(P-630) Oral Bisphosphonate Exposure Among Denosumab Users in Ontario, Canada

Background: Denosumab is a semi-annual injectable osteoporosis medication indicated for patients who do not tolerate first-line oral bisphosphonates, or who start a recommended drug holiday after 3-5 years of oral bisphosphonate therapy. While denosumab is an effective medication, imminent fracture risk has been reported within 6 months of discontinuation. Fortunately, bisphosphonates persist in bone, and thus may protect against imminent fracture risk after denosumab is discontinued.

Objectives: To estimate the length of oral bisphosphonate exposure prior to denosumab initiation among Ontario seniors, and the proportion of denosumab users returning to osteoporosis therapy following denosumab discontinuation.

Methods: We previously identified 260,784 community-dwelling residents of Ontario, Canada aged ≥65 years who received an oral bisphosphonate (alendronate or risedronate) as their first osteoporosis therapy between November 2000 and December 2016. Patients subsequently dispensed denosumab were eligible for the current study. We described oral bisphosphonate exposure prior to denosumab initiation and used Kaplan-Meier methods to estimate the proportion of patients returning to any osteoporosis therapy after their last denosumab dose, censoring on death or end of available data. Results were compared between patients initiating denosumab after long-term bisphosphonate use (≥3 years of continuous therapy with ≥80% adherence) or short-term use.

Results: We identified 41,187 patients initiating denosumab (mean age=80.4 years, SD=6.9, 91% female). Of these, half (51%) initiated denosumab after long-term bisphosphonate therapy. Patients initiating denosumab after long-term bisphosphonate therapy received their first dose of denosumab sooner (median=7 days, IQR=0-128) following bisphosphonate discontinuation compared to patients with short-term bisphosphonate therapy (median=193 days, IQR=2-1,098). Both groups received a median of 4 denosumab doses, equivalent to approximately 2 years of therapy. Only 9% of patients (12% after long-term bisphosphonate exposure, 7% after short-term) returned to any osteoporosis therapy within a year following their last denosumab dose.

Conclusions: Approximately half of patients who start denosumab have <3 years of oral bisphosphonate exposure. In addition, only 9% return to any osteoporosis therapy within a year of their last denosumab dose. Further research is warranted that considers fracture risk after denosumab therapy relative to amount of prior bisphosphonate exposure.