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Fracture prevention in patients with cognitive impairment presenting with a hip fracture: secondary analysis of data from the HORIZON Recurrent Fracture Trial

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Abstract

Summary

Patients with cognitive impairment (CI) often do not receive secondary fracture prevention. Use of zoledronic acid led to a similar reduction in re-fracture risk but the survival benefit was limited to those without CI.

Introduction

We tested whether the effects of zoledronic acid (Zol) on re-fracture and mortality differed in patients presenting with a hip fracture by cognitive status.

Methods

We used data from the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Recurrent Fracture Trial, of yearly intravenous 5 mg Zol vs. placebo in patients presenting with a hip fracture. Primary outcome was new fracture and secondary outcome mortality. Short Portable Mental Status Questionnaire (SPMSQ) with a cut-point of >2 was used to identify CI. Fine–Gray models for competing events were fitted to study the effect of Zol on re-fracture and Cox regression for death. A multiplicative term was introduced to study a potential interaction between treatment and cognitive status on outcomes.

Results

Baseline SPMSQ of 1,966/2,127 (92.4 %) patients was measured. Three hundred fifty (17.8 %) had CI, balanced between treatment arms. In the placebo arm, there was similar fracture incidence between those with and without CI (15.4 vs. 12.3 %, p = 0.26). There was no significant interaction for the effect of CI on Zol and re-fracture (p = 0.66). CI was associated with higher 1-year mortality (12.6 vs. 4.3 %, p < 0.001) and the interaction was bordering significance (interaction, p = 0.066). Zol prolonged survival only in patients with normal cognitive status [HR 0.56 (95 % CI 0.40–0.80)] and not in those with CI [HR 0.90 (95 % CI 0.59–1.38)].

Conclusions

While these results require confirmation, the findings support the use of bisphosphonates in patients with osteoporotic fracture and CI expected to live for more than 6 months.

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References

  1. Ström O, Borgström F, Kanis J, Compston J, Cooper C, McCloskey E, Jönsson B (2011) Osteoporosis: burden, health care provision and opportunities in the EU: a report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Arch Osteoporos 6(1–2):59–155

    Article  PubMed  Google Scholar 

  2. Marsh D, Akesson K, Beaton DE, Bogoch ER, Boonen S, Brandi ML, McLellan AR, Mitchell PJ, Sale JE, Wahl DA (2011) Coordinator-based systems for secondary prevention in fragility fracture patients. Osteoporos Int 22:2051–2065

    Article  CAS  PubMed  Google Scholar 

  3. Lloyd BD, Williamson DA, Singh NA, Hansen RD, Diamond TH, Finnegan TP, Allen BJ, Grady JN, Stavrinos TM, Smith EU, Diwan AD, Fiatarone Singh MA (2009) Recurrent and injurious falls in the year following hip fracture: a prospective study of incidence and risk factors from the Sarcopenia and Hip Fracture study. J Gerontol A Biol Sci Med Sci 64:599–609

    Article  PubMed  Google Scholar 

  4. Beringer TR, Clarke J, Elliott JR, Marsh DR, Heyburn G, Steele IC (2006) Outcome following proximal femoral fracture in Northern Ireland. Ulster Med J 75:200–206

    CAS  PubMed Central  PubMed  Google Scholar 

  5. Curtis JR, Arora T, Matthews RS, Taylor A, Becker DJ, Colon-Emeric C, Kilgore ML, Morrisey MA, Saag KG, Safford MM, Warriner A, Delzell E (2010) Is withholding osteoporosis medication after fracture sometimes rational? A comparison of the risk for second fracture versus death. J Am Med Dir Assoc 11:584–591

    Article  PubMed Central  PubMed  Google Scholar 

  6. Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, Cosman F, Lakatos P, Leung PC, Man Z, Mautalen C, Mesenbrink P, Hu H, Caminis J, Tong K, Rosario-Jansen T, Krasnow J, Hue TF, Sellmeyer D, Eriksen EF, Cummings SR (2007) Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 356:1809–1822

    Article  CAS  PubMed  Google Scholar 

  7. Vik SA, Jantzi M, Poss J, Hirdes J, Hanley DA, Hogan DB, Maxwell CJ (2007) Factors associated with pharmacologic treatment of osteoporosis in an older home care population. J Gerontol A Biol Sci Med Sci 62:872–878

    Article  PubMed  Google Scholar 

  8. Haasum Y, Fastbom J, Fratiglioni L, Johnell K (2012) Undertreatment of osteoporosis in persons with dementia? A population-based study. Osteoporos Int 23:1061–1068

    Article  CAS  PubMed  Google Scholar 

  9. 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 357:1799–1809

    Article  CAS  PubMed  Google Scholar 

  10. Pfeiffer E (1975) A short portable mental status questionnaire for the assessment of organic brain deficit in elderly patients. J Am Geriatr Soc 23:433–441

    CAS  PubMed  Google Scholar 

  11. Erkinjuntti T, Sulkava R, Wikstrom J, Autio L (1987) Short Portable Mental Status Questionnaire as a screening test for dementia and delirium among the elderly. J Am Geriatr Soc 35:412–416

    CAS  PubMed  Google Scholar 

  12. Berry SD, Ngo L, Samelson EJ, Kiel DP (2010) Competing risk of death: an important consideration in studies of older adults. J Am Geriatr Soc 58:783–787

    Article  PubMed Central  PubMed  Google Scholar 

  13. Fine JP, Gray RJ (1999) A proportional hazards model for the subdistributions of a competing risk. J Am Stat Assoc 94:496–509

    Article  Google Scholar 

  14. Altman DG, Bland JM (2003) Interaction revisited: the difference between two estimates. BMJ 326:219

    Article  PubMed  Google Scholar 

  15. Sun X, Briel M, Walter SD, Guyatt GH (2010) Is a subgroup effect believable? Updating criteria to evaluate the credibility of subgroup analyses. BMJ 340:c117

    Article  PubMed  Google Scholar 

  16. Leslie WD, Lix LM, Wu X (2012) Competing mortality and fracture risk assessment. Osteoporos Int 24:681–688

    Article  PubMed  Google Scholar 

  17. Tinetti ME, Kumar C (2010) The patient who falls: “It’s always a trade-off”. JAMA 303:258–266

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Gertz BJ, Holland SD, Kline WF, Matuszewski BK, Freeman A, Quan H, Lasseter KC, Mucklow JC, Porras AG (1995) Studies of the oral bioavailability of alendronate. Clin Pharmacol Ther 58:288–298

    Article  CAS  PubMed  Google Scholar 

  19. Ensberg MD, Paletta MJ, Galecki AT, Dacko CL, Fries BE (1993) Identifying elderly patients for early discharge after hospitalization for hip fracture. J Gerontol 48:M187–195

    Article  CAS  PubMed  Google Scholar 

  20. Heruti RJ, Lusky A, Barell V, Ohry A, Adunsky A (1999) Cognitive status at admission: does it affect the rehabilitation outcome of elderly patients with hip fracture? Arch Phys Med Rehabil 80:432–436

    Article  CAS  PubMed  Google Scholar 

  21. Cree M, Carriere KC, Soskolne CL, Suarez-Almazor M (2001) Functional dependence after hip fracture. Am J Phys Med Rehabil 80:736–743

    Article  CAS  PubMed  Google Scholar 

  22. Hirose J, Ide J, Yakushiji T, Abe Y, Nishida K, Maeda S, Anraku Y, Usuku K, Mizuta H (2010) Prediction of postoperative ambulatory status 1 year after hip fracture surgery. Arch Phys Med Rehabil 91:67–72

    Article  PubMed  Google Scholar 

  23. Ceder L, Elmqvist D, Svensson SE (1981) Cardiovascular and neurological function in elderly patients sustaining a fracture of the neck of the femur. J Bone Joint Surg Br 63B:560–566

    CAS  PubMed  Google Scholar 

  24. Wood DJ, Ions GK, Quinby JM, Gale DW, Stevens J (1992) Factors which influence mortality after subcapital hip fracture. J Bone Joint Surg Br 74:199–202

    CAS  PubMed  Google Scholar 

  25. Evans JG, Prudham D, Wandless I (1979) A prospective study of fractured proximal femur: factors predisposing to survival. Age Ageing 8:246–250

    Article  CAS  PubMed  Google Scholar 

  26. Maxwell MJ, Moran CG, Moppett IK (2008) Development and validation of a preoperative scoring system to predict 30 day mortality in patients undergoing hip fracture surgery. Br J Anaesth 101:511–517

    Article  CAS  PubMed  Google Scholar 

  27. Wiles MD, Moran CG, Sahota O, Moppett IK (2011) Nottingham Hip Fracture Score as a predictor of one year mortality in patients undergoing surgical repair of fractured neck of femur. Br J Anaesth 106(4):501–504

    Article  CAS  PubMed  Google Scholar 

  28. Currie C, Partridge M, Plant F, Roberts J, Wakeman R, Williams A (2011) The National Hip Fracture Database National Report 2011. In Partnership HQI (ed).

  29. Sato Y, Kanoko T, Satoh K, Iwamoto J (2005) The prevention of hip fracture with risedronate and ergocalciferol plus calcium supplementation in elderly women with Alzheimer disease: a randomized controlled trial. Arch Intern Med 165:1737–1742

    Article  PubMed  Google Scholar 

  30. Halbekath JM, Schenk S, von Maxen A, Meyer G, Muhlhauser I (2007) Risedronate for the prevention of hip fractures: concern about validity of trials. Arch Intern Med 167:513–514, author reply 514–515

    PubMed  Google Scholar 

  31. Colon-Emeric CS, Mesenbrink P, Lyles KW, Pieper CF, Boonen S, Delmas P, Eriksen EF, Magaziner J (2010) Potential mediators of the mortality reduction with zoledronic acid after hip fracture. J Bone Miner Res 25:91–97

    Article  CAS  PubMed  Google Scholar 

  32. Sun X, Briel M, Busse JW, You JJ, Akl EA, Mejza F, Bala MM, Bassler D, Mertz D, Diaz-Granados N, Vandvik PO, Malaga G, Srinathan SK, Dahm P, Johnston BC, Alonso-Coello P, Hassouneh B, Walter SD, Heels-Ansdell D, Bhatnagar N, Altman DG, Guyatt GH (2012) Credibility of claims of subgroup effects in randomised controlled trials: systematic review. BMJ 344:e1553

    Article  PubMed  Google Scholar 

  33. Oxman AD (2012) Subgroup analyses. BMJ 344:e2022

    Article  PubMed  Google Scholar 

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Acknowledgments

We wish to thank the patients, carers and research staff involved in the original trial and Professor A Munoz for his advice on competing risk models.

Conflicts of interest

All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare that: (1) DPA and AJ have no conflicts of interest to declare; (2) MKJ, NKA and CC have received honorarium, advisory boards and consortium research grants, respectively, from Novartis, Alliance for Better Health and Lilly; Merck, MSD, Roche, Novartis, Smith and Nephew, Q-MED, Nicox, Servier, GSK, Schering-Plough, Pfizer and Rottapharm; and Alliance for Better Bone Health, Amgen, Novartis, MSD, Servier, Eli Lilly and GSK; (3) Dr. Lyles reports 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 US 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; and (4) their spouses, partners, or children have no financial relationships that may be relevant to the submitted work.

Funding

While the parent study was sponsored by Novartis Pharmaceuticals Corporation and Novartis Pharma AG, the origination of the research question, statistical methodology, analysis and interpretation of the data, and authoring of the manuscript were performed independently by the Oxford NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, UK. The pre-submission manuscript was sent to Novartis Pharmaceuticals Corporation for comment.

Ethics approval

Informed consent was obtained from subjects, and investigations were approved by an institutional human research committee. The study was conducted according to the ethical principles of the 1989 Declaration of Helsinki and local applicable laws and regulations.

Author information

Authors and Affiliations

  1. Oxford NIHR Musculoskeletal Biomedical Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Windmill Road, Headington, OX, OX3 7LD, UK

    D. Prieto-Alhambra, A. Judge, N. K. Arden, C. Cooper & M. K. Javaid

  2. Institut Catala de la Salut, Barcelona, Spain

    D. Prieto-Alhambra & C. Cooper

  3. URFOA-IMIM, Parc de Salut Mar, Barcelona, Spain

    D. Prieto-Alhambra

  4. Medicine Department, Universitat Autonoma de Barcelona, Barcelona, Spain

    D. Prieto-Alhambra

  5. IDIAP Jordi Gol (Primary Care Research Institute), Barcelona, Spain

    D. Prieto-Alhambra

  6. MRC Lifecourse Epidemiology Unit, Southampton General Hospital, University of Southampton, Southampton, SO16 6YD, UK

    D. Prieto-Alhambra, A. Judge, N. K. Arden, C. Cooper & M. K. Javaid

  7. Duke University and VA Medical Centers, Durham, NC, 27705, USA

    K. W. Lyles

  8. The Carolinas Center for Medical Excellence, Cary, NC, 27518, USA

    K. W. Lyles

  9. The Botnar Research Centre Institute of Musculoskeletal Sciences, Nuffield Orthopaedic Centre, Windmill Road, OX3 7LD, Oxford, UK

    M. K. Javaid

Authors
  1. D. Prieto-Alhambra
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  2. A. Judge
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  3. N. K. Arden
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  4. C. Cooper
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  5. K. W. Lyles
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  6. M. K. Javaid
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Corresponding author

Correspondence to M. K. Javaid.

Additional information

Trial registration

clinicaltrials.gov number NCT00046254

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Prieto-Alhambra, D., Judge, A., Arden, N.K. et al. Fracture prevention in patients with cognitive impairment presenting with a hip fracture: secondary analysis of data from the HORIZON Recurrent Fracture Trial. Osteoporos Int 25, 77–83 (2014). https://doi.org/10.1007/s00198-013-2420-8

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  • DOI: https://doi.org/10.1007/s00198-013-2420-8

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