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Aromatase inhibitors attenuate the effect of alendronate in women with breast cancer

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Abstract

Introduction

Aromatase inhibitors are known to accelerate bone loss in patients with breast cancer. However, how much AIs affect the efficacy of antiresorptive agents has not been studied. The study aimed to compare the effect of alendronate on bone mineral density (BMD) between patients with and without AI treatment.

Materials and methods

In this retrospective study, 90 postmenopausal women with early breast cancer who were being treated with both AI and alendronate 70 mg weekly (ALN + AI), and 90 age- and body mass index (BMI)-matched patients who were only taking alendronate (ALN-only) were analyzed. BMD and bone turnover markers (BTMs) were assessed at the baseline and 12 months.

Results

The mean age was 63 years. At baseline, the ALN-only group had lower lumbar spine (LS), femur neck (FN), and total hip (TH) BMD than ALN + AI group. After 1-year of alendronate treatment, the LS and FN BMD were improved more in the ALN-only group than those in the ALN + AI group after adjustments for age, BMI, baseline BMD, diabetes, hypertension, renal function, and previous fracture history [LS BMD: 6.2% (3.1%; 9.2%) in ALN-only, 3.5% (−0.5%; 6.5%) in ALN + AI, p = 0.001; FN BMD: 2.5% (0.3%; 5.7%) in ALN-only, 0.9% (− 1.8%; 3.6%) in ALD + AI, p = 0.032]. BTMs were significantly decreased in both groups, but the changes between groups were similar.

Conclusion

The effect of alendronate on the LS and FN BMD was attenuated in postmenopausal women who were taking AI compared to those who were not on AI.

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References

  1. Burstein HJ, Temin S, Anderson H, Buchholz TA, Davidson NE, Gelmon KE, Giordano SH, Hudis CA, Rowden D, Solky AJ (2014) Adjuvant endocrine therapy for women with hormone receptor–positive breast cancer: American Society of clinical oncology clinical practice guideline focused update. J Clin Oncol 32:2255

    Article  Google Scholar 

  2. Hadji P (2009) Aromatase inhibitor-associated bone loss in breast cancer patients is distinct from postmenopausal osteoporosis. Critic Rev Oncol/Hematol 69:73–82

    Article  Google Scholar 

  3. Erbag G, Uygun K, Binnetoglu E, Korkmaz AN, Asik M, Sen H, Gunes F, Eroglu M, Gokmen F, Temiz S (2015) Aromatase inhibitor treatment for breast cancer: short-term effect on bone health. Contemp Oncol (Poznan, Poland) 19:374–377. https://doi.org/10.5114/wo.2014.45305

    Article  CAS  Google Scholar 

  4. Hines SL, Sloan JA, Atherton PJ, Perez EA, Dakhil SR, Johnson DB, Reddy PS, Dalton RJ, Mattar BI, Loprinzi CL (2010) Zoledronic acid for treatment of osteopenia and osteoporosis in women with primary breast cancer undergoing adjuvant aromatase inhibitor therapy. Breast (Edinburgh, Scotland) 19:92–96. https://doi.org/10.1016/j.breast.2009.12.001

    Article  Google Scholar 

  5. Safra T, Bernstein-Molho R, Greenberg J, Pelles-Avraham S, Stephansky I, Sarid D, Inbar MJ, Stemmer SM, Geffen DB (2011) The protective effect of zoledronic acid on bone loss in postmenopausal women with early breast cancer treated with sequential tamoxifen and letrozole: a prospective, randomized, phase II trial. Oncol 81:298–305. https://doi.org/10.1159/000334456

    Article  CAS  Google Scholar 

  6. Lee SA, Hwang SH, Ahn SG, Lee HM, Jeong J, Lee HD (2011) Effects of zoledronic acid on bone mineral density during aromatase inhibitor treatment of Korean postmenopausal breast cancer patients. Breast Can Res Treat 130:863–887. https://doi.org/10.1007/s10549-011-1728-3

    Article  CAS  Google Scholar 

  7. Van Poznak C, Hannon RA, Mackey JR, Campone M, Apffelstaedt JP, Clack G, Barlow D, Makris A, Eastell R (2010) Prevention of aromatase inhibitor-induced bone loss using risedronate: the SABRE trial. J Clin Oncol 28:967–975. https://doi.org/10.1200/jco.2009.24.5902

    Article  PubMed  Google Scholar 

  8. Greenspan SL, Vujevich KT, Brufsky A, Lembersky BC, van Londen GJ, Jankowitz RC, Puhalla SL, Rastogi P, Perera S (2015) Prevention of bone loss with risedronate in breast cancer survivors: a randomized, controlled clinical trial. Osteoporos Int 26:1857–1864. https://doi.org/10.1007/s00198-015-3100-7

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Lester JE, Dodwell D, Purohit OP, Gutcher SA, Ellis SP, Thorpe R, Horsman JM, Brown JE, Hannon RA, Coleman RE (2008) Prevention of anastrozole-induced bone loss with monthly oral ibandronate during adjuvant aromatase inhibitor therapy for breast cancer. Clin Can Res 14:6336–6342. https://doi.org/10.1158/1078-0432.CCR-07-5101

    Article  CAS  Google Scholar 

  10. Lester JE, Dodwell D, Brown JE, Purohit OP, Gutcher SA, Ellis SP, Thorpe R, Horsman JM, Coleman RE (2012) Prevention of anastrozole induced bone loss with monthly oral ibandronate: final 5 year results from the ARIBON trial. J Bone Oncol 1:57–62. https://doi.org/10.1016/j.jbo.2012.06.002

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Rhee Y, Song K, Park S, Park HS, Lim SK, Park BW (2013) Efficacy of a combined alendronate and calcitriol agent (Maxmarvil(R)) in Korean postmenopausal women with early breast cancer receiving aromatase inhibitor: a double-blind, randomized, placebo-controlled study. Endocrine J 60:167–172

    Article  CAS  Google Scholar 

  12. Lomax AJ, Yee Yap S, White K, Beith J, Abdi E, Broad A, Sewak S, Lee C, Sambrook P, Pocock N, Henry MJ, Yeow EG, Bell R (2013) Prevention of aromatase inhibitor-induced bone loss with alendronate in postmenopausal women: the BATMAN Trial. J Bone Oncol 2:145–153. https://doi.org/10.1016/j.jbo.2013.08.001

    Article  PubMed  PubMed Central  Google Scholar 

  13. Pineda‐Moncusí M, Garcia‐Giralt N, Diez‐Perez A, Servitja S, Tusquets I, Prieto‐Alhambra D, Nogués X (2019) Increased fracture risk in women treated with aromatase inhibitors versus tamoxifen: beneficial effect of bisphosphonates. J Bone Miner Res

  14. Galvano A, Scaturro D, Badalamenti G, Incorvaia L, Rizzo S, Castellana L, Cusenza S, Cutaia S, Santini D, Guadagni F (2019) Is there a role for denosumab and bone health for prostate and breast cancer patients undergoing endocrine therapy? A systematic review and a meta-analysis of randomized trials. J Bone Oncol 100:252

    Google Scholar 

  15. Waning DL, Mohammad KS, Reiken S, Xie W, Andersson DC et al (2015) Excess TGF-β mediates muscle weakness associated with bone metastases in mice. Nat Med 21:1262–1271. https://doi.org/10.1038/nm.3961

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Janni W, Hepp P (2010) Adjuvant aromatase inhibitor therapy: outcomes and safety. Can Treat Rev 36:249–261

    Article  CAS  Google Scholar 

  17. Paterson AH, Shea-Budgell MA (2013) Bone health in patients with breast cancer: recommendations from an evidence-based Canadian guideline. J Clin Med 2:283–301. https://doi.org/10.3390/jcm2040283

    Article  PubMed  PubMed Central  Google Scholar 

  18. Kalner M, Hadji P (2014) Breast cancer and osteoporosis—management of cancer treatment-induced bone loss in postmenopausal women with breast cancer. Breast Care (Basel, Switzerland) 9:312–317. https://doi.org/10.1159/000368843

    Article  Google Scholar 

  19. Hadji P, Hartenfels M, Kyvernitakis J, Hars O, Baumann KH, Kalder M (2012) Recommendations for antiresorptive therapy in postmenopausal patients with breast cancer: Marburg AIBL guideline evaluation study (MAGES). Breast Can Res Treat 133:1089–1096. https://doi.org/10.1007/s10549-012-2023-7

    Article  CAS  Google Scholar 

  20. Eastell R, Adams JE, Coleman RE, Howell A, Hannon RA, Cuzick J, Mackey JR, Beckmann MW, Clack G (2008) Effect of anastrozole on bone mineral density: 5-year results from the anastrozole, tamoxifen, alone or in combination trial 1823323. J Clin Oncol 26:1051–1057. https://doi.org/10.1200/jco.2007.11.0726

    Article  PubMed  CAS  Google Scholar 

  21. Hong A, Kim JH, Lee K-H, Kim T-Y, Im S-A, Moon H, Han W, Noh D, Kim S, Shin C (2017) Long-term effect of aromatase inhibitors on bone microarchitecture and macroarchitecture in non-osteoporotic postmenopausal women with breast cancer. Osteoporos Int 28:1413–1422

    Article  CAS  Google Scholar 

  22. Khosla S, Melton LJ III, Riggs BL (2011) The unitary model for estrogen deficiency and the pathogenesis of osteoporosis: is a revision needed? J Bone Miner Res 26:441–451

    Article  CAS  Google Scholar 

  23. Mirza FS, Padhi ID, Raisz LG, Lorenzo JA (2010) Serum sclerostin levels negatively correlate with parathyroid hormone levels and free estrogen index in postmenopausal women. J Clin Endocrinol Metab 95:1991–1997

    Article  Google Scholar 

  24. Mödder UI, Clowes JA, Hoey K, Peterson JM, McCready L, Oursler MJ, Riggs BL, Khosla S (2011) Regulation of circulating sclerostin levels by sex steroids in women and in men. J Bone Miner Res 26:27–34

    Article  CAS  Google Scholar 

  25. Morales-Santana S, Díez-Pérez A, Olmos JM, Nogués X, Sosa M, Díaz-Curiel M, Pérez-Castrillón JL, Pérez-Cano R, Torrijos A, Jodar E (2015) Circulating sclerostin and estradiol levels are associated with inadequate response to bisphosphonates in postmenopausal women with osteoporosis. Maturitas 82:402–410

    Article  CAS  Google Scholar 

  26. Shapiro CL, Recht A (2001) Side effects of adjuvant treatment of breast cancer. N Engl J Med 344:1997–2008. https://doi.org/10.1056/NEJM200106283442607

    Article  PubMed  CAS  Google Scholar 

  27. Bjarnason NH, Hitz M, Jorgensen NR, Vestergaard P (2008) Adverse bone effects during pharmacological breast cancer therapy. Acta Oncol 47:747–754. https://doi.org/10.1080/02841860802001467

    Article  PubMed  CAS  Google Scholar 

  28. Hadji P, Gottschalk M, Ziller V, Kalder M, Jackisch C, Wagner U (2007) Bone mass and the risk of breast cancer: the influence of cumulative exposure to oestrogen and reproductive correlates. Results of the Marburg breast cancer and osteoporosis trial (MABOT). Maturitas 56:312–321

    Article  CAS  Google Scholar 

  29. Kim W, Chung Y, Kim SH, Park S, Bae JH, Kim G, Lee SJ, Kim JE, Park B-W, Lim S-K (2015) Increased sclerostin levels after further ablation of remnant estrogen by aromatase inhibitors. Endocrinol Metab 30:58–64

    Article  CAS  Google Scholar 

  30. Inoue H, Hirano A, Ogura K, Hattori A, Kamimura M, Okubo F, Tagawa H, Sakaguchi S, Kinoshita J, Shimizu T (2015) The effect of anastrozole on bone mineral density during the first 5 years of adjuvant treatment in postmenopausal women with early breast cancer. SpringerPlus 4:303. https://doi.org/10.1186/s40064-015-1096-2

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by SHK. The first draft of the manuscript was written by SHK, and all authors commented on the manuscript. All authors read and approved the final manuscript.

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Correspondence to Chan Soo Shin.

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Kong, S.H., Kim, J.H., Kim, S.W. et al. Aromatase inhibitors attenuate the effect of alendronate in women with breast cancer. J Bone Miner Metab 38, 730–736 (2020). https://doi.org/10.1007/s00774-020-01111-3

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  • DOI: https://doi.org/10.1007/s00774-020-01111-3

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