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Risk factors for incident vertebral fractures in osteoporosis pharmacotherapy: a 2-year, prospective, observational study

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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.

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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.

Author information

Authors and Affiliations

  1. School of Health Science, Faculty of Medicine, Tottori University, Tottori, Japan

    Hiroshi Hagino

  2. Biostatistics Section, Department of Data Science, Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan

    Yukari Uemura

  3. Bone and Joint Surgery, Seirei Hamamatu General Hospital, Shizuoka, Japan

    Satoshi Mori

  4. Department of Nuclear Medicine, Kawasaki Medical School, Okayama, Japan

    Teruki Sone

  5. International Medical Center, Fujita Health University, Aichi, Japan

    Hiroaki Ohta

  6. Japan Osteoporosis Foundation, Tokyo, Japan

    Toshitaka Nakamura

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  1. Hiroshi Hagino
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Contributions

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.

Corresponding author

Correspondence to Hiroshi Hagino.

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Conflict of interest

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.

Ethics approval

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.

Consent to participate

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

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