Short-term Variability of Vitamin D-Related Biomarkers.
BACKGROUND
Quantifying the variability of biomarkers is important, as high within-person variability can lead to misclassification of individuals. Short-term variability of important markers of vitamin D metabolism is relatively unknown.


METHODS
A repeatability study was conducted in 160 Atherosclerosis Risk in Communities study participants (60% female, 28% black, mean age 76 years). Fasting serum was drawn at 2 time points, a median of 6 (range 3-13) weeks apart. Vitamin D binding protein (VDBP) and 25-hydroxyvitamin D [25(OH)D] were measured by LC-MS, fibroblast growth factor (FGF23) and parathyroid hormone (PTH) by enzyme-linked immunoassay, and calcium and phosphorus by Roche Cobas 6000. Free and bioavailable 25(OH)D were calculated. We calculated the within-person CV (CVW), intraclass correlation coefficient (ICC), Spearman rank correlation coefficient (r), and percent reclassified.


RESULTS
The CVWwas lowest for calcium (2.0%), albumin (3.6%), 25(OH)D (6.9%), VDBP (7.0%) and phosphorus (7.6%); intermediate for free 25(OH)D (9.0%) and bioavailable 25(OH)D (9.9%); and highest for PTH (16.7%) and FGF23 (17.8%). Reclassification was highest for PTH, VDBP, and phosphorus (all 7.5%). The ICC and r were highest (≥0.80) for 25(OH)D, free 25(OH)D, bioavailable 25(OH)D and PTH, but somewhat lower (approximately 0.60-0.75) for the other biomarkers.


CONCLUSIONS
Six-week short-term variability, as assessed by CVW, was quite low for VDBP, calcium and phosphorus, but fairly high for FGF23 and PTH. As such, multiple measurements of FGF23 and PTH may be needed to minimize misclassification. These results provide insight into the extent of potential misclassification of vitamin D markers in research and clinical settings.
Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN; Lutsey@umn.edu.
Pamela L
PL
Lutsey
Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY.
Christina M
CM
Parrinello
Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN.
Jeffrey R
JR
Misialek
Department of Laboratory Medicine, University of Washington, Seattle, WA.
Andy N
AN
Hoofnagle
Department of Laboratory Medicine, University of Washington, Seattle, WA.
Clark M
CM
Henderson
Department of Laboratory Medicine, University of Washington, Seattle, WA.
Thomas J
TJ
Laha
Division of Cardiology, Johns Hopkins University, Baltimore, MD.|Department of Epidemiology and the Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
Erin D
ED
Michos
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN.
John H
JH
Eckfeldt
Department of Epidemiology and the Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
Elizabeth
E
Selvin
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D005260:Female; D000089703:Fibroblast Growth Factor-23; D006801:Humans; D008297:Male; D008875:Middle Aged; D014807:Vitamin D / Q000097:blood* / Q000378:metabolism*
D015415:Biomarkers; C000717427:FGF23 protein, human; D014807:Vitamin D; D000089703:Fibroblast Growth Factor-23
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