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.Introduction: 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. Materials and 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 ‫ס‬ 1.62 per 10 years), male sex (HR ‫ס‬ 1.33), immobility (HR ‫ס‬ 1.94), co-morbidity (HR ‫ס‬ 0.31, mild versus severe), lower weight (HR ‫ס‬ 0.83 per 10-kg increase), impaired cognitive function (HR ‫ס‬ 2.14, severe versus normal), number of medications (HR ‫ס‬ 1.05 each), hip fracture (HR ‫ס‬ 2.26), log serum creatinine (HR ‫ס‬ 1.67), log PTH (HR ‫ס‬ 1.29), CTX-I (HR ‫ס‬ 1.70, highest 25% versus lowest 75%), and PINP (HR ‫ס‬ 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 ‫ס‬ 1.39; 95% CI: 1.14-1.70; p ‫ס‬ 0.002) and PINP (HR ‫ס‬ 1.25; 95% CI: 1.02-1.52; p ‫ס‬ 0.03). For individual causes of death, CTX-I was significantly associated with deaths from cardiac causes (HR ‫ס‬ 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.

Low bone mineral density at femoral neck is a predictor of increased mortality in elderly Japanese women

“…As previously mentioned, epidemiological research in three studies has shown that women with low BMD or a vertebral fracture were observed to have increased mortality caused by cardiovascular diseases [7,26,36]. Recently, Sambrook et al [37] reported that, in the frail elderly, high bone turnover is associated with all-cause mortality independent of age, sex, and hip fracture status. These authors estimated that the mechanism of the effect of bone turnover on mortality could also be due to cardiovascular causes.…”

Modified-Release Calcifediol Effectively Controls Secondary Hyperparathyroidism Associated with Vitamin D Insufficiency in Chronic Kidney Disease

“…OPKO Health recently completed a carcinogenicity evaluation of calcifediol in a rodent model, as requested by the US Food and Drug Administration, which showed no carcinogenicity potential at the highest dose tested (33 µg/kg/day) [unpublished data]. Other studies cited in the same IOM report failed to support these lower ranges [63,64]. Recent observational studies in CKD patients reported increased mortality with vitamin D insufficiency [65,66,67,68,69,70] suggesting that a higher serum 25-hydroxyvitamin D is associated with improved clinical outcomes.…”

Clinical application of biochemical markers of bone turnover

“…It is now widely accepted that the accelerated rate of bone loss seen after the menopause is mainly due to an uncoupling in bone turnover and an increase in bone resorption (26,27). Studies employing specific bone markers indicate that bone turnover continues to be increased (and to be associated with bone loss) during late menopause (28)(29)(30)(31)(32)(33). In some postmenopausal women (34), but particularly in the very elderly (35)(36)(37), this increase in bone turnover is often, but not always, found to be due to vitamin D and/or calcium deficiency and secondary hyperparathyroidism.…”

“…For example, markers of bone turnover may reflect changes in bone metabolism induced by oophorectomy (57,125), hyperparathyroidism (126,127), Paget's disease (128), physical exercise (129), immobilisation (32,130), alcoholism (131), smoking (132), vitamin D deficiency (33,35,37,133), chronic inflammatory bowel disease (134,135), chronic starvation (136), thyroid disorders (52,137) as well as the pharmacological effects of glucocorticosteroids (48,139,140), androgens (6,7,141), gonadotropin-releasing hormone agonists (142), warfarin (143), growth hormone or insulin-like growth factors (144). Bone turnover markers may be useful in the diagnosis and management of certain of the above conditions, but in most cases has not been rigorously examined.…”