Delayed Denosumab Injections and Fracture Risk Among Patients With Osteoporosis A Population-Based Cohort Study

Lyu, Houchen, Yoshida, Kazuki, Zhao, Sizheng S ORCID: 0000-0002-3558-7353, Wei, Jie, Zeng, Chao, Tedeschi, Sara K, Leder, Benjamin Z, Lei, Guanghua, Tang, Peifu and Solomon, Daniel H (2020) Delayed Denosumab Injections and Fracture Risk Among Patients With Osteoporosis A Population-Based Cohort Study. ANNALS OF INTERNAL MEDICINE, 173 (7). 516-+.

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Abstract

<h4>Background</h4>Denosumab is effective for osteoporosis, but discontinuation leads to rapid reversal of its therapeutic effect.<h4>Objective</h4>To estimate the risk for fracture among users of denosumab who delayed subsequent doses compared with users who received doses on time.<h4>Design</h4>Population-based cohort study.<h4>Setting</h4>The Health Improvement Network U.K. primary care database, 2010 to 2019.<h4>Patients</h4>Persons aged 45 years or older who initiated denosumab therapy for osteoporosis.<h4>Measurements</h4>Observational data were used to emulate an analysis of a hypothetical trial with 3 dosing intervals: subsequent 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"). The primary outcome was a composite of all fracture types at 6 months after the recommended date. Secondary outcomes were major osteoporotic fracture, vertebral fracture, hip fracture, and nonvertebral fracture.<h4>Results</h4>Investigators identified 2594 patients initiating denosumab therapy. The risk for composite fracture over 6 months was 27.3 in 1000 for on-time dosing, 32.2 in 1000 for short delay, and 42.4 in 1000 for long delay. Compared with on-time injections, short delay had a hazard ratio (HR) for composite fracture of 1.03 (95% CI, 0.63 to 1.69) and long delay an HR of 1.44 (CI, 0.96 to 2.17) (<i>P</i> for trend = 0.093). For vertebral fractures, short delay had an HR of 1.48 (CI, 0.58 to 3.79) and long delay an HR of 3.91 (CI, 1.62 to 9.45).<h4>Limitation</h4>Dosing schedules were not randomly assigned.<h4>Conclusion</h4>Although delayed administration of subsequent denosumab doses by more than 16 weeks is associated with increased risk for vertebral fracture compared with on-time dosing, evidence is insufficient to conclude that fracture risk is increased at other anatomical sites with long delay.<h4>Primary funding source</h4>National Clinical Research Center for Orthopedics, Sports Medicine & Rehabilitation.

Item Type:	Article
Uncontrolled Keywords:	Humans, Osteoporosis, Drug Administration Schedule, Risk Factors, Retrospective Studies, Aged, Female, Male, Fractures, Bone, Time-to-Treatment, Denosumab
Depositing User:	Symplectic Admin
Date Deposited:	03 Sep 2020 14:27
Last Modified:	18 Jan 2023 23:39
DOI:	10.7326/M20-0882
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3095578