Abstract
BackgroundThiazide, a first-line therapy for hypertension, lowers blood pressure, increases bone mineral density, and reduces the risk of fractures. However, hyponatremia, an adverse effect of thiazide, is associated with increased risk of osteoporosis and fractures. It is currently unclear whether thiazide-associated hyponatremia (TAH) outweighs the protective effects of thiazide.MethodsUsing data from Taiwan’s National Health Insurance Research Database, we identified patients who were prescribed thiazide between 1998 and 2010. Those diagnosed with hyponatremia within three years after initiation of thiazide were selected for the TAH group. Thiazide users without hyponatremia were selected for the control group. The association between TAH and fracture risk was further evaluated using multivariable Cox regression models adjusted for comorbidities and medications. Subjects were followed up from the index date until the appearance of a fracture, death, or the end of a 3-year period.ResultsA total of 1212 patients were included in the TAH group, matched with 4848 patients in the control group. The incidence rate of fracture was higher in the TAH group than in the control group (31.4 versus 20.6 per 1000 person-years). TAH was associated with a higher risk of total fractures (adjusted hazard ratio [aHR]: 1.47, 95% confidence interval [CI] = 1.15–1.88), vertebra fractures (aHR: 1.84, 95% CI = 1.12–3.01), and hip fractures (aHR: 1.66, 95% CI = 1.12–2.46) after controlling for comorbidities and other medications.ConclusionsThiazide users with hyponatremia have a higher risk of fracture than thiazide users without hyponatremia. The fracture-protective effect of thiazide is attenuated by TAH.
Highlights
Thiazide, a widely-used diuretic, is recommended as one of the first-line therapies for patients with hypertension [1]
thiazide-associated hyponatremia (TAH) was associated with a higher risk of total fractures, vertebra fractures, and hip fractures after controlling for comorbidities and other medications
Thiazide users with hyponatremia have a higher risk of fracture than thiazide users without hyponatremia
Summary
A widely-used diuretic, is recommended as one of the first-line therapies for patients with hypertension [1]. In addition to lowering blood pressure, thiazide increases bone mineral density (BMD) [2], and reduces the risk of fracture [3]. A Cochrane meta-analysis showed that thiazide use is associated with a 24% reduction in hip fracture risk, though it is uncertain whether this beneficial effect comes from increased BMD [3]. The effect of increasing BMD [10,11] and reducing fracture risk [12,13] seems to be linked to the duration of thiazide use. A first-line therapy for hypertension, lowers blood pressure, increases bone mineral density, and reduces the risk of fractures. Hyponatremia, an adverse effect of thiazide, is associated with increased risk of osteoporosis and fractures. It is currently unclear whether thiazide-associated hyponatremia (TAH) outweighs the protective effects of thiazide.
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