Eastell, R. orcid.org/0000-0002-0323-3366, Black, D.M., Lui, L. et al. (9 more authors) (2021) Treatment‐related changes in bone turnover and fracture risk reduction in clinical trials of antiresorptive drugs: proportion of treatment effect explained. Journal of Bone and Mineral Research, 36 (2). pp. 236-243. ISSN 0884-0431
Abstract
Few analyses of antiresorptive (AR) treatment trials relate short‐term changes in bone turnover markers (BTMs) to subsequent fracture reduction seeking to estimate the proportion of treatment effect explained (PTE) by BTMs. Pooling such information would be useful to assess new ARs or novel dosing regimens. In the Foundation for the National Institutes of Health (FNIH) Bone Quality project, we analyzed individual‐level data from up to 62,000 participants enrolled in 12 bisphosphonate (BP) and four selective estrogen receptor modulator (SERM) placebo‐controlled fracture endpoint trials. Using BTM results for two bone formation markers (bone‐specific alkaline phosphatase [bone ALP] and pro‐collagen I N‐propeptide [PINP]) and one bone resorption marker (C‐terminal telopeptide of type I collagen [CTX]) and incident fracture outcome data, we estimated the PTE using two different models. Separate analyses were performed for incident morphometric vertebral, nonvertebral, and hip fractures over 1 to 5 years of follow‐up. For vertebral fracture, the results showed that changes in all three BTMs at 6 months explained a large proportion of the treatment effect of ARs (57 to >100%), but not for and non‐vertebral or hip fracture. We conclude that short‐term AR treatment‐related changes in bone ALP, PINP, and CTX account for a large proportion of the treatment effect for vertebral fracture. Change in BTMs is a useful surrogate marker to study the anti‐fracture efficacy of new AR compounds or novel dosing regiments with approved AR drugs. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.
Metadata
Item Type: | Article |
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Authors/Creators: |
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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 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | BIOCHEMICAL MARKERS OF BONE TURNOVER; BONE MODELING AND REMODELING; DISEASES AND DISORDERS OF/RELATED TO BONE; EPIDEMIOLOGY; OSTEOPOROSIS |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 22 Oct 2020 11:47 |
Last Modified: | 28 Jan 2022 13:41 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1002/jbmr.4178 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:166719 |