Global Study Finds Variation in Bone Metabolism Biomarker Measurement

Global Survey Identifies Wide Discrepancies in Bone Marker Testing

Laboratories worldwide report substantial variation in bone metabolism biomarker measurement, according to a survey published on August 7, 2026, in Clinical Chemistry and Laboratory Medicine. The research was conducted by the Joint Committee on Bone Metabolism of the International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC).

The survey evaluated self-reported laboratory practices across 231 testing centers in 41 countries. Blood tests that track bone status indices (BSIs) evaluate bone turnover, monitor metabolic bone disease activity, and assess responses to medical therapy alongside dual-energy X-ray absorptiometry (DXA) imaging.

The authors documented widespread discrepancies that impair test standardization and data sharing across institutions. Participating laboratories differed significantly across six central operational areas.

• Analytical platforms and laboratory instruments
• Accepted biological specimen types
• Standard reporting units for test output
• Reference intervals and clinical decision thresholds
• Participation rates in external quality assessment (EQA) programs
• Reimbursement practices across regional jurisdictions

Differences in Reference Intervals and Assay Generations

Reference intervals varied considerably across testing sites, even among laboratories using identical instruments from the same manufacturer. This baseline variation makes it difficult to compare numerical values directly between facilities.

Measurements of parathyroid hormone (PTH) exhibited poor clinical harmonization across reporting sites. This divergence stemmed largely from the concurrent operational use of second-generation and third-generation PTH assays, which measure different circulating hormone fragments.

Vitamin D interpretation faced similar inconsistencies in the survey data. Laboratories reported divergent decision thresholds for defining deficiency, along with frequent inappropriate ordering of 1,25-dihydroxyvitamin D [1,25(OH)2D] instead of 25-hydroxyvitamin D [25(OH)D] to assess general vitamin D status.

Gaps in Quality Assessment and Marker Adoption

Participation in external quality assessment (EQA) programs differed sharply based on the specific biomarker evaluated. Rates of EQA enrollment remained high for established analytes like total alkaline phosphatase (ALP) and PTH, but participation dropped substantially for specialized markers.

Adoption of beta-isomerized C-terminal telopeptide of type I collagen (beta-CTX-I) and procollagen type I N-propeptide (PINP) remained incomplete across standard diagnostic settings. Laboratories that monitored osteoporosis patients specifically were more likely to utilize these two markers than general facilities.

General access to specialized diagnostic tests remained constrained globally. Laboratories reported restricted access to bone-specific ALP and tartrate-resistant acid phosphatase 5b (TRAP5b).

Clinical Implications for Interpreting Bone Metabolism Tests

These measurement discrepancies mean a single numerical result can yield conflicting interpretations depending on which facility processes the sample. Patients reviewing metabolic lab reports should talk to their clinician about which specific assay platform their facility used.

Tracking therapeutic changes over time requires consistent laboratory methods. Because reference intervals differ between systems, serial monitoring of bone turnover markers is most reliable when samples are drawn under matching conditions and analyzed using the same assay type.

Clinicians and researchers note that standardizing terminology, units, and reporting thresholds serves as the first step toward comparable results. Consistent terminology allows providers to share research data and integrate bone biomarker tracking into routine metabolic care.

Survey Limitations and Sourced Data Constraints

The survey relied on self-reported operational practices from 231 voluntary respondents, which may introduce selection bias toward laboratories with an active interest in bone diagnostics. Results reflect laboratory protocols rather than direct blinded comparisons of shared patient serum samples.

The 41 surveyed countries do not represent uniform global distribution, which may limit the applicability of specific findings to underrepresented regions. Further international initiatives by the IOF and IFCC aim to address these variations through published reporting recommendations.