Thiazide diuretics and the risk for hip fracture

Ann Intern Med. 2003 Sep 16;139(6):476-82. doi: 10.7326/0003-4819-139-6-200309160-00010.


Background: Since most hip fractures are related to osteoporosis, treating accelerated bone loss can be an important strategy to prevent hip fractures. Thiazides have been associated with reduced age-related bone loss by decreasing urinary calcium excretion.

Objective: To examine the association between dose and duration of thiazide diuretic use and the risk for hip fracture and to study the consequences of discontinuing use.

Design: Prospective population-based cohort study.

Setting: The Rotterdam Study.

Participants: 7891 individuals 55 years of age and older.

Measurements: Hip fractures were reported by the general practitioners and verified by trained research assistants. Details of all dispensed drugs were available on a day-to-day basis. Exposure to thiazides was divided into 7 mutually exclusive categories: never use, current use for 1 to 42 days, current use for 43 to 365 days, current use for more than 365 days, discontinuation of use since 1 to 60 days, discontinuation of use since 61 to 120 days, and discontinuation of use since more than 120 days.

Results: 281 hip fractures occurred. Relative to nonuse, current use of thiazides for more than 365 days was statistically significantly associated with a lower risk for hip fracture (hazard ratio, 0.46 [95% CI, 0.21 to 0.96]). There was no clear dose dependency. This lower risk disappeared approximately 4 months after thiazide use was discontinued.

Conclusions: Thiazide diuretics protect against hip fracture, but this protective effect disappears within 4 months after use is discontinued.

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Benzothiadiazines*
  • Bone Density
  • Calcium / urine
  • Calcium, Dietary / administration & dosage
  • Diuretics
  • Drug Administration Schedule
  • Female
  • Hip Fractures / epidemiology
  • Hip Fractures / prevention & control*
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors
  • Sodium Chloride Symporter Inhibitors / administration & dosage*


  • Benzothiadiazines
  • Calcium, Dietary
  • Diuretics
  • Sodium Chloride Symporter Inhibitors
  • Calcium