Bisphosphonates and glucose homeostasis: a population-based, retrospective cohort study.

Abstract

Evidence suggests that the human skeleton might be involved in the regulation of glucose homeostasis. The objective of the study was to investigate the effect of exposure to bisphosphonates on the risk of incident type 2 diabetes mellitus (T2DM). This was a population-based, retrospective, open cohort study over the period 1995-2010. The study was conducted from The Health Improvement Network database from the United Kingdom in a primary care setting. 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. There were no interventions. 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. 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. This observational evidence suggests exposure to bisphosphonates was associated with a significant 50% reduction in the risk of incident T2DM.