ankylosing Spondylitis having <10ng of vitamin D had a 2.2 X higher risk of dying - May 2020

Low Vitamin D Levels Predict Mortality in Ankylosing Spondylitis Patients: A Nationwide Population-Based Cohort Study
Nutrients, 12 May 2020, 12(5) DOI: 10.3390/nu12051400
Ben-Shabat N1, Watad A1, Shabat A2, Bragazzi NL3, Comaneshter D4, Cohen AD4, Amital H1

In this study, we aimed to examine the effect of vitamin D deficiency on all-cause mortality in ankylosing spondylitis (AS) patients and in the general population. This is a retrospective-cohort study based on the electronic database of the largest health-maintenance organization in Israel. AS patients who were first diagnosed between 2002-2007 were included. Controls were matched by age, gender and enrollment-time. Follow-up continued until death or end of study follow-up on 1 July 2019. Laboratory measures of serum 25-hydroxyvitamin-D levels during the entire follow-up period were obtained. A total of 919 AS patients and 4519 controls with a mean time of follow-up of 14.3 years were included. The mean age at the time of enrollment was 52 years, and 22% of them were females.
AS was associated with a higher proportion of vitamin D deficiency (odds ratio 1.27 [95% confidence-interval (CI) 1.03-1.58]). In AS patients, insufficient levels of vitamin D (< 30 ng/mL) were significantly associated with increased incidence of all-cause mortality (hazard ratio (HR) 1.59 [95% CI 1.02-2.50]).
This association was more prominent with the decrease in vitamin D levels (

  • < 20 ng/mL, HR 1.63 [95% CI 1.03-2.60];
  • <10 ng/mL, HR 1.79 [95% CI 1.01-3.20]) and among

male patients (

  • < 30 ng/mL, HR 2.11 [95% CI 1.20-3.72];
  • <20 ng/mL, HR 2.12 95% CI 1.19-3.80;
  • <10 ng/mL, HR 2.23 [95% CI 1.12-4.43]).

However, inadequate levels of vitamin D among controls were not associated with an increased all-cause mortality. Our study has shown that vitamin D deficiency is more common in AS patients than controls and is linked to an increased risk for all-cause mortality. These results emphasize the need for randomized-controlled trials to evaluate the benefits of vitamin D supplementation as a secondary prevention of mortality in patients with chronic inflammatory rheumatic disease.
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AS related to low Vitamin D - Sept 2018

Vitamin D levels in patients with ankylosing spondylitis: Is it related to disease activity?
Pak J Med Sci. 2018 Sep-Oct;34(5):1209-1214. doi: 10.12669/pjms.345.15739.
Kocyigit BF1, Akyol A2.
1 Dr. Burhan Fatih Kocyigit, Dept of Physical Medicine and Rehabilitation, Kahramanmaras Sutcu Imam U. School of Medicine, Kahramanmaras, Turkey.
2 Dr. Ahmet Akyol, Department of Physical Medicine and Rehabilitation, Nizip State Hospital.

OBJECTIVE: Ankylosing Spondylitis (AS) is an inflammatory rheumatic disease that mainly affects the axial spine. Osteopenia and osteoporosis are the main complications of AS. Vitamin D has functions on the immune system. In this study, we aimed to compare vitamin D levels and Bone Mineral Density (BMD) values between AS patients and controls.

METHODS: A total of 68 patients with axial AS and 34 healthy controls were enrolled in this study conducted between March 2018 and May 2018. Vitamin D concentrations, BMD values, disease activity, back mobility, functionality and radiologic damage were evaluated.

RESULTS: Vitamin D concentrations, the total BMD-femur and BMD-femur neck values were significantly lower in AS patients (p = 0.001, p = 0.011 and p = 0.003). No significant correlations were detected between vitamin D levels and BMD-femur total, BMD-femur neck values, disease activity, back mobility, functionality and radiologic damage scores (p > 0.05). Disease activity parameters were significantly and negatively correlated with total BMD-femur and BMD-femur neck values (p < 0.05).

CONCLUSION: Our study demonstrates that AS patients have lower vitamin D levels, total BMD-femur and BMD-femur neck values. Higher disease activity increases bone loss in AS. Regular measurement of BMD and vitamin D should be kept in mind when planning a treatment in AS.
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Higher Vitamin D associated with less risk of AS - review & meta-analysis Sept 2014

Vitamin D in ankylosing spondylitis: Review and meta-analysis.
Clin Chim Acta. 2014 Sep 5. pii: S0009-8981(14)00392-1. doi: 10.1016/j.cca.2014.08.040. [Epub ahead of print]
Cai G1, Wang L1, Fan D1, Xin L1, Liu L1, Hu Y1, Ding N1, Xu S2, Xia G1, Jin X3, Xu J2, Zou Y1, Pan F4.
   PDF is available at deepdyve.com and PDF is available free at Sci-Hub  10.1016/j.cca.2014.08.040

BACKGROUND:
The role of vitamin D in ankylosing spondylitis (AS) is largely unknown, this paper aims to examine the association between serum vitamin D levels and susceptibility and disease activity of AS.
METHODS:
We searched the relevant literatures in PubMed, Elsevier Science Direct, Chinese Biomedical Database (CBM), Chinese National Knowledge Infrastructure (CNKI) and Wanfang (Chinese) Database published before June 2014. Eight independent case-control studies with a total of 533 AS patients and 478 matching controls were selected into this meta-analysis. Standard mean differences (SMDs) with 95% confidence intervals (CIs) were used to assess the levels of serum vitamin D, parathyroid hormone (PTH), serum calcium and alkaline phosphatase (ALP) in cases and controls, respectively. Correlation coefficients (COR) have been performed to value the correlationship between vitamin D and disease activity (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)) of AS patients.
RESULTS:
Meta-analyses results suggested that vitamin D may play a protective role in AS. (For total vitamin D: SMD=-0.71, P<0.001; for 25OHD: SMD=-0.66, P=0.002; for 1,25OHD: SMD=-0.72, P=0.19). Differences in PTH and serum calcium levels were not significant in AS (SMD=-0.10, P=0.67; SMD=0.12, P=0.17 respectively), while ALP was associated with AS susceptibility (SMD=0.20, P=0.04).

Relationship between serum vitamin D levels and disease activity were statistically significant except for 25OHD versus (vs.) CRP or BASDAI (for CRP vs. 25OHD: COR=-0.22, P=0.08; for BASDAI vs. 25OHD: COR=-0.20, P=0.06, respectively).
CONCLUSION:
The higher levels of serum vitamin D were associated with a decreased risk of AS, and showed an inverse relationship with AS activity.

PMID: 25199851

Sponsdyloarthritis is 2.1 X more likely if Vitamin D Deficiency - Nov 2017

Vitamin D status in spondyloarthritis: results of the ASAS-COMOSPA international study.
Clin Exp Rheumatol. 2017 Nov 16. [Epub ahead of print]
Fernandes S1, Etcheto A2, van der Heijde D3, Landewé R4, van den Bosch F5, Dougados M2, Moltó A2.
1 Paris Descartes University, Rheumatology Department, Cochin Hospital, AP-HP, France; and Rheumatology and Metabolic Bone Diseases Department, Santa Maria Hospital, CHLN, Lisbon Academic Medical Centre, Lisbon, Portugal. silvia_tfernandes@yahoo.com.
2 Paris Descartes University, Rheumatology Department, Cochin Hospital, AP-HP; and INSERM (U1153): Clinical Epidemiology and Biostatistics, PRES Sorbonne Paris-Cité, France.
3 LUMC, Leiden, The Netherlands.
4 ARC, Amsterdam and Zuyderland Hospital Heerlen, The Netherlands.
5 Ghent University Hospital, Belgium.

OBJECTIVES:
Spondyloarthritis (SpA) encompasses both bone production and bone loss, and the latter is particularly linked to inflammation. Vitamin D deficiency has been associated with several inflammatory conditions (i.e. cardiovascular disease, rheumatoid arthritis), but it has been poorly evaluated in SpA patients. We aimed to a) describe the prevalence of vitamin D deficiency in SpA patients worldwide; b) compare SpA patients with and without vitamin D deficiency in terms of disease phenotype, activity severity and comorbidities.

METHODS: This is an ancillary study of the ASAS-COMOSPA study initiative, an international cross-sectional study of patients with SpA. Demographics, patients' phenotype, disease activity/severity measures and comorbidities were assessed. Serum 25-hydroxyvitamin D (25OHD) deficiency was defined as <20 ng/mL (<50 nmol/L).

STATISTICAL ANALYSIS: a) prevalence of vitamin D deficiency; b) comparison of the disease presentation/activity/severity and comorbidities in the group of patients with and without vitamin D deficiency by bi-variable and multivariable analysis.

RESULTS: Vitamin D deficiency was observed in 527(51.2%) of the 1030 patients with available data who were not receiving any supplementation. Vitamin D deficiency was independently associated with the presence of radiographic sacroiliitis (OR=2.1 [95%CI1.3; 3.3]) and a 25OHD measured in winter and spring (OR=1.88 [95%CI 1.2; 2.9]). No independent association between vitamin D deficiency and comorbidities was found.

CONCLUSIONS: This study suggests that vitamin D deficiency is common in SpA worldwide and is associated with season but also with more severe forms of SpA.

PMID: 29148411

Decreased plasma vitamin d levels in patients with undifferentiated spondyloarthritis and ankylosing spondylitis - 2013

Intern Med. 2013;52(3):339-44. Epub 2013 Feb 1.
Erten S, Kucuksahin O, Sahin A, Altunoglu A, Akyol M, Koca C.
Department of Rheumatology, Atatürk Education and Research Hospital, Turkey.

Objective The aim of the present study was to evaluate the plasma vitamin D (vit D) levels and their association with the disease activity in patients with ankylosing spondylitis (AS) and undifferentiated spondyloarthritis (uSpA) compared with healthy populations. Methods This study included 161 spondyloarthritis patients (113 uSpA patients and 48 AS patients) attending our rheumatology out-patient clinic, along with 92 controls.

Results The plasma vit D levels were 18 μg/L (8-38) in the AS group, 20 μg/L (4-92.3) in the uSpA group and 24.3 μg/L (7.2-76.8) in the control group. The plasma vit D levels of the AS patients were significantly lower than those of the patients in the control group (p=0.004). The men in the AS group had significanly lower vit D levels than those in the control group (p=0.005). On the other hand, the women in the uSpA group had significanly lower vit D levels than those in the control group (p=0.011). The vit D levels were inversely related to both erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in the AS patients (p=0.002, R=-0.428; p<0.001, R=-0.592, respectively). This correlation was not demonstrated in the uSpA patients. The vit D levels were not found to correlate with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) levels in either the AS or uSpA patients.

Conclusion 25-hydroxy-vit D deficiency is frequently observed in patients with SpAs. In this study, vit D deficiency was much more prominent in the male AS patients. On the other hand, among women, the uSpA patients exhibited much more prominent vit D deficiency than the control group subjects. The acute phase response may inversely affect the vit D levels in AS patients.

PMID: 23370741

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Systematic review of association between vitamin D levels and susceptibility and disease activity of ankylosing spondylitis - 2014

Rheumatology (2014); doi: 10.1093/rheumatology/keu042; published online: April 4, 2014
Sizheng Zhao1, Stephen J Duffield2, Robert J Moots1 and Nicola J Goodson1
1Department of Rheumatology, Aintree University Hospital and 2School of Medical Education, University of Liverpool, Liverpool, UK.
Correspondence to: Nicola Goodson, Department of Rheumatology, Clinical Sciences Centre, Aintree University Hospital, Longmoor Lane, Liverpool L9 7AL, UK. E-mail: ngoodson@liverpool.ac.uk
Submitted 4 October 2013 revised version accepted 29 January 2014

Objectives. Vitamin D appears to have significant effects on both innate and acquired immunity and deficiency may be associated with both susceptibility and disease severity in some autoimmune conditions. There has been little focus on the potential immunomodulatory role of vitamin D in AS. This study systematically reviews the evidence for an association between vitamin D deficiency and disease susceptibility and severity in AS.

Methods. A systematic review was conducted using Medline, EMBASE, Web of Science and conference abstracts of the European League Against Rheumatism (2002–13), British Society for Rheumatology (1993–2013) and ACR (2006–13).

Results. Fifteen original articles and five conference abstracts met the criteria for inclusion. All were cross-sectional in design. Seven of 11 studies identified lower concentrations of 25-hydroxyvitamin D (25OHD) in AS patients compared with healthy controls. A significant inverse correlation between 25OHD and disease activity was observed in 5 of 11 studies. The majority of studies that failed to demonstrate significant findings used inappropriate statistical methods.

Conclusion. Cross-sectional studies using appropriate statistical analyses have highlighted that AS is associated with lower vitamin D concentrations. Within groups of AS patients there is some evidence that low vitamin D concentrations are associated with higher disease activity. However, there are insufficient published data to support an immunomodulatory role for vitamin D in AS. Further study with a longitudinal design is required to understand whether optimizing vitamin D in AS has potential as a disease-modifying intervention.

PDF is available free at Sci-Hub   10.1093/rheumatology/keu042

4 out of 7 studies found AS associated with low vitamin D - July 2014

Vitamin D levels in ankylosing spondylitis: Does deficiency correspond to disease activity?
Rev. Bras. Reumatol. vol.54 no.4 São Paulo July/Aug. 2014; http://dx.doi.org/10.1016/j.rbr.2014.03.027
BRIEF COMMUNICATION

Gabriel G. Pokhai*, Sabiha Bandagi, Adriana Abrudescu
Department of Medicine, Division of Rheumatology, Icahn School of Medicine at Mount Sinai, Queens Hospital Center, New York, NY, USA

Ankylosing spondylitis (AS) is an inflammatory disorder that presents with arthritis of the axial skeleton, including sacroiliac joints. Vitamin D is a secosteroid hormone with a long-established role in calcium and phosphate homeostasis, and in the regulation of bone formation and resorption. It is now known that vitamin D plays an immunosuppressive role in the body, and there is interest of late in the role of vitamin D in autoimmune diseases. Inflammation may be responsible for some of the loss of bone mineral density seen in AS. We reviewed the literature for studies assessing vitamin D level as a marker of AS disease activity and those examining vitamin D levels in AS in comparison to healthy controls. Four of 7 studies found a significant negative correlation between vitamin D levels ALD

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