Exposure to bisphosphonates and risk of gastrointestinal cancers: series of nested case-control studies with QResearch and CPRD data

Objective To investigate the association between use of bisphosphonates estimated from prescription information and risk of gastrointestinal cancers. Design Series of nested case-control studies. Setting General practices in the United Kingdom contributing to the QResearch primary care database (660) and the Clinical Practice Research Datalink (CPRD) (643). Participants Patients aged ≥50 with a diagnosis of a primary gastrointestinal cancer in 1997-2011, each matched with up to five controls by age, sex, practice, and calendar year. Main outcome measures Odds ratios for incident gastrointestinal cancers (colorectal, oesophageal, gastric) and use of bisphosphonates, adjusted for smoking status, ethnicity, comorbidities, and use of other drugs. Results 20 106 and 19 035 cases of colorectal cancer cases, 5364 and 5135 cases of oesophageal cancer cases, and 3155 and 3157 cases of gastric cancer were identified from QResearch and CPRD, respectively. Overall bisphosphonate use (at least one prescription) was not associated with risk of colorectal, oesophageal, or gastric cancers in either database. Adjusted odds ratios (95% confidence interval) for QResearch and CPRD were 0.97 (0.79 to 1.18) and 1.18 (0.97 to 1.43) for oesophageal cancer; 1.12 (0.87 to 1.44) and 0.79 (0.62 to 1.01) for gastric cancer; and 1.03 (0.94 to 1.14) and 1.10 (1.00 to 1.22) for colorectal cancer. Additional analyses showed no difference between types of bisphosphonate for risk of oesophageal and colorectal cancers. For gastric cancer, alendronate use was associated with an increased risk (1.47, 1.11 to 1.95; P=0.008), but only in data from the QResearch database and without any association with duration and with no definitive confirmation from sensitivity analysis. Conclusions In this series of population based case-control studies in two large primary care databases, exposure to bisphosphonates was not associated with an increased risk of common gastrointestinal cancers.