Issue: November 2020
Perspective from Jacqueline Center, MBBS, PhD
Source/Disclosures
Disclosures: The authors report no relevant financial disclosures.
September 01, 2020
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Atypical femur fracture data support bisphosphonate ‘drug holiday’ after 5 years

Issue: November 2020
Perspective from Jacqueline Center, MBBS, PhD
Source/Disclosures
Disclosures: The authors report no relevant financial disclosures.
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Risk for atypical femur fractures with bisphosphonate therapy, while rare, was strongly associated with duration of use beyond about 5 years and was quickly and dramatically reduced after discontinuing, study data show.

However, risks for osteoporotic and hip fractures, which are more common, are reduced with continuing therapy.

Risk for atypical femur fractures with bisphosphonate therapy is associated with duration of use beyond about 5 years.

“Atypical fractures are extremely rare compared with much more common hip and other osteoporotic fractures that can be prevented with bisphosphonate therapy,” Dennis M. Black, PhD, professor of epidemiology and biostatistics at the University of California, San Francisco, and an adjunct investigator at Kaiser Permanente Southern California, told Healio. “We also were reassured to find that the atypical femur fracture risk was strongly associated with duration of use beyond about 5 years and was quickly and dramatically reduced after discontinuing. This strongly supports the concept of a ‘drug holiday,’ a temporary discontinuation of bisphosphonates after 5 years or so of treatment.”

Dennis M. Black

In a prospective study published in The New England Journal of Medicine, Black and colleagues analyzed data from 196,129 women aged at least 50 years receiving bisphosphonate therapy, who were enrolled in the Kaiser Permanente Southern California health care system; women were followed from 2007 to November 2017. The primary outcome was atypical femur fracture. Data on risk factors, including bisphosphonate use, were obtained from electronic health records. Fractures were radiographically adjudicated.

Researchers modeled a risk-benefit profile for 1 to 10 years of bisphosphonate use to compare associated atypical fractures with other fractures prevented.

Within the cohort, researchers observed 277 atypical femur fractures. After adjustment, risk for atypical fracture increased with longer duration of bisphosphonate use.

Compared with less than 3 months of bisphosphonate therapy, the HR for atypical femur fracture was 8.86 (95% CI, 2.79-28.2) for 3 to 5 years of therapy and rose markedly to 43.51 (95% CI, 13.7-138.15) for 8 years or more of bisphosphonate therapy.

Other risk factors included race; HR for Asian adults vs. white adults was 4.84 (95% CI, 3.57-6.56).

Height, weight and glucocorticoid use were also risk factors for atypical femur fracture, according to researchers.

Bisphosphonate discontinuation was associated with a rapid decrease in the risk for atypical fracture; however, a decrease in the risks for osteoporotic and hip fractures during 1 to 10 years of bisphosphonate use “far outweighed” the increased risk for atypical fracture among white adults. The association was less pronounced for Asian adults, Black said.

“After 3 years, 149 hip fractures were prevented and two bisphosphonate-associated atypical fractures occurred in whites, as compared with 91 and eight, respectively, in Asians,” the researchers wrote.

“The benefits of bisphosphonates and other osteoporosis treatments, including the reduction of the devastating consequences of hip and other fractures, far outweigh the risk for atypical fractures,” Black said. “Risks for atypical femur fracture can be greatly reduced by using drug holidays in many patients. The benefits far outweigh risks among white adults and other ethnic groups that we studied apart from Asian adults, where the balance was more modest. Clinicians might want to focus osteoporosis treatment in Asian women to those at higher risk for hip and spine fractures, for example, those aged 70 years or older or with very low bone density. Shorter duration of therapy and use of a drug holiday might be particularly valuable in Asian patients.”

Black said more research on the pathogenesis of atypical fractures is needed, including why these are more common among Asian Americans.

“Development of risk algorithms for atypical femur fracture that can be used to guide clinical decisions about starting bisphosphonates and taking drug holidays in individual patients is needed,” Black said. “The risk for atypical femur fracture can then be balanced against the benefits for other fracture reductions among individual patients.”

For more information:

Dennis M. Black, PhD, can be reached at dennis.black@ucsf.edu.