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Teriparatide and denosumab combination therapy and skeletal metabolism

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Abstract

Summary

Several therapies are available for osteoporis. Understanding the bone turnover changes and their mutual realtionship gives an overall view and might lead to a target therapy

Introduction

The aim of this study is to compare the changes in bone turnover markers in patients treated with either denosumab alone, teriparatide (TPTD) alone, or in a third therapeutic scheme, when TPTD was added to patients previously treated with denosumab.

Methods

Fifty-nine women over 65 years old with severe postmenopausal osteoporosis (evidence of at least two moderate-severe vertebral fractures) were enrolled in the study. Serum samples were collected every 3 months. They were assayed for intact N-propeptide of type I collagen (P1NP), C-terminal telopeptide of type I collagen (CTX), intact parathyroid hormone (PTH), 25 hydroxy-vitamin D (25 OHD), Sclerostin (SOST), and Dickkopf-related protein 1 (DKK1). Bone mass density was assessed by dual-energy X-ray absorptiometry at the lumbar spine and at the total hip.

Results

In the groups treated only with TPTD or with denosumab, bone turnover markers increased and decreased, respectively. In TPTD group, a later significant increase in DKK1 was observed, while in denosumab group, a progressive increase in SOST was associated with a progressive significant decrease in DKK1.

In the group treated first with denosumab and in which TPTD was added 3 months later, both CTX and P1NP increased 3 months after the beginning of TPTD. The strong effect of denosumab on bone turnover seems to be reversed by TPTD treatment.

Conclusions

In this study, we showed that TPTD is able to express its biological activity even when bone turnover is fully suppressed by denosumab treatment. The combination therapy is associated with significant increases in both DKK1 and SOST.

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Acknowledgments

We thank Caterina Fraccarollo and Cristina Bosco for the ELISA assays.

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Authors and Affiliations

  1. Rheumatology Unit - Department of Medicine, University of Verona, Piazzale A. Stefani 1, 37126, Verona, VR, Italy

    L. Idolazzi, M. Rossini, O. Viapiana, V. Braga, A. Fassio, C. Benini, V. Kunnathully, S. Adami & D. Gatti

Authors
  1. L. Idolazzi
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  2. M. Rossini
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  3. O. Viapiana
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  4. V. Braga
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  6. C. Benini
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  7. V. Kunnathully
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  8. S. Adami
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  9. D. Gatti
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Corresponding author

Correspondence to L. Idolazzi.

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Conflicts of interest

Luca Idolazzi has received speaking fees from Eli Lilly, UCB, Abbvie Davide Gatti has received speaking fees from Abiogen, Amgen, Eli-Lilly and Neopharmed-Gentili. Maurizio Rossini has received speaking and consulting fees from Abiogen, Amgen, Eli-Lilly and Merck Sharp & Dohme Corp. Silvano Adami has received consulting fees from Amgen, Merck Sharp & Dohme Corp., Eli-Lilly, Roche and Bristol-Myers Squibb. Ombretta Viapiana has received speaking fees from Abiogen, Amgen, Merck Sharp & Dohme Corp. Vania Braga, Angelo Fassio, Camilla Benini, and Vidya Kunnathully declare no conflict of interests.

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Idolazzi, L., Rossini, M., Viapiana, O. et al. Teriparatide and denosumab combination therapy and skeletal metabolism. Osteoporos Int 27, 3301–3307 (2016). https://doi.org/10.1007/s00198-016-3647-y

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  • DOI: https://doi.org/10.1007/s00198-016-3647-y

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