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

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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