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Global Survey Reveals Major Variation in the Measurement of Bone and Mineral Metabolism Biomarkers
Researchers from the International Osteoporosis Foundation (IOF) and International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Joint Committee on Bone Metabolism published a new study examining self-reported practices among laboratories that measure Bone Status Indices (BSIs) in blood tests. Published on 7 August 2026, in Clinical Chemistry and Laboratory Medicine, the study collected 231 responses across 41 countries. Findings show a landscape of global BSI laboratory practices marked by substantial variations that limit data sharing, test standardisation, and clinical impact.
For more than 20 years, IOF and IFCC have called for standardisation of BSI nomenclature, abbreviations, and measurement units. BSI tests complement dual-energy X-ray absorptiometry (DXA) by providing information on bone and mineral metabolism and can support the assessment of disease activity and treatment response. Yet variability in BSI laboratory testing practices continues to hinder meaningful comparisons and limit the clinical value of results
Researchers observed substantial heterogeneity across laboratories in:
- Analytical platforms and instruments
- Specimen types
- Reporting units
- Reference intervals and decision thresholds
- External quality assessment (EQA) participation
- Reimbursement practices
Key Findings:
- Reference intervals varied considerably, even among laboratories using the same manufacturer and instrument.
- EQA participation appeared high for total alkaline phosphatase (ALP) and parathyroid hormone (PTH), but substantially lower for β-isomerized C-terminal telopeptide of type I collagen (β-CTX-I) and procollagen type I N-propeptide (PINP).
- Adoption of β-CTX-I and PINP testing seemed incomplete, although more common use appeared among laboratories monitoring osteoporosis patients.
- Access to bone-specific ALP and tartrate-resistant acid phosphatase 5b (TRAP5b) remains limited.
- PTH testing showed poor harmonisation, largely due to the concurrent use of second- and third-generation PTH assays.
- Vitamin D decision thresholds varied widely between laboratories.
- Inappropriate ordering of 1,25(OH)₂D for the assessment of vitamin D status, rather than 25(OH)D, was frequently reported.
Overall, the findings indicate considerable international variability and incomplete harmonisation in laboratory testing for bone and mineral metabolism.
"The survey’s findings reveal the extent of variation in laboratory practices that can affect BSI test results," said Professor Etienne Cavalier, University of Liège, Belgium, Chair representing IOF on the IOF–IFCC Joint Committee on Bone Metabolism and corresponding author. "These findings show that the lack of harmonisation is not merely a laboratory issue. When the same biomarker is measured, reported or interpreted differently across laboratories, this limits the comparability of research data and can ultimately affect clinical decision-making. Greater harmonisation is therefore essential if these biomarkers are to reach their full clinical potential."
Building on the need for greater consistency in BSI testing, Professor Eugene McCloskey, Mellanby Centre for Musculoskeletal Research, University of Sheffield, UK, and Chair of the IOF Committee of Scientific Advisors (CSA), emphasised the practical steps that can be taken to address these challenges. "Some relatively straightforward first steps, such as greater consistency in clinical terminology and laboratory reporting, could improve the clinical utility of BSI testing," said Professor McCloskey. "This would facilitate the sharing and comparison of data across laboratories and clinical settings, ultimately supporting better patient care."
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Reference
Cavalier, E., et al., on behalf of the International Osteoporosis Foundation (IOF)–International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Joint Committee on Bone Metabolism (C-BM) (2026). IOF-IFCC international survey of global laboratory practices for bone status indices. Clinical Chemistry and Laboratory Medicine (CCLM). https://doi.org/10.1515/cclm-2026-0941
About IOF
The International Osteoporosis Foundation (IOF) is the world’s largest non-governmental organisation dedicated to the prevention, diagnosis, and treatment of osteoporosis and related musculoskeletal diseases. Its members — including committees of leading scientific researchers and 349 patient, medical, and research organisations across 152 countries — work together to make fracture prevention and healthy mobility a global healthcare priority.
www.osteoporosis.foundation @iofbonehealth
About IFCC
The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) is a global, non-political organisation for clinical chemistry and laboratory medicine. As such, it has a range of roles that include global standard setting in collaboration with other international bodies. It supports members in scientific and educational endeavours, and it provides a series of congresses, conferences, and meetings for laboratory medicine specialists to meet and present original findings and best practice.