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11-01-2022 | Osteoporosis | News

Hip fracture risk higher during risedronate versus alendronate drug holiday

Author: Laura Cowen


medwireNews: The risk for hip fracture is higher during a treatment break from risedronate than it is during a break from alendronate, study findings indicate.

Kaleen Hayes (Brown University School of Public Health, Providence, Rhode Island, USA) and colleagues explain that a drug holiday is generally recommended after 3 to 5 years of osteoporosis therapy, but the evidence for this mainly comes from the FLEX trial for alendronate.

They note that the “fracture risk during drug holidays has not been directly compared between alendronate and risedronate,” even though “risedronate has an approximately 50% weaker binding affinity than alendronate and a lower saturation point in bone due to the molecule's more neutral charge,” meaning that “the residual length of fracture protection may be shorter.”

To address this, Hayes et al analyzed propensity score-matched data for 50,154 individuals aged 66 years and older who received at least 3 years of continuous (≥80% adherence) risedronate or alendronate therapy followed by a drug holiday of at least 120 days.

During 3 years of follow-up, which began after a 120-day ascertainment period, 3.3% of all participants experienced a hip fracture.

The incidence rates were 12.4 events per 1000 person–years in the risedronate group and 10.6 events per 1000 person–years in the alendronate group, corresponding to a significant 18% higher risk during risedronate than alendronate drug holidays.

“This relative effect reflects a low increased absolute risk (3-year risk difference of 0.6 per- centage points), with a corresponding number needed to treat of 167 patients with alendronate instead of risedronate to prevent 1 hip fracture,” the researchers write in the Annals of Internal Medicine.

Of note, the association was attenuated and no longer statistically significant when the drug holiday duration was shortened to 1 or 2 years but the hazard ratio increased with increasing length of follow-up. Indeed, when the analyses were limited to 2 to 3 years of follow-up, the risk for hip fracture was a significant 34% higher in the risedronate versus alendronate groups.

Hayes and co-authors stress, however, that their findings “do not indicate that alendronate therapy should be preferred over risedronate therapy.”

“Indeed, several real-world studies identify little difference in fractures while treatment is received,” they say.

The researchers conclude: “To further inform clinical decision making on drug holidays, future research should examine when to start and restart osteoporosis therapy on the basis of initial length and type of treatment, patient characteristics, and relative risk for hip fractures versus [atypical femoral fractures].”

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Ann Intern Med 2022; doi:10.7326/M21-2512