Alendronate Use and Risk of Type 2 Diabetes: A Nationwide Danish Nested Case-Control Study

Objective: A link has been proposed between glucose homeostasis and bone metabolism. Bisphosphonates are first-line treatment of osteoporosis, and we aimed to investigate whether the risk of developing type 2 diabetes was associated with prior use of alendronate. Research Design and Methods: We conducted a population-based nested case-control study through access to all discharge diagnoses (ICD-10 system) from the National Danish Patient Registry along with all redeemed drug prescriptions (ATC classification system) from the Health Service Prescription Registry. All cases with a diagnosis of type 2 diabetes between 2008 and 2018 were matched on sex and age with 3 randomly selected controls by incidence-density sampling. Exposure was defined as ever use of alendronate and further grouped as effective and compliant use. ORs were calculated by conditional logistic regression analysis with adjustment for several confounders and test for trend for dose-response relationship. Results: We included 163,588 patients with type 2 diabetes and 490,764 matched control subjects with a mean age of 67 years and 55% male subjects. The odds of developing type 2 diabetes were lower among ever users of alendronate (multiple adjusted OR: 0.64 [95% CI 0.62-0.66]). A test for trend suggested a dose-response relationship between longer effective use of alendronate and lower risk of type 2 diabetes. Conclusion: These results suggest a possible protective effect of alendronate in a dose-dependent manner against development of type 2 diabetes.