Vitamin D association with systemic sclerosis and its clinical features: A systematic review, meta-analysis, and meta-regression

Abstract

Objectives: The aim of this review was to summarize existing data on the contribution of Vitamin D level and/or deficiency/insufficiency to systemic sclerosis susceptibility and its clinical features. Methods: An electronic literature search for eligible studies among all papers published prior to 30 June 2024 was conducted through PubMed, EMBASE, Web of science, and Scopus databases. Meta-analyses estimating pooled raw mean differences, odds ratios, and Pearson r together with subgroup analyses and meta-regressions were performed for the association of Vitamin D with susceptibility to systemic sclerosis and disease presentation. Results: Combined analysis revealed a significant decrease in Vitamin D level in systemic sclerosis patients comparatively to healthy controls, with raw mean differences 95% CI = −11.68 [−15.43 to −7.92] ng/mL, p < 1 E-10. Likewise, Vitamin D insufficiency (Vitamin D < 30 ng/mL) and deficiency (<10 ng/mL) were significantly associated with systemic sclerosis; odds ratios 95% CI = 3.58 [2.59–4.95], p < 1 E-10 and odds ratios 95% CI = 7.67 [3.97–14.83], p < 1 E-10, respectively. Moreover, decreased Vitamin D level was significantly associated with interstitial lung disease occurrence (raw mean differences 95% CI = −3.61 [−6.93 to −0.3], p = 0.003), while Vitamin D deficiency was associated with increased systolic pulmonary arterial pressure, raw mean differences (95% CI = 4.17 [1.44–6.89], p = 0.003). Besides, Vitamin D level was negatively correlated with the modified Rodnan skin score, r (95% CI = −0.26 [−0.44 to −0.08], p = 0.004). Conversely, Vitamin D level was significantly increased in systemic sclerosis patients with cutaneous calcinosis, raw mean differences (95% CI = 4.18 [1.07–7.28], p = 0.008). Conclusion: This meta-analysis showed that decreased Vitamin D level was associated with susceptibility to systemic sclerosis, interstitial lung disease occurrence, increased systolic pulmonary arterial pressure, and higher modified Rodnan skin score. Conversely, calcinosis was found to be associated with increased Vitamin D level. Registration: This review has been registered on PROSPERO: CRD42024565045, available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024565045