Skip to main content

Advertisement

SpringerLink
Log in

Effects of zoledronic acid versus placebo on bone mineral density and bone texture analysis assessed by the trabecular bone score in premenopausal women with breast cancer treatment-induced bone loss: results of the ProBONE II substudy

  • Original Article
  • Published:
Osteoporosis International Aims and scope Submit manuscript

Abstract

Summary

Changes in bone mineral density (BMD) and trabecular bone score (TBS) were assessed in 70 patients who received either zoledronate (ZOL) (n = 34) or placebo (n = 36) for 2 years. In premenopausal women with breast cancer treatment-induced bone loss, 24 months of intravenous ZOL treatment significantly increased the lumbar spine BMD and the TBS.

Introduction

The aim of this study was to compare the effects of 4 mg intravenous zoledronate (ZOL) versus placebo (PLB), every 3 months, on the lumbar spine (LS) bone mineral density (BMD) and the trabecular bone score (TBS) in premenopausal women with breast cancer (BC) treatment-induced bone loss. The TBS is a gray-level texture measurement which is related to the bone microarchitecture and considered to be independent of the BMD.

Methods

Changes in BMD and TBS were assessed in 70 patients who were recruited in the double-blind, placebo-controlled ProBONE-II trial and randomized to receive either ZOL (n = 34) or PLB (n = 36) for 2 years. The changes were assessed at baseline and at 12 and 24 months after treatment initiation.

Results

Patients receiving ZOL showed a mean increase in LS BMD from the baseline to 12 (2.17 %) and 24 months (3.14 %) of treatment and a mean increase in the TBS of 2.41 and 0.75 %, respectively. Conversely, patients receiving PLB showed a mean decrease in the LS BMD from the baseline to 12 (−5.02 %) and 24 (−6.43 %) months and a mean decrease of −0.52 and −2.16 % in the TBS, respectively. Changes in the BMD and the TBS from the baseline to 12 and 24 months were all significantly different for ZOL compared to PLB (p < 0.005). Furthermore, BMD and TBS showed a moderate correlation ranging from 0.28 (p = 0.087) to 0.47 (p = 0.003).

Conclusions

In premenopausal women with BC, 24 months of intravenous ZOL treatment significantly increased the LS BMD as well as the TBS.

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
Fig. 2

Similar content being viewed by others

References

  1. Silva BC, Leslie WD, Resch H, Lamy O, Lesnyak O, Binkley N, McCloskey EV, Kanis JA, Bilezikian JP (2014) Trabecular bone score: a non-invasive analytical method based upon the DXA image. J Bone Miner Res

  2. Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74–108

    Article  PubMed  Google Scholar 

  3. Howlader N, Noone AM, Krapcho M, Garshell J, Neyman N, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Cho H, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KAE (2013) SEER cancer statistics review, 1975–2010

  4. Fuleihan G, Salamoun M, Mourad YA, Chehal A, Salem Z, Mahfoud Z, Shamseddine A (2005) Pamidronate in the prevention of chemotherapy-induced bone loss in premenopausal women with breast cancer: a randomized controlled trial. J Clin Endocrinol Metab 90:3209–3214

    Article  Google Scholar 

  5. Hadji P, Ziller M, Maskow C, Albert U, Kalder M (2009) The influence of chemotherapy on bone mineral density, quantitative ultrasonometry and bone turnover in pre-menopausal women with breast cancer. Eur J Cancer 45:3205–3212

    Article  CAS  PubMed  Google Scholar 

  6. Kanis JA (2002) Diagnosis of osteoporosis and assessment of fracture risk. Lancet 359:1929–1936

    Article  PubMed  Google Scholar 

  7. Kanis JA, McCloskey EV, Johansson H, Oden A, Melton LJ III, Khaltaev N (2008) A reference standard for the description of osteoporosis. Bone 42:467–475

    Article  CAS  PubMed  Google Scholar 

  8. Siris ES, Miller PD, Barrett-Connor E, Faulkner KG, Wehren LE, Abbott TA, Berger ML, Santora AC, Sherwood LM (2001) Identification and fracture outcomes of undiagnosed low bone mineral density in postmenopausal women: results from the national osteoporosis risk assessment. JAMA 286:2815–2822

    Article  CAS  PubMed  Google Scholar 

  9. Hordon LD, Raisi M, Aaron JE, Paxton SK, Beneton M, Kanis JA (2000) Trabecular architecture in women and men of similar bone mass with and without vertebral fracture: I. Two-dimensional histology. Bone 27:271–276

    Article  CAS  PubMed  Google Scholar 

  10. Cummings SR, Nevitt MC, Browner WS, Stone K, Fox KM, Ensrud KE, Cauley J, Black D, Vogt TM (1995) Risk factors for hip fracture in white women. Study of osteoporotic fractures research group. N Engl J Med 332:767–773

    Article  CAS  PubMed  Google Scholar 

  11. Schuit SC, van der Klift M, Weel AE, de Laet CE, Burger H, Seeman E, Hofman A, Uitterlinden AG, van Leeuwen JP, Pols HA (2004) Fracture incidence and association with bone mineral density in elderly men and women: the Rotterdam study. Bone 34:195–202

    Article  CAS  PubMed  Google Scholar 

  12. Wainwright SA, Marshall LM, Ensrud KE, Cauley JA, Black DM, Hillier TA, Hochberg MC, Vogt MT, Orwoll ES (2005) Hip fracture in women without osteoporosis. J Clin Endocrinol Metab 90:2787–2793

    Article  CAS  PubMed  Google Scholar 

  13. Hans D, Barthe N, Boutroy S, Pothuaud L, Winzenrieth R, Krieg MA (2011) Correlations between trabecular bone score, measured using anteroposterior dual-energy X-ray absorptiometry acquisition, and 3-dimensional parameters of bone microarchitecture: an experimental study on human cadaver vertebrae. J Clin Densitom 14:302–312

    Article  PubMed  Google Scholar 

  14. Majumdar S (1998) A review of magnetic resonance (MR) imaging of trabecular bone micro-architecture: contribution to the prediction of biomechanical properties and fracture prevalence. Technol Health Care 6:321–327

    CAS  PubMed  Google Scholar 

  15. Rubin CD (2005) Emerging concepts in osteoporosis and bone strength. Curr Med Res Opin 21:1049–1056

    Article  PubMed  Google Scholar 

  16. Turner CH, Cowin SC, Rho JY, Ashman RB, Rice JC (1990) The fabric dependence of the orthotropic elastic constants of cancellous bone. J Biomech 23:549–561

    Article  CAS  PubMed  Google Scholar 

  17. Hans D, Goertzen AL, Krieg MA, Leslie WD (2011) Bone microarchitecture assessed by TBS predicts osteoporotic fractures independent of bone density: the Manitoba study. J Bone Miner Res 26:2762–2769

    Article  PubMed  Google Scholar 

  18. Pothuaud L, Barthe N, Krieg MA, Mehsen N, Carceller P, Hans D (2009) Evaluation of the potential use of trabecular bone score to complement bone mineral density in the diagnosis of osteoporosis: a preliminary spine BMD-matched, case-control study. J Clin Densitom 12:170–176

    Article  PubMed  Google Scholar 

  19. Hadji P, Aapro MS, Body JJ, Bundred NJ, Brufsky A, Coleman RE, Gnant M, Guise T, Lipton A (2011) Management of aromatase inhibitor-associated bone loss in postmenopausal women with breast cancer: practical guidance for prevention and treatment. Ann Oncol 22:2546–2555

    Article  CAS  PubMed  Google Scholar 

  20. Hadji P, Gnant M, Body JJ, Bundred NJ, Brufsky A, Coleman RE, Guise TA, Lipton A, Aapro MS (2012) Cancer treatment-induced bone loss in premenopausal women: a need for therapeutic intervention? Cancer Treat Rev 38:798–806

    Article  CAS  PubMed  Google Scholar 

  21. Hershman DL, McMahon DJ, Crew KD, Cremers S, Irani D, Cucchiara G, Brafman L, Shane E (2008) Zoledronic acid prevents bone loss in premenopausal women undergoing adjuvant chemotherapy for early-stage breast cancer. J Clin Oncol 26:4739–4745

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Shapiro CL, Halabi S, Hars V, Archer L, Weckstein D, Kirshner J, Sikov W, Winer E, Burstein HJ, Hudis C, Isaacs C, Schilsky R, Paskett E (2011) Zoledronic acid preserves bone mineral density in premenopausal women who develop ovarian failure due to adjuvant chemotherapy: final results from CALGB trial 79809. Eur J Cancer 47:683–689

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Gnant M, Mlineritsch B, Luschin-Ebengreuth G, Kainberger F, Kassmann H, Piswanger-Solkner JC, Seifert M, Ploner F, Menzel C, Dubsky P, Fitzal F, Bjelic-Radisic V, Steger G, Greil R, Marth C, Kubista E, Samonigg H, Wohlmuth P, Mittlbock M, Jakesz R (2008) Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 5-year follow-up of the ABCSG-12 bone-mineral density substudy. Lancet Oncol 9:840–849

    Article  CAS  PubMed  Google Scholar 

  24. Love RR, Young GS, Laudico AV, Van DN, Uy GB, Quang LH, De La Pena AS, Dofitas RB, Bisquera OC Jr, Siguan SS, Salvador JD, Mirasol-Lumague MR, Navarro NS Jr, Linh ND, Jarjoura D (2013) Bone mineral density following surgical oophorectomy and tamoxifen adjuvant therapy for breast cancer. Cancer 119:3746–3752

    Article  CAS  PubMed  Google Scholar 

  25. Hadji P, Kauka A, Ziller M, Birkholz K, Baier M, Muth M, Bauer M (2014) Effects of zoledronic acid on bone mineral density in premenopausal women receiving neoadjuvant or adjuvant therapies for HR + breast cancer: the ProBONE II study. Osteoporos Int 25:1369–1378

    Article  CAS  PubMed  Google Scholar 

  26. Dufour R, Winzenrieth R, Heraud A, Hans D, Mehsen N (2013) Generation and validation of a normative, age-specific reference curve for lumbar spine trabecular bone score (TBS) in French women. Osteoporos Int 24:2837–2846

    Article  CAS  PubMed  Google Scholar 

  27. Boutroy S, Hans D, Sornay-Rendu E, Vilayphiou N, Winzenrieth R, Chapurlat R (2013) Trabecular bone score improves fracture risk prediction in non-osteoporotic women: the OFELY study. Osteoporos Int 24:77–85

    Article  CAS  PubMed  Google Scholar 

  28. Link TM, Majumdar S (2004) Current diagnostic techniques in the evaluation of bone architecture. Curr Osteoporos Rep 2:47–52

    Article  PubMed  Google Scholar 

  29. Seeman E, Delmas PD (2006) Bone quality—the material and structural basis of bone strength and fragility. N Engl J Med 354:2250–2261

    Article  CAS  PubMed  Google Scholar 

  30. Davies KM, Stegman MR, Heaney RP, Recker RR (1996) Prevalence and severity of vertebral fracture: the Saunders County bone quality study. Osteoporos Int 6:160–165

    Article  CAS  PubMed  Google Scholar 

  31. Roux J, Wegrzyn J, Boutroy S (2012) Relationship between trabecular bone score (TBS). Bone mass and microarchitecture in human vertebrase: an ex vivo study. Osteoporos Int 23:S85–S386

    Article  Google Scholar 

  32. Winzenrieth R, Michelet F, Hans D (2012) Three-dimensional (3D) microarchitecture correlations with 2D projection image gray-level variations assessed by trabecular bone score using high-resolution computed tomographic acquisitions: effects of resolution and noise. J Clin Densitom

  33. Coates AS, Keshaviah A, Thurlimann B, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Castiglione-Gertsch M, Gelber RD, Colleoni M, Lang I, Del ML, Smith I, Chirgwin J, Nogaret JM, Pienkowski T, Wardley A, Jakobsen EH, Price KN, Goldhirsch A (2007) Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1-98. J Clin Oncol 25:486–492

    Article  CAS  PubMed  Google Scholar 

  34. Coombes RC, Kilburn LS, Snowdon CF, Paridaens R, Coleman RE, Jones SE, Jassem J, van de Velde CJ, Delozier T, Alvarez I, Del ML, Ortmann O, Diedrich K, Coates AS, Bajetta E, Holmberg SB, Dodwell D, Mickiewicz E, Andersen J, Lonning PE, Cocconi G, Forbes J, Castiglione M, Stuart N, Stewart A, Fallowfield LJ, Bertelli G, Hall E, Bogle RG, Carpentieri M, Colajori E, Subar M, Ireland E, Bliss JM (2007) Survival and safety of exemestane versus tamoxifen after 2–3 years’ tamoxifen treatment (intergroup exemestane study): a randomised controlled trial. Lancet 369:559–570

    Article  CAS  PubMed  Google Scholar 

  35. Forbes JF, Cuzick J, Buzdar A, Howell A, Tobias JS, Baum M (2008) Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol 9:45–53

    Article  PubMed  Google Scholar 

  36. Frenkel B, Hong A, Baniwal SK, Coetzee GA, Ohlsson C, Khalid O, Gabet Y (2010) Regulation of adult bone turnover by sex steroids. J Cell Physiol 224:305–310

    Article  CAS  PubMed  Google Scholar 

  37. Hadji P, Bundred N (2007) Reducing the risk of cancer treatment-associated bone loss in patients with breast cancer. Semin Oncol 34:S4–S10

    Article  CAS  PubMed  Google Scholar 

  38. Popp AW, Buffat H, Lamy O (2012) Beneficial effect of zoledronate compared to placebo on spine BMD and microarchitecture (TBS) parameters in postmenopausal women with osteoporosis. A 3-year study. Osteoporos Int 23:S86–S386

    Google Scholar 

  39. Kalder M, Hans D, Kyvernitakis I, Lamy O, Bauer M, Hadji P (2013) 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

  40. Günther B, Popp AW, Stoll D (2012) Beneficial effect of PTH on spine BMD and microarchitecture (TBS) parameters in postmenopausal women with osteoporosis. A 2-year study. Osteoporos Int 23:S85–S386

    Article  Google Scholar 

  41. Hans D, Krieg MA, Lamy O, Felsenberg D (2012) Beneficial effects of strontium ranelate compared to alendronate on trabecular bone score in post menopausal osteoporotic women. A 2-year study. Osteoporos Int 23:S85–S386

    Article  Google Scholar 

  42. Krieg MA, Aubry-Rozier B, Hans D, Leslie WD (2013) Effects of anti-resorptive agents on trabecular bone score (TBS) in older women. Osteoporos Int 24:1073–1078

    Article  CAS  PubMed  Google Scholar 

  43. Eastell R, Lang T, Boonen S, Cummings S, Delmas PD, Cauley JA, Horowitz Z, Kerzberg E, Bianchi G, Kendler D, Leung P, Man Z, Mesenbrink P, Eriksen EF, Black DM (2010) Effect of once-yearly zoledronic acid on the spine and hip as measured by quantitative computed tomography: results of the HORIZON Pivotal Fracture Trial. Osteoporos Int 21:1277–1285

    Article  CAS  PubMed  Google Scholar 

  44. Gamsjaeger S, Buchinger B, Zwettler E, Recker R, Black D, Gasser JA, Eriksen EF, Klaushofer K, Paschalis EP (2011) Bone material properties in actively bone-forming trabeculae in postmenopausal women with osteoporosis after three years of treatment with once-yearly zoledronic acid. J Bone Miner Res 26:12–18

    Article  CAS  PubMed  Google Scholar 

  45. Recker RR, Delmas PD, Halse J, Reid IR, Boonen S, Garcia-Hernandez PA, Supronik J, Lewiecki EM, Ochoa L, Miller P, Hu H, Mesenbrink P, Hartl F, Gasser J, Eriksen EF (2008) Effects of intravenous zoledronic acid once yearly on bone remodeling and bone structure. J Bone Miner Res 23:6–16

    Article  CAS  PubMed  Google Scholar 

  46. Coleman RE, Marshall H, Cameron D, Dodwell D, Burkinshaw R, Keane M, Gil M, Houston SJ, Grieve RJ, Barrett-Lee PJ, Ritchie D, Pugh J, Gaunt C, Rea U, Peterson J, Davies C, Hiley V, Gregory W, Bell R (2011) Breast-cancer adjuvant therapy with zoledronic acid. N Engl J Med 365:1396–1405

    Article  CAS  PubMed  Google Scholar 

Download references

Conflicts of interest

Peyman Hadji has received honoraria, unrestricted educational grants, and research funding from the following companies: Amgen, Eli Lilly, Novartis, Roche, Sanofi Aventis and Wyeth. Monika Baier is an employee of Novartis Pharma GmbH. Matthias Kalder, Ioannis Kyvernitakis and Ute Susann Albert declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Philipps University of Marburg, Baldingerstrasse, 35043, Marburg, Germany

    M. Kalder & I. Kyvernitakis

  2. Department of Obstetrics and Gynecology, Krankenhaus Nordwest, Frankfurt, Germany

    U. S. Albert

  3. Clinical & Regulatory Affairs/Biometrics Department, Novartis Pharma GmbH, Nuernberg, Germany

    M. Baier-Ebert

  4. Department of Bone Oncology, Endocrinology and Reproductive Medicine, Krankenhaus Nordwest, Frankfurt, Germany

    P. Hadji

Authors
  1. M. Kalder
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. Kyvernitakis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. U. S. Albert
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Baier-Ebert
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. P. Hadji
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Kalder.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kalder, M., Kyvernitakis, I., Albert, U.S. et al. Effects of zoledronic acid versus placebo on bone mineral density and bone texture analysis assessed by the trabecular bone score in premenopausal women with breast cancer treatment-induced bone loss: results of the ProBONE II substudy. Osteoporos Int 26, 353–360 (2015). https://doi.org/10.1007/s00198-014-2955-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-014-2955-3

Keywords

Search

Navigation