Bauer, D., Black, D., Bouxsein, M. et al. (8 more authors) (2018) Treatment-Related Changes in Bone Turnover and Fracture Risk Reduction in Clinical Trials of Anti-Resorptive Drugs: A Meta-Regression. Journal of Bone and Mineral Research, 33 (4). pp. 634-642. ISSN 0884-0431
Abstract
Few pooled analyses of antiresorptive (AR) treatment trials relate short-term changes in bone turnover markers (BTMs) to subsequent fracture reduction. 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 28,000 participants enrolled in 11 bisphosphonate (BP) and three 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 two bone resorption markers (N-terminal and C-terminal telopeptide of type I collagen) and incident fracture outcome data, we performed a meta-regression relating the mean net effect of treatment on change in bone turnover (active minus placebo % difference after 3 to 12 months) to the log of study-wide fracture risk reduction, and used linear regression to plot the best fitting line. Separate analyses were performed for incident morphometric vertebral, nonvertebral, and hip fractures over 1 to 4 years of follow-up. Change in bone ALP and PINP were available for over 16,000 and 10,000 participants, respectively. For vertebral fracture, the results showed a strong relationship between treatment-related bone ALP or PINP changes and vertebral fracture risk reduction (r2 = 0.82 [p < 0.001] and r2 = 0.75 [p = 0.011], respectively) Relationships were weaker and no longer statistically significant for nonvertebral (r2 = 0.33 [p = 0.053] and r2 = 0.53 [p = 0.065], respectively) and hip fracture (r2 = 0.17 [p = 0.24] and r2 = 0.43 [p = 0.11], respectively) outcomes. Analyses limited to BP trials gave similar results. For all fracture types, relationships were weaker and nonsignificant for bone resorption markers. We conclude that short-term AR treatment-related changes in bone ALP and PINP strongly predict vertebral fracture treatment efficacy, but not nonvertebral or hip fracture treatment efficacy. Change in bone formation markers might be useful to predict the anti-vertebral fracture efficacy of new AR compounds or novel dosing regiments with approved AR drugs.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 American Society for Bone and Mineral Research. This is the peer reviewed version of the following article: Bauer, D. C., Black, D. M., Bouxsein, M. L., Lui, L.-Y., Cauley, J. A., de Papp, A. E., Grauer, A., Khosla, S., McCulloch, C. E., Eastell, R. and for the Foundation for the National Institutes of Health (FNIH) Bone Quality Project (2018), Treatment-Related Changes in Bone Turnover and Fracture Risk Reduction in Clinical Trials of Anti-Resorptive Drugs: A Meta-Regression. J Bone Miner Res. , which has been published in final form at https://doi.org/10.1002/jbmr.3355. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. |
Keywords: | biochemical markers of bone turnover; bone modeling and remodeling; epidemiology; osteoporosis; diseases and disorders of/related to bone |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals |
Funding Information: | Funder Grant number NATIONAL INSTITUTE FOR HEALTH RESEARCH UNSPECIFIED |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 26 Feb 2018 12:09 |
Last Modified: | 07 Oct 2020 10:10 |
Status: | Published |
Publisher: | American Society for Bone and Mineral Research |
Refereed: | Yes |
Identification Number: | 10.1002/jbmr.3355 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:127732 |