A study across 231 clinical laboratories in 41 countries highlights major gaps in reference intervals, external quality assessment, and assay harmonization.
A global survey of clinical laboratories has revealed substantial variations in how bone and mineral metabolism biomarkers are measured, interpreted, and reimbursed, according to findings from the International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC).
The study, conducted by the IOF–IFCC Joint Committee on Bone Metabolism and published in Clinical Chemistry and Laboratory Medicine, evaluated self-reported practices from 231 laboratories across 41 countries. Bone status indices (BSIs) in blood tests provide key information regarding bone turnover and disease activity, serving as a complement to dual-energy X-ray absorptiometry in assessing osteoporosis and other metabolic bone disorders. However, the survey identified marked heterogeneity across analytical platforms, specimen types, reporting units, reference intervals, decision thresholds, external quality assessment (EQA) participation, and reimbursement models.
“The survey’s findings reveal the extent of variation in laboratory practices that can affect BSI test results,” says Etienne Cavalier, chair representing IOF on the IOF–IFCC Joint Committee on Bone Metabolism and corresponding author, in a release. “These findings show that the lack of harmonization 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 harmonization is therefore essential if these biomarkers are to reach their full clinical potential.”
Discrepancies in Reference Intervals and Quality Programs
A central finding of the survey was that reference intervals varied substantially between laboratories, even among facilities utilizing the same instrument and manufacturer.
Quality control engagement also varied depending on the analyte. While EQA participation was high for parathyroid hormone (PTH) and total alkaline phosphatase (ALP), participation was notably lower for bone turnover markers such as procollagen type I N-propeptide (PINP) and β-isomerized C-terminal telopeptide of type I collagen (β-CTX-I). Overall adoption of PINP and β-CTX-I testing remained incomplete globally, though usage was more frequent among laboratories actively monitoring patients with osteoporosis. Furthermore, access to specialized markers such as bone-specific ALP and tartrate-resistant acid phosphatase 5b was found to be limited.
The data also underscored persistent technical challenges in hormone and vitamin testing. PTH testing showed poor harmonization, driven largely by the concurrent clinical use of second- and third-generation assay formats. In addition, vitamin D clinical decision thresholds differed widely across institutions, and respondents frequently reported inappropriate ordering of 1,25(OH)₂D instead of 25(OH)D for general vitamin D status assessments.
Advancing Assay Harmonization
The IOF and IFCC have advocated for standardized nomenclature, abbreviations, and measurement units in bone marker testing for more than two decades. Despite these efforts, the current findings demonstrate that incomplete harmonization continues to impede data sharing across institutions and compromise test utility in patient management.
Addressing these variations will require coordinated efforts starting with basic reporting standards.
“Some relatively straightforward first steps, such as greater consistency in clinical terminology and laboratory reporting, could improve the clinical utility of BSI testing,” says Eugene McCloskey, chair of the IOF Committee of Scientific Advisors, in a release. “This would facilitate the sharing and comparison of data across laboratories and clinical settings, ultimately supporting better patient care.”
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