Optimal age of commencing and discontinuing thiazide therapy to protect against fractures

A study of national Danish patient data with regard to thiazide diuretics vs. non-treatment. We find that after age 83 years, thiazides increase the 10-year risk of major fractures. We also find that thiazides can be stopped after 63 years old to possibly protect against fracture occurrence.

INTRODUCTION: The purpose of this study was to retrospectively examine the optimal age for commencing and discontinuing thiazide therapy to protect from osteoporotic fractures.

METHODS: A population-based, retrospective matched cohort study was done using national data of 2.93 million Danish subjects. Ten-year crude and adjusted age-grouped hazard ratios (HRs) of fracture occurrence were stratified by age of commencing thiazides compared to non-exposure. Separate analyses were done on Anatomical Therapeutic Chemical Classification System (ATC) codes C03AA and C03AA + C03AB compiled. Ten-year crude HRs of fracture occurrence for discontinuing vs. continuing thiazides were estimated and stratified by age for the two groups.

RESULTS: For C03AB alone (97.1 % of thiazide prescriptions), adjusted 10-year HRs of fracture occurrence were significantly increased for thiazide commencement after age 83 years and comparable to non-exposure for commencement between ages 50 and 83 years. For C03AA + C03AB, 10-year adjusted HRs of fracture occurrence were significantly increased from ages 73 years and upwards. Crude 10-year HRs of fracture occurrence were significantly decreased for discontinuing vs. continuing thiazides at or after age 63 years for C03AB and age 77 years for C03AA + C03AB.

CONCLUSIONS: No significantly protective effect of thiazides was found on fracture occurrence compared to non-users, but evidence that thiazides increase the 10-year adjusted HR risk of fractures if prescribed after the age of 83 years for C03AB and 73 years for C03AA + C03AB. Discontinuing thiazides at or after age 63 years for C03AB or 77 years for C03AA & C03AB significantly decreases the 10-year risk of fractures compared to continuing thiazides. Further prospective studies are warranted.