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Adjuvant endocrine therapy effects on bone mineral density and microstructure in women with breast cancer

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Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

Introduction

Although aromatase inhibitors (AIs) are typical drugs for cancer treatment-induced bone loss, their effects on the bone microstructure remain unclear. In this study, we evaluated changes in the bone mineral density (BMD) and bone microstructure associated with AI treatment using high-resolution peripheral quantitative computed tomography (HR-pQCT) in patients with early breast cancer.

Materials and methods

This prospective, single-arm, observational study included non-osteoporotic, postmenopausal women with hormone receptor-positive breast cancer. Patients underwent dual-energy X-ray absorptiometry (DXA), HR-pQCT, and tartrate-resistant acid phosphatase-5b (TRACP-5b) or procollagen type-I N-terminal propeptide measurements at baseline and 6 and 12 months after AI therapy. The primary endpoint was changes in the total volumetric BMD (Tt.vBMD), trabecular vBMD (Tb.vBMD), and cortical vBMD (Ct.vBMD) longitudinally at the distal radius and tibia.

Results

Twenty women were included (median age 57.5 years; range 55–72 years). At 12 months, HR-pQCT indicated a significant decrease in the Tt.vBMD (median distal radius − 5.3%, p < 0.01; distal tibia − 3.2%, p < 0.01), Tb.vBMD (− 3.2%, p < 0.01; − 1.0%, p < 0.05, respectively), and Ct.vBMD (− 3.2%, p < 0.01; − 2.7%, p < 0.01, respectively). Estimated bone strength was also significantly decreased. The DXA BMD value in the total hip (p < 0.01) and femoral neck (p = 0.03), but not in the lumbar spine, was significantly decreased. The TRACP-5b levels was significantly negatively associated with changes in the Tt.vBMD in both the distal radius and tibia (r =  − 0.53, r =  − 0.47, respectively)

Conclusion

Postmenopausal women who received AIs for early breast cancer experienced significant trabecular and cortical bone deterioration and a decrease in estimated bone strength within only 1 year.

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Abbreviations

BMD:

Bone mineral density

BV/TV:

Trabecular bone volume fraction

CI:

Confidence interval

Ct.Ar:

Cortical area

Ct.Pm:

Cortical perimeter

Ct.Po.Dm:

Cortical pore diameter

Ct.Po:

Cortical porosity

Ct.Th:

Cortical thickness

Ct.vBMD:

Cortical volumetric bone mineral density

DXA:

Dual-energy X-ray absorptiometry

HR( +) EBC:

Hormone receptor-positive early breast cancer

HR-pQCT:

High-resolution peripheral quantitative computed tomography

OR:

Odds ratio

P1NP:

Procollagen type-I N-terminal propeptide

Tb.Inn.BMD:

Inner trabecular bone mineral density

Tb.Meta.BMD:

Meta trabecular bone mineral density

Tb.N:

Trabecular number

Tb.Sp:

Trabecular separation

Tb.Th:

Trabecular thickness

Tb.vBMD:

Trabecular volumetric bone mineral density

TRACP-5b:

Tartrate-resistant acid phosphatase-5b

Tt.vBMD:

Total volumetric bone mineral density

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Acknowledgements

The authors thank Ms. Haraguchi for creating and managing the database. The authors also thank Editage Group (https://www.editage.jp/) for editing a draft of this manuscript. This research was supported by a “Japan Osteoporosis Foundation Grant for Bone Research.” The sponsor had no role in the study design; collection, analysis, and interpretation of data; writing of the report; and decision to submit the article for publication.

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Authors and Affiliations

  1. Department of Surgery, Nagasaki University Graduate School of Biomedical Science, 1-7-1 Sakamoto-machi, Nagasaki, 852-8501, Japan

    Sayaka Kuba, Kosho Yamanouchi, Xiangyue Meng, Michi Morita, Kengo Kanetaka & Susumu Eguchi

  2. Department of Orthopedic Surgery, Nagasaki University Graduate School of Biomedical Science, Nagasaki, Japan

    Kounosuke Watanabe, Ko Chiba & Makoto Osaki

  3. Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Science, Nagasaki, Japan

    Megumi Matsumoto, Ayako Fukushima, Ryota Otsubo, Hiroshi Yano & Takeshi Nagayasu

Authors
  1. Sayaka Kuba
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  2. Kounosuke Watanabe
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  3. Ko Chiba
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  4. Megumi Matsumoto
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  5. Kosho Yamanouchi
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  6. Ayako Fukushima
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  7. Xiangyue Meng
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  8. Michi Morita
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  9. Ryota Otsubo
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  11. Kengo Kanetaka
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  12. Makoto Osaki
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  13. Takeshi Nagayasu
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  14. Susumu Eguchi
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Contributions

SK, WK, CK, Megumi Matsumoto, and KY were responsible for conceiving and designing the trial and planning data analysis. SK, Megumi Matsumoto, KY, AF, XM, Michi Morita, RO, and HY participated in data collection and were in charge of patient recruitment and treatment. KW and KC were responsible for HR-pQCT analysis. KK, MO, TN, and SE were responsible for planning the data analysis and analyzing the data resulting from the trial. All authors have contributed to and approved the final version of this manuscript for publication.

Corresponding author

Correspondence to Sayaka Kuba.

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Conflict of interest

All authors have no conflicts of interest.

Ethical approval

This study was approved by the Nagasaki University Hospital Clinical Research Ethical Committee (17041711). The protocol was designed and conducted in accordance with the Declaration of Helsinki (1964) and its later amendments.

Consent to participate

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

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Kuba, S., Watanabe, K., Chiba, K. et al. Adjuvant endocrine therapy effects on bone mineral density and microstructure in women with breast cancer. J Bone Miner Metab 39, 1031–1040 (2021). https://doi.org/10.1007/s00774-021-01239-w

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