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Open Access 26-07-2023 | Denosumab | Original Article

Comparison of anti-fracture effectiveness of zoledronate, ibandronate and alendronate versus denosumab in a registry-based cohort study

Authors: Judith Everts-Graber, Harald Bonel, Daniel Lehmann, Brigitta Gahl, HansJörg Häuselmann, Ueli Studer, Hans-Rudolf Ziswiler, Stephan Reichenbach, Thomas Lehmann

Published in: Osteoporosis International | Issue 11/2023

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Abstract

Summary

This registry-based study of 3068 patients with osteoporosis compared the anti-fracture effectiveness of denosumab versus bisphosphonates. Denosumab was associated with significantly greater risk reduction than alendronate or ibandronate for vertebral and any fractures. No difference in fracture risk reduction was found between zoledronate and denosumab.

Purpose

To analyse the fracture risk of patients with osteoporosis receiving bisphosphonates or denosumab in a real-world setting.

Methods

This registry-based cohort study evaluated patients taking denosumab, bisphosphonates or both sequentially. Fractures were analysed using rates, rate ratios and hazard ratios (HR), including both therapies as time-varying co-variates. Fracture risk hazards were adjusted (aHR) for baseline T-Scores and trabecular bone score (TBS) and were additionally analysed with inverse probability treatment weighting.

Results

A total of 3068 patients (89% female; median age at treatment onset, 69 years [63 to 76]) received denosumab (median duration 2.8 years, [2.2 to 4.7]), bisphosphonates (3.4 years, [2.1 to 5.7]) or both sequentially. Thus, 11,078 subject-years were assessed for bisphosphonates (41% alendronate, 36% ibandronate, 23% zoledronate) and 4216 for denosumab. Moreover, 48,375 subject-years were observed before treatment onset, in addition to 2593 years of drug holidays. A total of 1481 vertebral fractures (435 under therapy), 1508 non-vertebral fractures (499 under therapy) and 202 hip fractures (67 under therapy) occurred after age 50. The risks of vertebral, non-vertebral and hip fractures were significantly lower under all bisphosphonates, denosumab and drug holidays than before treatment onset (all p < 0.001). After adjusting for age, baseline T-scores and TBS, denosumab was associated with lower risk than alendronate or ibandronate for vertebral fractures (aHR 0.47 (0.35 to 0.64) and 0.70 [0.53 to 0.91], p < 0.001 and p = 0.009, respectively) and any fractures (aHR 0.62 [0.51 to 0.76] and 0.77 [0.64 to 0.92], p < 0.001 and p = 0.004). With propensity weighting, denosumab was associated with a lower hip fracture risk compared to alendronate (HR 0.54 [0.29 to 0.98], p = 0.044). No difference in fracture risk reduction (vertebral, non-vertebral or hip) was found between zoledronate and denosumab.

Conclusions

When adjusting for disease severity, denosumab was associated with significantly greater risk reduction than alendronate and ibandronate for vertebral fractures. No difference in fracture risk reduction was found between zoledronate and denosumab.
Appendix
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Literature
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Metadata
Title
Comparison of anti-fracture effectiveness of zoledronate, ibandronate and alendronate versus denosumab in a registry-based cohort study
Authors
Judith Everts-Graber
Harald Bonel
Daniel Lehmann
Brigitta Gahl
HansJörg Häuselmann
Ueli Studer
Hans-Rudolf Ziswiler
Stephan Reichenbach
Thomas Lehmann
Publication date
26-07-2023
Publisher
Springer London
Published in
Osteoporosis International / Issue 11/2023
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-023-06863-y

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