Low vitamin D status and long-term risk of incident fibromyalgia: a propensity score-matched cohort study

Cross-sectional studies have reported lower serum vitamin D concentrations in patients with fibromyalgia, but whether vitamin D deficiency (VDD) precedes fibromyalgia onset remains uncertain. We conducted a large retrospective cohort study to evaluate the association between VDD and the long-term risk of incident fibromyalgia.

Within the TriNetX Network, we identified adults (≥18 years of age) whose serum 25-hydroxyvitamin D was below 20 ng/mL and paired them 1:1 with controls having levels ≥30 ng/mL through propensity score matching. A 1-year landmark period was applied to reduce reverse causation, and outcomes were assessed within an analytic window of up to 10 years. The primary outcome was incident fibromyalgia. The secondary outcome was chronic pain-related diagnoses. All-cause mortality was examined separately as a contextual outcome reflecting overall prognostic burden and the competing risk of death. Sensitivity, sex- and age-stratified subgroup, and severity and chronicity analyses were performed, including severe deficiency defined as 25(OH)D < 10 ng/mL and chronic deficiency defined as two serum 25-hydroxyvitamin D measurements <20 ng/mL recorded within 1 year.

After matching, 561,418 patients were included in both cohorts. VDD conferred an elevated risk of incident fibromyalgia (hazard ratio [HR], 1.63; 95% confidence interval [CI], 1.56-1.71; p < 0.001) and chronic pain-related diagnosis (HR, 1.30; 95% CI, 1.28-1.31; p < 0.001). All-cause mortality was also higher in the VDD cohort. The association with fibromyalgia was consistent across sensitivity models (HR, 1.35-1.55; all p < 0.001), present in both sexes, and stronger among adults > 65 years (HR, 1.76; p for subgroup difference <0.001). The severity and chronicity analyses also showed associations with incident fibromyalgia under the severe deficiency definition (HR, 1.89; p < 0.001) and the chronic deficiency definition (HR, 1.97; p < 0.001).

Low vitamin D status was associated with a higher long-term risk of incident fibromyalgia, with associations also observed under the severe and chronic deficiency definitions. Further prospective studies with repeated vitamin D assessments, detailed pain phenotyping, and mechanistic biomarkers are needed to clarify the clinical and biological relevance of this association.