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The Journal of Clinical Endocrinology & Metabolism Vol. 89, No. 7 3152-3157
Copyright © 2004 by The Endocrine Society


Special Feature

Assay Variation Confounds the Diagnosis of Hypovitaminosis D: A Call for Standardization

N. Binkley, D. Krueger, C. S. Cowgill, L. Plum, E. Lake, K. E. Hansen, H. F. DeLuca and M. K. Drezner

Department of Medicine Osteoporosis Clinical Center and Research Program (N.B., D.K., C.S.C., K.E.H., M.K.D.); Institute on Aging (N.B., D.K., C.S.C., K.E.H., M.K.D.); Geriatric Research Education and Clinical Center, William S. Middleton Veterans Affairs Medical Center (M.K.D.); and Department of Biochemistry (L.P., E.L., H.F.D.), University of Wisconsin-Madison, Madison, Wisconsin 53705

Address all correspondence and requests for reprints to: Neil Binkley, M.D., 2870 University Avenue, Suite 100, Madison, Wisconsin 53705. E-mail: nbinkley{at}facstaff.wisc.edu.

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.

Abbreviation: 25OHD, 25-Hydroxyvitamin D.




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