Abstract
Observational studies suggest that thiazide-type diuretics reduce fracture risk compared to other antihypertensive medications. The effects of calcium channel blockers (CCB) and angiotensin converting-enzyme inhibitors (ACEi) on fracture risk have not been well studied. We examined the relationship of antihypertensive drug therapy and hip and pelvic fracture hospitalizations in the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ). It included >33,000 participants randomized to the thiazide-type diuretic chlorthalidone (C), ACEi lisinopril (L), or CCB amlodipine (A) as first line hypertension (HTN) therapy. Mean follow up was 4.9 years during the randomized phase (in-trial), and 5 additional years after the conclusion of the trial (post-trial) using linkage to national data bases. Risks of hip and pelvic fractures for L and A relative to C were derived from Cox models. There were 341 hip and pelvic fractures in-trial. Participants assigned C had the lowest risk and those assigned L the highest ( Figure 1a). The adjusted risk for L compared to C was 1.33 (95% CI 1.02-1.73; p=.04). Participants assigned A had intermediate risk compared to C (HR 1.22, 95% CI 0.93-1.59). During the combined in-trial and post-trial periods ( Figure 1b ), there were 646 fractures; the results were similar to the in-trial results, although differences were not statistically significant. Participants randomized to C continued to have the lowest risk of fractures after in-trial period, suggesting a legacy effect from prior C use. These findings have public health importance given the high prevalence of HTN in older adults and the widespread use of A and L in older adults.
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