High levels of bone turnover markers increase risk for all-cause mortality in older men
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Older men with higher concentrations of three bone turnover markers have a higher risk for all-cause mortality than those with lower concentrations, according to study findings published in the Journal of Bone and Mineral Research.
“Higher mortality was seen in men who had higher concentrations of undercarboxylated osteocalcin, and also those with higher concentrations of two other bone turnover markers, procollagen type 1 N-propeptide and collagen type 1 C-terminal cross-linked telopeptide,” Bu Yeap, MBBS, PhD, professor at the University of Western Australia School of Medicine and consultant endocrinologist in the department of endocrinology and diabetes at Fiona Stanley Hospital in Perth, Australia, told Healio. “Therefore, the underlying pathway appears to involve bone turnover, in general, and not specifically undercarboxylated osteocalcin. The results were similar even after excluding men who experienced bone fractures during follow-up, so there may be a broader effect of higher bone turnover to increase susceptibility to a range of conditions contributing to death.”
Yeap and colleagues analyzed data from participants in The Health In Men Study, a prospective cohort study of older men aged at least 65 years from Perth, Australia, randomly selected from the electoral roll from 1996 to 1999. Of the full cohort, 3,871 men were assessed and provided a blood sample during the second wave of the study from 2001 to 2004. Serum undercarboxylated osteocalcin, serum total osteocalcin, procollagen type 1 N-propeptide and collagen type 1 C-terminal cross-linked telopeptide were measured from the samples. Occurrence and cause of death were collected from the Western Australian Data Linkage System from the time of recruitment for the second wave until Dec. 31, 2016. Prevalent diabetes, cardiovascular disease, cancer, Paget’s disease of the bone, osteoporosis, bone fractures within the past 12 months, and current bisphosphonate or glucocorticoid use were collected using questionnaires. Incident bone fractures due to falls were obtained from the Western Australian Data Linkage System.
During a median follow-up time of 12.3 years, 61% of the study cohort died. The primary cause of death was 27% each for both CVD and cancer.
In fully adjusted analyses, each standard deviation increase in concentrations of undercarboxylated osteocalcin (HR = 1.12; 95% CI, 1.06-1.18; P < .001), procollagen type 1 N-propeptide (HR = 1.06; 95% CI, 1.01-1.11; P = .009) and collagen type 1 C-terminal cross-linked telopeptide (HR = 1.13; 95% CI, 1.08-1.19; P < .001) was associated with an increased risk for all-cause mortality. The associations were similar after 436 men with an incident fracture at follow-up were excluded.
The risk for CVD mortality was increased with each standard deviation increase in undercarboxylated osteocalcin (HR = 1.13; 95% CI, 1.05-1.22; P = .001) and collagen type 1 C-terminal cross-linked telopeptide (HR = 1.12; 95% CI, 1.04-1.2; P = .003). No associations were observed between CVD mortality and total osteocalcin or procollagen type 1 N-propeptide. A higher risk for cancer mortality was observed with each standard deviation increase in collagen type 1 C-terminal cross-linked telopeptide (HR = 1.12; 95% CI, 1.01-1.23; P = .024). No other bone turnover markers were associated with cancer mortality risk.
Yeap said bone turnover markers could be used to identify older men with the highest mortality risk, but more research is needed to assess how to move forward with treatment.
“Further research is needed to clarify the underlying mechanisms, and to look more closely at other causes of death beyond CVD and cancer,” Yeap said. “It would be interesting to do a study in which men with higher bone turnover could be identified and offered an intervention to improve their health.”
For more information:
Bu Yeap, MBBS, PhD, can be reached at bu.yeap@uwa.edu.au.
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