title: Optimal age of commencing and discontinuing thiazide therapy to protect against fractures.
abstract: 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.
  
  
  BACKGROUND
  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.
authors.affiliation: Department of Endocrinology, Aalborg University Hospital, Hobrovej 19, 9100, Aalborg, Denmark. ckruse@dcm.aau.dk.|Department of Clinical Medicine, Aalborg University Hospital, Aalborg, Denmark. ckruse@dcm.aau.dk.
authors.forename: C
authors.identifier: http://orcid.org/0000-0001-5590-2245
authors.initials: C
authors.lastname: Kruse
authors.affiliation: Department of Cardiology, Nephrology and Endocrinology, Nordsjaellands Hospital, Hilleroed, Denmark.|Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: P
authors.initials: P
authors.lastname: Eiken
authors.affiliation: Department of Endocrinology, Aalborg University Hospital, Hobrovej 19, 9100, Aalborg, Denmark.|Department of Clinical Medicine, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: P
authors.initials: P
authors.lastname: Vestergaard
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015897:Comorbidity; D003718:Denmark / Q000453:epidemiology; D004334:Drug Administration Schedule; D004363:Drug Utilization / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D008875:Middle Aged; D058866:Osteoporotic Fractures / Q000139:chemically induced / Q000453:epidemiology / Q000517:prevention & control*; D012042:Registries; D012189:Retrospective Studies; D018570:Risk Assessment / Q000379:methods; D049993:Sodium Chloride Symporter Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D028761:Withholding Treatment
chemical_list: D049993:Sodium Chloride Symporter Inhibitors
keywords: Bone metabolism; Fractures; Osteoporosis; Post-menopausal; Thiazides