Delayed Denosumab Injections and Fracture Risk Among Patients With Osteoporosis : A Population-Based Cohort Study.
BACKGROUND: Denosumab is effective for osteoporosis, but discontinuation leads to rapid reversal of its therapeutic effect.
OBJECTIVE: To estimate the risk for fracture among users of denosumab who delayed subsequent doses compared with users who received doses on time.
DESIGN: Population-based cohort study.
SETTING: The Health Improvement Network U.K. primary care database, 2010 to 2019.
PATIENTS: Persons aged 45 years or older who initiated denosumab therapy for osteoporosis.
MEASUREMENTS: 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.
RESULTS: 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) (P 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).
LIMITATION: Dosing schedules were not randomly assigned.
CONCLUSION: 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.
PRIMARY FUNDING SOURCE: National Clinical Research Center for Orthopedics, Sports Medicine & Rehabilitation.
|ジャーナル名||Annals of internal medicine|
|投稿者||Lyu, Houchen; Yoshida, Kazuki; Zhao, Sizheng S; Wei, Jie; Zeng, Chao; Tedeschi, Sara K; Leder, Benjamin Z; Lei, Guanghua; Tang, Peifu; Solomon, Daniel H|
|組織名||National Clinical Research Center for Orthopedics, Sports Medicine &;Rehabilitation, General Hospital of Chinese PLA, Beijing, China, Xiangya Hospital;of Central South University, Changsha, China, and Brigham and Women's Hospital,;Boston, Massachusetts (H.L.).;Brigham and Women's Hospital, Boston, Massachusetts (K.Y., S.K.T.).;Institute of Life Course and Medical Sciences, University of Liverpool,;Liverpool, United Kingdom (S.S.Z.).;Health Management Center, Xiangya Hospital of Central South University, Changsha,;China (J.W.).;Xiangya Hospital of Central South University, Changsha, China (C.Z.).;Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts;(B.Z.L.).;National Clinical Research Center for Geriatric Disorders, Xiangya Hospital of;Central South University, and Hunan Key Laboratory of Joint Degeneration and;Injury, Changsha, China (G.L.).;Rehabilitation, General Hospital of Chinese PLA, Beijing, China (P.T.).;Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts;(D.H.S.).|