Bisphosphonates and Glucose Homeostasis: A Population-Based, Retrospective Cohort Study

Context: Evidence suggests that the human skeleton might be involved in the regulation of glucose homeostasis. Objective: The objective of the study was to investigate the effect of exposure to bisphosphonates on the risk of incident type 2 diabetes mellitus (T2DM). Design: This was a population-based, retrospective, open cohort study over the period 1995-2010. Setting: The study was conducted from The Health Improvement Network database from the United Kingdom in a primary care setting. Patients: A total of 35 998 individuals aged older than 60 years, without diabetes at baseline and with more than 1 year's exposure to bisphosphonates, and 126 459 age-, gender-, body mass index- and general practice-matched unexposed individuals participated in the study. Interventions: There were no interventions. Main Outcome Measure: A new diagnosis of T2DM during the 16-year-long observation period, determined by Read codes and adjusted incidence rate ratio in bisphosphonate-exposed compared with unexposed groups, was the main outcome measure. Results: The risk of incident T2DM was significantly lower in patients exposed to bisphosphonates compared with matched controls [adjusted incidence rate ratio 0.52, 95% confidence interval (CI) 0.48-0.56, P < .0001]. In subgroup analyses, the findings remained consistent in males [0.77 (95% CI 0.66-0.89)], females [0.49 (95% CI 0.45-0.53)], obese [0.54 (95% CI 0.50-0.59)], individuals exposed to steroid treatment [0.47 (95% CI 0.34-0.64)], and over different types of bisphosphonate medication. Analysis of duration of treatment suggested a brief increase in the risk of T2DM (1 to 2.5 y of exposure), followed by a progressive, sustained decrease as the years of exposure accumulated. Conclusions: This observational evidence suggests exposure to bisphosphonates was associated with a significant 50% reduction in the risk of incident T2DM.