Association of Delayed Denosumab Dosing with Increased Risk of Fractures: A Population-Based Retrospective Study
Background Inhibitory effects of denosumab on bone remodeling are reversible and disappear once treatment is discontinued. Herein, we examined whether and to what extent delayed denosumab administration is also associated with fracture risk using nation-wide data. Methods The study cohort included w...
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Korean Endocrine Society
2024-12-01
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| Series: | Endocrinology and Metabolism |
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| Online Access: | http://www.e-enm.org/upload/pdf/enm-2024-2047.pdf |
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| author | Kyoung Min Kim Seol A Jang Nam Ki Hong Chul Sik Kim Yumie Rhee Seok Won Park Steven R. Cummings Gi Hyeon Seo |
| author_facet | Kyoung Min Kim Seol A Jang Nam Ki Hong Chul Sik Kim Yumie Rhee Seok Won Park Steven R. Cummings Gi Hyeon Seo |
| author_sort | Kyoung Min Kim |
| collection | DOAJ |
| description | Background Inhibitory effects of denosumab on bone remodeling are reversible and disappear once treatment is discontinued. Herein, we examined whether and to what extent delayed denosumab administration is also associated with fracture risk using nation-wide data. Methods The study cohort included women aged 45 to 89 years who were started on denosumab for osteoporosis between October 2017 and December 2019 using data from the Korean Health Insurance Review and Assessment service. Participants were stratified according to the time of their subsequent denosumab administration from the last denosumab administration, including those with within 30 days early dosing (ED30), within the planned time of 180–210 days (referent), within 30–90 days of delayed dosing (DD90), within 90–180 days of delayed dosing (DD180), and longer than 181 days of delayed dosing (DD181+). The primary outcome was the incidence of all clinical fractures. Results A total of 149,199 participants included and 2,323 all clinical fractures (including 1,223 vertebral fractures) occurred. The incidence of all fractures was significantly higher in the DD90 compared to reference group (hazard ratio [HR], 1.2; 95% confidence interval [CI], 1.1 to 1.4). The risk of all fracture was even higher in the longer delayed DD180 group (HR, 1.9; 95% CI, 1.6 to 2.3) and DD181+ group (HR, 1.8; 95% CI, 1.5 to 2.2). Increased risks of fractures with delayed dosing were consistently observed for vertebral fractures. Conclusion Delayed denosumab dosing, even by 1 to 3 months, was significantly associated with increased fracture risk. Maintaining the correct dosing schedule should be emphasized when starting denosumab. |
| format | Article |
| id | doaj-art-d8b90d1fc62a4aeeb53d73fd2c3dcdfc |
| institution | Kabale University |
| issn | 2093-596X 2093-5978 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Korean Endocrine Society |
| record_format | Article |
| series | Endocrinology and Metabolism |
| spelling | doaj-art-d8b90d1fc62a4aeeb53d73fd2c3dcdfc2025-01-03T05:15:26ZengKorean Endocrine SocietyEndocrinology and Metabolism2093-596X2093-59782024-12-0139694695510.3803/EnM.2024.20472552Association of Delayed Denosumab Dosing with Increased Risk of Fractures: A Population-Based Retrospective StudyKyoung Min Kim0Seol A Jang1Nam Ki Hong2Chul Sik Kim3Yumie Rhee4Seok Won Park5Steven R. Cummings6Gi Hyeon Seo7 Division of Endocrinology, Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Korea Division of Endocrinology, Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Korea Division of Endocrinology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea Division of Endocrinology, Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Korea Division of Endocrinology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea Division of Endocrinology, Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Korea Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA Health Insurance Review & Assessment Service, Wonju, KoreaBackground Inhibitory effects of denosumab on bone remodeling are reversible and disappear once treatment is discontinued. Herein, we examined whether and to what extent delayed denosumab administration is also associated with fracture risk using nation-wide data. Methods The study cohort included women aged 45 to 89 years who were started on denosumab for osteoporosis between October 2017 and December 2019 using data from the Korean Health Insurance Review and Assessment service. Participants were stratified according to the time of their subsequent denosumab administration from the last denosumab administration, including those with within 30 days early dosing (ED30), within the planned time of 180–210 days (referent), within 30–90 days of delayed dosing (DD90), within 90–180 days of delayed dosing (DD180), and longer than 181 days of delayed dosing (DD181+). The primary outcome was the incidence of all clinical fractures. Results A total of 149,199 participants included and 2,323 all clinical fractures (including 1,223 vertebral fractures) occurred. The incidence of all fractures was significantly higher in the DD90 compared to reference group (hazard ratio [HR], 1.2; 95% confidence interval [CI], 1.1 to 1.4). The risk of all fracture was even higher in the longer delayed DD180 group (HR, 1.9; 95% CI, 1.6 to 2.3) and DD181+ group (HR, 1.8; 95% CI, 1.5 to 2.2). Increased risks of fractures with delayed dosing were consistently observed for vertebral fractures. Conclusion Delayed denosumab dosing, even by 1 to 3 months, was significantly associated with increased fracture risk. Maintaining the correct dosing schedule should be emphasized when starting denosumab.http://www.e-enm.org/upload/pdf/enm-2024-2047.pdfdenosumabfracturesosteoporosisdiscontinuation |
| spellingShingle | Kyoung Min Kim Seol A Jang Nam Ki Hong Chul Sik Kim Yumie Rhee Seok Won Park Steven R. Cummings Gi Hyeon Seo Association of Delayed Denosumab Dosing with Increased Risk of Fractures: A Population-Based Retrospective Study Endocrinology and Metabolism denosumab fractures osteoporosis discontinuation |
| title | Association of Delayed Denosumab Dosing with Increased Risk of Fractures: A Population-Based Retrospective Study |
| title_full | Association of Delayed Denosumab Dosing with Increased Risk of Fractures: A Population-Based Retrospective Study |
| title_fullStr | Association of Delayed Denosumab Dosing with Increased Risk of Fractures: A Population-Based Retrospective Study |
| title_full_unstemmed | Association of Delayed Denosumab Dosing with Increased Risk of Fractures: A Population-Based Retrospective Study |
| title_short | Association of Delayed Denosumab Dosing with Increased Risk of Fractures: A Population-Based Retrospective Study |
| title_sort | association of delayed denosumab dosing with increased risk of fractures a population based retrospective study |
| topic | denosumab fractures osteoporosis discontinuation |
| url | http://www.e-enm.org/upload/pdf/enm-2024-2047.pdf |
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