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Osteoporos Int (2010) 21:15911597 DOI 10.1007/s00198-009-1091-y
ORIGINAL ARTICLE
Use of bisphosphonates and raloxifene and risk of deep venous thromboembolism and pulmonary embolism
P. Vestergaard & K. Schwartz & E. M. Pinholt &
L. Rejnmark & L. Mosekilde
Received: 31 August 2009 /Accepted: 2 October 2009 /Published online: 27 October 2009 # International Osteoporosis Foundation and National Osteoporosis Foundation 2009
AbstractSummary Prior studies have associated raloxifene and strontium ranelate with deep venous thromboembolism and pulmonary embolism. In a cohort study, we observed an increased risk also with the bisphosphonates. However, the increase was present already before the start of bisphosphonates pointing at an effect of the underlying condition.
Introduction We seek to study the association between use of drugs against osteoporosis and risk of deep venous thromboembolism (DVT) and pulmonary embolism (PE). Methods Nationwide register-based cohort study from Denmark with all users of bisphosphonates and other drugs against osteoporosis between 1996 and 2006 (n=103,562) as cases and three age- and gender-matched controls from the general population (n=310,683).
Results Before start of a drug against osteoporosis, an increased risk of DVT/PE was present in the crude analysis for alendronate, etidronate, and risedronate. However, upon adjustment, this increase in risk disappeared. Before start of
raloxifene, a decreased risk of DVT/PE was present (odds ratio (OR)=0.53, 95% confidence interval (CI), 0.390.71). After start of a drug, alendronate (HR=1.20, 95% CI, 1.001.43), clodronate (HR=4.06, 95% CI, 1.4711.2), and etidronate (HR=137, 95% CI, 1.231.51) were all associated with an increased risk of DVT/PE, while raloxifene was only borderline, significantly associated with risk of DVT/PE (HR=1.64, 95% CI, 0.972.77). No dosereponse relationship was present except for alendro-nate, where the risk was inversely associated with dose, i.e., the risk of DVT/PE decreased with increasing average daily dose. The HR for DVT/PE was higher with clodronate and etidronate than with alendronate. Alendronate and raloxifene carried the same risk for DVT/PE.
Conclusion Bisphosphonates seem associated with an increased risk of DVT/PE. However, the association does not seem to be causal.
Keywords Bisphosphonate . Deep venous thromboembolism . Raloxifene . Strontium ranelate
Raloxifene is a selective estrogen receptor modulator used to treat and prevent osteoporosis in postmenopausal women [15]. However, it has been associated with an increased risk of deep venous thromboembolism (DVT) and pulmonary embolism...