Delayed Denosumab Injections and Bone Mineral Density Response: An Electronic Health Record-based Study

J Clin Endocrinol Metab. 2020 May 1;105(5):1435-1444. doi: 10.1210/clinem/dgz321.

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.

Keywords: Osteoporosis; bone mineral density; denosumab; dosing delay.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Bone Density / drug effects*
  • Cohort Studies
  • Denosumab / administration & dosage*
  • Denosumab / adverse effects
  • Drug Administration Schedule
  • Electronic Health Records / statistics & numerical data
  • Female
  • Humans
  • Injections
  • Male
  • Massachusetts / epidemiology
  • Medication Adherence / statistics & numerical data*
  • Middle Aged
  • Osteoporosis / drug therapy*
  • Osteoporosis / epidemiology
  • Retrospective Studies

Substances

  • Denosumab