Alendronate Use and the Risk of Nonvertebral Fracture During Glucocorticoid Therapy: A Retrospective Cohort Study

Context: Glucocorticoids increase the risk of nonvertebral fracture, but no clinical trial has shown that nonvertebral fractures can be prevented by coadministration of an antiosteoporotic drug. Objective: To estimate the effect of alendronate on the risk of nonvertebral fracture in older adults taking oral glucocorticoids. Design: Retrospective cohort study using national Swedish registers. Setting: Hospitalized care and ambulatory specialist care. Patients: Among adults aged >= 50 years (N = 3,347,959), we identified those who initiated oral glucocorticoid therapy from 2006 through 2011 (>= 2.5 mg/d of prednisone or equivalent for >= 91 days). The final analysis included 16,890 alendronate users and 16,890 nonusers, who were matched using time-dependent propensity scores. Main Outcome Measure: Nonvertebral fracture. This was not prespecified. Results: Over a median follow-up of 14.5 months, the incidence rate of nonvertebral fracture was 2.0 cases/100 person-years in alendronate users and 2.4 cases in nonusers. This difference corresponded to a 16% lower rate in users (hazard ratio 0.84; 95% confidence interval, 0.75 to 0.94). For hip fractures specifically, the rate was 34% lower in alendronate users relative to nonusers (hazard ratio 0.66; 95% confidence interval, 0.55 to 0.78). The association of alendronate use with a lower risk of nonvertebral fracture was strongest in patients who received high doses of glucocorticoid. Conclusion: Alendronate use was associated with a lower risk of nonvertebral fracture, including hip fracture. Similar, but not statistically significant, associations have been reported in meta-analyses of clinical trials.