The effect of bisphosphonates on the risk of endometrial and ovarian malignancies

Gynecol Oncol. 2014 May;133(2):309-13. doi: 10.1016/j.ygyno.2014.02.014. Epub 2014 Feb 18.


Objective: The use of bisphosphonates has been associated with reduced risk and improved survival of breast and colorectal malignancies. This study was aimed at studying the effects of bisphosphonates on gynecological cancers.

Methods: The Cancer in the Ovary and Uterus Study (CITOUS) is a case-control study of newly diagnosed cases of gynecological malignancies and age/clinic/ethnic-group matched population controls. The use of bisphosphonates prior to, and following, diagnosis was assessed in 424 cases of ovarian and endometrial cancers and 341 controls, all postmenopausal at recruitment, enrolled in Clalit Health Services (CHS), using pharmacy records.

Results: The use of bisphosphonates for more than 1 year prior to diagnosis was associated with a significantly reduced risk of ovarian cancer (OR=0.49, 95% CI: 0.26-0.93) and endometrial cancer (OR=0.39, 95% CI: 0.24-0.63). The association with endometrial cancer (OR=0.48, 0.27-0.84) remained statistically significant after adjustment for a variety of putative effect modifiers (RR=0.48, 0.26-0.89). The association with ovarian cancer remained significant when adjusted to statin use (0.46, 0.23-0.90) but not for other modifiers (0.58, 0.29-1.18). A strong negative association was found in an adjusted model for the use of either bisphosphonates or statins for more than 1 year (0.40, 0.23-0.68).

Conclusion: The use of bisphosphonates, with or without statins, for more than 1 year before diagnosis was associated with reduced risk of endometrial and ovarian cancers.

Keywords: Bisphosphonates; Endometrial cancer; Ovarian cancer; Prevention; Risk.

MeSH terms

  • Aged
  • Bone Density Conservation Agents / therapeutic use*
  • Case-Control Studies
  • Diphosphonates / therapeutic use*
  • Endometrial Neoplasms / epidemiology*
  • Endometrial Neoplasms / prevention & control
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Middle Aged
  • Ovarian Neoplasms / epidemiology*
  • Ovarian Neoplasms / prevention & control
  • Risk Factors


  • Bone Density Conservation Agents
  • Diphosphonates
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors