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Romosozumab followed by denosumab in Japanese women with high fracture risk in the FRAME trial

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Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

Introduction

This post-hoc analysis of the FRAME study investigated the long-term efficacy and safety of romosozumab followed by denosumab in postmenopausal Japanese women with osteoporosis at high fracture risk.

Materials and methods

Data from Japanese women with a high fracture risk participating in the international, randomised, double-blind, placebo-controlled, phase 3 FRAME study were analysed. High risk of fracture was defined as ≥ 1 fragility fracture with bone mineral density (BMD) ≤ − 2.5 standard deviations [SD], > 2 prevalent vertebral fractures, prevalent semiquantitative grade 3 vertebral fracture, or lumbar spine BMD < − 3.3 SD. Endpoints included incidence of new vertebral fracture at 12, 24 and 36 months and percentage change from baseline in BMD at the lumbar spine, total hip and femoral neck.

Results

187 Japanese subjects at high risk of fracture were enrolled in FRAME. Incidence of new vertebral fractures was lower with romosozumab/denosumab vs. placebo/denosumab at 12, 24 and 36 months (relative risk reduction at all timepoints: 84%; p = 0.056). BMD increases at 12, 24 and 36 months were greater in subjects receiving romosozumab/denosumab than placebo/denosumab (lumbar spine: 16.3%, 21.5% and 23.2% vs 0.4%, 8.1% and 10.4%; total hip: 4.9%, 7.9% and 8.9% vs 0.4%, 2.8% and 4.1%; femoral neck: 4.8%, 7.6% and 8.1% vs 0.3%, 3.3% and 3.7%, respectively; all p < 0.001 vs placebo/denosumab). Adverse events were generally balanced between groups.

Conclusion

Romosozumab/denosumab in Japanese subjects at high risk of fracture resulted in significant BMD gains and numerically lower vertebral fracture rate vs. placebo/denosumab at all timepoints measured.

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Acknowledgements

The authors would like to thank Sheridan Henness, PhD, who wrote the outline and first draft of this manuscript on behalf of Springer Healthcare Communications. This medical writing assistance was funded by Amgen K.K. and Astellas Pharma Inc.

Funding

Amgen Inc., Astellas, and UCB Pharma sponsored this study (NCT01575834).

Author information

Authors and Affiliations

Authors

Contributions

AM enrolled patients. EH provided the concept for the study and contributed to subgroup analysis study design, interpretation, preparation of discussion and provision of references. WY, CL and CT were involved in conception and interpretation of the manuscript. KN contributed to the confirmation of the contents and interpretation of the safety results. JS performed the statistical analysis and provided interpretation. All authors read and approved drafts of the manuscript.

Corresponding author

Correspondence to Etsuro Hamaya.

Ethics declarations

Conflicts of interest

A Miyauchi received consulting fees from Amgen, Astellas BioPharma K.K., and Teijin Pharma. E Hamaya, K Nishi and J Shimauchi are employees of Amgen K.K., Japan and E Hamaya reports holding stock in Amgen Inc. W Yang is an employee of Amgen Inc., USA. C Libanati is an employee of UCB Pharma, Belgium, and reports holding stock in UCB Pharma. C Tolman is an employee of Amgen and holds stock in Amgen.

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Miyauchi, A., Hamaya, E., Yang, W. et al. Romosozumab followed by denosumab in Japanese women with high fracture risk in the FRAME trial. J Bone Miner Metab 39, 278–288 (2021). https://doi.org/10.1007/s00774-020-01147-5

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