Effect of Oral Bisphosphonate Drug Holiday on Mortality Following Hip Fracture

CONTEXT: Current clinical guidelines recommend a drug holiday after extended use of oral bisphosphonates. However, no studies have investigated the effect of drug holidays before hip fractures on postfracture mortality. 

OBJECTIVE: This work aimed to investigate the effect of a drug holiday on postfracture mortality in patients with extended use of oral bisphosphonates. 

METHODS: This retrospective, population-based cohort study took place among all patients with hip fractures in Victoria, Australia, from 2014 to 2018. Patients were adherent to oral alendronate or risedronate for 5 years or more prior to hip fracture. Group-based trajectory modeling categorized patients into different bisphosphonate usage after 5-year good adherence. The main outcome measure was postfracture mortality. 

RESULTS: We identified 365 patients with good adherence (medication possession ratio ≥80%) to oral alendronate/risedronate for 5 years or more. Most patients (69%) continued to use oral bisphosphonates until admission for hip fracture; 17% had discontinued for 1 year and 14% had discontinued for 2 years. Postfracture mortality was higher in patients who had discontinued risedronate for 1 year (hazard ratio [HR] 2.37; 95% CI, 1.24-4.53) and 2 years (HR 3.08; 95% CI, 1.48-6.41) prior to hip fracture. No increase or decrease in postfracture mortality was observed in patients who had discontinued alendronate for 1 year (HR 0.59; 95% CI, 0.29-1.18) or 2 years (HR 1.05; 95% CI, 0.57-1.93) prior to hip fracture. 

CONCLUSION: Postfracture mortality is higher in people who discontinue risedronate, but not alendronate, for 1 or 2 years after being adherent to treatment for at least 5 years. The type of bisphosphonate may be a factor to consider when planning drug holidays.