Skip to main content

Advertisement

Log in

Effects of zoledronic acid on bone mineral density during aromatase inhibitor treatment of Korean postmenopausal breast cancer patients

  • Clinical Trial
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

The age distribution of breast cancer patients in Korea, where most are less than 60 years of age and have recently entered menopause, differs from that in the West. The aim of this study was to evaluate bone mineral density (BMD) changes in Korean breast cancer patients treated with an aromatase inhibitor (AI) either alone or in combination with zoledronic acid (ZA). Changes in BMD of the lumbar spine and hip were evaluated in 107 patients receiving AI treatment, of which 59 were treated in combination with ZA. The mean age of the patients was 54.9 years, and the median follow-up period was 38.2 months. With AI treatment alone, BMD loss was significant (all P < 0.0001) in the lumbar spine and hip 12 months (4.18 and 3.95%, respectively), 24 months (6.28 and 5.44%), and 36 months (8.17 and 6.82%) after treatment. In contrast, the combination treatment resulted in increased BMD in the lumbar spine and hip 12 months (2.45 and 0.89%, respectively), 24 months (3.51 and 1.03%), and 36 months (3.85 and 1.80%) after treatment. BMD loss in the lumbar spine was significantly greater in AI alone-treated women who had entered menopause within the past year compared with those who had entered menopause more than 1 year ago, when measured 12 and 24 months after treatment (P = 0.017 and 0.021, respectively). Importantly, ZA effectively inhibited AI-associated bone loss, independent of the postmenopausal interval. Because the proportion of patients in this study who had recently entered menopause was high, bone loss in Korean breast cancer patients treated with AI alone was higher than data reported from the Arimidex, Tamoxifen Alone or in Combination (ATAC) trial. In conclusion, we have shown that ZA is very effective in preventing AI-induced bone loss in Korean postmenopausal breast cancer patients.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Baum M, Budzar AU, Cuzick J, Forbes J, Houghton JH, Klijn JG, Sahmoud T (2002) Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet 359:2131–2139

    Article  PubMed  CAS  Google Scholar 

  2. Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes JF, Hoctin-Boes G, Houghton J, Locker GY, Tobias JS (2005) Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet 365:60–62. doi:10.1016/S0140-6736(04)17666-6

    Article  PubMed  CAS  Google Scholar 

  3. Thurlimann B, Keshaviah A, Coates AS, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Castiglione-Gertsch M, Gelber RD, Rabaglio M, Smith I, Wardley A, Price KN, Goldhirsch A (2005) A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med 353:2747–2757

    Article  PubMed  Google Scholar 

  4. Buzdar A, Howell A, Cuzick J, Wale C, Distler W, Hoctin-Boes G, Houghton J, Locker GY, Nabholtz JM (2006) Comprehensive side-effect profile of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: long-term safety analysis of the ATAC trial. Lancet Oncol 7:633–643. doi:10.1016/S1470-2045(06)70767-7

    Article  PubMed  CAS  Google Scholar 

  5. Ibrahim A, Scher N, Williams G, Sridhara R, Li N, Chen G, Leighton J, Booth B, Gobburu JV, Rahman A, Hsieh Y, Wood R, Vause D, Pazdur R (2003) Approval summary for zoledronic acid for treatment of multiple myeloma and cancer bone metastases. Clin Cancer Res 9:2394–2399

    PubMed  CAS  Google Scholar 

  6. Gnant MF, Mlineritsch B, Luschin-Ebengreuth G, Grampp S, Kaessmann H, Schmid M, Menzel C, Piswanger-Soelkner JC, Galid A, Mittlboeck M, Hausmaninger H, Jakesz R (2007) Zoledronic acid prevents cancer treatment-induced bone loss in premenopausal women receiving adjuvant endocrine therapy for hormone-responsive breast cancer: a report from the Austrian Breast and Colorectal Cancer Study Group. J Clin Oncol 25:820–828. doi:10.1200/JCO.2005.02.7102

    Article  PubMed  CAS  Google Scholar 

  7. Bundred NJ, Campbell ID, Davidson N, DeBoer RH, Eidtmann H, Monnier A, Neven P, von Minckwitz G, Miller JC, Schenk NL, Coleman RE (2008) Effective inhibition of aromatase inhibitor-associated bone loss by zoledronic acid in postmenopausal women with early breast cancer receiving adjuvant letrozole: ZO-FAST Study results. Cancer 112:1001–1010. doi:10.1002/cncr.23259

    Article  PubMed  CAS  Google Scholar 

  8. Cauley JA (2011) Defining ethnic and racial differences in osteoporosis and fragility fractures. Clin Orthop Relat Res 469(7):1891–1899. doi:10.1007/s11999-011-1863-5

    Article  PubMed  Google Scholar 

  9. Coleman RE, Body JJ, Gralow JR, Lipton A (2008) Bone loss in patients with breast cancer receiving aromatase inhibitors and associated treatment strategies. Cancer Treat Rev 34(Suppl 1):S31–S42. doi:10.1016/j.ctrv.2008.03.005

    Article  PubMed  CAS  Google Scholar 

  10. Eastell R, Hannon RA, Cuzick J, Dowsett M, Clack G, Adams JE (2006) Effect of an aromatase inhibitor on bmd and bone turnover markers: 2-year results of the Anastrozole, Tamoxifen, Alone or in Combination (ATAC) trial (18233230). J Bone Miner Res 21:1215–1223. doi:10.1359/jbmr.060508

    Article  PubMed  CAS  Google Scholar 

  11. Shapiro CL, Manola J, Leboff M (2001) Ovarian failure after adjuvant chemotherapy is associated with rapid bone loss in women with early-stage breast cancer. J Clin Oncol 19:3306–3311

    PubMed  CAS  Google Scholar 

  12. Jeong J, The Korean Breast Cancer Society (2006) Nationwide Korean Breast Cancer Data of 2004 Using Breast Cancer Registration Program. The Korean Breast Cancer Society. J Breast Cancer 9:151–161

    Google Scholar 

  13. Hofbauer LC, Khosla S, Dunstan CR, Lacey DL, Spelsberg TC, Riggs BL (1999) Estrogen stimulates gene expression and protein production of osteoprotegerin in human osteoblastic cells. Endocrinology 140:4367–4370

    Article  PubMed  CAS  Google Scholar 

  14. Geisler J, Lonning PE (2010) Impact of aromatase inhibitors on bone health in breast cancer patients. J Steroid Biochem Mol Biol 118:294–299. doi:10.1016/j.jsbmb.2009.10.004

    Article  PubMed  CAS  Google Scholar 

  15. Perez EA, Josse RG, Pritchard KI, Ingle JN, Martino S, Findlay BP, Shenkier TN, Tozer RG, Palmer MJ, Shepherd LE, Liu S, Tu D, Goss PE (2006) Effect of letrozole versus placebo on bone mineral density in women with primary breast cancer completing 5 or more years of adjuvant tamoxifen: a companion study to NCIC CTG MA.17. J Clin Oncol 24:3629–3635. doi:10.1200/JCO.2005.05.4882

    Article  PubMed  CAS  Google Scholar 

  16. Jones S, Stokoe C, Sborov M, Braun M, Ethirajan S, Kutteh L, Pippen J, Patel M, Paul D, Blum JL, Holmes FA, Myron MC, Cantrell J, Hartung NL, Look RM, Di Salle E, Davis JC, Ilegbodu D, Asmar L (2008) The effect of tamoxifen or exemestane on bone mineral density during the first 2 years of adjuvant treatment of postmenopausal women with early breast cancer. Clin Breast Cancer 8:527–532. doi:10.3816/CBC.2008.n.065

    Article  PubMed  CAS  Google Scholar 

  17. Hong S, Ahn YH, Choi WH (2010) Age-, gender- and region- related changes in bone mineral density of Korean adult (2003~2004). J Korean Soc Osteoporos 8:188–195

    Google Scholar 

  18. Okishiro M, Taguchi T, Kim SJ, Tanji Y, Shimazu K, Tamaki Y, Noguchi S (2009) Incidence of joint symptoms and bone fractures in Japanese postmenopausal breast cancer patients treated with adjuvant anastrozole. J Cancer Res Clin Oncol 135:823–827. doi:10.1007/s00432-008-0518-8

    Article  PubMed  CAS  Google Scholar 

  19. Zhang HC, Kushida K, Atsumi K, Kin K, Nagano A (2002) Effects of age and menopause on spinal bone mineral density in Japanese women: a ten-year prospective study. Calcif Tissue Int 70:153–157. doi:10.1007/s00223-001-1037-7

    Article  PubMed  CAS  Google Scholar 

  20. 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. doi:10.1016/S1470-2045(08)70204-3

    Article  PubMed  CAS  Google Scholar 

  21. Barrett-Connor E, Siris ES, Wehren LE, Miller PD, Abbott TA, Berger ML, Santora AC, Sherwood LM (2005) Osteoporosis and fracture risk in women of different ethnic groups. J Bone Miner Res 20:185–194. doi:10.1359/JBMR.041007

    Article  PubMed  Google Scholar 

  22. Marshall LM, Zmuda JM, Chan BK, Barrett-Connor E, Cauley JA, Ensrud KE, Lang TF, Orwoll ES (2008) Race and ethnic variation in proximal femur structure and BMD among older men. J Bone Miner Res 23:121–130. doi:10.1359/jbmr.070908

    Article  PubMed  Google Scholar 

Download references

Disclosures

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Joon Jeong.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, S.A., Hwang, S.H., Ahn, S.G. et al. Effects of zoledronic acid on bone mineral density during aromatase inhibitor treatment of Korean postmenopausal breast cancer patients. Breast Cancer Res Treat 130, 863–870 (2011). https://doi.org/10.1007/s10549-011-1728-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-011-1728-3

Keywords

Navigation