Abstract
BackgroundIt is unclear whether bisphosphonates are associated with risk of cancers. Therefore, this meta-analysis aimed to evaluate the effect of bisphosphonates on overall cancers.MethodsA search in Pubmed, Embase, Cochrane Library and Web of Science databases was conducted, from the inception date of each resource to September 26, 2019. The summarised effect estimates with 95% CIs were calculated using a random-effect model. Heterogeneity and publication bias were explored.ResultsThirty-four articles were included in this study (4,508,261 participants; 403,196 cases). The results revealed that bisphosphonates significantly decreased the risk of colorectal cancer (RR = 0.89, 95% CI: 0.81–0.98), breast cancer (RR = 0.87, 95% CI: 0.82–0.93) and endometrial cancer (RR = 0.75, 95% CI: 0.61–0.94), but no significant association was observed in all-cause cancer. Furthermore, nitrogen-containing bisphosphonates only had protective effects both on breast cancer (RR = 0.94, 95% CI: 0.90–0.99) and endometrial cancer (RR = 0.70, 95% CI: 0.54–0.92). Non-nitrogen-containing bisphosphonates tended to increase the risk of liver cancer (RR = 2.14, 95% CI: 1.23–3.72) and pancreas cancer (RR = 1.75, 95% CI: 1.32–2.33).ConclusionBisphosphonates are significantly associated with risk reduction of colorectal, breast and endometrial cancer, especially nitrogen-containing bisphosphonates. It should be noted that non-nitrogen-containing bisphosphonates might increase the risk of liver and pancreas cancer. Large prospective cohort studies are needed to find the causal association between bisphosphonates and risk of cancers.
Highlights
It is unclear whether bisphosphonates are associated with risk of cancers
The data were available from 4,508,261 participants, including 403,196 cases originating from 19 types of cancers
Some articles focused on multiple types of cancers: 24 papers reported gastrointestinal cancers, 16 papers reported gynaecological cancers, 14 papers reported oesophageal cancer, 10 papers reported breast cancer, 7 papers reported hepatobiliary cancers, 5 papers reported lung cancer, 3 papers reported prostate cancer and 14 papers reported other cancers
Summary
It is unclear whether bisphosphonates are associated with risk of cancers. this meta-analysis aimed to evaluate the effect of bisphosphonates on overall cancers. Nitrogen-containing bisphosphonates only had protective effects both on breast cancer (RR = 0.94, 95% CI: 0.90–0.99) and endometrial cancer (RR = 0.70, 95% CI: 0.54–0.92). Non-nitrogen-containing bisphosphonates tended to increase the risk of liver cancer (RR = 2.14, 95% CI: 1.23–3.72) and pancreas cancer (RR = 1.75, 95% CI: 1.32–2.33). CONCLUSION: Bisphosphonates are significantly associated with risk reduction of colorectal, breast and endometrial cancer, especially nitrogen-containing bisphosphonates. It should be noted that non-nitrogen-containing bisphosphonates might increase the risk of liver and pancreas cancer. Preclinical studies have suggested that bisphosphonates have direct and indirect antitumour properties, including inhibition of tumour cell adhesion and proliferation,[4,5] induction apoptosis of tumour cells,[6] prevention of angiogenesis[7,8] as well as activation of immune cells.[9] Wysowski et al.[10] reported that the US Food and Drug Administration (FDA) received 23 cases of oesophageal cancer after the use of bisphosphonates. Some epidemiological studies were conducted on the association between bisphosphonates and the risk of some types of cancers, but the results of these studies were controversial.[11,12,13,14]
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