Skip to main content

Advertisement

SpringerLink
Log in

Quantitative ultrasound and DXA measurements in aromatase inhibitor-treated breast cancer women receiving denosumab

  • Original Article
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Purpose

Denosumab has been proven to reduce fracture risk in breast cancer (BC) women under aromatase inhibitors (AIs). Quantitative ultrasound (QUS) provides information on the structure and elastic properties of bone. Our aim was to assess bone health by phalangeal QUS and by dual-energy X-ray absorptiometry (DXA), and to evaluate bone turnover in AIs-treated BC women receiving denosumab.

Methods

35 Postmenopausal BC women on AIs were recruited (mean age 61.2 ± 4.5 years) and treated with denosumab 60 mg administered subcutaneously every 6 months. Phalangeal QUS parameters [Amplitude Dependent Speed of Sound (AD-SoS), Ultrasound Bone Profile Index (UBPI), Bone Transmission Time (BTT)] and DXA at lumbar spine and femoral neck were performed. Serum C-telopeptide of type 1 collagen (CTX) and bone-specific alkaline phosphatase (BSAP) were also measured. The main outcomes were compared with a control group not receiving denosumab (n = 39).

Results

In patients treated with denosumab, differently from controls, QUS and DXA measurements improved after 24 months, and a reduction of CTX and BSAP was detected at 12 and 24 months in comparison to baseline (P < 0.05). The percent changes (Δ) of QUS measurements were significantly associated with ΔBMD at femoral neck, and ΔCTX and ΔBSAP were associated with ΔBMD at lumbar spine (r = −0.39, P = 0.02; r = −0.49, P = 0.01, respectively).

Conclusions

Denosumab preserves bone health as assessed by phalangeal QUS and DXA. Since inexpensive and radiation-free, phalangeal QUS may be considered in the follow-up of AIs-treated BC women receiving denosumab.

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

Fig. 1

Similar content being viewed by others

References

  1. Coombes RC, Hall E, Gibson LJ et al (2004) A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med 350(11):1081–1092

    Article  CAS  PubMed  Google Scholar 

  2. Mouridsen H, Sun Y, Gershanovich M et al (2004) Superiority of letrozole to tamoxifen in the first-line treatment of advanced breast cancer: evidence from metastatic subgroups and a test of functional ability. Oncologist 9(5):489–496

    Article  CAS  PubMed  Google Scholar 

  3. Nabholtz JM, Buzdar A, Pollak M et al (2000) Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: results of a North American multicenter randomized trial. Arimidex Study Group. J Clin Oncol 18(22):3758–3767

    Article  CAS  PubMed  Google Scholar 

  4. Eastell R, Hannon R (2005) Long-term effects of aromatase inhibitors on bone. J Steroid Biochem Mol Biol 95(1–5):151–154

    Article  CAS  PubMed  Google Scholar 

  5. Vescini F, Attanasio R, Balestrieri A, Bandeira F, Bonadonna S, Camozzi V, Cassibba S, Cesareo R, Chiodini I, Francucci CM, Gianotti L, Grimaldi F, Guglielmi R, Madeo B, Marcocci C, Palermo A, Scillitani A, Vignali E, Rochira V, Zini M (2016) Italian association of clinical endocrinologists (AME) position statement: drug therapy of osteoporosis. J Endocrinol Invest 39(7):807–834

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Papadimitriou DT, Dermitzaki E, Papagianni M, Papaioannou G, Papaevangelou V, Papadimitriou A (2016) Anastrozole plus leuprorelin in early maturing girls with compromised growth: the “GAIL” study. J Endocrinol Invest 39(4):439–446

    Article  CAS  PubMed  Google Scholar 

  7. Hadji P, Aapro MS, Body JJ et al (2011) Management of aromatase inhibitor-associated bone loss in postmenopausal women with breast cancer: practical guidance for prevention and treatment. Ann Oncol 22(12):2546–2555

    Article  CAS  PubMed  Google Scholar 

  8. Rizzoli R, Body JJ, DeCensi A, Reginster JY, Piscitelli P, Brandi ML; European Society for Clinical and Economical aspects of Osteoporosis and Osteoarthritis (ESCEO) (2012) Guidance for the prevention of bone loss and fractures in postmenopausal women treated with aromatase inhibitors for breast cancer: an ESCEO position paper. Osteoporos Int 23(11):2567–2576

    Article  CAS  PubMed  Google Scholar 

  9. Kostenuik PJ, Nguyen HQ, McCabe J et al (2009) Denosumab, a fully human monoclonal antibody to RANKL, inhibits bone resorption and increases BMD in knock-in mice that express chimeric (murine/human) RANKL. J Bone Min Res 24:182–195

    Article  CAS  Google Scholar 

  10. Cummings SR, San Martin J, McClung MR et al (2009) Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 361(8):756–765

    Article  CAS  PubMed  Google Scholar 

  11. Orwoll E, Teglbjaerg CS, Langdahl BL et al (2012) A randomized, placebo-controlled study of the effects of denosumab for the treatment of men with low bone mineral density. J Clin Endocrinol Metab 97:3161–3169

    Article  CAS  PubMed  Google Scholar 

  12. Smith MR, Egerdie B, Hernandez Toriz N et al (2009) Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med 361:745–755

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ellis GK, Bone HG, Chlebowski R et al (2008) Randomized trial of denosumab in patients receiving adjuvant aromatase inhibitors for non metastatic breast cancer. J Clin Oncol 26:4875–4882

    Article  CAS  PubMed  Google Scholar 

  14. Gnant M, Pfeiler G, Dubsky PC et al (2015) Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet 386(9992):433–443

    Article  CAS  PubMed  Google Scholar 

  15. Kalder M, Hans D, Kyvernitakis I, Lamy O, Bauer M, Hadji P (2014) Effects of Exemestane and Tamoxifen treatment on bone texture analysis assessed by TBS in comparison with bone mineral density assessed by DXA in women with breast cancer. J Clin Densitom 17(1):66–71

    Article  PubMed  Google Scholar 

  16. Gluer CC (1997) Quantitative ultrasound techniques for the assessment of osteoporosis: expert agreement on current status. The International Quantitative Ultrasound Consensus Group. J Bone Miner Res 8:1280–1288

    Article  Google Scholar 

  17. Wüster C, Albanese C, De Aloysio D et al (2000) Phalangeal osteosonogrammetry study: age-related changes, diagnostic sensitivity, and discrimination power. The Phalangeal Osteosonogrammetry Study Group. J Bone Miner Res 15(8):1603–1614

    Article  PubMed  Google Scholar 

  18. Glüer CC, Eastell R, Reid DM et al (2004) Association of five quantitative ultrasound devices and bone densitometry with osteoporotic vertebral fractures in a population-based sample: the OPUS Study. J Bone Miner Res 19(5):782–793

    Article  PubMed  Google Scholar 

  19. Kanis JA, Johnell O, Oden A, De Laet C, De Terlizzi F (2005) Ten-year probabilities of clinical vertebral fractures according to phalangeal quantitative ultrasonography. Osteoporos Int 16(9):1065–1070

    Article  CAS  PubMed  Google Scholar 

  20. Catalano A, Morabito N, Basile G et al (2013) Fracture risk assessment in postmenopausal women referred to an Italian center for osteoporosis: a single day experience in Messina. Clin Cases Miner Bone Metab 10(3):191–194

    PubMed  Google Scholar 

  21. Catalano A, Morabito N, Di Vieste G et al (2013) Phalangeal quantitative ultrasound and metabolic control in pre-menopausal women with type 1 diabetes mellitus. J Endocrinol Invest 36(5):347–351

    CAS  PubMed  Google Scholar 

  22. Atteritano M, Lasco A, Mazzaferro S et al (2013) Bone mineral density, quantitative ultrasound parameters and bone metabolism in postmenopausal women with depression. Intern Emerg Med 8(6):485–491

    Article  PubMed  Google Scholar 

  23. Catalano A, Morabito N, Agostino RM et al (2016) Bone health assessment by quantitative ultrasound and dual-energy X-ray absorptiometry in postmenopausal women with breast cancer receiving aromatase inhibitors. Menopause. DOI:10.1097/GME.0000000000000722

    Google Scholar 

  24. Mauloni M, Rovati LC, Cadossi R, de Terlizzi F, Ventura V, de Aloysio D (2000) Monitoring bone effect of transdermal hormone replacement therapy by ultrasound investigation at the phalanx: a four-year follow-up study. Menopause 7(6):402–412

    Article  CAS  PubMed  Google Scholar 

  25. Machado ABC, Ingle BM, Eastell R (1999) Monitoring alendronate therapy with Quantitative Ultrasound (QUS) and Dual X-ray Absorptiometry (DXA). J Bone Miner Res 14(S1):S526

    Google Scholar 

  26. Catalano A, Pintaudi B, Morabito N et al (2014) Gender differences in sclerostin and clinical characteristics in type 1 diabetes mellitus. Eur J Endocrinol 171(3):293–300

    Article  CAS  PubMed  Google Scholar 

  27. Zebaze RM, Ghasem-Zadeh A, Bohte A et al (1010) Intracortical remodelling and porosity in the distal radius and post-mortem femurs of women: a cross-sectional study. The Lancet 375:1729–1736

    Article  Google Scholar 

  28. Sakata S, Barkmann R, Lochmüller EM, Heller M, Glüer CC (2004) Assessing bone status beyond BMD: evaluation of bone geometry and porosity by quantitative ultrasound of human finger phalanges. J Bone Miner Res 19(6):924–930

    Article  PubMed  Google Scholar 

  29. Zebaze RM, Libanati C, Austin M et al (2014) Differing effects of denosumab and alendronate on cortical and trabecular bone. Bone 59:173–179

    Article  CAS  PubMed  Google Scholar 

  30. Cheung AM, Tile L, Cardew S et al (2012) Bone density and structure in healthy postmenopausal women treated with exemestane for the primary prevention of breast cancer: a nested substudy of the MAP.3 randomised controlled trial. Lancet Oncol 13(3):275–284

    Article  CAS  PubMed  Google Scholar 

  31. Prasad C, Greenspan SL, Vujevich KT et al (2016) Risedronate may preserve bone microarchitecture in breast cancer survivors on aromatase inhibitors: A randomized, controlled clinical trial. Bone 90:123–126

    Article  CAS  PubMed  Google Scholar 

  32. Krishnan AV, Swami S, Peng L, Wang J, Moreno J, Feldman D (2010) Tissue-selective regulation of aromatase expression by calcitriol: implications for breast cancer therapy. Endocrinology 151(1):32–42

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank Dr Andrè Corrado for the DXA measurements.

Author information

Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, University Hospital of Messina, University Hospital “G. Martino”, Via C. Valeria, 98125, Messina, Italy

    A. Catalano, N. Morabito, G. Basile, M. Atteritano, E. Morini & A. Lasco

  2. Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

    A. Gaudio & A. Xourafa

  3. Department of Human Pathology, University of Messina, Messina, Italy

    R. M. Agostino

  4. Mineral Metabolism and Nephrology Clinic of Vibo Valentia Hospital, Vibo Valentia, Italy

    G. Natale

Authors
  1. A. Catalano
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Gaudio
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N. Morabito
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G. Basile
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R. M. Agostino
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. Xourafa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M. Atteritano
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. E. Morini
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. G. Natale
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. A. Lasco
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. Catalano.

Ethics declarations

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments.

Informed consent

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

Conflict of interest

Catalano Antonino, Gaudio Agostino, Morabito Nunziata, Basile Giorgio, Agostino Rita Maria, Xourafa Anastasia, Atteritano Marco, Morini Elisabetta, Natale Giuseppe and Lasco Antonino declare that they have no conflicts of interest.

Funding

This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Catalano, A., Gaudio, A., Morabito, N. et al. Quantitative ultrasound and DXA measurements in aromatase inhibitor-treated breast cancer women receiving denosumab. J Endocrinol Invest 40, 851–857 (2017). https://doi.org/10.1007/s40618-016-0606-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40618-016-0606-6

Keywords

Search

Navigation