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Romosozumab improves lumbar spine bone mass and bone strength parameters relative to alendronate in postmenopausal women: results from the Active-Controlled Fracture Study in Postmenopausal Women With Osteoporosis at High Risk (ARCH) trial |
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| Authors: | Jacques P Brown Klaus Engelke Tony M Keaveny Arkadi Chines Roland Chapurlat A Joseph Foldes Xavier Nogues Roberto Civitelli Tobias De Villiers Fabio Massari Cristiano AF Zerbini Zhenxun Wang Mary K Oates Christopher Recknor Cesar Libanati |
| Institution: | 1. Centre Hospitalier Universitaire (CHU) de Québec Research Centre, Department of Medicine, Rheumatology Division, Laval University, Quebec City, Québec, Canada;2. Bioclinica, Hamburg, Germany
Department of Medicine 3, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany Contribution: Conceptualization, Data curation, Formal analysis, Methodology, Resources, Validation, Visualization, Writing - review & editing;3. Departments of Mechanical Engineering and Bioengineering, University of California Berkeley, Berkeley, California, USA Contribution: Conceptualization, Data curation, Formal analysis, Methodology, Validation, Visualization, Writing - review & editing;4. Amgen Inc., Thousand Oaks, California, USA Contribution: Conceptualization, Data curation, Funding acquisition, Methodology, Supervision, Writing - original draft;5. Institut National de la Santé et de la Recherche Médicale (INSERM) Unités Mixtes de Recherche (UMR) 1033, Université de Lyon, Hôpital E Herriot, Lyon, France;6. Osteoporosis Center, Hadassah Hebrew University Medical Center, Jerusalem, Israel Contribution: Conceptualization, Data curation, Methodology, Writing - review & editing;7. Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable (CIBERFES), Autonomous University of Barcelona, Barcelona, Spain Contribution: Conceptualization, Data curation, Methodology, Writing - review & editing;8. Musculoskeletal Research Center, Washington University School of Medicine, St. Louis, Missouri, USA;9. Department of Obstetrics and Gynaecology, Stellenbosch University, Stellenbosch, South Africa Contribution: Conceptualization, Data curation, Methodology, Writing - review & editing;10. Instituto de Diagnóstico e Investigaciones Metabólicas, Buenos Aires, Argentina Contribution: Conceptualization, Data curation, Methodology, Writing - review & editing;11. Centro Paulista de Investigação Clinica, São Paulo, Brazil Contribution: Conceptualization, Data curation, Methodology, Writing - review & editing;12. Amgen Inc., Thousand Oaks, California, USA Contribution: Conceptualization, Data curation, Formal analysis, Methodology, Validation, Writing - review & editing;13. Amgen Inc., Thousand Oaks, California, USA Contribution: Conceptualization, Data curation, Methodology, Writing - review & editing;14. United Osteoporosis Centers, Gainesville, Georgia, USA Contribution: Conceptualization, Data curation, Methodology, Writing - review & editing;15. UCB Pharma, Brussels, Belgium |
| Abstract: | The Active-Controlled Fracture Study in Postmenopausal Women With Osteoporosis at High Risk (ARCH) trial (NCT01631214; https://clinicaltrials.gov/ct2/show/NCT01631214 ) showed that romosozumab for 1 year followed by alendronate led to larger areal bone mineral density (aBMD) gains and superior fracture risk reduction versus alendronate alone. aBMD correlates with bone strength but does not capture all determinants of bone strength that might be differentially affected by various osteoporosis therapeutic agents. We therefore used quantitative computed tomography (QCT) and finite element analysis (FEA) to assess changes in lumbar spine volumetric bone mineral density (vBMD), bone volume, bone mineral content (BMC), and bone strength with romosozumab versus alendronate in a subset of ARCH patients. In ARCH, 4093 postmenopausal women with severe osteoporosis received monthly romosozumab 210 mg sc or weekly oral alendronate 70 mg for 12 months, followed by open-label weekly oral alendronate 70 mg for ≥12 months. Of these, 90 (49 romosozumab, 41 alendronate) enrolled in the QCT/FEA imaging substudy. QCT scans at baseline and at months 6, 12, and 24 were assessed to determine changes in integral (total), cortical, and trabecular lumbar spine vBMD and corresponding bone strength by FEA. Additional outcomes assessed include changes in aBMD, bone volume, and BMC. Romosozumab caused greater gains in lumbar spine integral, cortical, and trabecular vBMD and BMC than alendronate at months 6 and 12, with the greater gains maintained upon transition to alendronate through month 24. These improvements were accompanied by significantly greater increases in FEA bone strength (p < 0.001 at all time points). Most newly formed bone was accrued in the cortical compartment, with romosozumab showing larger absolute BMC gains than alendronate (p < 0.001 at all time points). In conclusion, romosozumab significantly improved bone mass and bone strength parameters at the lumbar spine compared with alendronate. These results are consistent with greater vertebral fracture risk reduction observed with romosozumab versus alendronate in ARCH and provide insights into structural determinants of this differential treatment effect. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). |
| Keywords: | BONE STRENGTH BONE MINERAL CONTENT FINITE ELEMENT ANALYSIS POSTMENOPAUSAL OSTEOPOROSIS QUANTITATIVE COMPUTED TOMOGRAPHY |