Abstract
Background: Sjögren's syndrome (SjS) is a chronic systemic autoimmune disease associated with substantial extraglandular morbidity, including osteoporosis, cardiovascular disease, and renal involvement. Vitamin D deficiency (VDD) is highly prevalent in patients with SjS and has been linked to immune dysregulation, systemic inflammation, and adverse cardiorenal outcomes in other clinical settings. However, the prognostic significance of VDD in patients with SjS and osteoporosis remains incompletely characterized. Methods: We conducted a retrospective cohort study using de-identified electronic health records from the TriNetX research network between 2010 and 2024. Adult patients with SjS and osteoporosis who had at least one serum 25-hydroxyvitamin D measurement within six months before or after cohort entry were included. VDD was defined as a serum 25-hydroxyvitamin D concentration below 20 ng/mL, and vitamin D adequacy (VDA) as a concentration of 30 ng/mL or higher. Propensity score matching was performed at a 1: 1 ratio using 95 baseline covariates. The primary outcome was all-cause mortality. Secondary outcomes included major adverse cardiovascular events (MACEs), major adverse kidney events (MAKEs), and fractures. Results: Among 19,177 eligible patients, 1218 with VDD and 7659 with VDA met the inclusion criteria. After propensity score matching, 1067 well-balanced pairs were analyzed. Over five years of follow-up, VDD was associated with higher risks of all-cause mortality, MACEs, and MAKEs compared with VDA. In contrast, fracture risk did not differ significantly between groups. Sensitivity analyses demonstrated consistent associations across analytic approaches. Conclusions: In patients with SjS and osteoporosis, VDD was associated with increased risks of mortality, MACEs, and MAKEs, but not fractures. These findings suggest that VDD may serve as a marker of a high-risk clinical phenotype and may be useful for long-term risk stratification in this vulnerable population.