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The relationship between length of denosumab treatment for postmenopausal osteoporosis and serum TRAcP5b measured six months after the last injection

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Abstract

Summary

To test the hypothesis that during treatment with denosumab osteomorphs and precursors recycle to higher number of osteoclasts with time, we measured TRAcP5b in serum taken 6 months after the last injection in postmenopausal women treated for 1–10 years. Serum TRAcP5b values were not related to time of exposure to denosumab.

Purpose

In women with postmenopausal osteoporosis the aetiology of the observed inverse relationship between duration of denosumab (Dmab) therapy and bone loss after its discontinuation is currently unknown. In studies in mice inhibition of RANKL is associated with an increase in osteomorphs and osteoclast precursors that recycle into osteoclasts and may accumulate with time. We hypothesized that longer inhibition of RANKL by Dmab will be followed by the synchronous formation of a larger number of osteoclasts after stopping treatment. To test this hypothesis, we measured serum TRAcP5b, a marker of osteoclast numbers, in postmenopausal women treated with Dmab for different periods of time up to 10 years.

Methods

TRAcP5b, C-terminal telopeptide of type 1 collagen (CTX) and procollagen type 1 N-terminal propeptide (P1NP) were measured at 6.0 months ± 15 days after last Dmab injection in 59 women who had received Dmab for 4.0 ± 2.3 years (range 1–10 years). Of these, 38 were treatment naïve (group 1) and 21 had received other treatments prior Dmab (group 2).

Results

Duration of Dmab treatment was not related to serum TRAcP5b values or to TRAcP5b/CTX ratio either in the whole cohort or in each of the two groups separately. In contrast, serum TRAcP5b values were significantly correlated with serum CTX values (rs = 0.619; p < 0.001), but not with serum P1NP values or BMD at all skeletal sites.

Conclusion

Our observations indicate that serum TRAcP5b, measured at 6 months after a Dmab injection, is not a useful early marker for time-dependent increased accumulation of osteoclasts in humans and for identification of patients at risk for a higher rebound increase in bone resorption.

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Data availability

Data will be available upon reasonable request.

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Funding

This work was not supported by any grant, fund, or institution.

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Authors and Affiliations

  1. Department of Medical Research, 251 Hellenic Air Force & VA General Hospital, 3 Kanellopoulou st, 11525, Athens, Greece

    Polyzois Makras, Maria P. Yavropoulou, Socrates E. Papapoulos & Athanasios Papatheodorou

  2. Department of Endocrinology and Diabetes, 251 Hellenic Air Force & VA General Hospital, Athens, Greece

    Polyzois Makras & Danai Georgakopoulou

  3. Εndocrinology Unit, First Department of Propaedeutic and Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece

    Maria P. Yavropoulou

  4. First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece

    Stergios A. Polyzos

  5. Center for Bone Quality, Department of Internal Medicine, Section Endocrinology, Leiden University Medical Center, Leiden, The Netherlands

    Socrates E. Papapoulos

  6. Department of Endocrinology, 424 General Military Hospital, Thessaloniki, Greece

    Athanasios D. Anastasilakis

Authors
  1. Polyzois Makras
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  2. Maria P. Yavropoulou
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  3. Stergios A. Polyzos
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  4. Socrates E. Papapoulos
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  5. Danai Georgakopoulou
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  6. Athanasios Papatheodorou
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  7. Athanasios D. Anastasilakis
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Corresponding author

Correspondence to Polyzois Makras.

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Ethical approval

All procedures performed in the study were in accordance with the ethical standards of the institutional research committees and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

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

Conflict of interest in respect to the article

Polyzois Makras reports fees for lectures/advisory boards and research grants from Amgen and Galenica and fees for lectures/advisory boards from UCB, Elpen, Bianex, Eli-Lilly, ITF, Unipharma, and Rapharm; Maria P. Yavropoulou reports fees for lectures/advisory boards and research grants from Galenica; Socrates E. Papapoulos reports consulting/speaking fees from Amgen, Entera Bio, Qualix Dot, Radius Health and UCB; Athanasios D. Anastasilakis reports lecture fees from Amgen, Bianex, Eli-Lilly, Galenica, ITF, Unifarma, and UCB; Stergios A. Polyzos, Danai Georgakopoulou and Athanasios Papatheodorou have nothing to declare.

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Makras, P., Yavropoulou, M.P., Polyzos, S.A. et al. The relationship between length of denosumab treatment for postmenopausal osteoporosis and serum TRAcP5b measured six months after the last injection. Osteoporos Int 35, 365–370 (2024). https://doi.org/10.1007/s00198-023-06931-3

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  • DOI: https://doi.org/10.1007/s00198-023-06931-3

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