Common Questions
How does hydrochlorothiazide affect fracture risk?
Observational studies show that hydrochlorothiazide reduces fracture risk. However, randomized controlled trials have not been done to confirm this and it is unlikely that any will be done given the duration of the study that would be required and the lack of funding.
- A 4 year prospective study examined the effect of thiazide use on the incidence of hip fracture among >9,000 elderly men and women. The relative risk of hip fracture among thiazide users was 0.68 after adjusting for sex, age, impaired mobility, body-mass index, and current and former smoking status. Moreover, use of other antihypertensive medications was not associated with this risk reduction (1).
- A case control study was done to examine the effect of long-term thiazide use on hip fracture risk among women and men >65 years old who were not taking other medications known to affect BMD. Decreased risk of hip fracture was directly correlated to the length of duration of thiazide use. Relative risk was 1.2 for <2 years use, 0.8 for 2-5 years, and 0.6 for >6 years of use. These results were independent of age, sex, nursing hone residence, previous hospital admission, or use of other antihypertensive-diuretic drugs or psychotropic drugs (2).
- Another investigation sought to confirm this long-term benefit by following over 80,000 women for 10 years. A statistically significant 22% reduction in the risk of forearm fractures was observed among current thiazide users as compared to non-users (after controlling for age, body mass index, menopausal status, postmenopausal hormone use, cigarette smoking and dietary factors). This risk reduction increased with longer duration of use, with a 37% risk reduction among those taking thiazides for >8 years. Post-menopausal women had a reduction in relative risk of hip fractures as well (0.69) (3).
- A more recent study evaluated the effect of both dose and duration of thiazide diuretic use on the risk for hip fracture among >7,000 men and women 55 years and older. While no association between dose and fracture risk was observed, thiazide use for greater than 1 year correlated to a statistically significantly reduced risk (hazard ratio 0.46). However, unlike alendronate therapy, this risk disappeared 4 months following discontinuation (4).
- LaCroix AX, Wienpahl J, et al. Thiazide diuretic agents and the incidence of hip fracture. New England Journal of Medicine 1990; 322(5): 286-90.
- Ray WA, Griffen MR, Downey W, Melton LJ 3rd. Long-term use of thiazide diuretics and risk of hip fracture. Lancet 1989; 1(8640): 687-90.
- Feskanich D, Willett WC, Stampfer MJ, Colditz GA. A prospective study of thiazide use and fractures in women. Osteoporosis International 1997; 7(1): 79-84.
- Schoofs MW, van der Klift M. Thiazide diuretics and the risk for hip fracture. Annals of Internal Medicine 2003; 139(6): 476-82.