Key clinical point: Delaying denosumab doses by more than 16 weeks is associated with an increased risk of vertebral fracture in patients with osteoporosis vs. on-time injections. However, evidence is insufficient to conclude that fracture risk is increased at other anatomical sites with a long delay.

Major finding: Compared with on-time injections (within 4 weeks after the recommended date), short delay (by 4-16 weeks) had a hazard ratio (HR) of 1.03 and long delay (by more than 16 weeks) an HR of 1.44 (P for trend = .093) for composite fracture. For vertebral fractures, short delay had an HR of 1.48 and long delay an HR of 3.91 (P for trend = .005).

Study details: This U.K. population-based cohort study included 2,594 patients (age, 45 years or older) who initiated denosumab therapy for osteoporosis.

Disclosures: The study was supported by a grant from the National Institutes of Health and by the internal resources from the National Clinical Research Center for Orthopedics, Sports Medicine & Rehabilitation (Beijing) and Xiangya Hospital, Central South University. The authors declared no conflicts of interest in relation to the subject of the study. Three of the authors reported receiving grants from 1 or more pharma companies, outside the submitted work.

Commentary

“Denosumab is an effective antiosteoporosis medication, but its discontinuation results in rapid bone loss and, even more concerning, multiple vertebral fractures. While delayed denosumab dosing is associated with decreased improvements in bone mineral density, fracture risk is unknown in this common clinical scenario. Using data from the U.K. population-based cohort, the investigators simulated a hypothetical trial of denosumab discontinuation with 3 dosing intervals: denosumab injection given within 4 weeks after the recommended date (“on time”), delay by 4 to 16 weeks (“short delay”), and delay by more than 16 weeks (“long delay”).

At 6 months after the recommended injection date, compared to those who received denosumab on time, those who had a short delay in denosumab had a 3% increased risk for composite fractures while those who had a long delay had a 44% increased risk for composite fracture (P for trend = .093). A short delay increases the risk of vertebral fracture by 48%, while a long delay increased the risk by almost 4-fold (P for trend = .005). These results underscore the importance of timely denosumab administration and the need for clinical protocols that ensure optimal adherence to denosumab in routine care.”

Maria I. Danila, MD, MSc, MSPH

University of Alabama at Birmingham