The use of oral bisphosphonates, typically used to treat osteoporosis and bone metastases in breast cancer, has recently been found to reduce breast cancer risk. Now, researchers from the Carmel Medical Center in Haifa, Israel, analyzing a cohort of women in Northern Israel have found that this class of drugs may be associated with a 59% relative reduction in risk of colorectal cancer when taken for at least a year and after adjusting for other risk factors. The study is an online advanced release and will be published in the Journal of Clinical Oncology.
Researchers matched 933 postmenopausal women taking oral bisphosphonates prior to colorectal cancer diagnosis with control counterparts who matched the patient’s age, sex, clinic location, and ethnic group.
In order to show that the oral bisphosphonates were the likely reason for reduced cancer risk, the scientists tested variables known to be associated with colorectal cancer for confounding or modifying effects. The variables included family history of colorectal cancer, Jewish ethnic group, vegetable consumption, body mass index, statin use, long-term calcium and vitamin D supplement use, and use of postmenopausal hormones. Consistent with known epidemiology of colorectal cancer in Israel, low vegetable consumption and low physical activity were correlated with positive colorectal cancer risk. Conversely, use of statins for more than 12 months or low-dose daily aspirin for more than 3 years was inversely correlated with colorectal cancer risk.
Significant reduction in colorectal cancer risk was found only when bisphosphonates were used for at least 1 year and did not change significantly when taken longer. The researchers tested whether combining statin with bisphosphonate use reduced colorectal cancer risk, but no further risk reduction was found.
Oral bisphosphonates include Procter and Gamble’s Actonel, Fosamax from Merck, and Roche’s Boniva. This drug class has previously been shown to have an antitumor effect in in vitro studies by inhibiting cell division, inducing cell death and inhibiting new blood vessel formation that is crucial for the growth of a tumor. They act on a biosynthesis pathway important for these biological processes. The pre-clinical data and the potential link of bisphosphonates with reduced risk of both colorectal and breast cancer merits further studies for their use in cancer prevention.
However, oral bisphosphonates are known to be stable in the bone for years post-administration and have been associated with higher risk of fractures after prolonged treatment as well as a rare adverse effect of osteonecrosis of the jaw. There is also discrepancy between two recent British studies that used the same database of patients: one study found that the drug class increases risk of esophageal cancer by two-fold, the 2nd study found no such link. Clearly, more molecular biology research and epidemiology studies need to be done before it is known which subset of the population would benefit from their use for colorectal cancer risk reduction and whether it is safe to recommended their use for cancer prevention in the healthy population.