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Osteoporosis International

, Volume 22, Issue 9, pp 2539–2549 | Cite as

Zoledronic acid results in better health-related quality of life following hip fracture: the HORIZON–Recurrent Fracture Trial

  • J. D. Adachi
  • K. W. Lyles
  • C. S. Colón-Emeric
  • S. Boonen
  • C. F. Pieper
  • C. Mautalen
  • L. Hyldstrup
  • C. Recknor
  • L. Nordsletten
  • K. A. Moore
  • C. Bucci-Rechtweg
  • G. Su
  • E. F. Eriksen
  • J. S. Magaziner
Original Article

Abstract

Summary

This study evaluated the benefits of ZOL versus placebo on health-related quality of life (HRQoL) among patients from HORIZON–RFT. At month 24 and end of the study visit, ZOL significantly improved patients’ overall health state compared to placebo as assessed by the EQ-5D VAS.

Introduction

To evaluate the benefits of zoledronic acid (ZOL) versus placebo on health-related quality of life (HRQoL) among patients from The Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly Recurrent Fracture Trial (HORIZON–RFT).

Methods

In this randomized, double-blind, placebo-controlled trial, 2,127 patients were randomized to receive annual infusion of ZOL 5 mg (n = 1,065) or placebo (n = 1,062) within 90 days after surgical repair of low-trauma hip fracture. HRQoL was measured using EQ-5D Visual Analogue Scale (VAS) and utility scores (EuroQol instrument) at months 6, 12, 24, 36, and end of the study visit. Analysis of covariance model included baseline EQ-5D value, region, and treatment as explanatory variables.

Results

At baseline, patients (mean age 75 years; 24% men and 76% women) were well matched between treatment groups with mean EQ-5D VAS of 65.82 in ZOL and 65.70 in placebo group. At the end of the study, mean change from baseline in EQ-5D VAS was greater for ZOL vs. placebo in all patients (7.67 ± 0.56 vs. 5.42 ± 0.56), and in subgroups of patients experiencing clinical vertebral fractures (8.86 ± 4.91 vs. −1.69 ± 3.42), non-vertebral fractures (5.03 ± 2.48 vs. −1.07 ± 2.16), and clinical fractures (5.19 ± 2.25 vs. −0.72 ± 1.82) with treatment difference significantly in favor of ZOL. EQ-5D utility scores were comparable for ZOL and placebo groups, but more patients on placebo consistently had extreme difficulty in mobility (1.74% for ZOL vs. 2.13% for placebo; p = 0.6238), self-care (4.92% vs. 6.69%; p = 0.1013), and usual activities (10.28% vs. 12.91%; p = 0.0775).

Conclusion

ZOL significantly improves HRQoL in patients with low-trauma hip fracture.

Keywords

EQ-5D Health-related QoL Low-trauma hip fracture Zoledronic acid 

Notes

Acknowledgments

The authors thank Dr. Nandita Adhikary (Novartis Healthcare Pvt. Ltd.) for her assistance in writing the manuscript and incorporating authors’ comments into subsequent revisions. Dr. Boonen is a senior clinical investigator of the Fund for Scientific Research, Flanders, Belgium (F.W.O.-Vlaanderen) and holder of the Leuven University Chair in Gerontology and Geriatrics. This research was sponsored by Novartis Pharma AG, Basel, Switzerland.

Conflicts of interest

Dr. Adachi reports receiving consulting fees from Amgen, AstraZeneca, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Pfizer, Procter & Gamble, Roche, Sanofi-Aventis, and Servier and grant support from Amgen, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Pfizer, Procter & Gamble, and Roche.

Dr. Lyles, receiving grant support from Novartis, the Alliance for Better Bone Health (Sanofi-Aventis and Procter & Gamble), and Amgen, consulting fees from Novartis, Procter & Gamble, Merck, Amgen, GTx, GlaxoSmithKline, Eli Lilly, and Bone Medical, and being listed as an inventor on a U.S. patent application (20050272707) covering methods for preventing or reducing secondary fractures after hip fracture and on another provisional patent application for medication kits and formulations for preventing, treating, or reducing secondary fractures after a previous fracture.

Dr. Colón-Emeric, receiving consulting fees from Novartis, Amgen, and research grants from Novartis, Pfizer, and the Alliance for Better Bone Health.

Dr. Boonen, receiving consulting fees and research support from Novartis.

Dr. Pieper, receiving research support from Novartis.

Dr. Mautalen, receiving consulting and advisory board fees from Novartis.

Dr. Hyldstrup, receiving advisory board fees from Novartis, Eli Lilly, and Nycomed, lecture fees from Merck, Eli Lilly, Nycomed, Novartis, Novo Nordisk, and Servier, and grant support from Eli Lilly, Novartis, Pfizer, Nycomed, Roche, and GlaxoSmithKline.

Dr. Recknor, receiving consulting fees from Procter & Gamble, Roche, and Eli Lilly, lecture fees from Procter & Gamble, Eli Lilly, Roche, GlaxoSmithKline, Merck, and Aventis, and grant support from Procter & Gamble.

Dr. Nordsletten, receiving consulting and advisory board fees from Novartis and DePuy, lecture fees from Wyeth, and grant support from Biomet.

Dr. Bucci-Rechtweg and Dr. Su, being employees of and owning stock in Novartis.

Dr. Eriksen (now an employee of Oslo University, Oslo, Norway), being an employee of Novartis during the design and initiation of the study, and receiving advisory board fees from Novartis, Eli Lilly and Amgen.

Dr. Magaziner, receiving consulting fees from Amgen, Merck, Eli Lilly and Novartis, and grant support from Novartis and Merck.

Ms. Moore, no disclosures.

References

  1. 1.
    Adachi JD, Ioannidis G, Pickard L, Berger C, Prior JC, Joseph L, Hanley DA, Olszynski WP, Murray TM, Anastassiades T, Hopman W, Brown JP, Kirkland S, Joyce C, Papaioannou A, Poliquin S, Tenenhouse A, Papadimitropoulos EA (2003) The association between osteoporotic fractures and health-related quality of life as measured by the Health Utilities Index in the Canadian Multicentre Osteoporosis Study (CaMos). Osteoporos Int 14:895–904PubMedCrossRefGoogle Scholar
  2. 2.
    Papaioannou A, Kennedy CC, Ioannidis G, Sawka A, Hopman WM, Pickard L, Brown JP, Josse RG, Kaiser S, Anastassiades T, Goltzman D, Papadimitropoulos M, Tenenhouse A, Prior JC, Olszynski WP, Adachi JD (2009) The impact of incident fractures on health-related quality of life: 5 years of data from the Canadian Multicentre Osteoporosis Study. Osteoporos Int 20:703–714PubMedCrossRefGoogle Scholar
  3. 3.
    Oleksik AM, Ewing S, Shen W, van Schoor NM, Lips P (2005) Impact of incident vertebral fractures on health related quality of life (HRQOL) in postmenopausal women with prevalent vertebral fractures. Osteoporos Int 16:861–870PubMedCrossRefGoogle Scholar
  4. 4.
    Lips P, Jameson K, Bianchi ML, Goemaere S, Boonen S, Reeve J, Stepan J, Johnell O, van Schoor NM, Dennison E, Kanis JA, Cooper C (2009) Validation of the IOF quality of life questionnaire for patients with wrist fracture. Osteoporos Int 21:61–70PubMedCrossRefGoogle Scholar
  5. 5.
    Tosteson AN, Gabriel SE, Grove MR, Moncur MM, Kneeland TS, Melton LJ 3rd (2001) Impact of hip and vertebral fractures on quality-adjusted life years. Osteoporos Int 12:1042–1049PubMedCrossRefGoogle Scholar
  6. 6.
    Ioannidis G, Papaioannou A, Hopman WM, Akhtar-Danesh N, Anastassiades T, Pickard L, Kennedy CC, Prior JC, Olszynski WP, Davison KS, Goltzman D, Thabane L, Gafni A, Papadimitropoulos EA, Brown JP, Josse RG, Hanley DA, Adachi JD (2009) Relation between fractures and mortality: results from the Canadian Multicentre Osteoporosis Study. CMAJ 181:265–271PubMedCrossRefGoogle Scholar
  7. 7.
    Cummings SR, Melton LJ (2002) Epidemiology and outcomes of osteoporotic fractures. Lancet 359:1761–1767PubMedCrossRefGoogle Scholar
  8. 8.
    Boonen S, Autier P, Barette M, Vanderschueren D, Lips P, Haentjens P (2004) Functional outcome and quality of life following hip fracture in elderly women: a prospective controlled study. Osteoporos Int 15:87–94PubMedCrossRefGoogle Scholar
  9. 9.
    Haentjens P, Autier P, Barette M, Boonen S (2001) The economic cost of hip fractures among elderly women. A one-year, prospective, observational cohort study with matched-pair analysis. Belgian Hip Fracture Study Group. J Bone Joint Surg Am 83-A:493–500PubMedGoogle Scholar
  10. 10.
    Osnes EK, Lofthus CM, Meyer HE, Falch JA, Nordsletten L, Cappelen I, Kristiansen IS (2004) Consequences of hip fracture on activities of daily life and residential needs. Osteoporos Int 15:567–574PubMedCrossRefGoogle Scholar
  11. 11.
    Magaziner J, Hawkes W, Hebel JR, Zimmerman SI, Fox KM, Dolan M, Felsenthal G, Kenzora J (2000) Recovery from hip fracture in eight areas of function. J Gerontol A Biol Sci Med Sci 55:M498–M507PubMedCrossRefGoogle Scholar
  12. 12.
    Sawka AM, Thabane L, Papaioannou A, Gafni A, Ioannidis G, Papadimitropoulos EA, Hopman WM, Cranney A, Hanley DA, Pickard L, Adachi JD (2005) Health-related quality of life measurements in elderly Canadians with osteoporosis compared to other chronic medical conditions: a population-based study from the Canadian Multicentre Osteoporosis Study (CaMos). Osteoporos Int 16:1836–1840PubMedCrossRefGoogle Scholar
  13. 13.
    Papaioannou A, Kennedy CC, Ioannidis G, Brown JP, Pathak A, Hanley DA, Josse RG, Sebaldt RJ, Olszynski WP, Tenenhouse A, Murray TM, Petrie A, Goldsmith CH, Adachi JD (2006) Determinants of health-related quality of life in women with vertebral fractures. Osteoporos Int 17:355–363PubMedCrossRefGoogle Scholar
  14. 14.
    Silverman SL, Cranney A (1997) Quality of life measurement in osteoporosis. J Rheumatol 24:1218–1221PubMedGoogle Scholar
  15. 15.
    Silverman SL, Minshall ME, Shen W, Harper KD, Xie S (2001) The relationship of health-related quality of life to prevalent and incident vertebral fractures in postmenopausal women with osteoporosis: results from the Multiple Outcomes of Raloxifene Evaluation Study. Arthritis Rheum 44:2611–2619PubMedCrossRefGoogle Scholar
  16. 16.
    The EuroQol Group (1990) EuroQol—a new facility for the measurement of health-related quality of life. Health Policy 16:199–208CrossRefGoogle Scholar
  17. 17.
    Brooks R (1996) EuroQol: the current state of play. Health Policy 37:53–72PubMedCrossRefGoogle Scholar
  18. 18.
    Brazier JE, Walters SJ, Nicholl JP, Kohler B (1996) Using the SF-36 and Euroqol on an elderly population. Qual Life Res 5:195–204PubMedCrossRefGoogle Scholar
  19. 19.
    Dhillon V, Hurst N, Hannan J, Nuki G (2005) Association of low general health status, measured prospectively by Euroqol EQ5D, with osteoporosis, independent of a history of prior fracture. Osteoporos Int 16:483–489PubMedCrossRefGoogle Scholar
  20. 20.
    Lyles KW, Colon-Emeric CS, Magaziner JS, Adachi JD, Pieper CF, Mautalen C, Hyldstrup L, Recknor C, Nordsletten L, Moore KA, Lavecchia C, Zhang J, Mesenbrink P, Hodgson PK, Abrams K, Orloff JJ, Horowitz Z, Eriksen EF, Boonen S (2007) Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med 357:1799–1809PubMedCrossRefGoogle Scholar
  21. 21.
    Colon-Emeric CS, Caminis J, Suh TT, Pieper CF, Janning C, Magaziner J, Adachi J, Rosario-Jansen T, Mesenbrink P, Horowitz ZD, Lyles KW (2004) The HORIZON Recurrent Fracture Trial: design of a clinical trial in the prevention of subsequent fractures after low trauma hip fracture repair. Curr Med Res Opin 20:903–910PubMedCrossRefGoogle Scholar
  22. 22.
    Rosen CJ, Brown S (2003) Severe hypocalcemia after intravenous bisphosphonate therapy in occult vitamin D deficiency. N Engl J Med 348:1503–1504PubMedCrossRefGoogle Scholar
  23. 23.
    Guyatt GH, Feeny DH, Patrick DL (1993) Measuring health-related quality of life. Ann Intern Med 118:622–629PubMedGoogle Scholar
  24. 24.
    Dolan P (1997) Modeling valuations for EuroQol health states. Med Care 35:1095–1108PubMedCrossRefGoogle Scholar
  25. 25.
    Oleksik A, Lips P, Dawson A, Minshall ME, Shen W, Cooper C, Kanis J (2000) Health-related quality of life in postmenopausal women with low BMD with or without prevalent vertebral fractures. J Bone Miner Res 15:1384–1392PubMedCrossRefGoogle Scholar
  26. 26.
    Silverman SL, Piziak VK, Chen P, Misurski DA, Wagman RB (2005) Relationship of health related quality of life to prevalent and new or worsening back pain in postmenopausal women with osteoporosis. J Rheumatol 32:2405–2409PubMedGoogle Scholar
  27. 27.
    Meunier PJ, Roux C, Ortolani S, Diaz-Curiel M, Compston J, Marquis P, Cormier C, Isaia G, Badurski J, Wark JD, Collette J, Reginster JY (2009) Effects of long-term strontium ranelate treatment on vertebral fracture risk in postmenopausal women with osteoporosis. Osteoporos Int 20:1663–1673PubMedCrossRefGoogle Scholar
  28. 28.
    Marquis P, Cialdella P, De la Loge C (2001) Development and validation of a specific quality of life module in post-menopausal women with osteoporosis: the QUALIOST. Qual Life Res 10:555–566PubMedCrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2011

Authors and Affiliations

  • J. D. Adachi
    • 1
  • K. W. Lyles
    • 2
  • C. S. Colón-Emeric
    • 2
  • S. Boonen
    • 3
  • C. F. Pieper
    • 2
  • C. Mautalen
    • 4
  • L. Hyldstrup
    • 5
  • C. Recknor
    • 6
  • L. Nordsletten
    • 7
  • K. A. Moore
    • 2
  • C. Bucci-Rechtweg
    • 8
  • G. Su
    • 8
  • E. F. Eriksen
    • 9
  • J. S. Magaziner
    • 10
  1. 1.St. Joseph’s HealthcareMcMaster UniversityHamiltonCanada
  2. 2.Duke University Medical Center and the Geriatrics Research Education and Clinical Center, Veterans Affairs Medical CenterDurhamUSA
  3. 3.University of LeuvenLeuvenBelgium
  4. 4.Centro de Osteopatías MédicasBuenos AiresArgentina
  5. 5.Hvidovre HospitalHvidovreDenmark
  6. 6.United Osteoporosis CentersGainesvilleUSA
  7. 7.Ullevål University HospitalOsloNorway
  8. 8.Novartis Pharmaceuticals CorporationEast HanoverUSA
  9. 9.Oslo University Hospital AkerOsloNorway
  10. 10.University of MarylandBaltimoreUSA

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