Invasive Oral Procedures and Events in Postmenopausal Women With Osteoporosis Treated With Denosumab for Up to 10 Years

Abstract

Context Antiresorptive therapy has been associated with osteonecrosis of the jaw (ONJ), an infrequent but potentially serious adverse event. Objective To assess information on invasive oral procedures and events (OPEs) – dental implants, tooth extraction, natural tooth loss, scaling/root planing, jaw surgery – during the 7-year FREEDOM Extension and to present details of positively adjudicated ONJ cases. Design Randomized, double-blind, placebo-controlled 3-year trial (FREEDOM) followed by 7 years of open-label denosumab (FREEDOM Extension). At Extension Year 3, women were asked to record their history of invasive OPEs since the start of the Extension to Year 2.5 and oral events in the prior 6 months. The questionnaire was then administered every 6 months (Q6M) until the end of the Extension. Setting Multicenter, multinational clinical trial. Patients Women with postmenopausal osteoporosis. Interventions Subcutaneous denosumab 60mg or placebo Q6M for 3-years, then 7 years of open-label denosumab. Main Outcome Measures Self-reports of OPEs and adjudicated cases of ONJ. Results 45.1% of respondents reported at least one invasive OPE. The exposure-adjusted ONJ rate in FREEDOM Extension was 5.2 per 10,000 subject-years. ONJ incidence was higher in those reporting an OPE (0.68%) than not (0.05%). Conclusions While invasive OPEs were common in these denosumab-treated women and were associated with an increased ONJ incidence, the overall rate of ONJ was low, and all cases with complete follow-up resolved with treatment.