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Oral bisphosphonates are associated with reduced mortality after hip fracture

Abstract

Summary

Intravenous bisphosphonates reduce mortality following hip fracture. We determined whether new use of oral bisphosphonates was also associated with reductions in mortality in 209 hip fracture patients. Oral bisphosphonate exposure led to relative reduction of 8% per month of use (p = 0.001) or about a 60% reduction in mortality per year of use.

Introduction

Intravenous bisphosphonates reduce mortality following hip fracture. Using prospectively collected long-term data from a randomized trial of osteoporosis quality improvement for hip fracture, we determined whether new use of oral bisphosphonates was associated with reductions in mortality or the composite outcome of death or new fracture.

Methods

Originally, 220 hip fracture patients were randomized to case manager (n = 110) or usual care followed by facilitated bone mineral density (BMD) testing (n = 110) interventions. All were eligible for bisphosphonate treatment. Post-randomization, we followed patients for 3 years and ascertained bisphosphonate treatment, medication adherence and persistence, all-cause mortality, and new clinical fractures. Proportional hazards analyses with time-varying treatment status were undertaken.

Results

The final study cohort included 209 patients: 136 (65%) females, 104 (50%) older than 75 years, 90 (43%) with poor self-reported health, and 38 (18%) underweight. Of these, 76 (36%) had a previous fracture before hip fracture and 132 (81%) had low BMD. A total of 101 (46%) patients started oral bisphosphonates and 65 (64%) remained on treatment at the final evaluation. Overall, 24 (11%) patients died, 19 (9%) had new fractures, and 42 (20%) reached the composite outcome of death or fracture. Compared to no treatment, bisphosphonate exposure was independently associated with reduced mortality (17[16%] vs. 7[7%]; adjusted hazard ratio (aHR) = 0.92 per month treated; 95%CI, 0.88–0.97) and composite endpoints (28[26%] vs. 5[15%]; aHR = 0.94 per month treated; 95%CI, 0.91–0.97).

Conclusion

Like intravenous bisphosphonates after hip fracture, our study suggests that oral bisphosphonates may be associated with reductions in all-cause mortality.

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Acknowledgements

This study was supported by the Health Research Fund of the Alberta Heritage Fund for Medical Research (AHFMR) and the Royal Alexandra Hospital Foundation.

Conflicts of interest

Dr. Beaupre receives salary support from AHFMR (population health investigator).

Dr. Majumdar receives salary support from AHFMR (health scholar) and the Canadian Institutes of Health Research (new investigator).

Dr. Maksymowych receives salary support from AHFMR (scientist).

Dr. Morrish has received unrestricted educational grants from Sanofi-aventis Canada Inc. and honoraria for membership on advisory boards for Amgen Canada Inc and Novartis Canada.

Dr. Hanley has been an investigator in sponsored clinical trials of alendronate and risedronate and has received honoraria for speaking and membership on advisory boards from Merck Frosst Canada Ltd, Proctor & Gamble Pharmaceuticals Canada Inc., and Novartis Canada.

Dr. Juby has received honoraria for membership on advisory boards from Novartis, Eli Lilly, Aventis/Proctor and Gamble Pharmaceuticals Canada Inc., and Merck Frosst Canada Ltd.

None of the above grants were associated with the results reported in this article.

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Correspondence to L. A. Beaupre.

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Beaupre, L.A., Morrish, D.W., Hanley, D.A. et al. Oral bisphosphonates are associated with reduced mortality after hip fracture. Osteoporos Int 22, 983–991 (2011). https://doi.org/10.1007/s00198-010-1411-2

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  • DOI: https://doi.org/10.1007/s00198-010-1411-2

Keywords

  • Bisphosphonates
  • Hip fracture
  • Mortality
  • Osteoporosis