Vitamin D status and risk of rheumatoid arthritis: systematic review and meta-analysis

Abstract Background Vitamin D is important for immunomodulation and may play a role in autoimmune diseases. Studies have reported a high prevalence of vitamin D deficiency in rheumatoid arthritis (RA) patients, and vitamin D status, assessed by circulating 25-hydroxyvitamin D [25(OH)D] concentration...

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Main Authors: Joanna L. Clasen, Rachel Cole, Dagfinn Aune, Edward Sellon, Alicia K. Heath
Format: Article
Language:English
Published: BMC 2023-03-01
Series:BMC Rheumatology
Subjects:
Online Access:https://doi.org/10.1186/s41927-023-00325-y
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author Joanna L. Clasen
Rachel Cole
Dagfinn Aune
Edward Sellon
Alicia K. Heath
author_facet Joanna L. Clasen
Rachel Cole
Dagfinn Aune
Edward Sellon
Alicia K. Heath
author_sort Joanna L. Clasen
collection DOAJ
description Abstract Background Vitamin D is important for immunomodulation and may play a role in autoimmune diseases. Studies have reported a high prevalence of vitamin D deficiency in rheumatoid arthritis (RA) patients, and vitamin D status, assessed by circulating 25-hydroxyvitamin D [25(OH)D] concentration, is inversely associated with RA disease activity. However, it is unclear whether vitamin D deficiency increases the risk of later developing RA. We conducted a systematic review and meta-analysis of pre-diagnostic 25(OH)D concentrations and risk of RA. Methods Medline and Embase databases were searched in December 2021 using various keywords for ‘vitamin D’, ‘rheumatoid arthritis’, and ‘prospective study’. Publications identified from the search were screened for eligibility, studies were excluded if vitamin D status was measured at or after RA diagnosis, and data were extracted from relevant articles. Bayesian meta-analysis was used to estimate the summary relative risk (RR) and 95% credible interval (CrI) for risk of RA in relation to circulating 25(OH)D concentrations, as well as the between-study heterogeneity. Results The search strategy yielded 908 records, of which 4 publications reporting on 7 studies, involving a total of 15,604 participants and 1049 incident RA cases, were included in the meta-analysis. There was no suggestion of an association between 25(OH)D concentration and subsequent risk of RA. The pooled RR per 25 nmol/L increment in 25(OH)D was 0.96 (95% CrI 0.82–1.13; I 2 = 52%). No associations were evident in men (RR = 1.02, 95% CrI 0.65–1.61; I 2 = 77%, 2 studies) or women (RR = 0.94, 95% CrI 0.73–1.22; I 2 = 71%, 4 studies). Conclusions This systematic review and meta-analysis did not identify evidence of an association between 25(OH)D and RA risk, but there was notable between-study heterogeneity and a lack of precision. Investigations in large-scale prospective studies with long follow-up or suitably designed Mendelian randomisation studies with consideration of potential non-linear relationships are needed to determine whether vitamin D is involved in RA aetiology.
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spelling doaj.art-0d972718e7524c5cb0ee6ffefa12bcf82023-03-22T12:39:58ZengBMCBMC Rheumatology2520-10262023-03-017111410.1186/s41927-023-00325-yVitamin D status and risk of rheumatoid arthritis: systematic review and meta-analysisJoanna L. Clasen0Rachel Cole1Dagfinn Aune2Edward Sellon3Alicia K. Heath4Department of Epidemiology and Biostatistics, School of Public Health, Imperial College LondonDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College LondonDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College LondonOxford University Hospitals NHS Foundation TrustDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College LondonAbstract Background Vitamin D is important for immunomodulation and may play a role in autoimmune diseases. Studies have reported a high prevalence of vitamin D deficiency in rheumatoid arthritis (RA) patients, and vitamin D status, assessed by circulating 25-hydroxyvitamin D [25(OH)D] concentration, is inversely associated with RA disease activity. However, it is unclear whether vitamin D deficiency increases the risk of later developing RA. We conducted a systematic review and meta-analysis of pre-diagnostic 25(OH)D concentrations and risk of RA. Methods Medline and Embase databases were searched in December 2021 using various keywords for ‘vitamin D’, ‘rheumatoid arthritis’, and ‘prospective study’. Publications identified from the search were screened for eligibility, studies were excluded if vitamin D status was measured at or after RA diagnosis, and data were extracted from relevant articles. Bayesian meta-analysis was used to estimate the summary relative risk (RR) and 95% credible interval (CrI) for risk of RA in relation to circulating 25(OH)D concentrations, as well as the between-study heterogeneity. Results The search strategy yielded 908 records, of which 4 publications reporting on 7 studies, involving a total of 15,604 participants and 1049 incident RA cases, were included in the meta-analysis. There was no suggestion of an association between 25(OH)D concentration and subsequent risk of RA. The pooled RR per 25 nmol/L increment in 25(OH)D was 0.96 (95% CrI 0.82–1.13; I 2 = 52%). No associations were evident in men (RR = 1.02, 95% CrI 0.65–1.61; I 2 = 77%, 2 studies) or women (RR = 0.94, 95% CrI 0.73–1.22; I 2 = 71%, 4 studies). Conclusions This systematic review and meta-analysis did not identify evidence of an association between 25(OH)D and RA risk, but there was notable between-study heterogeneity and a lack of precision. Investigations in large-scale prospective studies with long follow-up or suitably designed Mendelian randomisation studies with consideration of potential non-linear relationships are needed to determine whether vitamin D is involved in RA aetiology.https://doi.org/10.1186/s41927-023-00325-yVitamin D25-hydroxyvitamin DRheumatoid arthritisAutoimmune disease
spellingShingle Joanna L. Clasen
Rachel Cole
Dagfinn Aune
Edward Sellon
Alicia K. Heath
Vitamin D status and risk of rheumatoid arthritis: systematic review and meta-analysis
BMC Rheumatology
Vitamin D
25-hydroxyvitamin D
Rheumatoid arthritis
Autoimmune disease
title Vitamin D status and risk of rheumatoid arthritis: systematic review and meta-analysis
title_full Vitamin D status and risk of rheumatoid arthritis: systematic review and meta-analysis
title_fullStr Vitamin D status and risk of rheumatoid arthritis: systematic review and meta-analysis
title_full_unstemmed Vitamin D status and risk of rheumatoid arthritis: systematic review and meta-analysis
title_short Vitamin D status and risk of rheumatoid arthritis: systematic review and meta-analysis
title_sort vitamin d status and risk of rheumatoid arthritis systematic review and meta analysis
topic Vitamin D
25-hydroxyvitamin D
Rheumatoid arthritis
Autoimmune disease
url https://doi.org/10.1186/s41927-023-00325-y
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