Delayed Denosumab Injections Increase Vertebral Fracture Risks

Takeaway

• Delayed administration of subsequent denosumab doses by >16 weeks is associated with an increased risk of vertebral fracture among patients with osteoporosis compared with on-time administration.
• However, evidence is insufficient to conclude that fracture risk is increased at other anatomical sites with a long delay.

Why this matters

• Findings highlight the importance of timely administration of denosumab for long-term management of osteoporosis.

Study design

• This population-based cohort study included 2594 patients (age, ≥45 years) who initiated denosumab therapy for osteoporosis using data from The Health Improvement Network (THIN).
• Fracture risk was estimated among denosumab users who delayed subsequent doses (delay by 4-16 weeks [short delay] and delay by >16 weeks [long delay]) vs users who received doses on time (within 4 weeks after the recommended date).           
• Funding: National Clinical Research Center for Orthopedics, Sports Medicine & Rehabilitation.

Key results

• Composite fracture:
  • The cumulative risk over 6 months was as follows:
    • on-time injections: 27.3 in 1000;
    • short delay: 32.2 in 1000; and
    • long delay: 42.4 in 1000.
  • Compared with on-time injections:
    • short delay had a fracture risk difference of 4.8 (95% CI, −1.2 to 10.1) in 1000 over 6 months, with an HR of 1.03 (95% CI, 0.63-1.69); and
    • long delay of 15.0 (95% CI, 1.4-33.5) in 1000, with an HR of 1.44 (95% CI, 0.96-2.17).
• Vertebral fracture:
  • The cumulative risk over 6 months was as follows:
    • on-time injections: 2.2 in 1000;
    • short delay: 3.6 in 1000; and
    • long delay: 10.1 in 1000.
  • Compared with on-time injections:
    • short delay had a fracture risk difference of 1.4 (95% CI, −0.6 to 2.4) in 1000 over 6 months, with an HR of 1.48 (95% CI, 0.58-3.79); and
    • long delay of 7.9 (95% CI, 1.1-16.6) in 1000, with an HR of 3.91 (95% CI, 1.62-9.45).

Limitations

• Dosing schedules were not randomly assigned.

This clinical summary first appeared on Univadis, part of the Medscape Professional Network.