Adherence to denosumab therapy and fracture risk associated with drug withdrawal: a retrospective study

To assess the prevalence of fragility fractures after denosumab discontinuation and to identify the factors affecting treatment adherence.

We retrospectively reviewed the medical records of 3876 osteoporosis patients who were treated with denosumab at Trakya University Osteoporosis Clinic between 2015 and 2021. A total of 210 patients who received at least two regular doses of denosumab were eligible for inclusion. Patients were categorized as denosumab-adherent and denosumab-non-adherent. Adherence was defined as receiving the six-month scheduled dose with a maximum delay of up to eight weeks.

Overall, 124 (59.05%) patients were denosumab-adherent and 86 patients (40.95%) were denosumab-non-adherent. New fragility fractures were identified in 32 patients: 17 in the denosumab-adherent group and 15 in the denosumab-non-adherent group. The groups did not significantly differ in the risk or types of new fractures, irrespective of patients' fracture history.

Our findings suggest that some fractures after denosumab discontinuation may stem from the natural progression of osteoporosis rather than from the rebound effect. Still, unscheduled treatment discontinuation should be prevented.