Comparative Fracture Risk During Osteoporosis Drug Holidays After Long-Term Risedronate Versus Alendronate Therapy

A Propensity Score–Matched Cohort Study



An osteoporosis drug holiday is recommended for most patients after 3 to 5 years of therapy. Risedronate has a shorter half-life than alendronate, and thus the residual length of fracture protection may be shorter.


To examine the comparative risks of drug holidays after long-term (≥3 years) risedronate versus alendronate therapy.


Population-based, matched, cohort study.


Province-wide health care administrative databases providing comprehensive coverage to Ontario residents aged 65 years or older between November 2000 and March 2020.


Persons aged 66 years or older who had long-term risedronate therapy and a drug holiday were matched 1:1 on propensity score to those who had long-term alendronate therapy and a drug holiday.


The primary outcome was hip fracture within 3 years after a 120-day ascertainment period. Secondary analyses included shorter follow-up and sex-specific estimates. Cox proportional hazards models were used to estimate hazard ratios (HRs) for fracture risk between groups.


A total of 25 077 propensity score–matched pairs were eligible (mean age, 81 years; 81% women). Hip fracture rates were higher among risedronate than alendronate drug holidays (12.4 and 10.6 events, respectively, per 1000 patient-years; HR, 1.18 [95% CI, 1.04 to 1.34]; 915 total hip fractures). The association was attenuated when any fracture was included as the outcome (HR, 1.07 [CI, 1.00 to 1.16]) and with shorter drug holidays (1 year: HR, 1.03 [CI, 0.85 to 1.24]; 2 years: HR, 1.14 [CI, 0.96 to 1.32]).


Analyses were limited to health care administrative data (potential unmeasured confounding), and some secondary analyses contained few events.


Drug holidays after long-term therapy with risedronate were associated with a small increase in risk for hip fracture compared with alendronate drug holidays. Future research should examine how best to mitigate this risk.

Primary Funding Source:

Canadian Institutes of Health Research.

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