The Carcinogenicity of Alendronate in Patients with Osteoporosis: Evidence from Cohort Studies

Abstract

ContextAlendronate may relate to the incidence of cancers, especially esophageal and colon cancer. But the results are inconsistent in different studies.ObjectiveTo quantify the association between the use of alendronate and the occurrence of different types of cancer.Data SourcesWe searched Embase, Pubmed, CENTRAL, SIGLE and clinicaltrials.gov, up to 2014 June.Study SelectionCohort studies reporting association between alendronate or bisphosphonate therapy including alendronate in patients with osteoporosis and risk of cancer were selected by two authors.Data ExtractionTwo authors independently extracted the data. The Chi-square test and the I-square test were used for testing heterogeneity between studies.Data SynthesisEight cohort studies were included in the meta-analysis. Meta-analysis result manifested that alendronate significantly increased the incidence of lung cancer (HR 1.23, 95%CI 1.03 to 1.47, P value = 0.03), nevertheless, there was no significant difference after we excluded either Lee’s 2012 study (HR 1.17, 95%CI 0.95 to 1.44, P value = 0.13) or Chiang’s 2012 study (HR 1.47, 95%CI 1 to 2.17, P value = 0.05). For the incidence of colorectal cancer, no significant difference occurred (HR 0.91, 95%CI 0.74 to 1.13, P value = 0.39), but there was a positive relationship when we used fixed model (HR 0.85, 95%CI 0.78 to 0.93, P value = 0.004). For the incidence of liver cancer, there was no significant difference (HR 1.36, 95%CI 0.9 to 2.04, P value = 0.14), however, the result changed after we excluded Chiang’s 2012 study (HR 1.69, 95%CI 1.03 to 2.77, P value = 0.04). There was no significant difference in other types of cancer.ConclusionBased on current evidences, alendronate therapy may be associated with a high risk of lung cancer, may with an excess risk of liver cancer, a low risk of colorectal and no related risk of other cancers.

Differential protective effects of bisphosphonates and denosumab on primary breast cancer risk, potentially to be modified by statins: a retrospective study using electronic health records

“…However, the randomized control trials were not initially designed to study breast cancer outcome and they might be at high risk of selective reporting bias. Overall, systemic reviews and metaanalyses agreed upon a signi cantly decreased risk of primary breast cancer in bisphosphonates users [24][25][26]. This is in accordance with our ndings.…”

“…The entangled and far-reached regulatory network is summarized in Figure 1 Epidemiological studies have shown that bisphosphonates have variable non-adverse, e.g. protective or no related risk towards female breast cancer [15][16][17][18][19][20][21][22][23][24], although some reports showed that alendronate may be associated with higher risks in lung and liver cancers [25,26]. A recent study suggests a potential protective effect of denosumab ever use on breast cancer risk in a cohort of older women previously treated with bisphosphonates [27].…”

Differential effects of bisphosphonates and denosumab on primary breast cancer risk, potentially to be modified by statins

“…Overall, systemic reviews and meta-analyses agreed upon a significantly decreased risk of primary breast cancer in bisphosphonates users [24][25][26]. This is in accordance with our findings.…”

Bisphosphonate use and the risk of endometrial cancer: a meta‐analysis of observational studies

“…There is a long‐standing debate about the relationship between bisphosphonate use and cancer risk. Several observational studies have discussed the use of bispho1sphonate as potential chemoprevention against various cancers—colorectal cancer, breast cancer, gastrointestinal cancer, and esophageal cancer, but the results were inconsistent. It still remains unclear whether bisphosphonate exert an anticancer effect or not.…”