Fractures from Delays in Denosumab Reinfusions Save

Denosumab is effective in osteoporosis when used on schedue, but research suggests that discontinuation leads to rapid reversal of effect; a new observational study has shown that delays in denosumab administration of more than 16 weeks results in an increased vertebral fracture risk, according to a report in Annals of Internal Medicine.

Using data from a U.K. primary care database (The Health Improvement Network), researchers looked at adults initiating denosumab therapy for osteoporosis between 2010 to 2019 and compared fracture rates based on 3 denosumab dosing intervals: 1) on time (denosumab injection given within 4 weeks); 2) short delay (delay of 4 to 16 weeks); and 3) long delay (delay more than 16 weeks).

The cohort included 2594 patients starting denosumab therapy. The risk for composite fracture over 6 months (compared to on-time infusions): 

• Short delay - 32.2 in 1000 (HR 1.03; 95% CI, 0.63 to 1.69)  
• Long delay - 42.4 in 1000 (HR of 1.44; 95% CI, 0.96 to 2.17) (P for trend = 0.093).

A significant increase was noted for vertebral fractures (compared to on-time):

• Short delay - HR of 1.48; CI, 0.58 to 3.79)
• Long delay - HR of 3.91; CI, 1.62 to 9.45)

Delays in denosumab reinfusion by more than 16 weeks was associated with an increased risk for vertebral fracture, but fractures at other sites were no significantly augmented and may require further study. The benefits of denosumab are best when the drug is administered on-time according to plan.