Bisphosphonates and risk of stroke: self controlled case series study

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The problem

Calcium, vitamin D and bisphosphonates are commonly and increasingly being prescribed to prevent fragility fractures due to osteoporosis. Concerns arise that these drugs may adversely affect cardiovascular risk since calcium and vitamin D have been found to be associated with a higher incidence of stroke and myocardial infarction. We aimed to investigate whether there is similar association between bisphosphonate use and risk of stroke using the self-controlled case series method.

The approach

We used a within person case series design to assess the risk of stroke associated with use of bisphosphonate drugs. The Clinical Practice Research Database (CPRD) was used to extract records of patients aged 18 years or over (living or dead) recorded with stroke (fatal or non-fatal) from September 2001 to May 2009. Statistical modelling with conditional Poisson regression in Stata12 was employed to compute incidence rate ratios (IRR) for stroke in patients on bisphosphonates commonly used to prevent fragility fracture including alendronic acid, etidronate disodium, ibandronic acid and risedronate sodium in different doses and formulations. The incidence rate of stroke during prescription of bisphosphonates was compared with the incidence rate during a baseline period.


We included 1386 patients with stroke in the analysis. The incidence rate ratio of stroke showed no statistical significance for exposure to bisphosphonates compared with the baseline period. The lack of association between bisphosphonates and risk of stroke (IRR 0.87; 95% CI 0.76-1.01) persisted even taking into account different durations of exposure.


We found no association between bisphosphonate treatment and risk of stroke. Bisphosphonates may be a safer alternative to calcium, vitamin D or combinations of these drugs for prevention of osteoporosis and fractures in people at risk of cardiovascular disease.


  • Zahid Asghar
  • Ana Ana L G Caballero
  • Niroshan Siriwardena