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Comparison of the Efficacy of Zoledronate Acid or Denosumab After Switching from Romosozumab in Japanese Postmenopausal Patients

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Abstract

We aimed to compare the efficacy of switching from romosozumab (RMAb) to denosumab (DMAb) or zoledronic acid (Zol) with respect to changes in bone mineral density (BMD) and bone metabolism. We also aimed to determine predictors of changes in BMD among patients who received sequential therapy from RMAb. One hundred patients who received RMAb therapy were recruited for this study. A total 49 patients received bisphosphonate (BP) pre-treatment and 51 received active vitamin D3 analog pre-treatment or no treatment. Forty-two patients were switched to Zol (BP–RMAb–Zol; 20 and RMAb–Zol; 22), and 58 patients were switched to DMAb (BP–RMAb–DMAb; 29 and RMAb–DMAb; 29). Longitudinal changes in bone metabolic markers (P1NP and TRACP-5b) and BMD were also evaluated. In the BP–RMAb–Zol group, TRACP-5b increased after administration of Zol, and the mean BMD of the lumbar spine (LS) was significantly lower than those in the BP–RMAb–DMAb, RMAb–Zol and RMAb–DMAb groups at 24 months. The % changes in BMD of the LS after 24 months were associated with TRACP-5b values at baseline and at 12 months in patients who received Zol therapy, and with TRACP-5b value at baseline in patients who received DMAb therapy. The DMAb follow-on regimen could be considered more effective than Zol as a sequential agent for the enhancement of BMD after RMAb in patients with BP pretreatment. TRACP-5b, especially the baseline value, may predict the efficacy of sequential therapy from RMAb, as well as previous treatments.

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Funding

This project was supported in part by a Grant-in-Aid for Young Scientists from the Ministry of Education, Culture, Sports, Science, and Technology of Japan 20K17948 (T. Shimizu), and a Japan Osteoporosis Foundation Grant for Bone Research (D. Takahashi).

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Authors and Affiliations

  1. Department of Orthopedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita-15 Nishi-7, Kita-ku, Sapporo, 060-8638, Japan

    Tetsuro Oue, Tomohiro Shimizu, Hotaka Ishizu, Kosuke Arita & Norimasa Iwasaki

  2. Department of Orthopedic Surgery, KKR Sapporo Medical Center, Sapporo, Japan

    Tsuyoshi Asano

  3. Department of Orthopedic Surgery, Kushiro City General Hospital, Kushiro, Japan

    Shun Shimodan

Authors
  1. Tetsuro Oue
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  2. Tomohiro Shimizu
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  3. Tsuyoshi Asano
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  4. Shun Shimodan
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  5. Hotaka Ishizu
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  6. Kosuke Arita
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  7. Norimasa Iwasaki
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Contributions

Conceptualization: TS; Methodology: TS, TA, SS, and KA; Formal analysis and investigation: TO, TS, and HI; Writing—original draft preparation: TO and TS; Writing—review and editing: TS and NI; Funding acquisition: TS; Supervision: NI.

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Correspondence to Tomohiro Shimizu.

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Conflict of interest

Tetsuro Oue, Tomohiro Shimizu, Tsuyoshi Asano, Shun Shimodan, Hotaka Ishizu, Kosuke Arita, and Norimasa Iwasaki declare that they have no conflicts of interest.

Ethical Approval

This study was conducted in accordance with the ethical standards of the Declaration of Helsinki and was approved by the Hokkaido University Hospital Institutional Review Board (Number 020-0188).

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Informed consent was obtained from all participants included in the study.

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Oue, T., Shimizu, T., Asano, T. et al. Comparison of the Efficacy of Zoledronate Acid or Denosumab After Switching from Romosozumab in Japanese Postmenopausal Patients. Calcif Tissue Int 112, 683–690 (2023). https://doi.org/10.1007/s00223-023-01079-y

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  • DOI: https://doi.org/10.1007/s00223-023-01079-y

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