Prof Douglas Bauer

The absolute risk of atypical femoral fractures (AFF) with bisphosphonate use is very small and disappears after stopping therapy,  a nationwide Danish analysis has confirmed.

With uncertainty over the risk of atypical fractures still deterring use of bisphosphonates and also creating doubts about the need for ‘drug holidays’, US researchers investigated the absolute numbers of AFF using a national radiographic imaging database that encompassed all fractures reported for the Danish population between 2010 and 2015.

Presenting the findings at ASBMR 2020 virtual meeting, Professor Douglas Bauer, an osteoporosis researcher at the University of California, San Francisco (UCSF) said the study showed there were just 189 AFF found out of 4973 subtrochanteric and femoral shaft fractures in the over 50 population database after review by blinded radiologists, and one third of AFF were in patients who had no history of bisphosphonate use.

For comparison, a matched control group of almost 36,000 people over the age of 50 was used to compare risk factors. The national medication database showed that almost 10% of the older population had used bisphosphonates.

The investigators calculated the absolute risk of AFF to be 0.07/10,000 person years for people unexposed to bisphosphonates, 0.64 for people with less than one year of use and 4.19/10,000 for people with five to seven years of bisphosphonate use.

By comparison, the risk of hip fracture in the same age group was around 43/10,000 person years, Professor Bauer noted.

So while the relative risk of AFF appeared to be high with bisphosphonate use – at around ten times higher up to one year of use and 35 times higher  with three to five years use, the absolute numbers were extremely low, he said.

Other risk factors for AFF included use of corticosteroid and PPIs, and a history of rheumatoid arthritis.

The study also showed that after stopping bisphosphonates, the risk of AFF fell by almost 75% after one year (RR 0.26) compared to current use.

“This suggests that bisphosphonate holidays may be useful in some patients to reduce the risk of AFF,” said Professor Bauer.

The study was funded by the US government National Institute for Arthritis, Musculoskeletal and Skin Diseases (NIAMS).