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Comparison of orally administered bisphosphonate drugs in reducing the risk of hip fracture in older adults: a population-based cohort study

Cadarette SM, Levesque L, Mamdani M, Perreault S, Juurlink DN, Paterson JM, Carney G, Gunraj N, Hawker GA, Tadrous M, Wong L, Dormuth CR. CMAJ Open. 2013; 1(3):E97-105.


Background — Orally administered bisphosphonate drugs (i.e., alendronate, etidronate, risedronate) can reduce the risk of vertebral fracture. However, only alendronate and risedronate have proven efficacy in reducing the risk of hip fracture. The authors sought to examine the comparative effectiveness of orally administered bisphosphonate drugs in reducing hip fractures among older adults.

Methods — The authors identified new users of orally administered bisphosphonate drugs in British Columbia and Ontario between 2001 and 2008. They used province- and sex-specific propensity score–matching strategies to maximize comparability between exposure groups. Cox proportional hazards models were used to compare time-to-hip fracture within 1 year of treatment between exposures by sex in each province. The secondary analyses considered hip fracture rates within 2 and 3 years’ follow-up. The authors used alendronate as the reference for all comparisons and pooled provincial estimates using random effects variance-weighted meta-analysis.

Results — The authors identified 321 755 patients who were eligible for inclusion in the study. They found little difference in fracture rates between men (pooled hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.74–1.14) or women (pooled HR 1.15, 95% CI 0.73–1.56) taking risedronate and those taking alendronate. Similarly the authors identified little difference in fracture rates between women taking etidronate and those taking alendronate (pooled HR 1.00, 95% CI 0.82–1.18). However, we identified lower rates of hip fracture among men taking etidronate relative to alendronate (pooled HR 0.77, 95% CI 0.60–0.94). Results extended to 2 and 3 years’ follow-up were similar. However, with 3 years’ follow-up, rates of hip fracture were lower among women in British Columbia who had taken alendronate.

Interpretation — The authors identified little overall difference between alendronate and risedronate in reducing the risk of hip fracture in men or women. The finding that etidronate is associated with lower fracture risk among men is likely due to selection bias. The long-term comparative effects of orally administered bisphosphonate drugs warrant further study.

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Keywords: Drug therapy

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