Skip to main content
SpringerLink
Log in

Bone Loss

  • Chapter
  • First Online:
Common Issues in Breast Cancer Survivors

  • 653 Accesses

Abstract

Breast cancer survivors are at increased risk for bone loss and fragility fractures due to a combination of disease, treatment, and age-related factors. A thorough clinical evaluation including history, physical examination, and laboratory and imaging studies can help identify opportunities to mitigate fracture risk. Clinicians should employ risk stratification tools such as dual-energy x-ray absorptiometry (DXA) and FRAX to assist with clinical decision-making. Robust data exists to support the use of selective estrogen receptor modulators, bisphosphonates, and denosumab in breast cancer survivors. An understanding of fracture risk along with potential treatment-related adverse effects is essential to appropriately individualize treatment decisions for bone protection.

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

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. DeSantis CE, et al. Breast cancer statistics, 2017, racial disparity in mortality by state. CA Cancer J Clin. 2017;67(6):439–48.

    Article  PubMed  Google Scholar 

  2. DeSantis CE, et al. Cancer treatment and survivorship statistics, 2014. CA Cancer J Clin. 2014;64(4):252–71.

    Article  PubMed  Google Scholar 

  3. Ganz PA. Survivorship: adult cancer survivors. Prim Care. 2009;36(4):721–41.

    Article  PubMed  Google Scholar 

  4. Chen Z, et al. Fracture risk among breast cancer survivors: results from the Women's Health Initiative Observational Study. Arch Intern Med. 2005;165(5):552–8.

    Article  PubMed  Google Scholar 

  5. Robinson PJ, et al. Minimal-trauma fracture in women with breast cancer surviving for at least 5 years from diagnosis. Osteoporos Int. 2015;26(2):795–800.

    Article  CAS  PubMed  Google Scholar 

  6. Kanis JA, et al. A high incidence of vertebral fracture in women with breast cancer. Br J Cancer. 1999;79(7–8):1179–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Dyer SM, et al. A critical review of the long-term disability outcomes following hip fracture. BMC Geriatr. 2016;16:158.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Newcomb PA, et al. Postmenopausal fracture history and survival after reproductive cancer diagnosis. JNCI Cancer Spectr. 2018;2(1):pky001.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Runowicz CD, et al. American Cancer Society/American Society of Clinical Oncology breast cancer survivorship care guideline. J Clin Oncol. 2016;34(6):611–35.

    Article  CAS  PubMed  Google Scholar 

  10. Gyori DJ, et al. Evaluation of appropriate use of bisphosphonates and denosumab in patients with cancer. J Oncol Pharm Pract. 2020;26(2):286–92.

    Article  PubMed  Google Scholar 

  11. Boyce BF. Advances in osteoclast biology reveal potential new drug targets and new roles for osteoclasts. J Bone Miner Res. 2013;28(4):711–22.

    Article  CAS  PubMed  Google Scholar 

  12. D'Oronzo S, et al. Cancer treatment-induced bone loss (CTIBL): pathogenesis and clinical implications. Cancer Treat Rev. 2015;41(9):798–808.

    Article  CAS  PubMed  Google Scholar 

  13. Coleman RE, et al. Skeletal effects of exemestane on bone-mineral density, bone biomarkers, and fracture incidence in postmenopausal women with early breast cancer participating in the Intergroup Exemestane Study (IES): a randomised controlled study. Lancet Oncol. 2007;8(2):119–27.

    Article  CAS  PubMed  Google Scholar 

  14. Eastell R, et al. Long-term effects of anastrozole on bone mineral density: 7-year results from the ATAC trial. Ann Oncol. 2011;22(4):857–62.

    Article  CAS  PubMed  Google Scholar 

  15. Rabaglio M, et al. Bone fractures among postmenopausal patients with endocrine-responsive early breast cancer treated with 5 years of letrozole or tamoxifen in the BIG 1-98 trial. Ann Oncol. 2009;20(9):1489–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Goss PE, et al. Exemestane versus anastrozole in postmenopausal women with early breast cancer: NCIC CTG MA.27–a randomized controlled phase III trial. J Clin Oncol. 2013;31(11):1398–404.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Greep NC, et al. The effects of adjuvant chemotherapy on bone density in postmenopausal women with early breast cancer. Am J Med. 2003;114(8):653–9.

    Article  PubMed  Google Scholar 

  18. Kennecke H, et al. Metastatic behavior of breast cancer subtypes. J Clin Oncol. 2010;28(20):3271–7.

    Article  PubMed  Google Scholar 

  19. Weaver CM, et al. The National Osteoporosis Foundation's position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations. Osteoporos Int. 2016;27(4):1281–386.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Yang S, et al. Objectively verified parental hip fracture is an independent risk factor for fracture: a linkage analysis of 478,792 parents and 261,705 offspring. J Bone Miner Res. 2016;31(9):1753–9.

    Article  PubMed  Google Scholar 

  21. Johansson H, et al. Imminent risk of fracture after fracture. Osteoporos Int. 2017;28(3):775–80.

    Article  CAS  PubMed  Google Scholar 

  22. van Geel TA, et al. Timing of subsequent fractures after an initial fracture. Curr Osteoporos Rep. 2010;8(3):118–22.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Leslie WD, et al. Measured height loss predicts incident clinical fractures independently from FRAX: a registry-based cohort study. Osteoporos Int. 2020;31(6):1079–87.

    Article  CAS  PubMed  Google Scholar 

  24. Siminoski K, et al. Accuracy of physical examination using the rib-pelvis distance for detection of lumbar vertebral fractures. Am J Med. 2003;115(3):233–6.

    Article  PubMed  Google Scholar 

  25. Eastell R, et al. Pharmacological management of osteoporosis in postmenopausal women: an Endocrine Society* Clinical Practice Guideline. J Clin Endocrinol Metab. 2019;104(5):1595–622.

    Article  PubMed  Google Scholar 

  26. Johnell O, et al. Predictive value of BMD for hip and other fractures. J Bone Miner Res. 2005;20(7):1185–94.

    Article  PubMed  Google Scholar 

  27. Leslie WD, Lix LM. Absolute fracture risk assessment using lumbar spine and femoral neck bone density measurements: derivation and validation of a hybrid system. J Bone Miner Res. 2011;26(3):460–7.

    Article  PubMed  Google Scholar 

  28. Wood K, et al. What is the utility of distal forearm DXA in primary hyperparathyroidism? Oncologist. 2012;17(3):322–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Licata AA, et al. Consensus statement by the American association of clinical endocrinologists and American college of endocrinology on the quality of DXA scans and reports. Endocr Pract. 2018;24(2):220–9.

    Article  PubMed  Google Scholar 

  30. Leslie WD, et al. Performance of FRAX in women with breast cancer initiating aromatase inhibitor therapy: a registry-based cohort study. J Bone Miner Res. 2019;34(8):1428–35.

    Article  CAS  PubMed  Google Scholar 

  31. Cosman F, et al. Clinician's guide to prevention and treatment of osteoporosis. Osteoporos Int. 2014;25(10):2359–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Kopecky SL, et al. Lack of evidence linking calcium with or without vitamin D supplementation to cardiovascular disease in generally healthy adults: a clinical guideline from the National Osteoporosis Foundation and the American Society for Preventive Cardiology. Ann Intern Med. 2016;165(12):867–8.

    Article  PubMed  Google Scholar 

  33. Curhan GC, et al. Comparison of dietary calcium with supplemental calcium and other nutrients as factors affecting the risk for kidney stones in women. Ann Intern Med. 1997;126(7):497–504.

    Article  CAS  PubMed  Google Scholar 

  34. Yao P, et al. Vitamin D and calcium for the prevention of fracture: a systematic review and meta-analysis. JAMA Netw Open. 2019;2(12):e1917789.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Datta M, Schwartz GG. Calcium and vitamin D supplementation and loss of bone mineral density in women undergoing breast cancer therapy. Crit Rev Oncol Hematol. 2013;88(3):613–24.

    Article  PubMed  Google Scholar 

  36. Lahart IM, et al. Physical activity for women with breast cancer after adjuvant therapy. Cochrane Database Syst Rev. 2018;1(1):Cd011292.

    PubMed  Google Scholar 

  37. Fisher B, et al. Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst. 2005;97(22):1652–62.

    Article  CAS  PubMed  Google Scholar 

  38. Vogel VG, et al. Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA. 2006;295(23):2727–41.

    Article  CAS  PubMed  Google Scholar 

  39. Love RR, et al. Effects of tamoxifen on bone mineral density in postmenopausal women with breast cancer. N Engl J Med. 1992;326(13):852–6.

    Article  CAS  PubMed  Google Scholar 

  40. Powles TJ, et al. Effect of tamoxifen on bone mineral density measured by dual-energy x-ray absorptiometry in healthy premenopausal and postmenopausal women. J Clin Oncol. 1996;14(1):78–84.

    Article  CAS  PubMed  Google Scholar 

  41. Sverrisdottir A, et al. Bone mineral density among premenopausal women with early breast cancer in a randomized trial of adjuvant endocrine therapy. J Clin Oncol. 2004;22(18):3694–9.

    Article  CAS  PubMed  Google Scholar 

  42. Kyvernitakis I, Kostev K, Hadji P. The tamoxifen paradox-influence of adjuvant tamoxifen on fracture risk in pre- and postmenopausal women with breast cancer. Osteoporos Int. 2018;29(11):2557–64.

    Article  CAS  PubMed  Google Scholar 

  43. Cummings SR, et al. The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation. JAMA. 1999;281(23):2189–97.

    Article  CAS  PubMed  Google Scholar 

  44. Silverman SL, Gold DT. Compliance and persistence with osteoporosis therapies. Curr Rheumatol Rep. 2008;10(2):118–22.

    Article  PubMed  Google Scholar 

  45. Miller PD, et al. Renal safety in patients treated with bisphosphonates for osteoporosis: a review. J Bone Miner Res. 2013;28(10):2049–59.

    Article  CAS  PubMed  Google Scholar 

  46. Lomax AJ, et al. Prevention of aromatase inhibitor-induced bone loss with alendronate in postmenopausal women: the BATMAN Trial. J Bone Oncol. 2013;2(4):145–53.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Greenspan SL, et al. Prevention of bone loss with risedronate in breast cancer survivors: a randomized, controlled clinical trial. Osteoporos Int. 2015;26(6):1857–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Van Poznak C, et al. Prevention of aromatase inhibitor-induced bone loss using risedronate: the SABRE trial. J Clin Oncol. 2010;28(6):967–75.

    Article  PubMed  CAS  Google Scholar 

  49. Livi L, et al. Phase 2 placebo-controlled, single-blind trial to evaluate the impact of oral ibandronate on bone mineral density in osteopenic breast cancer patients receiving adjuvant aromatase inhibitors: 5-year results of the single-centre BONADIUV trial. Eur J Cancer. 2019;108:100–10.

    Article  CAS  PubMed  Google Scholar 

  50. Lester JE, et al. Prevention of anastrozole induced bone loss with monthly oral ibandronate: final 5 year results from the ARIBON trial. J Bone Oncol. 2012;1(2):57–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Monda V, et al. Improvement of Bone physiology and life quality due to association of risedronate and anastrozole. Front Pharmacol. 2017;8:632.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Rennert G, et al. Oral bisphosphonates and improved survival of breast cancer. Clin Cancer Res. 2017;23(7):1684–9.

    Article  CAS  PubMed  Google Scholar 

  53. Hadji P, et al. Effect of adjuvant bisphosphonates on disease-free survival in early breast cancer: retrospective analysis results in an unselected single-center cohort. J Bone Oncol. 2013;2(1):2–10.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Early Breast Cancer Trialists' Collaborative, G. Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials. Lancet. 2015;386(10001):1353–61.

    Article  CAS  Google Scholar 

  55. Adler RA, et al. Managing osteoporosis in patients on long-term bisphosphonate treatment: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2016;31(1):16–35.

    Article  CAS  PubMed  Google Scholar 

  56. Coleman R, et al. Zoledronic acid (zoledronate) for postmenopausal women with early breast cancer receiving adjuvant letrozole (ZO-FAST study): final 60-month results. Ann Oncol. 2013;24(2):398–405.

    Article  CAS  PubMed  Google Scholar 

  57. Gnant M, et al. Zoledronic acid combined with adjuvant endocrine therapy of tamoxifen versus anastrozol plus ovarian function suppression in premenopausal early breast cancer: final analysis of the Austrian Breast and Colorectal Cancer Study Group Trial 12. Ann Oncol. 2015;26(2):313–20.

    Article  CAS  PubMed  Google Scholar 

  58. Nuzzo F, et al. Bone effect of adjuvant tamoxifen, letrozole or letrozole plus zoledronic acid in early-stage breast cancer: the randomized phase 3 HOBOE study. Ann Oncol. 2012;23(8):2027–33.

    Article  CAS  PubMed  Google Scholar 

  59. Brufsky AM, et al. Final 5-year results of Z-FAST trial: adjuvant zoledronic acid maintains bone mass in postmenopausal breast cancer patients receiving letrozole. Cancer. 2012;118(5):1192–201.

    Article  CAS  PubMed  Google Scholar 

  60. Gnant M, et al. Endocrine therapy plus zoledronic acid in premenopausal breast cancer. N Engl J Med. 2009;360(7):679–91.

    Article  CAS  PubMed  Google Scholar 

  61. Wilson C, et al. Adjuvant zoledronic acid reduces fractures in breast cancer patients; an AZURE (BIG 01/04) study. Eur J Cancer. 2018;94:70–8.

    Article  CAS  PubMed  Google Scholar 

  62. Coleman RE, et al. Benefits and risks of adjuvant treatment with zoledronic acid in stage II/III breast cancer. 10 years follow-up of the AZURE randomized clinical trial (BIG 01/04). J Bone Oncol. 2018;13:123–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Lyles KW, et al. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med. 2007;357(18):1799–809.

    Article  CAS  PubMed  Google Scholar 

  64. Crotti C, et al. Acute phase reactions after Zoledronic acid infusion: protective role of 25-Hydroxyvitamin d and previous oral bisphosphonate therapy. Endocr Pract. 2018;24(5):405–10.

    Article  PubMed  Google Scholar 

  65. Ellis GK, et al. Randomized trial of denosumab in patients receiving adjuvant aromatase inhibitors for nonmetastatic breast cancer. J Clin Oncol. 2008;26(30):4875–82.

    Article  CAS  PubMed  Google Scholar 

  66. Gnant M, et al. Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2015;386(9992):433–43.

    Article  CAS  PubMed  Google Scholar 

  67. Gnant M, et al. Adjuvant denosumab in postmenopausal patients with hormone receptor-positive breast cancer (ABCSG-18): disease-free survival results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20(3):339–51.

    Article  CAS  PubMed  Google Scholar 

  68. Bonani M, et al. Infections in De novo kidney transplant recipients treated with the RANKL inhibitor denosumab. Transplantation. 2017;101(9):2139–45.

    Article  CAS  PubMed  Google Scholar 

  69. Bone HG, et al. Effects of denosumab treatment and discontinuation on bone mineral density and bone turnover markers in postmenopausal women with low bone mass. J Clin Endocrinol Metab. 2011;96(4):972–80.

    Article  CAS  PubMed  Google Scholar 

  70. Cummings SR, et al. Vertebral fractures after discontinuation of denosumab: a post hoc analysis of the randomized placebo-controlled FREEDOM trial and its extension. J Bone Miner Res. 2018;33(2):190–8.

    Article  CAS  PubMed  Google Scholar 

  71. Tsourdi E, et al. Discontinuation of denosumab therapy for osteoporosis: a systematic review and position statement by ECTS. Bone. 2017;105:11–7.

    Article  PubMed  Google Scholar 

  72. Bone HG, et al. 10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension. Lancet Diabetes Endocrinol. 2017;5(7):513–23.

    Article  CAS  PubMed  Google Scholar 

  73. Reid IR, et al. Bone loss after denosumab: only partial protection with zoledronate. Calcif Tissue Int. 2017;101(4):371–4.

    Article  CAS  PubMed  Google Scholar 

  74. Crawford SL, et al. Menopausal hormone therapy trends before versus after 2002: impact of the Women's Health Initiative Study Results. Menopause. 2018;26(6):588–97.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Levin VA, Jiang X, Kagan R. Estrogen therapy for osteoporosis in the modern era. Osteoporos Int. 2018;29(5):1049–55.

    Article  CAS  PubMed  Google Scholar 

  76. Mudhune GH, Armour M, McBride KA. Safety of menopausal hormone therapy in breast cancer survivors older than fifty at diagnosis: a systematic review and meta-analysis. Breast. 2019;47:43–55.

    Article  PubMed  Google Scholar 

  77. Neer RM, et al. Effect of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med. 2001;344(19):1434–41.

    Article  CAS  PubMed  Google Scholar 

  78. Miller PD, et al. Effect of abaloparatide vs placebo on new vertebral fractures in postmenopausal women with osteoporosis: a randomized clinical trial. JAMA. 2016;316(7):722–33.

    Article  CAS  PubMed  Google Scholar 

  79. Cosman F, et al. Romosozumab treatment in postmenopausal women with osteoporosis. N Engl J Med. 2016;375(16):1532–43.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Duke University Department of Medicine, Durham, NC, USA

    Patrick B. Cacchio

  2. Duke University Cancer Center, Durham, NC, USA

    Jennie Petruney

  3. Duke University School of Medicine, Durham VA Medical Center, Durham, NC, USA

    Kenneth W. Lyles

Authors
  1. Patrick B. Cacchio
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jennie Petruney
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kenneth W. Lyles
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Patrick B. Cacchio .

Editor information

Editors and Affiliations

  1. Medical Oncology, Duke University School of Medicine/Duke Cancer Institute, Durham, NC, USA

    Gretchen G. Kimmick

  2. Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA

    Rebecca A. Shelby

  3. Duke University School of Medicine Duke Cancer Network, Durham, NC, USA

    Linda M. Sutton

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Cacchio, P.B., Petruney, J., Lyles, K.W. (2021). Bone Loss. In: Kimmick, G.G., Shelby, R.A., Sutton, L.M. (eds) Common Issues in Breast Cancer Survivors. Springer, Cham. https://doi.org/10.1007/978-3-030-75377-1_15

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-75377-1_15

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-75376-4

  • Online ISBN: 978-3-030-75377-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation