Nitrogen-Based Bisphosphonate Use and Risk of Cancer in Women Aged 50 Years and Older: A National Data Linkage Study

Bisphosphonates are used widely to treat osteoporosis and to manage bone metastases in patients with breast cancer. Some studies suggest that nitrogen-based bisphosphonates (NBBs) may also reduce cancer risk more broadly, although evidence is inconsistent. Using linked administrative health data from Australian women aged > 50 years, we conducted nested case-control studies and used conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CI) for the association between use of bisphosphonates (nitrogen-based and other) and other medicines approved for treatment of low bone mineral density, and risk of breast, colorectal, lung, uterus, thyroid, pancreas, kidney, cervical, stomach, liver, brain, bladder and gallbladder cancers and melanoma. In total, 243,629 incident cancer cases were matched to 1,218,075 controls. Compared to no use of osteoporosis medicines, use of nitrogen-based bisphosphonates (NBBs) was associated with reductions in breast (OR = 0.85, 95% CI: 0.83, 0.87), uterine (OR = 0.61, 95% CI: 0.57, 0.66) and cervical cancer risk (OR = 0.83, 95% CI: 0.71, 0.97) with the greatest reduction in risk observed for women who used NBBs for over 5 years. However, NBBs were also associated with increased risk of lung (OR = 1.16, 95% CI: 1.12, 1.21) and liver cancers (OR = 1.15, 95% CI: 1.02, 1.29), although there was no clear dose response. Raloxifene was also associated with lower risk of breast, colorectal, uterine and cervical cancer. Our exploratory study suggests links between some osteoporosis medicines and cancers related to reproductive hormones. Our results require confirmation but may provide new insights for cancer prevention.