Chotiyarnwong, P., McCloskey, E. orcid.org/0000-0003-0177-8140, Eastell, R. orcid.org/0000-0002-0323-3366 et al. (7 more authors) (2020) A pooled analysis of fall incidence from placebo‐controlled trials of denosumab. Journal of Bone and Mineral Research, 35 (6). pp. 1014-1021. ISSN 0884-0431
Abstract
Recent studies suggest that the RANK/RANKL system impacts muscle function and/or mass. In the pivotal placebo‐controlled fracture trial of the RANKL inhibitor denosumab in women with postmenopausal osteoporosis, treatment was associated with a lower incidence of non‐fracture‐related falls (p = 0.02). This ad hoc exploratory analysis pooled data from five placebo‐controlled trials of denosumab to determine consistency across trials, if any, of the reduction of fall incidence. The analysis included trials in women with postmenopausal osteoporosis and low bone mass, men with osteoporosis, women receiving adjuvant aromatase inhibitors for breast cancer, and men receiving androgen deprivation therapy for prostate cancer. The analysis was stratified by trial, and only included data from the placebo‐controlled period of each trial. A time‐to‐event analysis of first fall and exposure‐adjusted subject incidence rates of falls were analyzed. Falls were reported and captured as adverse events. The analysis comprised 10,036 individuals; 5030 received denosumab 60 mg subcutaneously once every 6 months for 12 to 36 months and 5006 received placebo. Kaplan–Meier estimates showed an occurrence of falls in 6.5% of subjects in the placebo group compared with 5.2% of subjects in the denosumab group (hazard ratio = 0.79; 95% confidence interval 0.66–0.93; p = 0.0061). Heterogeneity in study designs did not permit overall assessment of association with fracture outcomes. In conclusion, denosumab may reduce the risk of falls in addition to its established fracture risk reduction by reducing bone resorption and increasing bone mass. These observations require further exploration and confirmation in studies with muscle function or falls as the primary outcome.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, (http://creativecommons.org/licenses/by-nc-nd/4.0/) which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
Keywords: | aging; antiresorptives; fracture prevention; osteoporosis |
Dates: |
|
Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 24 Apr 2020 16:31 |
Last Modified: | 24 Nov 2021 13:42 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1002/jbmr.3972 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:159664 |