Skip to main content

Advertisement

SpringerLink
Log in

Effect of chemotherapy and different chemotherapy regimens on bone health among Chinese breast cancer women in different menstrual status: a self-control study

  • Research
  • Published:
Supportive Care in Cancer Aims and scope Submit manuscript

Abstract

Purpose

Although the therapy-related bone loss attracts increasing attention nowadays, the differences in chemotherapy-induced bone loss and bone metabolism indexes change among breast cancer (BC) women with different menstrual statuses or chemotherapy regimens are unknown. The aim of the study is to explore the effects of different regimens of chemotherapy on bone health.

Method

The self-control study enrolled 118 initially diagnosed BC women without distant metastasis who underwent dual-energy X-ray absorptiometry (DXA) bone mineral density (BMD) screening and (or) bone metabolism index monitoring during chemotherapy at Chongqing Breast Cancer Center. Mann-Whitney U test, Cochran’s Q test, and Wilcoxon sign rank test were performed.

Results

After chemotherapy, the BMD in the lumbar 1–4 and whole lumbar statistically decreased (− 1.8%/per 6 months), leading to a significantly increased proportion of osteoporosis (27.1% vs. 20.5%, P < 0.05), which were mainly seen in the premenopausal group (− 7.0%/per 6 months). Of the chemotherapeutic regimens of EC (epirubicin + cyclophosphamide), TC (docetaxel + cyclophosphamide), TEC (docetaxel + epirubicin + cyclophosphamide), and EC-T(H) [epirubicin + cyclophosphamide-docetaxel and/or trastuzumab], EC regimen had the least adverse impact on BMD, while the EC-TH regimen reduced BMD most (P < 0.05) inspite of the non-statistical difference between EC-T regimen, which was mainly seen in the postmenopausal group. Chemotherapy-induced amenorrhea (estradiol 94 pg/ml vs, 22 pg/ml; FSH 9.33 mIU/ml vs. 61.27 mIU/ml) was proved in premenopausal subgroup (P < 0.001). Except the postmenopausal population with calcium/VitD supplement, the albumin-adjusted calcium increased significantly (2.21 mmol/l vs. 2.33 mmol/l, P < 0.05) after chemotherapy. In postmenopausal group with calcium/VitD supplement, β-CTX decreased significantly (0.56 ng/ml vs. 0.39 ng/ml, P < 0.05) and BMD were not affected by chemotherapy (P > 0. 05). In premenopausal group with calcium/VitD supplement, PTH decreased significantly (52.90 pg/ml vs. 28.80 pg/ml, P = 0. 008) and hip BMD increased after chemotherapy (0.845 g/m2 vs. 0.952 g/m2, P = 0. 006). As for both postmenopausal and premenopausal group without calcium/VitD supplement, there was a significant decrease in bone mass in hip and lumbar vertebrae after chemotherapy (0.831 g/m2 vs. 0.776 g/m2; 0.895 g/m2 vs. 0.870 g/m2, P < 0.05).

Conclusion

Chemotherapy might induce lumbar vertebrae BMD loss and spine osteoporosis with regimen differences among Chinese BC patients. Calcium/VitD supplementation could improve bone turnover markers, bone metabolism indicators, and bone mineral density. Early interventions on bone health are needed for BC patients during chemotherapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Data availability

The data that support the fndings of this study are available from the frst author upon reasonable request. The data are not publicly available due to privacy or ethical restrictions.

References

  1. Sung H, Ferlay J, Siegel RL et al (2021) Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71(3):209–249. https://doi.org/10.3322/caac.21660

    Article  PubMed  Google Scholar 

  2. Ferlay J, Colombet M, Soerjomataram I et al (2021) Cancer statistics for the year 2020: an overview. Int J Cancer. https://doi.org/10.1002/ijc.33588

  3. Akram M, Iqbal M, Daniyal M et al (2017) Awareness and current knowledge of breast cancer. Biol Res 50(1):33. https://doi.org/10.1186/s40659-017-0140-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Diana A, Carlino F, Giunta EF et al (2021) Cancer treatment-induced bone loss (CTIBL): state of the art and proper management in breast cancer patients on endocrine therapy. Curr Treat Options Oncol 22(5):45. https://doi.org/10.1007/s11864-021-00835-2

    Article  PubMed  PubMed Central  Google Scholar 

  5. Nisha Y, Dubashi B, Bobby Z et al (2021) Effect of cytotoxic chemotherapy on bone health among breast cancer patients. Does it require intervention? Support Care Cancer 29(11):6957–6972. https://doi.org/10.1007/s00520-021-06231-8

    Article  PubMed  Google Scholar 

  6. Chen Z, Maricic M, Aragaki AK et al (2009) Fracture risk increases after diagnosis of breast or other cancers in postmenopausal women: results from the Women's Health Initiative. Osteoporos Int 20(4):527–536. https://doi.org/10.1007/s00198-008-0721-0

    Article  CAS  PubMed  Google Scholar 

  7. Peppone LJ, Mustian KM, Rosier RN et al (2014) Bone health issues in breast cancer survivors: a Medicare Current Beneficiary Survey (MCBS) study. Support Care Cancer 22(1):245–251. https://doi.org/10.1007/s00520-013-1967-4

    Article  PubMed  Google Scholar 

  8. Rozenberg S, Al-Daghri N, Aubertin-Leheudre M et al (2020) Is there a role for menopausal hormone therapy in the management of postmenopausal osteoporosis? Osteoporos Int 31(12):2271–2286. https://doi.org/10.1007/s00198-020-05497-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Clynes MA, Harvey NC, Curtis EM et al (2020) The epidemiology of osteoporosis. Br Med Bull 133(1):105–117. https://doi.org/10.1093/bmb/ldaa005

    Article  PubMed  Google Scholar 

  10. Shapiro CL (2020) Osteoporosis: a long-term and late-effect of breast cancer treatments. Cancers 12(11). https://doi.org/10.3390/cancers12113094

  11. Hadji P, Ziller M, Maskow C et al (2009) The influence of chemotherapy on bone mineral density, quantitative ultrasonometry and bone turnover in pre-menopausal women with breast cancer. Eur J Cancer 45(18):3205–3212. https://doi.org/10.1016/j.ejca.2009.09.026

    Article  CAS  PubMed  Google Scholar 

  12. Cameron DA, Douglas S, Brown JE et al (2010) Bone mineral density loss during adjuvant chemotherapy in pre-menopausal women with early breast cancer: is it dependent on oestrogen deficiency? Breast Cancer Res Treat 123(3):805–814. https://doi.org/10.1007/s10549-010-0899-7

    Article  CAS  PubMed  Google Scholar 

  13. Lower EE, Blau R, Gazder P et al (1999) The risk of premature menopause induced by chemotherapy for early breast cancer. J Womens Health Gend Based Med 8(7):949–954. https://doi.org/10.1089/jwh.1.1999.8.949

    Article  CAS  PubMed  Google Scholar 

  14. Bines J, Oleske DM, Cobleigh MA (1996) Ovarian function in premenopausal women treated with adjuvant chemotherapy for breast cancer. J Clin Oncol 14(5):1718–1729. https://doi.org/10.1200/JCO.1996.14.5.1718

    Article  CAS  PubMed  Google Scholar 

  15. Yip C, Liem GS, Mo F et al (2020) Bone health in premenopausal chinese patients after adjuvant chemotherapy for early breast cancer. Breast Care 15(6):655–666. https://doi.org/10.1159/000506465

    Article  PubMed  PubMed Central  Google Scholar 

  16. Vestergaard P (2020) Drugs causing bone loss. Handb Exp Pharmacol 262:475–497. https://doi.org/10.1007/164_2019_340

    Article  CAS  PubMed  Google Scholar 

  17. Payne RB, Little AJ, Williams RB et al (1973) Interpretation of serum calcium in patients with abnormal serum proteins. Br Med J 4(5893):643–646. https://doi.org/10.1136/bmj.4.5893.643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kailajärvi ME, Salminen EK, Paija OM et al (2004) Serum bone markers in breast cancer patients during 5-fluorouracil, epirubicin and cyclophosphamide (FEC) therapy. Anticancer Res 24(2C):1271–1274

    PubMed  Google Scholar 

  19. Taxel P, Faircloth E, Idrees S et al (2018) Cancer treatment-induced bone loss in women with breast cancer and men with prostate cancer. J Endocr Soc 2(7):574–588. https://doi.org/10.1210/js.2018-00052

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Safaei-Nodehi R, Esmaili J, Sharifian R et al (2017) Does adjuvant chemotherapy change bone mineral density and related serum biomarkers in women with breast cancer? Caspian J Intern Med 8(2):91–98. https://doi.org/10.22088/cjim.8.2.91

    Article  PubMed  PubMed Central  Google Scholar 

  21. Axelsen CT, Jensen AB, Jakobsen EH et al (2018) Bone loss during neoadjuvant/adjuvant chemotherapy for early stage breast cancer: a retrospective cohort study. Mol Clin Oncol 8(6):767–772. https://doi.org/10.3892/mco.2018.1615

    Article  CAS  PubMed  Google Scholar 

  22. Kim M, Kim H, Ahn SH et al (2020) Changes in bone mineral density during 5 years of adjuvant treatment in premenopausal breast cancer patients. Breast Cancer Res Treat 180(3):657–663. https://doi.org/10.1007/s10549-020-05566-w

    Article  CAS  PubMed  Google Scholar 

  23. Davies JH, Evans BA, Jenney ME et al (2002) In vitro effects of chemotherapeutic agents on human osteoblast-like cells. Calcif Tissue Int 70(5):408–415. https://doi.org/10.1007/s002230020039

    Article  CAS  PubMed  Google Scholar 

  24. Young DR, Virolainen P, Inoue N et al (1997) The short-term effects of cisplatin chemotherapy on bone turnover. J Bone Miner Res 12(11):1874–1882. https://doi.org/10.1359/jbmr.1997.12.11.1874

    Article  CAS  PubMed  Google Scholar 

  25. Kang C, Syed YY (2020) Atezolizumab (in combination with nab-paclitaxel): a review in advanced triple-negative breast cancer. Drugs 80(6):601–607. https://doi.org/10.1007/s40265-020-01295-y

    Article  CAS  PubMed  Google Scholar 

  26. Glück S (2005) Adjuvant chemotherapy for early breast cancer: optimal use of epirubicin. Oncologist 10(10):780–791. https://doi.org/10.1634/theoncologist.10-10-780

    Article  PubMed  Google Scholar 

  27. Shandala T, Shen NY, Hopwood B et al (2012) The role of osteocyte apoptosis in cancer chemotherapy-induced bone loss. J Cell Physiol 227(7):2889–2897. https://doi.org/10.1002/jcp.23034

    Article  CAS  PubMed  Google Scholar 

  28. Fan C, Georgiou KR, McKinnon RA et al (2016) Combination chemotherapy with cyclophosphamide, epirubicin and 5-fluorouracil causes trabecular bone loss, bone marrow cell depletion and marrow adiposity in female rats. J Bone Miner Metab 34(3):277–290. https://doi.org/10.1007/s00774-015-0679-x

    Article  CAS  PubMed  Google Scholar 

  29. Fan C, Georgiou KR, Morris HA et al (2017) Combination breast cancer chemotherapy with doxorubicin and cyclophosphamide damages bone and bone marrow in a female rat model. Breast Cancer Res Treat 165(1):41–51. https://doi.org/10.1007/s10549-017-4308-3

    Article  CAS  PubMed  Google Scholar 

  30. Takahashi M, Mizoguchi T, Uehara S et al (2009) Docetaxel inhibits bone resorption through suppression of osteoclast formation and function in different manners. J Bone Miner Metab 27(1):24–35. https://doi.org/10.1007/s00774-008-0013-y

    Article  CAS  PubMed  Google Scholar 

  31. Ang ES, Pavlos NJ, Chim SM et al (2012) Paclitaxel inhibits osteoclast formation and bone resorption via influencing mitotic cell cycle arrest and RANKL-induced activation of NF-κB and ERK. J Cell Biochem 113(3):946–955. https://doi.org/10.1002/jcb.23423

    Article  CAS  PubMed  Google Scholar 

  32. Friedlaender GE, Tross RB, Doganis AC et al (1984) Effects of chemotherapeutic agents on bone. I. Short-term methotrexate and doxorubicin (adriamycin) treatment in a rat model. J Bone Joint Surg Am 66(4):602–607

    Article  CAS  PubMed  Google Scholar 

  33. Xian CJ, Cool JC, Pyragius T et al (2006) Damage and recovery of the bone growth mechanism in young rats following 5-fluorouracil acute chemotherapy. J Cell Biochem 99(6):1688–1704. https://doi.org/10.1002/jcb.20889

    Article  CAS  PubMed  Google Scholar 

  34. Peymanfar Y, Su YW, Xian CJ (2022) Notch2 blockade mitigates methotrexate chemotherapy-induced bone loss and marrow adiposity. Cells 11(9). https://doi.org/10.3390/cells11091521

  35. Frost HM (1994) Wolff's Law and bone's structural adaptations to mechanical usage: an overview for clinicians. Angle Orthod 64(3):175–188. https://doi.org/10.1002/jcb.23423

    Article  CAS  PubMed  Google Scholar 

  36. Kanis JA, McCloskey EV, Johansson H et al (2008) A reference standard for the description of osteoporosis. Bone 42(3):467–475. https://doi.org/10.1016/j.bone.2007.11.001

    Article  CAS  PubMed  Google Scholar 

  37. Kanis JA, Glüer CC (2000) An update on the diagnosis and assessment of osteoporosis with densitometry. Committee of Scientific Advisors, International Osteoporosis Foundation. Osteoporos Int 11(3):192–202. https://doi.org/10.1007/s001980050281

    Article  CAS  PubMed  Google Scholar 

  38. Delmas PD, van de Langerijt L, Watts NB et al (2005) Underdiagnosis of vertebral fractures is a worldwide problem: the IMPACT study. J Bone Miner Res 20(4):557–563. https://doi.org/10.1359/JBMR.041214

    Article  PubMed  Google Scholar 

  39. Lindsay R, Silverman SL, Cooper C et al (2001) Risk of new vertebral fracture in the year following a fracture. JAMA 285(3):320–323. https://doi.org/10.1001/jama.285.3.320

    Article  CAS  PubMed  Google Scholar 

  40. Garnero P, Hausherr E, Chapuy MC et al (1996) Markers of bone resorption predict hip fracture in elderly women: the EPIDOS Prospective Study. J Bone Miner Res 11(10):1531–1538. https://doi.org/10.1002/jbmr.5650111021

    Article  CAS  PubMed  Google Scholar 

  41. Chen Y, Xu G, Yang F (2015) Effect of neoadjuvant chemotherapy on the serum levels of bone turnover markers in women with early-stage breast cancer. PloS One 10(4):e126053. https://doi.org/10.1371/journal.pone.0126053

    Article  CAS  Google Scholar 

  42. Jacot W, Pouderoux S, Thezenas S et al (2012) Increased prevalence of vitamin D insufficiency in patients with breast cancer after neoadjuvant chemotherapy. Breast Cancer Res Treat 134(2):709–717. https://doi.org/10.1007/s10549-012-2084-7

    Article  CAS  PubMed  Google Scholar 

  43. Christensen CØ, Cronin-Fenton D, Frøslev T et al (2016) Change in bone mineral density during adjuvant chemotherapy for early-stage breast cancer. Support Care Cancer 24(10):4229–4236. https://doi.org/10.1007/s00520-016-3250-y

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors gratefully acknowledge the support from the related hospitals and all the participants for their sharing of their datas in this study.

Author information

Author notes

  1. Bai-qing Peng, Juan Wu, Shen Tian, Xiu-quan Qu, Xin-yu Liang and Jun-han Feng contributed equally to this work.

Authors and Affiliations

  1. Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China

    Bai-qing Peng, Juan Wu, Shen Tian, Xiu-quan Qu, Xin-yu Liang, Jun-han Feng, Yu-ling Chen, Rui-ling She, Chen-yu Ma, Jing-yu Song, Zhao-xing Li, Zhi-yu Jiang, Kai-nan Wu & Ling-quan Kong

Authors
  1. Bai-qing Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Juan Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shen Tian
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiu-quan Qu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xin-yu Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jun-han Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yu-ling Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Rui-ling She
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Chen-yu Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jing-yu Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Zhao-xing Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Zhi-yu Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Kai-nan Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Ling-quan Kong
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All the authors contributed to the conception and design of the study. Bai-qing Peng and Juan Wu performed the data collection and analysis. The first draft of the manuscript was written by Bai-qing Peng, Juan Wu, Shen Tian, Xiu-quan Qu, Xin-yu Liang, Jun-han Feng, Yu-ling Chen, Rui-ling She, Chen-yu Ma, Jing-yu Song, Zhao-xing Li, Zhi-yu Jiang, Kai-nan Wu, and Ling-quan Kong, and all the authors commented on the previous versions of the manuscript. All the authors have read and approved the final manuscript.

Corresponding author

Correspondence to Ling-quan Kong.

Ethics declarations

Ethics approval and consent to participate

This study was approved by the Ethics Committee of the First Affiliated Hospital of Chongqing Medical University. All procedures performed involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Declaration of Helsinki and its later amendments. Informed consent was not obtained as this was a retrospective study, meeting the requirements for the informed consent waiver.

Consent for publication

All authors consented for publication.

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Peng, Bq., Wu, J., Tian, S. et al. Effect of chemotherapy and different chemotherapy regimens on bone health among Chinese breast cancer women in different menstrual status: a self-control study. Support Care Cancer 31, 540 (2023). https://doi.org/10.1007/s00520-023-07960-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00520-023-07960-8

Keywords

Search

Navigation