Bone turnover markers including undercarboxylated osteocalcin are associated with mortality risk in older men

Courtney L Robertson, Gaurav Ghosh, Patrick Fitzgerald, Graeme J Hankey, Itamar Levinger, Jonathan Golledge, Osvaldo P Almeida, Leon Flicker, Peter R Ebeling, Bu B Yeap

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Osteocalcin in its undercarboxylated form (ucOC) may influence diabetes risk, however its relationship with all-cause and cause-specific mortality is unclear. Whether other bone turnover markers (BTMs) are associated with mortality risk differently from ucOC, also remains uncertain. Our aim was to determine associations of serum ucOC with all-cause and cause-specific mortality, and compare these with the corresponding associations of serum total osteocalcin (TOC), procollagen type I N-propeptide (PINP) and collagen type 1 C-terminal cross-linked telopeptide (CTX), in older men. We conducted a prospective cohort study of 3,871 community-dwelling men, aged 77.0±3.6 years at baseline, followed for a median of 12.3 years. Exposure variables were ucOC, TOC, PINP and CTX concentrations assayed in serum. Outcomes were incidence of all deaths, and deaths due to cardiovascular disease (CVD) or cancer, ascertained using death registry data. Cox regression analyses adjusted for cardiovascular risk factors and prevalent CVD, and for prevalent cancer in analyses of cancer-related mortality. Higher concentrations of ucOC, PINP and CTX were associated with all-cause mortality (hazard ratio [HR] per 1 standard deviation increase: ucOC 1.12, 95% confidence interval [CI] 1.06-1.18, P<0.001; PINP HR=1.06, CI=1.01-1.11, P=0.009; CTX HR=1.13, CI=1.08-1.19, P<0.001), TOC was not associated. Similar results were seen after excluding men with an incident fracture during follow-up. Higher ucOC and CTX were associated with CVD mortality (ucOC HR per 1 SD increase 1.13, CI=1.05-1.22, P=0.001; CTX HR=1.12, CI=1.04-1.20, P=0.003), but this result was not significant in competing risks analysis. Higher CTX was also associated with cancer mortality (HR=1.12, CI=1.01-1.23, P=0.024). In conclusion, in older men higher bone turnover, assessed by BTMs including ucOC, is a biomarker for all-cause mortality risk. Undercarboxylated osteocalcin was a more informative biomarker for this outcome than TOC. Higher CTX was associated with all-cause and cancer-related mortality. Further evaluation of causality and potential underlying mechanisms is warranted. This article is protected by copyright. All rights reserved.

Original languageEnglish
Pages (from-to)1464-1472
Number of pages9
JournalJournal of Bone & Mineral Research
Issue number8
Early online date11 Jun 2022
Publication statusPublished - Aug 2022


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