Colorectal cancer (CRC) is the third most common cancer, as well as the third most common cause of cancer deaths in the United States, and is associated with obesity, a reduced fiber intake and reduced physical activity. Bisphosphonates are antiresorptive agents widely used in the treatment and prevention of osteoporosis. Several large studies have recently reported a reduced risk of CRC with bisphosphonate use, however no meta-analysis on the subject exists. The aim of this study was to provide a quantitative estimate of the association between bisphosphonate use and the risk of CRC.
A search was conducted through Medline, PubMed, Embase, and Current Contents Connect to July 19, 2012. No language restrictions were used. We calculated pooled odds ratios and 95% confidence intervals using a random effects model for the relationship between the use of bisphosphonates and CRC.
Seven studies, with 21 511 CRC cases, met our inclusion criteria from 858 studies initially identified. The use of bisphosphonates was associated with a reduced risk of CRC, with an odds ratio (OR) of 0.78 with a 95% confidence interval (CI) of 0.68-0.87. A subgroup analysis by female gender (OR 0.80; 95% CI, 0.69-0.92), prospective study design (OR 0.80; 95% CI, 0.70-0.90), cohort study design (OR 0.80; 95% CI, 0.30-1.00) and nested case-control study design (OR 0.84; 95% CI, 0.77-0.92) also showed a decreased risk of CRC associated with the use of bisphosphonates. The relationship was not significant for different durations of bisphosphonate use. Moderate but statistically non-significant heterogeneity was observed. Publication bias was not present.
The use of bisphosphonates was associated with a reduction in the risk of CRC, suggesting that bisphosphonates may confer a protective effect on the development of this cancer. Controlled prospective studies adjusting for significant confounders are needed to further elucidate the relationship.