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- Title
Changes in vitamin D-related mineral metabolism after induction with anti-tumor necrosis factor-α therapy in Crohn's disease.
- Authors
Augustine, Marianne V; Leonard, Mary B; Thayu, Meena; Baldassano, Robert N; de Boer, Ian H; Shults, Justine; Denson, Lee A; DeBoer, Mark D; Herskovitz, Rita; Denburg, Michelle R
- Abstract
<bold>Context: </bold>Preclinical studies suggest that TNF-α suppresses PTH synthesis, inhibits renal 1α-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).<bold>Objective: </bold>The objective of the study was to assess short-term changes in vitamin D-related mineral metabolism in CD after anti-TNF-α induction therapy.<bold>Design/participants: </bold>Eighty-seven CD participants, aged 5-39 years, were assessed at the initiation of anti-TNF-α therapy and 10 weeks later.<bold>Outcomes: </bold>Indices of clinical disease activity and serum concentrations of vitamin D metabolites, vitamin D-binding protein (DBP), calcium, PTH, FGF23, IL-6, and TNF-α 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)2D] concentrations at each visit.<bold>Results: </bold>After anti-TNF-α therapy, cytokines and inflammatory markers [IL-6, TNF-α, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP)] concentrations decreased (all P < .0001), and PTH and 1,25(OH)2D 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-α, 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)2D 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)2D 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)2D.<bold>Conclusions: </bold>Greater inflammation was associated with lower PTH and 1,25(OH)2D concentrations. After anti-TNF-α induction, PTH and 1,25(OH)2D 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)2D.
- Publication
Journal of Clinical Endocrinology & Metabolism, 2014, Vol 99, Issue 6, pE991
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/jc.2013-3846