Use of oral bisphosphonates and risk of venous thromboembolism: a population-based case-control study

Abstract

Oral bisphosphonates are widely used for fracture prevention, but there is a concern regarding potential adverse cardiovascular effects of bisphosphonates. In this large, population-based case-control study, we found no evidence of an association between bisphosphonate use and risk of venous thromboembolism (VTE). We examined the relation between the use of oral bisphosphonates for osteoporosis and the risk of VTE. We conducted a population-based case-control study in Northern Denmark (population, 1.7 million). Using the Danish National Registry of Patients, we identified all women with a first-time hospital diagnosis of VTE between 1999 and 2006. For each case, we selected up to ten female population controls, matched on date of the index VTE event and age. Data on use of oral bisphosphonates, other medications, and comorbidity were obtained from medical databases. We used logistic regression to estimate odds ratios (OR) for VTE associated with bisphosphonate users while adjusting for potential confounding factors. Four thousand one hundred ninety-three cases and 41,197 controls were included in the study. One hundred forty-nine cases (3.6%) and 1,078 controls (2.6%) were current bisphosphonate users. The adjusted OR for VTE among the current bisphosphonate users compared with nonusers was 1.03 (95% confidence interval (CI): 0.84-1.26), and when restricted to cases of unprovoked thromboembolism, the adjusted OR was 1.08 (95% CI: 0.82-1.42). There was no association either for pulmonary embolism or for deep venous thrombosis. We found no evidence of an association of oral bisphosphonate use with the risk of VTE.