TY - JOUR
T1 - Bone Turnover Markers Including Undercarboxylated Osteocalcin Are Associated With Mortality Risk in Older Men
AU - Robertson, Courtney L.
AU - Ghosh, Gaurav
AU - Fitzgerald, Patrick
AU - Hankey, Graeme J.
AU - Levinger, Itamar
AU - Golledge, Jonathan
AU - Almeida, Osvaldo P.
AU - Flicker, Leon
AU - Ebeling, Peter R.
AU - Yeap, Bu B.
N1 - Funding Information:
This work was supported by Grant‐in‐Aid G11P5662 from the National Heart Foundation of Australia. BBY held a Clinical Investigator Award from the Sylvia and Charles Viertel Charitable Foundation, New South Wales. PRE is supported by a National Health and Medical Research Council of Australia Investigator Grant (1197958). LF is supported by a Medical Research Future Fund Next Generation Clinical Researchers Practitioner Fellowship (1155669). JG is supported by a National Health and Medical Research Council of Australia Practitioner Fellowship (1117061) and Senior Clinical Research Fellowship from the Queensland Government. The Health in Men Study was funded by Project Grants from the National Health and Medical Research Council of Australia. The funding sources had no involvement in the planning, analysis, and writing of the manuscript.
Publisher Copyright:
© 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
PY - 2022/8
Y1 - 2022/8
N2 - 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 3871 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, 95% CI 1.01–1.11, p = 0.009; CTX HR = 1.13, 95% CI 1.08–1.19, p < 0.001), but TOC was not associated. Similar results were found 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, 95% CI 1.05–1.22, p = 0.001; CTX HR = 1.12, 95% 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, 95% 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.
AB - 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 3871 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, 95% CI 1.01–1.11, p = 0.009; CTX HR = 1.13, 95% CI 1.08–1.19, p < 0.001), but TOC was not associated. Similar results were found 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, 95% CI 1.05–1.22, p = 0.001; CTX HR = 1.12, 95% 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, 95% 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.
KW - BIOCHEMICAL MARKERS OF BONE TURNOVER
KW - CANCER
KW - CARDIOVASCULAR DISEASE
KW - MORTALITY
UR - https://www.scopus.com/pages/publications/85133647487
U2 - 10.1002/jbmr.4631
DO - 10.1002/jbmr.4631
M3 - Article
C2 - 35689459
AN - SCOPUS:85133647487
SN - 0884-0431
VL - 37
SP - 1464
EP - 1472
JO - Journal of Bone and Mineral Research
JF - Journal of Bone and Mineral Research
IS - 8
ER -
SDG 3 Good Health and Well-being