Osteoporosis International

, Volume 30, Issue 1, pp 187–200 | Cite as

Hormone therapy and osteoporosis in breast cancer survivors: assessment of risk and adherence to screening recommendations

  • R. Hamood
  • H. HamoodEmail author
  • I. Merhasin
  • L. Keinan-Boker
Original Article



The long-term impact of hormone therapy for breast cancer on risk of osteoporosis and the extent to which bone screening recommendations are implemented in daily practice remain unknown. We found that the aromatase inhibitor-induced risk of osteoporosis did not continue in the off-treatment follow-up. Adherence to screening recommendations was suboptimal.


A case-cohort study was undertaken to better understand the impact of hormone therapy on breast cancer patients’ risk of osteoporosis, and to estimate the extent to which current bone mineral density screening recommendations are implemented in real-life daily practice.


This study is based on 1692 female breast cancer survivors recruited from “Leumit” healthcare fund, who were diagnosed with primary nonmetastatic invasive breast cancer between 2002 and 2012. A 20% random subcohort was sampled at baseline, and all osteoporosis cases were identified. Adjusted hazard ratios (HR) with 95% confidence intervals (CI) were estimated by weighted Cox proportional hazards models.


Of 1692 breast cancer survivors, 312 developed osteoporosis during a median follow-up of 5 years. The crude cumulative incidence of osteoporosis accounting for death as a competing risk was 25.7% (95% CI, 21.9–29.5%). In multivariable analyses, osteoporosis was positively associated with the aromatase inhibitor (AI) sequential treatment after tamoxifen (HR, 3.14; 95% CI, 1.44–6.88; P = .004) but was more pronounced with AI use as upfront monotherapy (HR, 5.53; 95% CI, 1.46–20.88; P = .012). This effect did not continue in the off-treatment follow-up. In subgroup analysis by menopausal status, tamoxifen did not seem to confer a protective effect on bone health in postmenopausal patients. Adherence to screening recommendations in AI-treated postmenopausal women was suboptimal, particularly at baseline and after 48 months of continuous AI use.


The natural, age-related reduction in bone density is exacerbated by breast cancer active AI treatment. Future research should focus on investigating screening adherence-related barriers/facilitators and effective strategies to bring practice in line with agreed standards.


Aromatase inhibitor Bone health Breast cancer Osteoporosis Survivorship Tamoxifen 



Aromatase inhibitor


Attributable risk fraction


Anatomic therapeutic chemical


Breast cancer/survivors


Bone mineral density


Confidence interval


Cumulative incidence function


Hazard ratio


Hormone therapy


International classification of diseases, ninth revision


Incidence density rate


Incidence density rate ratio


Israel National Cancer Registry


Interquartile range


Leumit Health Services


P value


Population attributable fraction


Standard error


Standardized incidence density rate ratio


Chi square



We gratefully acknowledge all participating breast cancer survivors, Dr. Natan Kahan, and the Ph.D. advisory committee for their invaluable contribution.


Funding of this study was in part provided by a grant from the Council for Higher Education (grant no. 11658745) in collaboration with the Graduate Studies Authority at the University of Haifa (grant no. 11658760). The sponsors have no role in the collection, analysis, and interpretation of data.

Compliance with ethical standards

Ethics approval

The study protocol was duly approved by the Institutional Review Boards of LHS and the University of Haifa.

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

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

Conflicts of interest



The results, conclusions, view and opinions contained herein are those of the authors and not to be construed as the official policy of Israel’s Ministry of Health, or of Leumit Health Organization.

Supplementary material

198_2018_4758_MOESM1_ESM.ppt (142 kb)
ESM 1 Flow chart of participants in the study. (PPT 141 kb)
198_2018_4758_MOESM2_ESM.pdf (44 kb)
ESM 2 (PDF 43 kb)


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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2018

Authors and Affiliations

  1. 1.School of Public HealthUniversity of HaifaHaifaIsrael
  2. 2.Leumit Health ServicesKarmielIsrael
  3. 3.Leumit Health ServicesNetanyaIsrael
  4. 4.Ministry of HealthIsrael Center for Disease ControlRamat GanIsrael

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