Osteoporosis Drugs and Atrial Fibrillation (AF)

The bisphosphonate drugs have had a long run. They were first investigated in the 1960s for their actions on bone metabolism; by interfering with the action of the osteoclasts cells, they delay the breakdown of bone that occurs in certain diseases, like osteoporosis and Paget’s disease of bone. Starting with once daily administration, the drugs in this class have progressed to once-a-week, once-a-month, and then once-a-year-by-IV-infusion.

The first reports that a bisphosphonate therapy might be associated with an increased risk of atrial fibrillation (AF) came with a study of once-yearly zoledronic acid reported in the New England Journal of Medicine. Over a 3-year period, in 7,750 women in their 70s, 50 on zoledronic acid and 20 on placebo developed severe AF. This led to the study with alendronate (Fosamax®) recently reported in the Archives of Internal Medicine.

Researchers at a large healthcare system in Washington State , USA , identified roughly 700 older women who had experienced AF, and matched them with nearly 1000 women who had not. Overall, 6.5% of the AF women and 4.1% of the ‘controls’ had used alendronate at one time or another. After adjusting for possibly confusing factors, such as previous cardiovascular disease, the odds of developing AF was 1.8 times higher in the alendronate users. The risk associated with alendronate was higher in women with diabetes, as well as in current statin users.
The authors of the alendronate study concluded: "The benefits of fracture prevention in patients at high risk for fracture will generally outweigh the possible risk of AF. However, it is important to carefully weigh the benefits against the possible risk of AF in women who have only modestly increased fracture risk and in women who have risk factors for AF, such as diabetes mellitus, coronary disease, or heart failure." That seems a fair position for the decision to use alendronate or not. But what about a once-a-year intravenous infusion? You can’t readily stop exposure to the drug by not taking it . . .