PURPOSE: Bisphosphonates are commonly used for the treatment of osteoporosis and bone metastases caused by breast cancer and were recently reported to be associated with a reduced risk of breast cancer, possibly acting through the mevalonate pathway, but their association with risk of other cancers is unknown. PATIENTS AND METHODS: The Molecular Epidemiology of Colorectal Cancer study is a population-based, case-control study in northern Israel of patients with colorectal cancer and age-, sex-, clinic-, and ethnic group-matched controls. Long-term use of bisphosphonates before diagnosis was assessed in a subset of 933 pairs of postmenopausal female patients and controls, enrolled in Clalit Health Services, using computerized pharmacy records. RESULTS: The use of bisphosphonates for more than 1 year before diagnosis, but not for less than 1 year, was associated with a significantly reduced relative risk (RR) of colorectal cancer (RR, 0.50; 95% CI, 0.35 to 0.71). This association remained statistically significant after adjustment in a model for vegetable consumption, sports activity, family history of colorectal cancer, body mass index, and use of low-dose aspirin, statins, vitamin D, and postmenopausal hormones (RR, 0.41; 95% CI, 0.25 to 0.67). Concomitant use of bisphosphonates and statins did not further reduce the risk. CONCLUSION: The use of oral bisphosphonates for more than 1 year was associated with a 59% relative reduction in the risk of colorectal cancer, similar to the recently reported association of this drug class with reduction in breast cancer risk.
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