Changes in Vitamin D-Related Mineral Metabolism After Induction With Anti-Tumor Necrosis Factor-α Therapy in Crohn's Disease

Context: Preclinical studies suggest that TNF-alpha suppresses PTH synthesis, inhibits renal 1 alpha-hydroxylase activity, and impairs fibroblast growth factor 23 (FGF23) degradation. The impact of inflammation on vitamin D and mineral metabolism has not been well-characterized in Crohn's disease (CD). Objective: The objective of the study was to assess short-term changes in vitamin D-related mineral metabolism in CD after anti-TNF-alpha induction therapy. Design/Participants: Eighty-seven CD participants, aged 5-39 years, were assessed at the initiation of anti-TNF-alpha therapy and 10 weeks later. Outcomes: Indices of clinical disease activity and serum concentrations of vitamin D metabolites, vitamin D-binding protein (DBP), calcium, PTH, FGF23, IL-6, and TNF-alpha were measured at each visit. A multivariable generalized estimating equation (GEE) regression analysis was used to examine the correlates of PTH and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] concentrations at each visit. Results: After anti-TNF-alpha therapy, cytokines and inflammatory markers [IL-6, TNF-alpha, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP)] concentrations decreased (all P < .0001), and PTH and 1,25(OH)(2)D concentrations increased (median 21 vs 30 pg/mL, P < .0001, and median 41.7 vs 48.1 pg/mL, P = .014, respectively). Levels of 25-hydroxyvitamin D [25(OH)D], 24,25-dihydroxyvitamin D, DBP, and FGF23 did not change. In GEE analyses, higher IL-6, TNF-alpha, ESR, and CRP were associated with lower PTH concentrations (all P < .001), adjusted for corrected calcium and 25(OH)D levels. Higher PTH was associated with higher 1,25(OH)(2)D concentrations (P < .001) at each visit, independent of 25(OH)D concentrations. Higher levels of all inflammatory markers were associated with lower 1,25(OH)(2)D concentrations (all P < .05). However, when PTH was added to these models, the inflammatory markers (with the exception of CRP) were no longer significantly associated with 1,25(OH)(2)D. Conclusions: Greater inflammation was associated with lower PTH and 1,25(OH)(2)D concentrations. After anti-TNF-alpha induction, PTH and 1,25(OH)(2)D concentrations increased without concomitant changes in 25(OH)D and FGF23, consistent with effects of inflammation on PTH and thereby renal conversion of 25(OH)D to 1,25(OH)(2)D.