Skip to main content
SpringerLink
Log in

Direct comparison of eight national FRAX® tools for fracture prediction and treatment qualification in Canadian women

  • Published:
Archives of Osteoporosis Aims and scope Submit manuscript

Abstract

Summary

We compared the calibration of FRAX tools from Canada, the US (white), UK, Sweden, France, Australia, New Zealand, and China when used to assess fracture risk in 36,730 Canadian women. Our data underscores the importance of applying country-specific FRAX tools that are based upon high-quality national fracture epidemiology.

Purpose

A FRAX® model for Canada was constructed for prediction of hip fracture and major osteoporotic fracture (MOF) using national hip fracture and mortality data. We examined the calibration of this model in Canadian women and compared it with seven other FRAX tools.

Methods

In women aged ≥50 years with baseline bone mineral density (BMD) measures identified from the Manitoba Bone Density Program, Canada (n = 36,730), 10-year fracture probabilities were calculated with and without BMD using selected country-specific FRAX tools. FRAX risk estimates were compared with observed fractures ≤10 years (506 hip, 2,380 MOF). Ten-year fracture risk was compared with predicted probabilities, and proportions exceeding specific treatment thresholds contrasted.

Results

For hip fracture prediction, good calibration was observed for FRAX Canada and most other country-specific FRAX tools, excepting Sweden (risk overestimated) and China (risk underestimated). For MOF prediction, greater between-country differences were seen; FRAX Sweden and FRAX China showed the largest over- and underestimation in this Canadian population. Relative to treatment qualification based upon FRAX Canada, treatment of high-hip fracture probability (≥3 %) was greater by FRAX Sweden (ratio 1.41 without and 1.55 with BMD), and markedly less by FRAX China (ratio 0.09 without and 0.11 with BMD). Greater between-country differences were observed for treat4ment of high MOF (≥20 %); FRAX Sweden again greatly increased (ratio 1.76 without and 1.83 with BMD), and FRAX China severely reduced treatment qualification (ratio 0.00 without and 0.01 with BMD).

Conclusions

The use of country-specific FRAX tools, accurately calibrated to the target population, is essential. Relatively small calibration differences can have large effects on high-risk categorization and treatment qualification.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Kanis JA, Oden A, Johansson H, Borgstrom F, Strom O, McCloskey E (2009) FRAX and its applications to clinical practice. Bone 44:734–743

    Article  PubMed  Google Scholar 

  2. Kanis JA et al (2002) International variations in hip fracture probabilities: implications for risk assessment. J Bone Miner Res 17:1237–1244

    Article  PubMed  Google Scholar 

  3. Steverberg EW (2008) Clinical prediction models: a practical approach to development, validation, and updating. Springer, New York

    Google Scholar 

  4. Ettinger B, Black DM, Dawson-Hughes B, Pressman AR, Melton LJ III (2010) Updated fracture incidence rates for the US version of FRAX. Osteoporos Int 21:25–33

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. CaMos Research Group, Fraser LA, Langsetmo L, Berger C, Ionnidis G, Goltzman D, Adachi JD, Papaoiannou A, Josse R, Kovacs CS, Olszynski WP, Towheed T, Hanley DA, Kaiser SM, Prior J, Jamal S, Kreiger N, Brown JP, Johansson H, Oden A, McCloskey E, Kanis JA, Leslie WD (2011) Fracture prediction and calibration of a Canadian FRAX tool: a population-based report from CaMos. Osteoporos Int 22:829–837

    Article  PubMed  Google Scholar 

  6. NOF (2013) Clinician's Guide to Prevention and Treatment of Osteoporosis. In. National Osteoporosis Foundation, Washington, DC. http://www.nof.org/files/nof/public/content/file/950/upload/523.pdf. Accessed 14 Jan 2013

  7. Dawson-Hughes B, Tosteson AN, Melton LJ III et al (2008) Implications of absolute fracture risk assessment for osteoporosis practice guidelines in the USA. Osteoporos Int 19:449–458

    Article  CAS  PubMed  Google Scholar 

  8. Dawson-Hughes B (2008) A revised clinician's guide to the prevention and treatment of osteoporosis. J Clin Endocrinol Metab 93:2463–2465

    Article  CAS  PubMed  Google Scholar 

  9. Leslie WD, Caetano PA, MacWilliam LR et al (2005) Construction and validation of a population-based bone densitometry database. J Clin Densitom 8:25–30

    Article  PubMed  Google Scholar 

  10. Roos NP, Shapiro E (1999) Revisiting the Manitoba Centre for Health Policy and Evaluation and its population-based health information system. Med Care 37:JS10–JS14

    CAS  PubMed  Google Scholar 

  11. Norwegian Institute of Public Health, World Health Organization, Collaborating Centre for Drug Statistics Methodology (2005) Guidelines for ATC classification and DDD assignment. Norwegian Institute of Public Health, WHO, Collaborating Centre for Drug Statistics Methodology, Oslo

    Google Scholar 

  12. Leslie WD, Lix LM, Johansson H, Oden A, McCloskey E, Kanis JA, Program MBD (2010) Independent clinical validation of a Canadian FRAX tool: fracture prediction and model calibration. J Bone Miner Res 25:2350–2358

    Article  PubMed  Google Scholar 

  13. Leslie WD, Majumdar SR, Lix LM, Johansson H, Oden A, McCloskey E, Kanis JA, Program MBD (2012) High fracture probability with FRAX usually indicates densitometric osteoporosis: implications for clinical practice. Osteoporos Int 23:391–397

    Article  CAS  PubMed  Google Scholar 

  14. Binkley N, Kiebzak GM, Lewiecki EM et al (2005) Recalculation of the NHANES database SD improves T score agreement and reduces osteoporosis prevalence. J Bone Miner Res 20:195–201

    Article  PubMed  Google Scholar 

  15. Kanis JA, McCloskey EV, Johansson H, Oden A, Melton LJ III (2008) A reference standard for the description of osteoporosis. Bone 42:467–475

    Article  CAS  PubMed  Google Scholar 

  16. Leslie WD, Lix LM, Wu X, Manitoba Bone Density Program (2013) Competing mortality and fracture risk assessment. Osteoporos Int 24(2):681–688

    Article  CAS  PubMed  Google Scholar 

  17. Leslie WD, Lix LM, Langsetmo L, Berger C, Goltzman D, Hanley DA, Adachi JD, Johansson H, Oden A, McCloskey E, Kanis JA (2011) Construction of a FRAX model for the assessment of fracture probability in Canada and implications for treatment. Osteoporos Int 22:817–827

    Article  CAS  PubMed  Google Scholar 

  18. Harris ST, Watts NB, Genant HK, McKeever CD, Hangartner T, Keller M, Chesnut CG III, Brown J, Eriksen EF, Hosevni MS, Axelrod DW, Miller PD (1999) Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral efficacy with risedronate therapy (VERT) study group. JAMA 282:1344–1352

    Article  CAS  PubMed  Google Scholar 

  19. Cranney A, Guyatt G, Griffith L, Wells G, Tugwell P, Rosen C (2002) Meta-analyses of therapies for postmenopausal osteoporosis, IX: summary of meta-analyses of therapies for postmenopausal osteoporosis. Endocr Rev 23:570–578

    Article  CAS  PubMed  Google Scholar 

  20. Goeree R, Blackhouse G, Adachi J (2006) Cost-effectiveness of alternative treatments for women with osteoporosis in Canada. Curr Med Res Opin 22:1425–1436

    Article  PubMed  Google Scholar 

  21. Siminoski K, Leslie WD, Frame H et al (2005) Recommendations for bone mineral density reporting in Canada. Can Assoc Radiol J 56:178–188

    PubMed  Google Scholar 

  22. Leslie WD, Lix LM, Program MBD (2011) Effects of FRAX model calibration on intervention rates: a simulation study. J Clin Densitom 14:272–278

    Article  PubMed  Google Scholar 

  23. Leslie WD, O'Donnell S, Lagace C, Walsh P, Bancej C, Jean S, Siminoski K, Kaiser S, Kendler DL, Jaglal S (2009) Population based Canadian hip fracture rates with international comparisons. Osteoporos Int 21:1317–1322

    Article  PubMed  Google Scholar 

  24. Lix LM, Azimaee M, Osman BA, Caetano P, Morin S, Metge C, Goltzman D, Kreiger N, Prior J, Leslie WD (2012) Osteoporosis-related fracture case definitions for population-based administrative data. BMC Publ Health 12:301

    Article  Google Scholar 

Download references

Acknowledgments

The authors are indebted to Manitoba Health for the provision of data (HIPC File No. 2007/2008-49). The results and conclusions are those of the authors, and no official endorsement by Manitoba Health is intended or should be inferred. This article has been reviewed and approved by the members of the Manitoba Bone Density Program Committee. SL Brennan is supported by a National Health and Medical Research Council of Australia Early Career Fellowship (1012472), and a Dyason Fellowship, The University of Melbourne.

Conflicts of interest

William D Leslie has served on advisory boards for Novartis, Amgen, Genzyme; received unrestricted research grants from Amgen; and received speaker fees from Amgen.

Eugene McCloskey has received speaker fees and/or unrestricted research grants from Novartis, Amgen, AstraZeneca, Pfizer, Bayer, Warner-Chilcott/Procter & Gamble, Lilly, Roche, Servier, and Hologic.

John A Kanis is associated with the following industries: Abiogen, Italy; Amgen, USA, Switzerland and Belgium; Bayer, Germany; Besins-Iscovesco, France; Biosintetica, Brazil; Boehringer Ingelheim, UK; Celtrix, USA; D3A, France; Gador, Argentina; General Electric, USA; GSK, UK, USA; Hologic, Belgium and USA; Kissei, Japan; Leiras, Finland; Leo Pharma, Denmark; Lilly, USA, Canada, Japan, Australia and UK; Merck Research Labs, USA; Merlin Ventures, UK; MRL, China; Novartis, Switzerland and USA; Novo Nordisk, Denmark; Nycomed, Norway; Ono, UK and Japan; Organon, Holland; Parke-Davis, USA; Pfizer USA; Pharmexa, Denmark; Procter and Gamble, UK, USA; ProStrakan, UK; Roche, Germany, Australia,Switzerland, USA; Rotta Research, Italy; Sanofi-Aventis, USA; Schering, Germany and Finland; Servier, France and UK; Shire, UK; Solvay, France and Germany; Strathmann, Germany; Tethys, USA; Teijin, Japan; Teva, Israel; UBS, Belgium; Unigene, USA; Warburg-Pincus, UK; Warner-Lambert, USA; Wyeth, USA. He is also associated with the following government organizations and NGOs: National Institute for Health and Clinical Excellence (NICE), UK; International Osteoporosis Foundation; National Osteoporosis Guideline Group (NOGG), UK; INSERM, France; Ministry of Public Health, China; Ministry of Health, Australia; National Osteoporosis Society (UK); WHO.

Helena Johansson is supported by ESCEO-AMGEN Osteoporosis Fellowship Award.

The rest of the authors have no competing interests.

Author information

Authors and Affiliations

  1. Department of Medicine (C5121), University of Manitoba, 409 Tache Avenue, St Boniface General Hospital, Winnipeg, R2H 2A6, Canada

    W. D. Leslie

  2. NorthWest Academic Centre, The University of Melbourne, Sunshine Hospital, 176 Furlong Road, St Albans, 3021, Australia

    S. L. Brennan

  3. Australian Institute for Musculoskeletal Sciences, 176 Furlong Road St Albans, Brimbank, 3021, Australia

    S. L. Brennan

  4. School of Medicine, Deakin University, Geelong, 3220, Australia

    S. L. Brennan

  5. WHO Collaborating Centre, University of Sheffield, Sheffield, UK

    L. M. Lix, H. Johansson, A. Oden, E. McCloskey & J. A. Kanis

Authors
  1. W. D. Leslie
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. L. Brennan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. M. Lix
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H. Johansson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. Oden
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. E. McCloskey
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J. A. Kanis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to W. D. Leslie.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Leslie, W.D., Brennan, S.L., Lix, L.M. et al. Direct comparison of eight national FRAX® tools for fracture prediction and treatment qualification in Canadian women. Arch Osteoporos 8, 145 (2013). https://doi.org/10.1007/s11657-013-0145-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11657-013-0145-0

Keywords

Search

Navigation