Delayed Denosumab Injections Associated With Increased Vertebral Fracture Risk

Compared with on-time dosing, delayed administration of subsequent denosumab doses by >16 weeks is associated with increased risk for vertebral fracture, according to the results of an observational study published in the Annals of Internal Medicine.

Previous studies have shown that the discontinuation of denosumab injections leads to a rapid reversal of its therapeutic effect in patients with osteoporosis, but the effect of delayed subsequent doses on fracture risk is not yet known.

To estimate the risk for fracture among users of denosumab who received delayed subsequent doses compared with users who received doses on time, data from 2594 patients (94.4% women) aged ≥45 years who were initiating denosumab therapy between 2010 and 2019 were analyzed. The mean age of patients was 75.8±9.5 years. The recommended date of a subsequent denosumab dose was set as 6 months after the prior dose. Patients were categorized as “on time” if they received a subsequent denosumab injection within 4 weeks after the recommended date, those who received delayed subsequent injections by 4 to 16 weeks were categorized as “short delay,” and those who received delayed subsequent injections by >16 weeks were categorized as “long delay.”

No significant increase in cumulative risk for composite fracture was observed in the short and long delay groups compared with the on-time group (32.3 and 42.4 vs 27.3 in 1000, respectively). An increased risk for vertebral fractures was observed in the short delay group (fully adjusted hazard ratio [HR], 1.48; 95% CI, 0.58-3.79) and long delay group (fully adjusted HR, 3.91; 95% CI, 1.62-9.45; P =.005 for trend) compared with the on-time group. When excluding data of individuals who had not experienced a fracture in the 6 months before the start of follow-up, a significant correlation between delayed subsequent injections and major osteoporotic fractures was observed (P =.013 for trend). Major osteoporotic fractures included fractures at the hip, vertebrae, wrist, humerus, pelvis, and rib.

Results of the study indicated that delaying subsequent denosumab doses by >4 months vs on-time dosing was associated with increased risk for vertebral fracture. Timely administration of denosumab injections may be important when used for long-term osteoporosis management.

Study limitations included lack of a placebo group, which prevented analysis in comparison to baseline, and that only the first fracture during follow-up was accounted for.

Researchers concluded, “Because patients who [received] denosumab were at high risk for vertebral fracture, strategies to improve timely administration of denosumab in routine clinical settings are needed.”

Disclosure: One study author declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of author’s disclosures.

Reference

Lyu H, Yoshida K, Zhao SS, et al. Delayed denosumab injections and fracture risk among patients with osteoporosis. Published online July 28, 2020. Ann Intern Med. doi:10.7326/M20-0882