Associations of total and free 25OHD and 1,25(OH)2D with serum markers of inflammation in older men

P. Srikanth, R. F. Chun, M. Hewison, J. S. Adams, R. Bouillon, D. Vanderschueren, Nancy E Lane, P. M. Cawthon, T. Dam, E. Barrett-Connor, L. B. Daniels, J. M. Shikany, M. L. Stefanick, J. A. Cauley, E. S. Orwoll, C. M. Nielson

Research output: Contribution to journalArticle

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Abstract

Summary: 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. Introduction: 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. Methods: 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. Results: 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). Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)2291-2300
Number of pages10
JournalOsteoporosis International
Volume27
Issue number7
DOIs
StatePublished - Jul 1 2016

Fingerprint

Free Association
Interleukin-6
Biomarkers
Inflammation
Vitamin D
Tumor Necrosis Factor-alpha
Confidence Intervals
Interleukin-10 Receptors
Vitamin D-Binding Protein
Osteoporotic Fractures
Serum
C-Reactive Protein
Carrier Proteins
Odds Ratio
Population

Keywords

  • Elderly
  • Free 1,25(OH)D
  • Free 25OHD
  • Inflammation
  • Men
  • Total 1,25(OH)D
  • Total 25OHD

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

Cite this

Srikanth, P., Chun, R. F., Hewison, M., Adams, J. S., Bouillon, R., Vanderschueren, D., ... Nielson, C. M. (2016). Associations of total and free 25OHD and 1,25(OH)2D with serum markers of inflammation in older men. Osteoporosis International, 27(7), 2291-2300. https://doi.org/10.1007/s00198-016-3537-3

Associations of total and free 25OHD and 1,25(OH)2D with serum markers of inflammation in older men. / Srikanth, P.; Chun, R. F.; Hewison, M.; Adams, J. S.; Bouillon, R.; Vanderschueren, D.; Lane, Nancy E; Cawthon, P. M.; Dam, T.; Barrett-Connor, E.; Daniels, L. B.; Shikany, J. M.; Stefanick, M. L.; Cauley, J. A.; Orwoll, E. S.; Nielson, C. M.

In: Osteoporosis International, Vol. 27, No. 7, 01.07.2016, p. 2291-2300.

Research output: Contribution to journalArticle

Srikanth, P, Chun, RF, Hewison, M, Adams, JS, Bouillon, R, Vanderschueren, D, Lane, NE, Cawthon, PM, Dam, T, Barrett-Connor, E, Daniels, LB, Shikany, JM, Stefanick, ML, Cauley, JA, Orwoll, ES & Nielson, CM 2016, 'Associations of total and free 25OHD and 1,25(OH)2D with serum markers of inflammation in older men', Osteoporosis International, vol. 27, no. 7, pp. 2291-2300. https://doi.org/10.1007/s00198-016-3537-3
Srikanth, P. ; Chun, R. F. ; Hewison, M. ; Adams, J. S. ; Bouillon, R. ; Vanderschueren, D. ; Lane, Nancy E ; Cawthon, P. M. ; Dam, T. ; Barrett-Connor, E. ; Daniels, L. B. ; Shikany, J. M. ; Stefanick, M. L. ; Cauley, J. A. ; Orwoll, E. S. ; Nielson, C. M. / Associations of total and free 25OHD and 1,25(OH)2D with serum markers of inflammation in older men. In: Osteoporosis International. 2016 ; Vol. 27, No. 7. pp. 2291-2300.
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abstract = "Summary: 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. Introduction: 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. Methods: 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. Results: 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). Conclusions: 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.",
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TY - JOUR

T1 - Associations of total and free 25OHD and 1,25(OH)2D with serum markers of inflammation in older men

AU - Srikanth, P.

AU - Chun, R. F.

AU - Hewison, M.

AU - Adams, J. S.

AU - Bouillon, R.

AU - Vanderschueren, D.

AU - Lane, Nancy E

AU - Cawthon, P. M.

AU - Dam, T.

AU - Barrett-Connor, E.

AU - Daniels, L. B.

AU - Shikany, J. M.

AU - Stefanick, M. L.

AU - Cauley, J. A.

AU - Orwoll, E. S.

AU - Nielson, C. M.

PY - 2016/7/1

Y1 - 2016/7/1

N2 - Summary: 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. Introduction: 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. Methods: 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. Results: 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). Conclusions: 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.

AB - Summary: 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. Introduction: 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. Methods: 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. Results: 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). Conclusions: 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.

KW - Elderly

KW - Free 1,25(OH)D

KW - Free 25OHD

KW - Inflammation

KW - Men

KW - Total 1,25(OH)D

KW - Total 25OHD

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