Purpose: Several previous studies have shown that oral bisphosphonates (BPs) are associated with the incidence of 13 specific cancers, including lung cancer, esophageal cancer, gastric cancer, and colorectal cancer (CRC). However, the findings are heterogeneous.
Methods and results: Relevant studies published in databases such as PubMed, Embase database, and Cochrane library were systematically retrieved from inception to August 25th, 2018, regardless of language, by two investigators independently. Afterwards, the maximum adjusted hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were extracted from the retrieved studies. Finally, 13 cohort studies involving 1,510,763 participants were enrolled into this meta-analysis. No significant relationship was found between oral BPs and the risk of all-cause cancer in osteoporosis (OP) patients among the entire population (HR 0.97, 95% CI 0.80-1.18; I2 92.5%). Besides, oral BPs could remarkably reduce the incidence of breast cancer (HR 0.79, 95% CI 0.68-0.92; I2 54%) and endometrial cancer (HR 0.79, 95% CI 0.64-0.96; I2 0%) in postmenopausal OP females. In addition, oral BPs were also found to evidently reduce the incidence of upper gastrointestinal cancer in OP patients among the entire population (HR 0.73, 95% CI 0.54-0.98; I2 36.1%). However, oral BPs may lead to increased risk of liver cancer in mixed genders (HR 1.69, 95% CI 1.03-2.77; I2 30.7%).
Conclusions: Taken together, oral BPs do not increase the risk of incidence of all-cause cancer; instead, they can reduce the incidence of breast, endometrial, and upper gastrointestinal cancers among the postmenopausal OP females. Our analysis stratified by gender suggests that oral BPs may increase the incidence of liver cancer in mixed genders, while no significant association was observed in females. Careful analysis of post-marketing data should be conducted to address the clinical relevance of our results on the putative association of oral BP use and liver cancer suggested by our meta-analysis.
Keywords: Bisphosphonates; Cancer; Meta-analysis; Osteoporosis.