OUP accepted manuscript

There are few readily modifiable risk factors for epithelial ovarian cancer; pre-clinical studies suggest bisphosphonates could have chemo-preventive actions. Our study aimed to assess the association between use of nitrogen-based bisphosphonate medicine and risk of epithelial ovarian cancer, overall and by histotype.We conducted a case-control study nested within a large linked administrative dataset including all Australian women enrolled for Medicare, Australia's universal health insurance scheme, between July 2002 and December 2013. We included all women with epithelial ovarian cancer diagnosed at age 50 years and older between 1st July 2004 and 31st December 2013 (n = 9,367) and randomly selected up to five controls per case, individually matched to cases by age, state of residence, area-level socioeconomic status, and remoteness of residence category (n = 46,830). We used prescription records to ascertain use of nitrogen-based bisphosphonates (ever use and duration of use), raloxifene and other osteoporosis medicines (non-nitrogen-based bisphosphonates, strontium and denosumab). We calculated adjusted odds ratios (OR) and 95% confidence intervals (CI) using conditional logistic regression.Ever use of nitrogen-based bisphosphonates was associated with a reduced risk of epithelial ovarian cancer compared to non-use (OR = 0.81, 95%CI : 0.75-0.88). There was a reduced risk of both endometrioid (OR = 0.51, 95%CI : 0.33-0.79) and serous histotypes (OR = 0.84, 95%CI : 0.75-0.93), but no association with the mucinous or clear cell histotypes.Use of nitrogen-based bisphosphonates was associated with a reduced risk of endometrioid and serous ovarian cancer. This suggests the potential for use for prevention, although validation of our findings is required.