title: High bone turnover is an independent predictor of mortality in the frail elderly.
abstract: Osteoporotic fractures are associated with accelerated bone turnover and excess mortality. In a prospective study of 1112 frail subjects (79% female; mean age, 86 years), high bone turnover was an independent predictor of all-cause mortality. This association seemed to be mainly manifested in deaths from cardiovascular causes.
  
  
  BACKGROUND
  Osteoporotic fractures are associated with accelerated bone turnover and excess mortality. In a prospective cohort study of elderly men and women, we assessed whether the rate of bone turnover measured by markers of bone remodeling is a direct predictor of mortality.
  
  
  METHODS
  We measured serum concentrations of the aminoterminal propeptide of type I collagen (PINP), a marker of bone formation, and of the carboxyterminal telopeptide of type I collagen (CTX-I), a marker of bone resorption, along with serum PTH and 25-hydroxyvitamin D [25(OH)D] levels in 1112 subjects (79% female; mean age, 86 years) living in residential care. Co-morbidity was measured using the Implicit Illness Severity Scale. Fracture data were validated by a radiology report. Mortality and causes of death were ascertained from death certificates.
  
  
  RESULTS
  Over a median follow-up of 817 days, 559 (50.3%) subjects died. In univariate analyses, time to death from all causes was significantly (p < 0.01) associated with age (HR = 1.62 per 10 years), male sex (HR = 1.33), immobility (HR = 1.94), co-morbidity (HR = 0.31, mild versus severe), lower weight (HR = 0.83 per 10-kg increase), impaired cognitive function (HR = 2.14, severe versus normal), number of medications (HR = 1.05 each), hip fracture (HR = 2.26), log serum creatinine (HR = 1.67), log PTH (HR = 1.29), CTX-I (HR = 1.70, highest 25% versus lowest 75%), and PINP (HR = 1.46, highest 25% versus lowest 75%). In multivariate analysis adjusting for age, sex, immobility, co-morbidity, weight, cognitive function, number of medications, PTH, and hip fracture status, the highest quartile was significantly more likely to die than the rest for both serum CTX-I (HR = 1.39; 95% CI: 1.14-1.70; p = 0.002) and PINP (HR = 1.25; 95% CI: 1.02-1.52; p = 0.03). For individual causes of death, CTX-I was significantly associated with deaths from cardiac causes (HR = 1.78: 95% CI: 1.27-2.50; p < 0.001).
  
  
  CONCLUSIONS
  We conclude that in the frail elderly, high bone turnover is associated with all cause mortality independently of age, sex, health status, serum PTH levels, and hip fracture status. The mechanism of the effect of bone turnover on mortality seems to be mainly manifested in deaths from cardiovascular causes.
authors.affiliation: Institute of Bone & Joint Research, Royal North Shore Hospital, The University of Sydney, Sydney, Australia.
authors.forename: Philip N
authors.initials: PN
authors.lastname: Sambrook
authors.forename: Charles J S
authors.initials: CJ
authors.lastname: Chen
authors.forename: Lyn
authors.initials: L
authors.lastname: March
authors.forename: Ian D
authors.initials: ID
authors.lastname: Cameron
authors.forename: Robert G
authors.initials: RG
authors.lastname: Cumming
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Lord
authors.forename: Judy M
authors.initials: JM
authors.lastname: Simpson
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Seibel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016723:Bone Remodeling / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000401:mortality; D005260:Female; D016330:Frail Elderly / Q000706:statistics & numerical data*; D006801:Humans; D008297:Male; D009026:Mortality; D015999:Multivariate Analysis; D012307:Risk Factors