The tamoxifen paradox-influence of adjuvant tamoxifen on fracture risk in pre- and postmenopausal women with breast cancer

Osteoporos Int. 2018 Nov;29(11):2557-2564. doi: 10.1007/s00198-018-4642-2. Epub 2018 Jul 21.


Our data demonstrate that tamoxifen does not reduce fracture risk. Close surveillance is necessary to prevent bone loss in premenopausal women with breast cancer upon treatment initiation.

Introduction: Endocrine treatment of breast cancer may interfere with bone turnover and influence fracture risk.

Methods: Out of a cohort of almost 5 million patients in total, we identified 5520 women between 18 and 90 years of age with breast cancer receiving tamoxifen, matched them with 5520 healthy controls using the Disease Analyzer Database, and investigated the fracture risk.

Results: We found a cumulative incidence of fractures of 6.3% in patients aged between 18 and 50 years (n = 3634) treated with tamoxifen versus a cumulative incidence of 3.6% in the control group (p < 0.001). As such, the risk of fracture was 75% higher for patients receiving tamoxifen than that for healthy controls (HR 1.75; 95% CI 1.25-2.48). With regard to patients aged between 55 and 90 years (n = 7406), the cumulative incidence of fractures in patients treated with tamoxifen was 10.1% compared to 9.3% in the control group (p = 0.740), i.e., there was no significant difference between the two groups (HR 0.97; 95% CI 0.81-1.16).

Conclusions: Compared to healthy controls, premenopausal women with breast cancer treated with tamoxifen showed an increased risk of fracture, while postmenopausal women on tamoxifen did not show any risk reduction.

Keywords: Breast cancer; Fracture risk; Menopause; Osteoporosis; Tamoxifen.

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Hormonal / adverse effects*
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / epidemiology
  • Chemotherapy, Adjuvant / adverse effects
  • Databases, Factual
  • Female
  • Germany / epidemiology
  • Humans
  • Incidence
  • Middle Aged
  • Osteoporotic Fractures / chemically induced*
  • Osteoporotic Fractures / epidemiology
  • Postmenopause
  • Premenopause
  • Retrospective Studies
  • Risk Assessment / methods
  • Tamoxifen / adverse effects*
  • Tamoxifen / therapeutic use
  • Young Adult


  • Antineoplastic Agents, Hormonal
  • Tamoxifen