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Bisphosphonates increase risk of serious atrial fibrillation by a small amount

Sharma A, Chatterjee S, Arbab-Zadeh A, et al. Risk of serious atrial fibrillation and stroke with use of bisphosphonates: evidence from a meta-analysis. Chest. 2013;144:1311-22.

Review question

Are bisphosphonates associated with serious atrial fibrillation, stroke, or cardiovascular death?


Osteoporosis is a condition that causes the bones to become weak or brittle and more likely to break if a person falls. Older people and women who have reached menopause are at greater risk of osteoporosis. Bisphosphonates are a type of drug used to increase bone strength and prevent bone fractures (or breaks) in people with osteoporosis. There is some concern that bisphosphonates may increase the risk of atrial fibrillation, stroke, or death due to cardiovascular causes.

How the review was done

The researchers did a systematic review, searching for studies published up to April 2012. They found 12 studies, including 6 randomized controlled trials with 41,375 people (average age 67 to 75 years).

Key features of the 6 randomized controlled trials were:

  • people were men or postmenopausal women with osteoporosis, or men and women 50 years or older who had surgery for hip fracture;
  • bisphosphonates included zoledronic acid (Reclast®, Zometa®), alendronate (Fosamax®), risedronate (Actonel®, Atelvia®), and ibandronate (Boniva®), and were taken by mouth (pills) or intravenously (by needle into a vein); and
  • bisphosphonates were compared with placebo in 5 trials and with a low-dose bisphosphonate (ibandronate) in 1 trial.

What the researchers found

All 6 randomized trials were rated as good quality.

Compared with placebo or low-dose ibandronate, bisphosphonates:

  • increased serious atrial fibrillation by about 0.13% (from 0.66% to 0.79%)
  • did not increase risk of stroke; and
  • did not increase risk of death due to cardiovascular causes.


Bisphosphonates increase risk of serious atrial fibrillation by a small amount. They do not increase risks of stroke or death due to cardiovascular causes.

Bisphosphonates vs placebo or low-dose ibandronate*


Number of trials (people)

Rate of events with bisphosphonates

Rate of events with placebo or low-dose ibandronate

Absolute effect of bisphosphonates at 2 to 6 years

Serious atrial fibrillation

6 trials (41,375)

0.79% (less than 1%)

0.66% (less than 1%)

13 more people out of 10,000 had serious atrial fibrillation


4 trials (26,159)



No difference†

Death due to cardiovascular causes

4 trials (26,159)



No difference†

*Based on results from randomized controlled trials only.

†Although the rates for the 2 groups look a little different, the differences were not statistically significant. This means that the differences could simply be due to chance rather than due to the different treatments.


A harmless, inactive, and simulated treatment.
Randomized controlled trials
Studies where people are assigned to one of the treatments purely by chance.
Systematic review
A comprehensive evaluation of the available research evidence on a particular topic.
The body's network of blood vessels. It includes the arteries, veins, and capillaries that carry blood to and from the heart.
Vascular death
Death from circulatory problems.

Related Web Resources

  • Preventing Blood Clots After Hip or Knee Replacement Surgery or Surgery for a Broken Hip: A Review of the Research for Adults

    This patient decision aid helps adults considering or planning to have a total hip or knee replacement surgery or surgery for a broken hip decide on the best method for preventing blood clots after surgery. It facilitates the process by outlining and comparing the benefits, risks and side effects of each treatment option.
  • Healthy Bones: A Decision Aid for Women After Menopause

    This patient decision aid helps women who have gone through menopause and may have osteoporosis decide on methods to keep your bones healthy. It facilitates the process by outlining and comparing the choices such as medicine, menopausal hormone therapy (MHT), and exercise.
  • Osteoporosis screening: topic overview

    Health Link B.C.
    Osteoporosis Canada recommends everyone over age 65 have routine bone density tests. Start routine testing earlier if you are at increased risk for broken bones. Use the FRAX tool to predict your risk of having a fracture related to osteoporosis (link in this resource).
DISCLAIMER These summaries are provided for informational purposes only. They are not a substitute for advice from your own health care professional. The summaries may be reproduced for not-for-profit educational purposes only. Any other uses must be approved by the McMaster Optimal Aging Portal (

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