Exposure to bisphosphonates and risk of common non-gastrointestinal cancers: series of nested case–control studies using two primary-care databases

Abstract

Background:Bisphosphonates are the most commonly prescribed osteoporosis drugs but long-term effects are unclear, although antitumour properties are known from preclinical studies.Methods:Nested case–control studies were conducted to investigate bisphosphonate use and risks of common non-gastrointestinal cancers (breast, prostate, lung, bladder, melanoma, ovarian, pancreas, uterus and cervical). Patients 50 years and older, diagnosed with primary cancers between 1997 and 2011, were matched to five controls using the UK practice-based QResearch and Clinical Practice Research Datalink (CPRD) databases. The databases were analysed separately and the results combined.Results:A total of 91 556 and 88 845 cases were identified from QResearch and CPRD, respectively. Bisphosphonate use was associated with reduced risks of breast (odds ratio (OR): 0.92, 95% confidence interval (CI): 0.87–0.97), prostate (OR: 0.87, 95% CI: 0.79–0.96) and pancreatic (OR: 0.79, 95% CI: 0.68–0.93) cancers in the combined analyses, but no significant trends with duration. For alendronate, reduced risk associations were found for prostate cancer in the QResearch (OR: 0.81, 95% CI: 0.70–0.93) and combined (OR: 0.84, 95% CI: 0.75–0.93) analyses (trend with duration P-values 0.009 and 0.001). There were no significant associations from any of the other analyses.Conclusion:In this series of large population-based case–control studies, bisphosphonate use was not associated with increased risks for any common non-gastrointestinal cancers.

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

“…The Vinogradova et al . study in our meta‐analysis had the most weight (39%). Therefore, we should not exclude the Vinogradova et al .…”

“…Seven studies met the inclusion criteria and were included in this meta‐analysis (Figure ), including four cohort studies and three case–control studies …”

“… or the study of Vinogradova et al . , that may contain a small number of overlapped individuals, the significance of the combined estimate was not altered.…”

“…11,12 Recently, the association between endometrial cancer and the use of bisphosphonate was observed in several observational studies, suggesting that bisphosphonate might also be associated with reduced risk of endometrial cancer [13][14][15] , while other studies reported no identified effects. [16][17][18] One study reported that bisphosphonate use for more than one year significantly lowered the risk of endometrial cancer. 13 However, the existing results are controversial.…”

Medical Prevention of Breast Cancer

“…The majority of patients used oral bisphosphonates. These results were supported by a British cohort analysis (HR 0.71, 95% CI 0.62-0.81) and a British nested case-control study (OR 0.92; 95% CI 0.87-0.97) - both found a decreased breast cancer risk after bisphosphonate use [57,58]. However, the relation between low estrogen levels, decreased bone mass and breast cancer risk remains unclear, and prospective trials investigating the chemopreventive impact of bisphosphonates still underway.…”