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Can nitrogen-based bisphosphonates protect against ovarian cancer?

Journal of the National Cancer Institute
Reuters Health - 18/03/2022 - Use of nitrogen-based bisphosphonates was associated with a lower risk of endometrioid and serous ovarian cancer in a nested case-control study conducted in Australia.

"There are few readily modifiable risk factors for epithelial ovarian cancer; pre-clinical studies suggest bisphosphonates could have chemo-preventive actions," researchers note in the Journal of the National Cancer Institute (JNCI).

Using a large linked administrative dataset, Karen Tuesley of the University of Queensland School of Public Health, in Brisbane, and colleagues studied the association between use of nitrogen-based bisphosphonates and risk of epithelial ovarian cancer, overall and by histotype.

Nitrogen-based bisphosphonates, widely used to treat osteoporosis, include alendronate, pamidronate, risedronate and zoledronic acid.

The researchers identified 9,367 women with epithelial ovarian cancer diagnosed at age 50 or later and matched each with up to five controls, yielding a control group of 46,830 women.

Ever use of nitrogen-based bisphosphonates was associated with a reduction of 29% in the odds of developing epithelial ovarian cancer compared with non-use (odds ratio, 0.81; 95% CI, 0.75 to 0.88).

The odds of endometrioid ovarian cancer were reduced by 49% (OR, 0.51; 95% CI, 0.33 to 0.79) and those of serous histotypes by 16% (OR, 0.84; 95% CI, 0.75 to 0.93), with no association with the mucinous or clear-cell histotypes.

The apparent protective effect appeared stronger for use longer than one year, but did not clearly reduce further beyond this timeframe.

The researchers say their findings are in line with a previous meta-analysis of observational studies.

They note that nitrogen-based bisphosphonates have been shown to inhibit the mevalonate pathways within macrophages and monocytes, thereby reducing activity of tumor-associated macrophages and activating gamma delta T cells.

"These mechanisms potentially inhibit cancer cell proliferation, including in ovarian tumor cells," they note.

"The possible benefit of using an existing chronic disease medication, potentially just a yearly injection, to reduce the risk of ovarian cancer warrants further investigation," they conclude.

This research was supported by a project grant from the Australian National Health and Medical Research Council.

SOURCE: https://bit.ly/3tiaeAy Journal of the National Cancer Institute, online March 9, 2022.

By Reuters Staff

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