Impact of oral bisphosphonate drug holiday on mortality following hip fracture: a population-based cohort study

J Clin Endocrinol Metab. 2024 Apr 17:dgae272. doi: 10.1210/clinem/dgae272. Online ahead of print.

Abstract

Context: Current clinical guidelines recommend a drug holiday after extended use of oral bisphosphonates. However, no studies have investigated the impact of drug holidays before hip fractures on post-fracture mortality.

Objective: To investigate the effect of drug holiday on post-fracture mortality in patients with extended use of oral bisphosphonates.

Design: Retrospective population-based cohort study.

Setting: All patients with hip fractures in Victoria, Australia from 2014-18.

Patients: Patients adherent to oral alendronate or risedronate for ≥5 years prior to hip fracture.

Intervention(s): Group-based trajectory modelling categorized patients into different bisphosphonate usage after 5-year good adherence.

Main outcome measure(s): Post-fracture mortality.

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

Conclusions: Post-fracture 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.

Keywords: antiresorptive medication; bisphosphonate; hip fracture; osteoporosis.