Treatment-Related Changes in Bone Turnover and Fracture Risk Reduction in Clinical Trials of Antiresorptive Drugs: Proportion of Treatment Effect Explained.

Autor: Eastell R; Academic Unit of Bone Metabolism, University of Sheffield, Sheffield, UK., Black DM; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA., Lui LY; California Pacific Medical Center, San Francisco, CA, USA., Chines A; Amgen Inc., Thousand Oaks, CA, USA., Marin F; Eli Lilly and Company, Lilly Research Centre, Windlesham, UK., Khosla S; Mayo Clinic College of Medicine, Rochester, MN, USA., de Papp AE; Merck & Co., Inc., Kenilworth, NJ,, USA., Cauley JA; Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA., Mitlak B; Radius Health, Waltham, MA, USA., McCulloch CE; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA., Vittinghoff E; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA., Bauer DC; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Jazyk: angličtina
Zdroj: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research [J Bone Miner Res] 2021 Feb; Vol. 36 (2), pp. 236-243. Date of Electronic Publication: 2020 Oct 02.
DOI: 10.1002/jbmr.4178
Abstrakt: 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.
(© 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.)
Databáze: MEDLINE
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