title: Changes in vitamin D-related mineral metabolism after induction with anti-tumor necrosis factor-α therapy in Crohn's disease.
abstract: BACKGROUND
  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).
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  Eighty-seven CD participants, aged 5-39 years, were assessed at the initiation of anti-TNF-α therapy and 10 weeks later.
  
  
  RESULTS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: The Children's Hospital of Philadelphia (M.V.A., M.B.L., M.T., R.N.B., J.S., R.H., M.R.D.), Perelman School of Medicine at the University of Pennsylvania (M.B.L., R.N.B., J.S., M.R.D.), Philadelphia, Pennsylvania 19104; Kidney Research Institute, University of Washington (I.H.d.B.), Seattle, Washington 98104; Department of Pediatrics, Cincinnati Children's Hospital Medical Center (L.A.D.), Cincinnati, Ohio 45229; and Department of Pediatrics, University of Virginia Health System (M.D.D.), Charlottesville, Virginia 22908.
authors.forename: Marianne V
authors.initials: MV
authors.lastname: Augustine
authors.forename: Mary B
authors.initials: MB
authors.lastname: Leonard
authors.forename: Meena
authors.initials: M
authors.lastname: Thayu
authors.forename: Robert N
authors.initials: RN
authors.lastname: Baldassano
authors.forename: Ian H
authors.initials: IH
authors.lastname: de Boer
authors.forename: Justine
authors.initials: J
authors.lastname: Shults
authors.forename: Lee A
authors.initials: LA
authors.lastname: Denson
authors.forename: Mark D
authors.initials: MD
authors.lastname: DeBoer
authors.forename: Rita
authors.initials: R
authors.lastname: Herskovitz
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Denburg
mesh_terms: D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003424:Crohn Disease / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D000089703:Fibroblast Growth Factor-23; D006801:Humans; D060828:Induction Chemotherapy; D000069285:Infliximab; D008297:Male; D008903:Minerals / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology; D014807:Vitamin D / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; C000717427:FGF23 protein, human; D008903:Minerals; D014409:Tumor Necrosis Factor-alpha; D014807:Vitamin D; D000089703:Fibroblast Growth Factor-23; D000069285:Infliximab