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

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, and jaw surgery-during the 7-year Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months (FREEDOM) Extension study 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 until the end of the Extension.

SETTING: Multicenter, multinational clinical trial.

PATIENTS: Postmenopausal women with osteoporosis.

INTERVENTIONS: Subcutaneous denosumab 60 mg or placebo every 6 months for 3 years, then 7 years of open-label denosumab.

MAIN OUTCOME MEASURES: Self-reports of OPEs and adjudicated cases of ONJ.

RESULTS: Of respondents, 45.1% reported at least one invasive OPE. The exposure-adjusted ONJ rate in FREEDOM Extension was 5.2 per 10,000 person-years. ONJ incidence was higher in those reporting an OPE (0.68%) than not (0.05%).

CONCLUSIONS: Although 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.