Global Survey Finds Wide Variation in How Bone Metabolism Biomarkers Are Measured

Laboratory tests that measure the chemical signals of bone health are far less consistent around the world than many clinicians might assume. A new international survey, conducted by researchers from the International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Joint Committee on Bone Metabolism, has documented substantial differences in how laboratories measure, report, and interpret Bone Status Indices, the blood-based biomarkers used in the assessment of bone and mineral metabolism disorders, including osteoporosis. The study was published on 7 August 2026 in the journal Clinical Chemistry and Laboratory Medicine.

The survey collected 231 responses from laboratories across 41 countries, making it the first international descriptive survey of its kind to examine self-reported practices for Bone Status Indices (BSIs) in blood testing. The researchers set out to map the real-world landscape of laboratory medicine as it applies to bone metabolism, and what they found was a field marked by heterogeneity at nearly every step of the testing process. According to the authors, this variation limits data sharing, impedes test standardisation, and ultimately constrains the clinical impact of the measurements themselves.

Bone Status Indices are laboratory markers that complement dual-energy X-ray absorptiometry, commonly known as DXA, which remains the standard imaging technique for assessing bone mineral density. While DXA provides a structural snapshot of the skeleton, BSI tests offer dynamic biochemical information on bone and mineral metabolism. These markers can support the assessment of disease activity and treatment response, giving clinicians a window into the biological processes of bone formation and bone resorption as they unfold. For more than 20 years, the IOF and the IFCC have called for the standardisation of BSI nomenclature, abbreviations, and measurement units, yet the new findings confirm that variability in laboratory testing practices continues to hinder meaningful comparisons and to limit the clinical value of results.

The scale of the inconsistency emerged across multiple dimensions of laboratory practice. The survey documented substantial heterogeneity in analytical platforms and instruments, in the types of specimens used, in the units in which results are reported, and in the reference intervals and decision thresholds applied to interpret them. Participation in external quality assessment (EQA) schemes, a key mechanism for ensuring that laboratories produce reliable and comparable results, also varied considerably from one biomarker to another. Even reimbursement practices differed across the responding laboratories, shaping which tests are ordered and how often they reach patients in routine care.

Some of the most striking findings concerned specific biomarkers. Reference intervals varied considerably even among laboratories using the same manufacturer and the same instrument, a result that underscores how local conventions and calibration choices can diverge even when the underlying technology is identical. Participation in external quality assessment appeared high for total alkaline phosphatase (ALP) and parathyroid hormone (PTH), two of the most established markers in the field, but was substantially lower for β-isomerized C-terminal telopeptide of type I collagen (β-CTX-I) and procollagen type I N-propeptide (PINP), the biomarkers that reflect bone resorption and bone formation respectively.

The adoption of β-CTX-I and PINP testing also appeared incomplete across the surveyed laboratories, although more common use was seen among laboratories that monitor osteoporosis patients, suggesting that clinical demand drives uptake where it exists. Access to two more specialised markers, bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase 5b (TRAP5b), remains limited, restricting the biochemical toolkit available to many clinicians. Parathyroid hormone testing showed poor harmonisation, a problem the survey attributes largely to the concurrent use of second- and third-generation PTH assays, which differ in what they measure and can yield different numerical results for the same patient sample.

Vitamin D assessment emerged as another area of widespread inconsistency. Decision thresholds for vitamin D varied widely between laboratories, meaning that the same blood concentration could be classified differently depending on where a patient is tested. The survey also frequently reported inappropriate ordering of 1,25(OH)₂D, the active hormonal form of vitamin D, for the assessment of vitamin D status, rather than 25(OH)D, the storage form that clinical guidelines identify as the correct measure for this purpose. Taken together, the findings indicate considerable international variability and incomplete harmonisation in laboratory testing for bone and mineral metabolism.

Professor Etienne Cavalier of the University of Liège in Belgium, Chair representing the IOF on the IOF–IFCC Joint Committee on Bone Metabolism and corresponding author of the study, said the survey exposes the practical consequences of fragmented practice. “The survey’s findings reveal the extent of variation in laboratory practices that can affect BSI test results,” he said. “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.”

The implications extend beyond the laboratory bench. Biomarkers such as β-CTX-I and PINP are used in research on osteoporosis and in the clinical monitoring of patients receiving treatment, and differences in measurement and reporting can make it difficult to pool data across centres, compare trial results, or apply evidence-based thresholds in everyday practice. Professor Eugene McCloskey of the Mellanby Centre for Musculoskeletal Research at the University of Sheffield in the United Kingdom, Chair of the IOF Committee of Scientific Advisors, emphasised that practical remedies are within reach. “Some relatively straightforward first steps, such as greater consistency in clinical terminology and laboratory reporting, could improve the clinical utility of BSI testing,” he said. “This would facilitate the sharing and comparison of data across laboratories and clinical settings, ultimately supporting better patient care.”

The study, titled “IOF-IFCC international survey of global laboratory practices for bone status indices,” was published in Clinical Chemistry and Laboratory Medicine (CCLM) with the DOI 10.1515/cclm-2026-0941. Its authors write on behalf of the IOF–IFCC Joint Committee on Bone Metabolism, a body that has spent two decades pressing for uniform nomenclature, abbreviations, and units in this field. The survey’s message is that the technical foundations for better bone health care already exist in laboratories worldwide, but that without coordinated standardisation, the same biomarker measured in Liège, Sheffield, or anywhere else may not mean the same thing. For patients with osteoporosis and the clinicians who treat them, closing that gap is presented as an essential step toward making biochemical bone testing deliver its full clinical value.

Subject of Research: International variation in laboratory measurement practices for bone and mineral metabolism biomarkers used in osteoporosis assessment

Article Title: Global survey reveals major variation in the measurement of bone and mineral metabolism biomarkers

Article References: Global survey reveals major variation in the measurement of bone and mineral metabolism biomarkers. (n.d.). Original publication

Image Credits: AI Generated

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Keywords: bone status indices, osteoporosis, biomarkers, laboratory medicine, harmonisation, International Osteoporosis Foundation, IFCC, parathyroid hormone, vitamin D, beta-CTX-I, PINP, clinical chemistry