Oral Virtual Presentation (Virtual only) ESA-SRB-ANZBMS 2021

Markers of higher bone turnover are associated with all-cause and cardiovascular disease mortality risk in older men. (#52)

Courtney L Robertson 1 , Gaurav Ghosh 2 , Patrick Fitzgerald 3 , Graeme J Hankey 4 , Peter R Ebeling 5 , Itamar Levinger 6 7 , Jonathan Golledge 8 9 , Osvaldo P Almeida 3 4 , Leon Flicker 3 4 , Bu B Yeap 2 4
  1. Fiona Stanley hospital, Muroch, WA, Australia
  2. Department of Endocrinology and Diabetes, Fiona Stanley hospital, Perth, WA, Australia
  3. Western Australian Centre for Healthy Ageing, University of Western Australia, Perth, WA, Australia
  4. Medical School, University of Western Australia, Perth, WA, Australia
  5. School of Clinical Sciences, Monash University, Clayton, VIC, Australia
  6. Institute for Health and Sport, Victorian University, Melbourne, VIC, Australia
  7. Australian Institute for Musculoskeletal Science, University of Melbourne and Western Health, St Albans, VIC, Australia
  8. Queensland Research Centre for Peripheral Vascular Disease, James Cook University, Townsville, Queensland, Australia
  9. Department of Vascular and Endovascular Surgery, Townsville University Hospital, Townsville, Queensland, Australia

Background:
Osteocalcin in its undercarboxylated form (ucOC) may influence diabetes risk, however its relationship with all-cause and cardiovascular disease mortality is unclear. Whether other bone turnover markers (BTMs) are associated with mortality risk differently from ucOC also remains uncertain.

Objective:
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 1 N-propeptide (P1NP) and collagen type 1 C-terminal cross-linked telopeptide (CTX).

Design, setting and participants:
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. 

Methods:
Serum ucOC, TOC, P1NP and CTX were assayed. Incidence of all deaths, and deaths due to cardiovascular disease (CVD) or cancer, were ascertained by data linkage. Cox regression analyses were adjusted for cardiovascular risk factors.

Results:
Men in the highest quartile of ucOC had higher all-cause and CVD mortality compared to those in Q1 (Q4 vs Q1: hazard ratio [HR]=1.17, 95% confidence interval [CI]=1.02-1.35, p=0.029; HR=1.25, CI=1.01-1.54, p=0.037, respectively). Similar results were seen for TOC (HR=1.20, CI=1.04-1.39, p=0.016; HR=1.27, CI=1.03-1.58, p=0.029, respectively) and CTX (HR=1.24, CI=1.07-1.44, p=0.004; HR=1.27, CI=1.03-1.57, p=0.028). P1NP was associated with all-cause (HR=1.20, CI=1.04-1.38, p=0.013) but not CVD mortality. Only P1NP and CTX were associated with cancer mortality (HR=1.32, CI=1.01-1.72, p=0.042; HR=1.37, CI=1.04-1.80, p=0.023 respectively).

Conclusions:
Higher bone turnover, assessed by ucOC and other BTMs in older men, is a biomarker for all-cause and cause-specific mortality risk. Further evaluation of causality and potential underlying mechanisms is warranted.