TY - JOUR
T1 - Use of bisphosphonates and raloxifene and risk of deep venous thromboembolism and pulmonary embolism
AU - Vestergaard, P
AU - Schwartz, K
AU - Pinholt, E M
AU - Rejnmark, Lars
AU - Mosekilde, Leif
PY - 2010/9/1
Y1 - 2010/9/1
N2 - 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), 0.39-0.71). After start of a drug, alendronate (HR=1.20, 95% CI, 1.00-1.43), clodronate (HR=4.06, 95% CI, 1.47-11.2), and etidronate (HR=1-37, 95% CI, 1.23-1.51) 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, 0.97-2.77). No dose-reponse relationship was present except for alendronate, 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.
AB - 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), 0.39-0.71). After start of a drug, alendronate (HR=1.20, 95% CI, 1.00-1.43), clodronate (HR=4.06, 95% CI, 1.47-11.2), and etidronate (HR=1-37, 95% CI, 1.23-1.51) 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, 0.97-2.77). No dose-reponse relationship was present except for alendronate, 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.
KW - Aged
KW - Aged, 80 and over
KW - Bone Density Conservation Agents
KW - Denmark
KW - Diphosphonates
KW - Dose-Response Relationship, Drug
KW - Epidemiologic Methods
KW - Female
KW - Humans
KW - Male
KW - Middle Aged
KW - Organometallic Compounds
KW - Osteoporosis
KW - Pulmonary Embolism
KW - Raloxifene
KW - Thiophenes
KW - Venous Thromboembolism
U2 - 10.1007/s00198-009-1091-y
DO - 10.1007/s00198-009-1091-y
M3 - Journal article
C2 - 19859641
SN - 0937-941X
VL - 21
SP - 1591
EP - 1597
JO - Osteoporosis International
JF - Osteoporosis International
IS - 9
ER -