Delayed denosumab injections and bone mineral density response: An Electronic Health Record-based Study

Abstract

Context: Discontinuation of denosumab leads to a rapid reversal of its therapeutic effect. However, there are no data regarding how unintended delays or missed injections of denosumab impact bone mineral density (BMD) response. Objective: We examined the association of delays in injections of denosumab with BMD change. Design: We used electronic medical records from two academic hospitals from 2010 to 2017. Participants: Patients older than 45 years of age and used at least 2 doses of 60 mg denosumab. Denosumab adherence was evaluated by the medication coverage ratio (MCR). Good adherence corresponds to a dosing interval ≤7 months (defined by MCR ≥93%), moderate adherence corresponds to an interval of 7 to 10 months (MCR 75%–93%), and poor adherence corresponds to an interval ≥10 months (MCR ≤75%). Outcome Measures: Annualized percent BMD change from baseline at the lumbar spine, total hip, and femoral neck. Results: We identified 938 denosumab injections among 151 patients; the mean (SD) age was 69 (10) years, and 95% were female. Patients with good adherence had an annualized BMD increase of 3.9% at the lumbar spine, compared with patients with moderate (3.0%) or poor adherence (1.4%, P for trend .002). Patients with good adherence had an annualized BMD increase of 2.1% at the total hip, compared with patients with moderate (1.3%) or poor adherence (0.6%, P for trend .002). Conclusions: A longer interval between denosumab injections is associated with suboptimal BMD response at both spine and total hip. Strategies to improve the timely administration of denosumab in real-world settings are needed.