Abstract
Introduction
To identify predictors for incident fractures in patients on pharmaceutical treatment for osteoporosis by a secondary analysis of the Japanese Osteoporosis Intervention Trial protocol number 4 (JOINT-04), which was a 2-year, randomized, parallel-group, controlled trial of minodronate and raloxifene in women with primary osteoporosis.
Materials and Methods
This was a prospective, observational study using JOINT-04 data, in which biomarkers, such as undercarboxylated osteocalcin (ucOC), N-telopeptide of type 1 collagen, tartrate-resistant acid phosphatase 5b (TRACP-5b), bone alkaline phosphatase, homocysteine, and pentosidine in blood, and physical functions, such as the timed up and go test and one-leg standing test with eyes open (OLST), and the fall risk index, were measured. The relationships of incident morphometric vertebral fractures during the treatment period, as well as prevalent vertebral fractures, and baseline data were analyzed.
Results
The full analysis set of the JOINT-04 included 3247 patients (1623 in the minodronate group and 1624 in the raloxifene group). The hazard ratio (95% confidence interval) for incident vertebral fractures over 2 years of pharmacotherapy, adjusted for confounders, was 0.93 (0.90–0.96) for ucOC, 1.15 (1.08–1.23) for TRACP-5b, 1.02 (1.01–1.03) for pentosidine, 0.91 (0.88–0.94) for the OLST, and 1.27 (1.01–1.60) for the fall risk index, which were all independent predictors.
Conclusion
Evaluating fracture risk for patients with osteoporosis considering these potential risk factors for fracture in addition to the established risk factors may be useful when starting pharmaceutical treatment.
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Data availability
The datasets generated and analyzed during the current study are not publicly available because of professional discretion, as they were part of patients’ records, but are available as de-identified data from the corresponding author on reasonable request.
Change history
18 July 2024
A Correction to this paper has been published: https://doi.org/10.1007/s00774-024-01522-6
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Acknowledgements
The authors would like to thank those who participated as clinical investigators in JOINT-04. The authors would also like to express their sincere thanks to Mr. Teruhiko Miyazaki, Ms. Yuko Iwata, and Ms. Mayumi Tsukiyama for their secretarial help.
Funding
This JOINT study was sponsored by the Public Health Research Foundation. This study was also supported in part by funding of the Project Promoting Clinical Trials for Development of New Drugs (19lk0201061t0004) from the AMED to ST.
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All authors contributed to the study conception and design. HH helped design the study, participated in the study, conducted analysis, interpretation of data, and wrote the manuscript. YU conducted statistical analysis. SM, TS, HO, and TN helped with the data analysis, supervised, and reviewed the manuscript. All authors read and approved the final version of the manuscript.
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HH has received lecture fees or grants outside the submitted work from Amgen Inc., Asahi Kasei Pharma Corp., Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan Co., Ltd., Mitsubishi Tanabe Pharma Corp., Mochida Pharma Corp., Ono Pharmaceutical Co., Ltd., Pfizer Inc., Taisho Pharmaceutical Co., Ltd., Teijin Pharma Co., Ltd., and UCB Japan. YU has received a consultancy fee from Teijin Pharma Ltd. and Daiichi Sankyo and outsourcing fees from Chugai Pharmaceutical Co. SM and HO have nothing to disclose. TS has received research grants from Asahi Kasei Pharma Corp., Astellas Pharma, Taisho Toyama Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., Pfizer, and Teijin Pharma Ltd., and consulting fees from Kissei pharmaceutical Co. Ltd., Shimadzu Corp., and Takeda Pharmaceutical Co. Ltd. TN has received personal fees and other from Asahi Pharma, Teijin Pharma, Daiichi-Sankyo Pharma, UCB Pharma, AMGEN, ASTELAS, Chugai Pharma, and MERCK.
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This study was registered at the University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR) under trial identification number UMIN000005433. The protocol was approved by the Central Ethical committee for Adequate Treatment of Osteoporosis (A-TOP) group (Dr. Rikushi Morita, Chairman) and was reviewed by the institutional review board of each participating institution. The trial was conducted in accordance with the Declaration of Helsinki.
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Written, informed consent was obtained prior to patient enrollment after a thorough explanation of the trial objectives, duration, and procedures.
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Hagino, H., Uemura, Y., Mori, S. et al. Risk factors for incident vertebral fractures in osteoporosis pharmacotherapy: a 2-year, prospective, observational study. J Bone Miner Metab 39, 668–677 (2021). https://doi.org/10.1007/s00774-021-01208-3
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DOI: https://doi.org/10.1007/s00774-021-01208-3