The role of biomarkers in the management of osteoporosis.

Dual-energy X-ray absorptiometry (DXA) and FRAX remain the validated foundation of osteoporosis diagnosis and fracture-risk stratification, yet important gaps persist: treatment response on DXA is detectable only after eighteen to twenty-four months, risk within any FRAX category is heterogeneous, and the kinetics of therapy transitions are invisible on densitometry. Circulating biomarkers are candidate adjuncts to close these gaps. Serum C-terminal telopeptide of type I collagen (s-CTX) and procollagen type I N-terminal propeptide (s-P1NP), reaffirmed as reference markers by the 2025 IOF-IFCC consensus, reflect bone remodeling within weeks and can verify adherence, confirm on-target response and flag rebound resorption after denosumab discontinuation. Emerging analytes - sclerostin, RANKL/OPG, circulating microRNAs, proteomic and metabolomic panels, and polygenic risk scores - promise refinement of risk prediction and precision monitoring but are not yet ready for routine clinical use. This review critically examines the biological basis, analytical performance, clinical-trial evidence and practical application of bone biomarkers, positioning them as complements to, not replacements for, DXA and FRAX.