title: Associations of total and free 25OHD and 1,25(OH)2D with serum markers of inflammation in older men.
abstract: Vitamin D is hypothesized to suppress inflammation. We tested total and free vitamin D metabolites and their association with inflammatory markers. Interleukin-6 levels were lower with higher 25-hydroxyvitamin D. 1,25-dihydroxyvitamin D and free 25OHD associations mirrored those of 25OHD. However, associations for the two metabolites diverged for tumor necrosis factor alpha (TNF-α) soluble receptors.
  
  
  
  Vitamin D is hypothesized to suppress inflammation, and circulating 25-hydroxyvitamin D (25OHD) and inflammatory markers are inversely correlated. However, total serum 25OHD may not be the best indicator of biologically active vitamin D.
  
  
  
  We tested serum total 25OHD, total 1,25(OH)2D, vitamin D binding protein (DBP), and estimated free 25OHD and free 1,25(OH)2D associations with inflammatory markers serum interleukin-6 (IL-6), TNF-α and their soluble receptors, interleukin-10 (IL-10), and C-reactive protein (CRP) as continuous outcomes and the presence of ≥2 inflammatory markers in the highest quartile as a dichotomous outcome, in a random subcohort of 679 men in the Osteoporotic Fractures in Men (MrOS) study.
  
  
  
  IL-6 was lower in men with higher 25OHD (-0.23 μg/mL per standard deviation (SD) increase in 25OHD, 95 % confidence intervals (CI) -0.07 to -0.38 μg/mL) and with higher 1,25(OH)2D (-0.20 μg/mL, 95 % CI -0.0004 to -0.39 μg/mL); free D associations were slightly stronger. 25OHD and DBP, but not 1,25(OH)2D, were independently associated with IL-6. TNF-α soluble receptors were inversely associated with 1,25(OH)2D but positively associated with 25OHD, and each had independent effects. The strongest association with ≥2 inflammatory markers in the highest quartile was for free 1,25(OH)2D (odds ratios (OR) 0.70, 95 % CI 0.54 to 0.89 per SD increase in free 1,25(OH)2D).
  
  
  
  Associations of 1,25(OH)2D and free 25OHD with IL-6 mirrored those of 25OHD, suggesting that 1,25(OH)2D and free D do not improve upon 25OHD in population-based IL-6 studies. However, associations for the two metabolites diverged for TNF-α soluble receptor, warranting examination of both metabolites in studies of TNF-α and its antagonists.
authors.affiliation: Department of Public Health and Preventive Medicine, Oregon Health & Science University, Portland, OR, USA.
authors.forename: P
authors.initials: P
authors.lastname: Srikanth
authors.affiliation: Department of Orthopaedic Surgery and Orthopaedic Hospital Research Center, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
authors.forename: R F
authors.initials: RF
authors.lastname: Chun
authors.affiliation: Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham, Birmingham, UK.
authors.forename: M
authors.initials: M
authors.lastname: Hewison
authors.affiliation: Department of Orthopaedic Surgery and Orthopaedic Hospital Research Center, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Adams
authors.affiliation: Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium.|Department of Endocrinology, University Hospital, Leuven, Belgium.
authors.forename: R
authors.initials: R
authors.lastname: Bouillon
authors.affiliation: Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium.|Department of Endocrinology, University Hospital, Leuven, Belgium.
authors.forename: D
authors.initials: D
authors.lastname: Vanderschueren
authors.affiliation: Division of Rheumatology, University of California Davis, Davis, CA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Lane
authors.affiliation: California Pacific Medical Center Research Institute, San Francisco, CA, USA.
authors.forename: P M
authors.initials: PM
authors.lastname: Cawthon
authors.affiliation: Department of Medicine, Division of Geriatric Medicine and Aging, Columbia University, New York, NY, USA.
authors.forename: T
authors.initials: T
authors.lastname: Dam
authors.affiliation: Division of Epidemiology, Department of Family and Preventive Medicine, University of California, San Diego, CA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Barrett-Connor
authors.affiliation: Division of Epidemiology, Department of Family and Preventive Medicine, University of California, San Diego, CA, USA.|Division of Cardiology, Department of Medicine, University of California, San Diego, CA, USA.
authors.forename: L B
authors.initials: LB
authors.lastname: Daniels
authors.affiliation: University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Shikany
authors.affiliation: Stanford Prevention Research Center, School of Medicine, Stanford University, Stanford, CA, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Stefanick
authors.affiliation: Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Cauley
authors.affiliation: Bone and Mineral Unit, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, CR113, Portland, OR, 97239, USA. orwoll@ohsu.edu.
authors.forename: E S
authors.initials: ES
authors.lastname: Orwoll
authors.affiliation: Department of Public Health and Preventive Medicine, Oregon Health & Science University, Portland, OR, USA.|Bone and Mineral Unit, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, CR113, Portland, OR, 97239, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Nielson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D006801:Humans; D007249:Inflammation / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D015415:Biomarkers; C508600:IL6 protein, human; D015850:Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D; C104450:25-hydroxyvitamin D
keywords: Elderly; Free 1,25(OH)2D; Free 25OHD; Inflammation; Men; Total 1,25(OH)2D; Total 25OHD