Effects of antihypertensive drug treatments on fracture outcomes: a meta-analysis of observational studies

Objective. To quantitatively pool findings from observational studies on the risk of fracture outcomes associated with exposure to five antihypertensive drug classes: angiotensin-converting enzyme (ACE) inhibitors, diuretics (in particular thiazide diuretics), beta-blockers, calcium-channel blockers and alpha-blockers. Design. Systematic review and meta-analysis. Data sources. Publications listed in the MEDLINE, EMBASE and LILACS databases, the ISI proceedings, and bibliographies of retrieved articles. Sources were searched from the earliest possible dates through December 2005. Review methods. We included case-control and cohort studies presenting relative risks and confidence intervals (CIs) for the association between exposure to antihypertensive agents and fracture outcomes. Data were extracted onto a standardized computer worksheet. Study quality was assessed using a 10-point questionnaire specific to case-control or cohort study design. Results. Fifty-four studies were identified. Pooled estimates were computed using the software HEpiMA. The pooled relative risk (RR) of any fracture with use of thiazide diuretics was 0.86 (95% CI 0.81-0.92) and 1.14 (95% CI 0.84-1.54) with use of nonthiazide diuretics. There was a statistically significant reduction of any fracture with use of beta-blockers, (RR 0.86, 95% CI 0.70-0.98). The one study with ACE inhibitor data showed protection (RR 0.81, 95% CI 0.73-0.89). No significant associations were found between fractures and exposure to alpha-blockers or calcium-channel blockers. Conclusions. Thiazide diuretics and beta-blockers appear to lower the risk of fractures in older adults. However, these agents cannot be recommended as preventive therapies for fractures until data from randomized controlled trials have established their efficacy. Patients who use these inexpensive drugs as treatments for hypertension may also benefit from a reduction in fracture risk.