It has been estimated that 25% of postmenopausal women in the United States will sustain a vertebral fracture, with the prevalence increasing with advancing age. Among older adults in the United States, hydrochlorothiazide, a diuretic, is the second most commonly used prescription or over-the-counter drug. Thiazides have been shown to decrease urinary calcium excretion, improve calcium balance, but can also cause hyponatremia, a condition associated with an increased risk of fractures. Loop diuretics increase urinary calcium excretion and lower bone mineral density, but rarely cause hyponatremia. This prospective study compared the association between thiazide and loop diuretic use and vertebral fractures.

Data were obtained from the Nurses′ Health Study, an ongoing, prospective, cohort study begun in 1976, and enrolling 121，700 female registered nurses, 30 to 55 years of age. Data from this study included 55，780 women who completed both the 2002 questionnaire including questions of diuretic use, and the 2012 questionnaire which included questions about vertebral fractures. Potential confounders for fracture risk were also recorded.

During 543，209 person-years of follow-up, there were 420 confirmed cases of incident vertebral fracture. In the multivariable-adjusted analysis, thiazide diuretic as well as loop diuretic use were both associated with a significantly increased risk of vertebral fracture (relative risk 1.47 and 1.59, respectively) compared to nonusers.

This study found that both thiazide diuretics and loop diuretics are independently associated with an increased risk of vertebral fracture in women.