A practical tool to support harmonization and quality improvement in vitamin D testing

Accurate laboratory results are essential for clinical decisions — but every measurement carries some uncertainty. 

Addressing this challenge, the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC)–International Osteoporosis Foundation (IOF) Committee on Bone Metabolism has published a new study in Clinical Chemistry and Laboratory Medicine: Assessment of measurement uncertainty of immunoassays and LC-MS/MS methods for serum 25-hydroxyvitamin D.

The multicentre study evaluates the measurement uncertainty (MU) of various 25-(OH)D assays and their ability to detect physiologically relevant changes over time. Thirteen immunoassays and two LC-MS/MS methods for 25-hydroxyvitamin D [25(OH)D] were compared, applying strict analytical performance specifications to assess and compare their performance.

Lead author, Etienne Cavalier, Dept. of Clinical Chemistry, University of Liège, CIRM, CHU de Liège, Liège, Belgium, stated: “This new paper details how to calculate, interpret, and integrate measurement uncertainty (MU) into clinical practice, and includes a clear graphic illustrating MU estimation. It provides a practical tool for laboratories and clinicians to visualize variability and make informed decisions.”

Why this matters:

• MU provides transparency in laboratory reporting
• It supports better patient care by framing results within their confidence limits
• It is a key step toward harmonization and quality improvement in vitamin D testing

Overall, this study highlights the persistent variability in 25-(OH)D assay performance despite ongoing standardization efforts. While LC-MS/MS methods have demonstrated superior accuracy and lower measurement uncertainty, certain immunoassays also met the established analytical performance specifications. The study underscores the importance of integrating measurement uncertainty into performance evaluations and introduces novel graphical representations to enhance the interpretation of assay reliability. 

Professor Cavalier added, “Understanding measurement uncertainty is not just a matter of analytical rigor — it is a bridge between laboratory performance and patient outcomes. It is important that limitations such as inter-laboratory variability, potential matrix effects, and the absence of commutability assessments be considered when interpreting laboratory findings.”

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Reference:
Cavalier, Etienne, Bhattoa, Harjit P., Heijboer, Annemieke C., Lombardi, Giovanni, Delatour, Vincent, Van Uytfanghe, Katleen, Makris, Konstantinos, Jørgensen, Niklas Rye, Herrmann, Markus, Pikner, Richard, Lukas, Pierre, Vasikaran, Samuel D., Fraser, Callum G. and On behalf of the IFCC-IOF Committee on Bone Metabolism. Assessment of measurement uncertainty of immunoassays and LC-MS/MS methods for serum 25-hydroxyvitamin D. Clinical Chemistry and Laboratory Medicine (CCLM), vol. 63, no. 10, 2025, pp. 1981-1991. https://doi.org/10.1515/cclm-2025-0554

About IOF
The International Osteoporosis Foundation (IOF) is the world’s largest nongovernmental organization dedicated to the prevention, diagnosis, and treatment of osteoporosis and related musculoskeletal diseases. IOF’s membership committees include leading scientific experts, 340 patient organizations and medical societies in more than 150 countries, as well as universities worldwide. The IOF Capture the Fracture® initiative counts over 1,200 Fracture Liaison Services across all regions of the world. Together, this global network works to prioritize bone health and fracture prevention, sharing a vision of a world free from fragility fractures, where healthy mobility is a reality for all. @iofbonehealth
Websites: www.osteoporosis.foundation ; www.capturethefracture.org ; www.worldosteoporosisday.org ; www.buildbetterbones.org ; www.iofacademy.org/

About IFCC
The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) is a worldwide, non-political organization for clinical chemistry and laboratory medicine. As such it has a range of roles that include (1) global standard setting in collaboration with other international organizations, (2) supporting its members through scientific and educational endeavour, and (3) providing a series of congresses, conferences and focussed meetings in order for laboratory medicine specialists to meet and present original findings and best practice. www.ifcc.org/