Suzanne M Cadarette1, Linda Lévesque2, Muhammad Mamdani3, Sylvie Perreault4, David N Juurlink5, J Michael Paterson6, Greg Carney7, Nadia Gunraj8, Gillian A Hawker9, Mina Tadrous10, Lindsay Wong10, Colin R Dormuth7. 1. Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ont. ; Institute for Clinical Evaluative Sciences, Toronto, Ont. 2. Institute for Clinical Evaluative Sciences, Toronto, Ont. ; Department of Community Health and Epidemiology, Queen's University, Kingston, Ont. 3. Institute for Clinical Evaluative Sciences, Toronto, Ont. ; Applied Health Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ont. 4. Faculty of Pharmacy, University of Montreal, Montreal, Que. 5. Sunnybrook Research Institute, Toronto, Ont. 6. Institute for Clinical Evaluative Sciences, Toronto, Ont. ; Department of Family Medicine, McMaster University, Hamilton, Ont. 7. Therapeutics Initiative, University of British Columbia, Victoria, BC. 8. Institute for Clinical Evaluative Sciences, Toronto, Ont. 9. Institute for Clinical Evaluative Sciences, Toronto, Ont. ; Women's College Research Institute, Women's College Hospital, Toronto, Ont. 10. Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ont.
Abstract
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. We sought to examine the comparative effectiveness of orally administered bisphosphonate drugs in reducing hip fractures among older adults. METHODS: We identified new users of orally administered bisphosphonate drugs in British Columbia and Ontario between 2001 and 2008. We used province- and sex-specific propensity score-matching strategies to maximize comparability between exposure groups. We used Cox proportional hazards models to compare time-to-hip fracture within 1 year of treatment between exposures by sex in each province. Our secondary analyses considered hip fracture rates within 2 and 3 years' follow-up. We used alendronate as the reference for all comparisons and pooled provincial estimates using random effects variance-weighted meta-analysis. RESULTS: We identified 321 755 patients who were eligible for inclusion in the study. We 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. We similarly 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: We identified little overall difference between alendronate and risedronate in reducing the risk of hip fracture in men or women. Our 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.
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. We sought to examine the comparative effectiveness of orally administered bisphosphonate drugs in reducing hip fractures among older adults. METHODS: We identified new users of orally administered bisphosphonate drugs in British Columbia and Ontario between 2001 and 2008. We used province- and sex-specific propensity score-matching strategies to maximize comparability between exposure groups. We used Cox proportional hazards models to compare time-to-hip fracture within 1 year of treatment between exposures by sex in each province. Our secondary analyses considered hip fracture rates within 2 and 3 years' follow-up. We used alendronate as the reference for all comparisons and pooled provincial estimates using random effects variance-weighted meta-analysis. RESULTS: We identified 321 755 patients who were eligible for inclusion in the study. We 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. We similarly 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: We identified little overall difference between alendronate and risedronate in reducing the risk of hip fracture in men or women. Our 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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