Personalized reference intervals based on biological variation for serum bone turnover markers in healthy older adults

Abstract Objectives The clinical utility of serum bone turnover markers (BTMs) in managing osteoporosis in the elderly is constrained by the absence of personalized reference intervals (prRI) based on biological variation (BV). Methods This longitudinal study tracked monthly serum levels of β-CTX, PINP, OC, PTH, and 25(OH)D over six months in 40 healthy elderly participants aged 60–75 years (16 males and 24 females). The study calculated estimates of within-subject BV (CV I ), between-subject BV (CV G ), within-person BV (CV P ), analytical variation (CV A ), and reference change values (RCVs).These parameters were subsequently used to establish the personalized reference interval (prRI). Results Considerable variability in CV I , CV P , and CV G was observed for BTMs in older adults. Gender differences in baseline concentrations were observed for PINP, OC, and 25(OH)D (p<0.05), but no significant differences were found in BV parameters. Among the markers, OC exhibited the lowest CV I (7.9 %), while β-CTX had the highest (14.8 %). Other markers had CV I values ranging from 11.0 to 14.2 %. RCVs ranged from −19.8 to −33.7 % and 24.6 to 50.8 %. For all five BTMs, the CV I -based prRI ranges were narrower than the popRI, whereas the CV P -based prRIs showed wide inter-individual variation, reflecting substantial heterogeneity in prRIs among older adults. Conclusions This study establishes BV-based prRI for BTMs in older adults, which offers a more clinically relevant interpretation of individual-level data than popRI and facilitates more accurate clinical decision-making.