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

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

Affiliations

¹Medical School, University of Western Australia, Perth, Australia

²Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, Australia

³Western Australian Centre for Healthy Ageing, University of Western Australia, Perth, Australia

⁴Institute for Health and Sport, Victoria University, Melbourne, Australia

⁵Australian Institute for Musculoskeletal Science, University of Melbourne and Western Health, St Albans, Australia

⁶Queensland Research Centre for Peripheral Vascular Disease, James Cook University, Townsville, Australia

⁷Department of Vascular and Endovascular Surgery, Townsville University Hospital, Townsville, Australia

⁸Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Australia

Abstract and keywords

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.

Keywords: BIOCHEMICAL MARKERS OF BONE TURNOVER; MORTALITY; CARDIOVASCULAR DISEASE; CANCER

Links

DOI: 10.1002/jbmr.4631

PubMed: 35689459

WoS: 000822214600001

History

Received: 2021-11-10

Revised: 2022-06-05

Accepted: 2022-06-09

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