Antihypertensive Medications and Fracture Risk

Study Questions:

Is thiazide diuretic treatment of hypertension associated with reduced fracture risk compared with nonuse?


The authors used Veterans Affairs and Medicare claims data to examine hip and pelvic fracture hospitalizations in ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) participants randomized to first-step therapy with a thiazide-type diuretic (chlorthalidone), amlodipine, or lisinopril. Recruitment was from February 1994 to January 1998. For this secondary analysis, which used an intention-to-treat approach, data were analyzed from February 1, 1994, through December 31, 2006.


A total of 22,180 participants (mean [SD] age, 70.4 [6.7] years; 43.0% female; and 49.9% white non-Hispanic, 31.2% African American, and 19.1% other ethnic groups) were followed for up to 8 years (mean [SD], 4.9 [1.5] years) during masked therapy. After trial completion, 16,622 participants for whom claims data were available were followed for up to 5 additional years (mean [SD] total follow-up, 7.8 [3.1] years). During the trial, 338 fractures occurred. Using one-year post-randomization as baseline, participants randomized to chlorthalidone versus amlodipine or lisinopril had a 21% lower risk of fracture on adjusted analyses (hazards ratio [HR], 0.79; p = 0.04). Risk of fracture was 25% lower in participants randomized to chlorthalidone versus lisinopril (HR, 0.75; p = 0.04), but not significantly different compared with those randomized to amlodipine.


The findings from a large randomized clinical trial provide evidence of a beneficial effect of thiazide-type diuretic therapy in reducing hip and pelvic fracture risk compared with treatment with other antihypertensive medications.


Using 1 year after randomization may have mitigated the fracture risk related to hypotension-associated falls. Low bone mineral density has been related to increased cardiovascular mortality, cardiovascular morbidity, and subclinical measures of atherosclerosis. It is important that clinical trials assess the impact of treatment of one or the other, and that older men and women with coronary disease and heart failure be assessed for osteoporosis.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Prevention, Atherosclerotic Disease (CAD/PAD), Lipid Metabolism, Statins, Acute Heart Failure, Hypertension

Keywords: Geriatrics, Metabolic Syndrome X, Secondary Prevention, Accidental Falls, Amlodipine, Antihypertensive Agents, Atherosclerosis, Bone Density, Chlorthalidone, Coronary Artery Disease, Diuretics, Heart Failure, Hypertension, Hypotension, Lipids, Lisinopril, Medicare, Myocardial Infarction, Osteoporosis, Primary Prevention, Thiazides, Veterans

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