Exposure to oral bisphosphonates and risk of cancer

Abstract

Recently oral bisphosphonate use has increased markedly in the United States and elsewhere. Little is known about cancer risks associated with these drugs. A few studies have observed associations between bisphosphonates and the risk of breast, colorectal and esophageal cancer. However, the risk of all cancer and the risk of other cancers have not been investigated. In this study we examined the risk of all cancer and site specific cancers in individuals taking bisphosphonates. Data were extracted from the UK General Practice Research Database to compare site-specific cancer incidence in a cohort of oral bisphosphonate users and a control cohort. Hazard ratios were calculated using Cox regression modelling. The bisphosphonate and control cohort contained 41,826 participants (mean age 70, 81% female). Overall, the bisphosphonate cohort compared with the control cohort had a reduced risk of all cancer after any bisphosphonate usage (HR=0.87, 95% CI 0.82, 0.92). In the bisphosphonate cohort, compared with the control cohort, there was no evidence of a difference in the risk of lung (HR=1.03, 95% CI 0.88, 1.20) or prostate cancer (HR=0.86, 95%CI 0.67, 1.09) but breast (HR= 0.71, 95% CI 0.62, 0.81) and colorectal cancer (HR=0.74, 95% CI, 0.60–0.91) were both reduced. Our findings indicate that bisphosphonates do not appear to increase cancer risk. Although reductions in breast and colorectal cancer incidence were observed in bisphosphonate users it is unclear, particularly for breast cancer, to what extent confounding by low bone density may explain the association.

Combination of alendronate and genistein synergistically suppresses osteoclastic differentiation of RAW267.4 cells in vitro

“…There is evidence indicating that bisphosphonate drugs have toxic effects, leading to impaired bone remodeling, bisphosphonate-related osteonecrosis of the jaw, gastrointestinal side effects and risk of cancer (11)(12)(13). The present study demonstrated that a combination comprising a relatively low effective dose of a bisphosphonate-type drug and genistein exhibits an inhibitory effect on osteoclastic differentiation.…”

“…Oral bisphosphonates such as alendronate, risedronate and etidronate are used beneficially to reduce the risk of skeletal fractures in patients with osteoporosis and in metastatic bone cancer (10). However, recent studies have suggested that the inhibitory effects of bisphosphonates on osteoclasts lead to impaired bone remodeling, bisphosphonate-related osteonecrosis of the jaw, gastrointestinal side effects and risk of cancer (11)(12)(13).…”

Oral bisphosphonates and colon cancer: an update

“…Some studies [Rennert et al 2011;Singh et al 2012;Pazianas et al 2012;Chiang et al 2012;Vestergaard, 2011] considered the pharmacy records of filling a prescription as a measure of exposure, while some considered the number of written prescriptions as a measure [Green et al 2010;Vinogradova et al 2013;Cardwell et al 2012]. Khalili and colleagues considered use of BPs as based on an individual's response to the survey of questions, putting them at risk of recall bias [Khalili et al 2012], whereas Passarelli and colleagues confirmed use of BPs, type and intravenous preparation via assessments of medication bottles [Passarelli et al 2013].…”

“…Short-term use was defined as use: <210 days [Singh et al 2012]; <1 year [Rennert et al 2011;Green et al 2010]; >1 year [Cardwell et al 2012]; 1-2 years [Khalili et al 2012]; and <2 years [Vestergaard, 2011;Chiang et al 2012]. Long-term use was defined as: >2 years [Chiang et al 2012]; >3 years [Rennert et al 2011;Green et al 2010]; >1250 days [Singh et al 2012]; >4 years [Cardwell et al 2012]; and >5 years [Khalili et al 2012;Vestergaard, 2011].…”

“…There are six cohort studies: two from the same Danish pharmacy prescription database [Pazianas et al 2012;Vestergaard, 2011], two from the US [Passarelli et al 2013;Khalili et al 2012], one from Taiwan [Chiang et al 2012] and one from the UK [Cardwell et al 2012]. There are four case-control studies: one from Israel [Rennert et al 2011], two from the UK [Green et al 2010;Vinogradova et al 2013] and one from Canada [Singh et al 2012] (Table 1), all addressing the question of the possible association between use of oral BPs against osteoporosis and risk of developing colon cancer and on survival.…”