Standardizing vitamin D assays: The way forward
Open accessAbstract
For a number of years it has been widely assumed that measurement of serum 25-hydroxyvitamin D [25(OH)D] concentration is the best approach to assessing an individual's vitamin D status.(1, 2) However, it has also been recognized that there is substantial within-assay variation in 25(OH)D measurement and even greater between-assay variability.(3, 4, 5) Such assay variation clearly confounds attempts to define what constitutes the diagnosis of hypovitaminosis D. Importantly, assay variability makes pooling of 25(OH)D results from different studies in systematic reviews for the specific purpose of determining dose-response and/or clinical cut points at best problematic. Therefore, to develop and implement evidence-based clinical guidelines, it is essential that 25(OH)D measurement be standardized in both clinical and research laboratories. In this Perspective we outline a way forward toward achieving this goal—the Vitamin D Standardization Program (VDSP). © 2014 American Society for Bone and Mineral Research
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25(OH)D and testosterone assays varied across trials.
“These issues are particularly relevant because several androgen outcomes were secondary biomarkers, and because 25(OH)D and testosterone assays varied across trials [3,10,35,36].”
From Vitamin D Supplementation, Total Testosterone, and Androgen Bioavailability Markers in Adult Men: A Systematic Review and Meta-Analysis of Randomized Controlled Trials (2026) · cites this paper as [35]
The Conclusion (page unavailable) says that substantial variation remains in 25(OH)D assays used in clinical and research settings. That supports the 25(OH)D portion, but the paper does not establish that testosterone assays varied across the trials in question. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSeveral androgen outcomes were secondary biomarkers.
“These issues are particularly relevant because several androgen outcomes were secondary biomarkers, and because 25(OH)D and testosterone assays varied across trials [3,10,35,36].”
From Vitamin D Supplementation, Total Testosterone, and Androgen Bioavailability Markers in Adult Men: A Systematic Review and Meta-Analysis of Randomized Controlled Trials (2026) · cites this paper as [35]
The Conclusion discusses variation in vitamin D assays, but does not describe androgen outcomes in any trials. Searches for androgen outcomes, testosterone, and secondary biomarkers found no passage identifying androgen outcomes as secondary biomarkers; a sex-steroid assay appears only in the References. (LLM, conf=0.72)
Experimental — accuracy not yet measured
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Cites
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Research works printed but not linked: 28
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Sempos, C. T., Heijboer, A. C., Bikle, D. D., Bollerslev, J., Bouillon, R., Brannon, P. M., DeLuca, H. F., Jones, G., Munns, C. F., Bilezikian, J. P., et al. (2018) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.13652 · Cited by 331 · see citing works
Self-citationThiamine deficiency disorders: Diagnosis, prevalence, and a roadmap for global control programs
Whitfield, K. C., Bourassa, M. W., Adamolekun, B., Bergeron, G., Bettendorff, L., Brown, K. H., Cox, L., Fattal‐Valevski, A., Fischer, P. R., Frank, E. L., et al. (2018) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13919 · Cited by 336 · see citing works
Paez-Allendes, L., Valenzuela-Fuenzalida, J. J., Moya, M. P., Oyanedel, G., Cifuentes-Suazo, G., Figueroa-Puig, J., Orellana-Donoso, M., Mateluna-Valls, E., Cabezas-Salgado, J. J., Sanchis-Gimeno, J., et al. (2026) · Nutrients · doi:10.3390/nu18132090
- Authors
- Binkley, N., Sempos, C. T., & (VDSP), F. T. V. D. S. P.
- Affiliations
- University of Wisconsin–Madison (US)
- National Institutes of Health (US)
- Corresponding author
- Sempos, Christopher T
- Venue
- Journal of Bone and Mineral Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-04-16
- Volume
- 29
- Issue
- 8
- Pages
- 1709-1714
- ISSN
- 0884-0431 (ISSN-L)
- 1523-4681
- PMC
- PMC5443565
- OpenAlex
- W2026047392
- Cited by
- 204
- References
- 1
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 12 · 2023: 10 · 2022: 8 · 2021: 14 · 2020: 22 · 2019: 11 · 2018: 26 · 2017: 29 · 2016: 23 · 2015: 20 · 2014: 4
- FWCI
- 17.62
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Journal of Bone and Mineral Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Health and Human Services
- National Institutes of Health
- Centers for Disease Control and Prevention
- National Center on Minority Health and Health Disparities
- Office of Disease Prevention
- National Institute on Minority Health and Health Disparities (1P60/R01 MD 003428‐01, P60MD003428)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Vitamin D Research Studies
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Scientific Measurement and Uncertainty Evaluation
- Keywords
- vitamin D, 25-hydroxyvitamin D, assay standardization, clinical guidelines, dose-response relationship, serum vitamin D measurement
- MeSH terms
- Biological Assay, Blood Chemical Analysis, Humans, Vitamin D, Vitamin D Deficiency
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