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Letters to the Editor |
1 Osteoporosis Clinical Research Program, University of Wisconsin, Madison, WI
2 Medical University of South Carolina, Charleston, SC
aAddress correspondence to this author at: Osteoporosis Clinical Research Program, University of Wisconsin, 2870 University Avenue, Suite 100 Madison, WI 53705, Fax 608-265-6409; e-mail nbinkley{at}wisc.edu.
To the Editor:
Vitamin D deficiency is a common health problem, and healthcare providers frequently measure circulating 25-hyroxyvitamin D concentration, the accepted standard for clinical assessment of vitamin D status (1). In the past, assay of this analyte was mainly performed by RIA in which the sum of 25(OH)D3 and 25(OH)D2 was measured (2). Newer HPLC and liquid chromatography mass spectroscopy (LC-MS) assays can measure the 2 forms separately (3)(4). Although the number of laboratories using HPLC or LC-MS for clinical 25(OH)D determination is not known, 17 of 153 laboratories participating in a recent QC survey used these methods, and some large commercial laboratories, which may analyze as many as 30 000 clinical specimens per month, use these methods. It has recently come to our attention that reporting both 25(OH)D2 and 25(OH)D3 may be confusing to physicians-in-training, who might consider a low 25(OH)D2 or 25(OH)D3 concentration to indicate vitamin D deficiency even if the total 25(OH)D result is within the reference interval.
To investigate whether the possibility of misinterpretation extends to healthcare providers who have completed training and are in clinical practice, we e-mailed an internet survey to 341 healthcare providers. The survey presented a hypothetical patient history [an 82-year-old person with a hip fracture in whom 25(OH)D was measured] with 3 potential 25(OH)D laboratory results with, for each set of results, the same 4 possible interpretations (vitamin D deficiency, vitamin D2 deficiency, vitamin D3 deficiency, or optimal vitamin D status). The clinical decision values for circulating 25(OH)D (see Table 1
) were provided. The survey asked which patients should receive treatment with vitamin D. We e-mailed the survey to providers who were selected because they had ordered 1 or more 25(OH)D determinations in the preceding year. Only practicing healthcare providers received this survey; physicians-in-training were excluded.
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In one scenario, the total 25(OH)D result was 16 ng/mL; all responding healthcare providers (45 physicians, 12 physicians assistants and nurse practitioners) correctly identified this as vitamin D deficiency in need of vitamin D treatment (Table 1
). However, for the scenario reporting 25(OH)D3 <5 ng/mL and 25(OH)D2 40 ng/mL, 13 (23%) interpreted these results to indicate either vitamin D deficiency or vitamin D3 deficiency requiring vitamin D treatment (Table 1
).
The important objective in assessing vitamin D status is to obtain a measure of the total circulating 25(OH)D, whether from a validated RIA, HPLC, or LC-MS assay. To achieve this objective, there is no advantage to reporting circulating 25(OH)D2 and 25(OH)D3 separately. Moreover, the results of this survey suggest that reporting 25(OH)D2, 25(OH)D3, and total 25(OH)D can confuse practicing healthcare providers, thereby leading to incorrect clinical decisions. We believe that, until a specific advantage for separate reporting of these metabolites is identified, laboratory reports should be limited to total circulating 25(OH)D or, if individual metabolites are listed, such reports must indicate clearly that the total circulating 25(OH)D is the measurement that should be used in clinical decision-making about vitamin D status.
The above recommendation does not diminish the important observation of D2 and D3 differing effects on maintenance of circulating 25(OH)D. Moreover, we acknowledge that there may be physiologic differences between D2 and D3. However, such theoretical differences have not been established and current dogma is that circulating 25(OH)D2 and 25(OH)D3 have equal clinical efficacy.
Acknowledgments
Dr. Hollis is a consultant for the Diasorin corporation.
References
The following articles in journals at HighWire Press have cited this article:
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  C. Massart and J.-C. Souberbielle Serum 25-Hydroxyvitamin D Immunoassays: Recommendations for Correct Clinical Interpretation Clin. Chem., June 1, 2009; 55(6): 1247 - 1248. [Full Text] [PDF]
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 S. Knox, J. Harris, L. Calton, and A M. Wallace A simple automated solid-phase extraction procedure for measurement of 25-hydroxyvitamin D3 and D2 by liquid chromatography-tandem mass spectrometry Ann Clin Biochem, May 1, 2009; 46(3): 226 - 230. [Abstract] [Full Text] [PDF]
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S J Costelloe, E Woolman, S Rainbow, L Stratiotis, G O'Garro, S Whiting, and M Thomas Is high-throughput measurement of 25-hydroxyvitamin D3 without 25-hydroxyvitamin D2 appropriate for routine clinical use? Ann Clin Biochem, January 1, 2009; 46(1): 86 - 87. [Full Text] [PDF]
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 J. A. Cauley, A. Z. LaCroix, L. Wu, M. Horwitz, M. E. Danielson, D. C. Bauer, J. S. Lee, R. D. Jackson, J. A. Robbins, C. Wu, et al. Serum 25-Hydroxyvitamin D Concentrations and Risk for Hip Fractures Ann Intern Med, August 19, 2008; 149(4): 242 - 250. [Abstract] [Full Text] [PDF]
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 B. W Hollis Measuring 25-hydroxyvitamin D in a clinical environment: challenges and needs Am. J. Clinical Nutrition, August 1, 2008; 88(2): 507S - 510S. [Abstract] [Full Text] [PDF]
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