title: Assay variation confounds the diagnosis of hypovitaminosis D: a call for standardization.
abstract: Endemic hypovitaminosis D contributes to osteoporosis development. However, variation in 25-hydroxyvitamin D (25OHD) measurement is reported and confounds the diagnosis of vitamin D insufficiency/deficiency. This report emphasizes the marked variability observed in serum 25OHD measurements between laboratories.Initially, postmenopausal women had serum 25OHD determinations: 42 in laboratory A, 20 in laboratory B. Their mean (sem) serum 25OHD concentrations were 46 (2.1) and 21 (2.3) ng/ml in laboratories A and B, respectively. Furthermore, there was little overlap in serum 25OHD among these clinically similar individuals. Specifically, 17% of those measured in laboratory A but 90% in laboratory B were below an arbitrary threshold value of 32 ng/ml.Subsequently, serum was obtained from 10 healthy adults. Two aliquots from each individual, one of which was spiked with 20 ng/ml 25OHD, were sent to six laboratories. Substantial variability was noted between these six laboratories. The mean serum 25OHD concentration ranged from 17.1-35.6 ng/ml. Similarly, the mean increase produced by spiking with 20 ng/ml ranged from 7.7-18.0 ng/ml.In conclusion, 25OHD assays yield markedly differing results; whether an individual is found to have low or normal vitamin D status is a function of the laboratory used. If the medical community is to make progress in correcting widespread hypovitaminosis D, 25OHD measurement must be standardized.
authors.affiliation: Department of Medicine, Osteoporosis Clinical Center and Research Program, University of Wisconsin-Madison, 2870 University Avenue, Suite 100, Madison, WI 53705, USA. nbinkley@facstaff.wisc.edu
authors.forename: N
authors.initials: N
authors.lastname: Binkley
authors.forename: D
authors.initials: D
authors.lastname: Krueger
authors.forename: C S
authors.initials: CS
authors.lastname: Cowgill
authors.forename: L
authors.initials: L
authors.lastname: Plum
authors.forename: E
authors.initials: E
authors.lastname: Lake
authors.forename: K E
authors.initials: KE
authors.lastname: Hansen
authors.forename: H F
authors.initials: HF
authors.lastname: DeLuca
authors.forename: M K
authors.initials: MK
authors.lastname: Drezner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019411:Clinical Laboratory Techniques / Q000592:standards; D005260:Female; D006403:Hematologic Tests / Q000592:standards*; D006801:Humans; D008875:Middle Aged; D009994:Osmolar Concentration; D012015:Reference Standards; D015203:Reproducibility of Results; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood* / Q000175:diagnosis*
chemical_list: D014807:Vitamin D; C104450:25-hydroxyvitamin D