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Oral bisphosphonates are associated with reduced mortality after hip fracture



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.


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.


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.


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).


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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  1. Abrahamsen B, van Staa T, Ariely R, Olson M, Cooper C (2009) Excess mortality following hip fracture: a systematic epidemiological review. Osteoporos Int 20(10):1633–1650

    CAS  Article  PubMed  Google Scholar 

  2. Empana JP, Dargent-Molina P, Breart G (2004) Effect of hip fracture on mortality in elderly women: the EPIDOS prospective study. J Am Geriatri Soc 52(5):685–690

    Article  Google Scholar 

  3. Bliuc D, Nguyen ND, Milch VE, Nguyen TV, Eisman JA, Center JR (2009) Mortality risk associated with low-trauma osteoporotic fracture and subsequent fracture in men and women. JAMA 301(5):513–521

    CAS  Article  PubMed  Google Scholar 

  4. Egan M, Jaglal S, Byrne K, Wells J, Stolee P (2008) Factors associated with a second hip fracture: a systematic review. Clin Rehabil 22(3):272–282

    Article  PubMed  Google Scholar 

  5. Klotzbuecher CM, Ross PD, Landsman PB, Abbott TA III, Berger M (2000) Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis. J Bone Min Res 15(4):721–739

    CAS  Article  Google Scholar 

  6. Andrade SE, Majumdar SR, Chan KA, Buist DS, Go AS, Goodman M et al (2003) Low frequency of treatment of osteoporosis among postmenopausal women following a fracture. Arch Int Med 163(17):2052–2057

    Article  Google Scholar 

  7. Cree MW, Juby AG, Carriere KC (2003) Mortality and morbidity associated with osteoporosis drug treatment following hip fracture. Osteoporos Int 14(9):722–727

    Article  PubMed  Google Scholar 

  8. Danese MD, Badamgarav E, Bauer DC (2009) Effect of adherence on lifetime fractures in osteoporotic women treated with daily and weekly bisphosphonates. J Bone Min Res 24(11):1819–1826

    Article  Google Scholar 

  9. Nurmi-Luthje I, Luthje P, Kaukonen JP, Kataja M, Kuurne S, Naboulsi H et al (2009) Post-fracture prescribed calcium and vitamin D supplements alone or, in females, with concomitant anti-osteoporotic drugs is associated with lower mortality in elderly hip fracture patients: a prospective analysis. Drugs Aging 26(5):409–421

    CAS  Article  PubMed  Google Scholar 

  10. Lyles KW, Colon-Emeric CS, Magaziner JS, Adachi JD, Pieper CF, Mautalen C et al (2007) Zoledronic acid and clinical fractures and mortality after hip fracture. NEJM 357(18):1799–1809

    CAS  Article  PubMed  Google Scholar 

  11. Colon-Emeric CS, Mesenbrink P, Lyles KW, Pieper CF, Boonen S, Delmas P et al (2010) Potential mediators of the mortality reduction with zoledronic acid after hip fracture. J Bone Miner Res 25(1):91–97. doi:101359/jbmr0907042009

    CAS  Article  PubMed  Google Scholar 

  12. Eriksen EF, Lyles KW, Colon-Emeric CS, Pieper CF, Magaziner JS, Adachi JD et al (2009) Antifracture efficacy and reduction of mortality in relation to timing of the first dose of zoledronic acid after hip fracture. J Bone Min Res 24(7):1308–1313

    CAS  Article  Google Scholar 

  13. Bolland MJ, Grey AB, Gamble GD, Reid IR (2010) Effect of osteoporosis treatment on mortality: a meta-analysis. J Clin Endocrinol Metab 95(3):1174–1181

    CAS  Article  PubMed  Google Scholar 

  14. Eurich DT, Marrie TJ, Johnstone J, Majumdar SR (2008) Mortality reduction with influenza vaccine in patients with pneumonia outside “flu” season: pleiotropic benefits or residual confounding? Am J Respir Crit Care Med 178(5):527–533

    Article  PubMed  Google Scholar 

  15. Petri H, Urquhart J (1991) Channeling bias in the interpretation of drug effects. Stat Med 10(4):577–581

    CAS  Article  PubMed  Google Scholar 

  16. Psaty BM, Koepsell TD, Lin D, Weiss NS, Siscovick DS, Rosendaal FR et al (1999) Assessment and control for confounding by indication in observational studies. J Am Geriatr Soc 47(6):749–754

    CAS  PubMed  Google Scholar 

  17. Ray WA (2003) Evaluating medication effects outside of clinical trials: new-user designs. Am J Epidemiol 158(9):915–920

    Article  PubMed  Google Scholar 

  18. Suissa S (2007) Immortal time bias in observational studies of drug effects. Pharmacoepidemiol Drug Safety 16(3):241–249

    Article  Google Scholar 

  19. Majumdar SR, Beaupre LA, Harley CH, Hanley DA, Lier DA, Juby AG et al (2007) Use of a case manager to improve osteoporosis treatment after hip fracture: results of a randomized controlled trial. Arch Intern Med 167(19):2110–2115

    Article  PubMed  Google Scholar 

  20. Morrish DW, Beaupre LA, Bell NR, Cinats JG, Hanley DA, Harley CH et al (2009) Facilitated bone mineral density testing versus hospital-based case management to improve osteoporosis treatment for hip fracture patients: additional results from a randomized trial. Arthritis Rheum 61(2):209–215

    Article  PubMed  Google Scholar 

  21. National Population Health Survey. Government of Canada (2008) Available from: URL:

  22. Charlson M, Szatrowski TP, Peterson J, Gold J (1994) Validation of a combined comorbidity index. J Clin Epidemiol 47(11):1245–1251

    CAS  Article  PubMed  Google Scholar 

  23. Hays RD, Sherbourne CD, Mazel RM (1993) The RAND 36-item health survey 1.0. Health Econ 2(3):217–227

    CAS  Article  PubMed  Google Scholar 

  24. Majumdar SR, Lier DA, Beaupre LA, Hanley DA, Maksymowych WP, Juby AG et al (2009) Osteoporosis case manager for patients with hip fractures: results of a cost-effectiveness analysis conducted alongside a randomized trial. Arch Int Med 169(1):25–31

    Article  Google Scholar 

  25. Geusens P, Hochberg MC, van der Voort DJ, Pols H, van der Klift M, Siris E et al (2002) Performance of risk indices for identifying low bone density in postmenopausal women. Mayo Clin Proc 77(7):629–637

    Article  PubMed  Google Scholar 

  26. Eurich DT, Majumdar SR, MacAlister FA, Tsuyuki RT, Yasui Y, Johnson JA (2010) Analyzing composite outcomes in cardiovascular studies: Traditional Cox proportional hazard versus quality-of-life-adjusted approaches. Open Medicine 4(1):E-40-E-48

    Google Scholar 

  27. Maksymowych W (2002) Bisphosphonates: anti-inflammatory properties. Curr Med Chem 1:15–28

    CAS  Google Scholar 

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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).

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  • Bisphosphonates
  • Hip fracture
  • Mortality
  • Osteoporosis