Shau-Huai Fu1,2,3, Chen-Yu Wang4,5,6, Chih-Chien Hung1, Chia-Che Lee3, Rong-Sen Yang3, Chuan-Ching Huang3, Chui-Jia Farn3, Wei-Hsin Lin3, Ho-Min Chen7, Fei-Yuan Hsiao4,5,8, Jou-Wei Lin9, Chung-Yi Li2,10,11. 1. Department of Orthopedics, National Taiwan University Hospital Yunlin Branch, Douliu, Taiwan. 2. Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan. 3. Department of Orthopedics, National Taiwan University Hospital, Taipei, Taiwan. 4. School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan. 5. Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan. 6. Department of Pharmacy, National Taiwan University Hospital Yunlin Branch, Douliu, Taiwan. 7. Health Data Research Center, National Taiwan University, Taipei, Taiwan. 8. Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan. 9. Cardiovascular Center, National Taiwan University Hospital YunlinBranch, Douliu, Taiwan. 10. Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan. 11. Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung, Taiwan.
Abstract
BACKGROUND: To compare the risks of major osteoporotic, vertebral, and non-vertebral fractures between patients who discontinued anti-osteoporosis medications. METHODS: We conducted a comparative effectiveness study with a nationwide population-based cohort study design. Patients aged ≥50 years admitted between 2012 and 2015 for incident hip fractures and receiving denosumab or bisphosphonates with sufficient compliance for at least 1 year were included. Patients were categorized into persistent or non-persistent denosumab or bisphosphonates users based on their subsequent use pattern. The main outcomes were subsequent hospitalizations for a major osteoporotic, vertebral or non-vertebral fracture. Multivariate, time-varying Cox proportional hazards model was used to evaluate the risk of major outcomes. RESULTS: Compared with persistent denosumab users, non-persistent denosumab users had a significantly higher risk of major osteoporotic fractures (hazard ratio [HR] = 1.60; 95% confidence interval [CI], 1.20-2.14), vertebral fractures (HR = 2.18; 95% CI, 1.46-3.24) and death (HR = 3.57; 95%CI, 2.63-4.84). However, the increased risk of fracture was not found in both persistent and non-persistent bisphosphonates users. Noteworthy, the increased risk of vertebral fractures in non-persistent denosumab users was more pronounced within 1 year post-discontinuation (HR = 2.90; 95% CI, 1.77-4.74) and among patients who discontinued from 2-year denosumab therapy (HR = 3.58; 95% CI, 1.74-7.40). DISCUSSION: Discontinuation of denosumab resulted in an increased risk of major osteoporotic fractures, especially vertebral fractures. The increased risk tends to reveal within 1 year post-discontinuation and be greater after a longer treatment duration. Notably, only fracture with hospitalization was identified as our research outcome, the real risk of osteoporotic fracture post discontinuation is believed to be higher, especially for vertebral fracture.
BACKGROUND: To compare the risks of major osteoporotic, vertebral, and non-vertebral fractures between patients who discontinued anti-osteoporosis medications. METHODS: We conducted a comparative effectiveness study with a nationwide population-based cohort study design. Patients aged ≥50 years admitted between 2012 and 2015 for incident hip fractures and receiving denosumab or bisphosphonates with sufficient compliance for at least 1 year were included. Patients were categorized into persistent or non-persistent denosumab or bisphosphonates users based on their subsequent use pattern. The main outcomes were subsequent hospitalizations for a major osteoporotic, vertebral or non-vertebral fracture. Multivariate, time-varying Cox proportional hazards model was used to evaluate the risk of major outcomes. RESULTS: Compared with persistent denosumab users, non-persistent denosumab users had a significantly higher risk of major osteoporotic fractures (hazard ratio [HR] = 1.60; 95% confidence interval [CI], 1.20-2.14), vertebral fractures (HR = 2.18; 95% CI, 1.46-3.24) and death (HR = 3.57; 95%CI, 2.63-4.84). However, the increased risk of fracture was not found in both persistent and non-persistent bisphosphonates users. Noteworthy, the increased risk of vertebral fractures in non-persistent denosumab users was more pronounced within 1 year post-discontinuation (HR = 2.90; 95% CI, 1.77-4.74) and among patients who discontinued from 2-year denosumab therapy (HR = 3.58; 95% CI, 1.74-7.40). DISCUSSION: Discontinuation of denosumab resulted in an increased risk of major osteoporotic fractures, especially vertebral fractures. The increased risk tends to reveal within 1 year post-discontinuation and be greater after a longer treatment duration. Notably, only fracture with hospitalization was identified as our research outcome, the real risk of osteoporotic fracture post discontinuation is believed to be higher, especially for vertebral fracture.
Authors: E C-C Lai; T-C Lin; J L Lange; L Chen; I C K Wong; C-W Sing; C-L Cheung; S-C Shao; Y-H Kao Yang Journal: Osteoporos Int Date: 2022-01-15 Impact factor: 4.507