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Effect of aromatase inhibition on serum levels of sclerostin and dickkopf-1, bone turnover markers and bone mineral density in women with breast cancer

  • Original Article – Cancer Research
  • Published:
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Abstract

Purpose

While their negative impact on bone health is well established, the effects of aromatase inhibition (AI) on Wnt inhibitors and osteoprotegerin (OPG) are unknown. The aim of the study was to investigate the effects of AI on serum levels of sclerostin, DKK-1 and OPG, as well as their associations with PINP and CTX as markers of bone turnover and bone mineral density (BMD) assessed by DXA.

Methods

We conducted a prospective longitudinal analysis of 70 postmenopausal women with hormone receptor-positive early breast cancer (BC) treated with anastrozole. All measurements were performed at baseline, 12 and 24 months of treatment. We measured the association of the investigated variables with circulating bone turnover markers, as well as with the BMD.

Results

After 24 months of AI therapy, sclerostin and OPG concentrations increased from 29.5 pmol/l (SD = 15.1) and 6.8 pmol/l (SD = 2.2) at baseline to 43.2 pmol/l (SD = 20.6) (p < 0.001) and 7.4 pmol/l (SD = 2.2) (p = 0.028), respectively. DKK-1 levels decreased from 34.3 pmol/l (SD = 13.5) at baseline to 29.7 pmol/l (SD = 12.3) at the 24-month visit (p = 0.005). Sclerostin levels significantly correlated with PTH, OPG and BMD of the lumbar spine, while DKK-1 correlated with the BMD of the femoral neck and of the total hip.

Conclusions

The observed increase in sclerostin levels indicates a central role of osteocytes in bone turnover in women with BC.

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Acknowledgments

IK and PH conceived the study, participated in its design and coordination, helped to draft the manuscript and made substantial contributions to analysis and interpretation of the data. TR and LH participated in the design of the study, made substantial contributions to acquisition of data and helped to draft the manuscript. AU made substantial contributions to acquisition of data and helped to draft the manuscript. OH participated in the design of the study and performed statistical analyses. All authors read and approved the final manuscript. This work was supported by AstraZeneca (to PH), and the Grants RA 2151/2-1 (to TDR and LCH) and Forschergruppe-1586 SKELMET to LCH from the Deutsche Forschungsgemeinschaft.

Conflict of interest

The authors have received grants or honorarium for advisory boards or lectures to the individual or the institution by Amgen (TDR, LCH, PH), AstraZeneca (PH), Eli Lilly (PH), GlaxoSmithKline (PH), Novartis (TDR, LCH, PH), Pfizer (PH), Roche (PH), Servier (LCH), Merck (LCH, TDR) and Nycomed (LCH). IK, VZ, MS and OH have no conflicts of interest to report.

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Authors and Affiliations

  1. Department of Gynecological Endocrinology, Reproductive Medicine and Osteoporosis, Philipps-University of Marburg, Baldingerstr. 1, 35041, Marburg, Germany

    Ioannis Kyvernitakis, Anja Urbschat & Peyman Hadji

  2. Division of Endocrinology and Metabolic Bone Diseases, Department of Medicine III, Technical University, Dresden, Germany

    Tilman D. Rachner & Lorenz C. Hofbauer

  3. Statistical Consulting, Berlin, Germany

    Olaf Hars

  4. Center for Regenerative Therapies, Technical University, Dresden, Germany

    Lorenz C. Hofbauer

Authors
  1. Ioannis Kyvernitakis
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  2. Tilman D. Rachner
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  3. Anja Urbschat
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  4. Olaf Hars
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  5. Lorenz C. Hofbauer
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  6. Peyman Hadji
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Corresponding author

Correspondence to Ioannis Kyvernitakis.

Additional information

Ioannis Kyvernitakis and Tilman D. Rachner have contributed equally to this work.

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Kyvernitakis, I., Rachner, T.D., Urbschat, A. et al. Effect of aromatase inhibition on serum levels of sclerostin and dickkopf-1, bone turnover markers and bone mineral density in women with breast cancer. J Cancer Res Clin Oncol 140, 1671–1680 (2014). https://doi.org/10.1007/s00432-014-1726-z

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  • DOI: https://doi.org/10.1007/s00432-014-1726-z

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