Delayed denosumab injections up fracture risk in osteoporotic patients

Delayed administration of subsequent denosumab doses by >16 weeks may lead to additional vertebral fracture risk compared with on-time dosing, results of a population-based cohort study have shown. However, there is not enough evidence to conclude that fracture risk is elevated at other anatomical sites with long delay.

The investigators accessed the Health Improvement Network UK primary care database to identify patients aged ≥45 years who initiated denosumab therapy for osteoporosis between 2010 and 2019. They used observational data to emulate an analysis of a hypothetical trial with three dosing intervals: subsequent denosumab injection given within 4 weeks after the recommended data (on time), delay by 4–16 weeks (short delay), and delay by >16 weeks (long delay).

A total of 2,594 patients initiating denosumab therapy were identified. Over 6 months, the risk for composite fracture was 27.3 in 1,000 for on-time dosing, 32.2 in 1,000 for short delay, and 42.4 in 1,000 for long delay.

Delays in denosumab injections were associated with increased composite fracture risk compared with on-time dosing: short delay hazard ratio (HR), 1.03, 95 percent confidence interval [CI], 0.63–1.69; long delay HR, 1.44, 95 percent CI, 0.96–2.17 (p_trend=0.093). Both short delay (HR, 1.48, 95 percent CI, 0.58–3.79) and long delay (HR, 3.91, 95 percent CI, 1.62–9.45) increased the risk for vertebral fractures.

This study, however, was limited by dosing schedules that were not randomly assigned.

“Denosumab is effective for osteoporosis, but discontinuation leads to rapid reversal of its therapeutic effect,” the investigators noted.