Bone Abstracts (2013) 1 OC1.5 | DOI: 10.1530/boneabs.01.OC1.5

Heart failure in patients treated with bisphosphonates

Erik Grove1, Bo Abrahamsen2,3 & Peter Vestergaard4,5


1Aarhus University Hospital, Aarhus, Denmark; 2Gentofte Hospital, Hellerup, Denmark; 3University of Southern Denmark, Odense, Denmark; 4Aalborg University, Aalborg, Denmark; 5Aalborg University Hospital, Aalborg, Denmark.


Background: Bisphosphonates are widely used to prevent and treat osteoporosis. Limited evidence suggest that these drugs may reduce mortality, perhaps by protecting against cardiovascular disease. This study investigated the occurrence of heart failure in patients treated with bisphosphonates.

Methods: Nationwide retrospective cohort study from Denmark. All users of bisphosphonates and raloxifene (n=4.831) between 1996 and 2006 (n=102.342) were used as exposed group and three age- and gender-matched controls (n=307.026) from the general population as unexposed group. The risk of the main outcome, heart failure, was estimated by Cox proportional hazard analyses.

Results: The absolute risk of heart failure was 4.4% in the exposed group and 3.7% among controls (P<0.01). The relative risk (RR) of heart failure was significantly increased in users of bisphophonates; crude RR of 1.71 (1.63–1.79), adjusted RR 1.41 (1.34–1.48). In comparison, raloxifene, which is used for the same indication but has a different mechanism of action, was not associated with an increased risk of heart failure (crude RR 1.23 (0.89–1.71), adjusted RR 1.07 (0.76–1.50)). The mean follow-up time was 2.8 years for alendronate, 5.5 years for etidronate, and 4.9 years for raloxifene. When the two most commonly used bisphosphonates were analyzed separately, significant trends in the risk of heart failure were observed across refill compliance strata. This dose–effect relationship differed between the first generation bisphosphonate etidronate and the newer nitrogen-containing bisphosphonate alendronate. Thus, the risk of heart failure increased significantly with increasing refill compliance for etidronate (P for trend <0.01), whereas it decreased for alendronate (P for trend <0.01).

Conclusion: Bisphosphonate users as a group were at increased risk of heart failure compared to age- and sex-matched controls but the dose-response relationship suggests that alendronate could reduce the risk.

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