Skip to main content
SpringerLink
Log in

Adjusting conventional FRAX estimates of fracture probability according to the recency of sentinel fractures

  • Position Paper
  • Published:
Osteoporosis International Aims and scope Submit manuscript

Abstract

Summary

The risk of a recurrent fragility fracture is particularly high immediately following the fracture. This study provides adjustments to FRAX-based fracture probabilities accounting for the site of a recent fracture.

Introduction

The recency of prior fractures affects subsequent fracture risk. The aim of this study was to quantify the effect of a recent sentinel fracture, by site, on the 10-year probability of fracture determined with FRAX.

Methods

The study used data from the Reykjavik Study fracture register that documented prospectively all fractures at all skeletal sites in a large sample of the population of Iceland. Fracture probabilities were determined after a sentinel fracture (humeral, clinical vertebral, forearm and hip fracture) from the hazards of death and fracture. Fracture probabilities were computed on the one hand for sentinel fractures occurring within the previous 2 years and on the other hand, probabilities for a prior osteoporotic fracture irrespective of recency. The probability ratios provided adjustments to conventional FRAX estimates of fracture probability for recent sentinel fractures.

Results

Probability ratios to adjust 10-year FRAX probabilities of a major osteoporotic fracture for recent sentinel fractures were age dependent, decreasing with age in both men and women. Probability ratios varied according to the site of sentinel fracture with higher ratios for hip and vertebral fracture than for humerus or forearm fracture. Probability ratios to adjust 10-year FRAX probabilities of a hip fracture for recent sentinel fractures were also age dependent, decreasing with age in both men and women with the exception of forearm fractures.

Conclusion

The probability ratios provide adjustments to conventional FRAX estimates of fracture probability for recent sentinel fractures.

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
Fig. 3

Similar content being viewed by others

References

  1. Kanis JA on behalf of the World Health Organization Scientific Group (2008a) Assessment of osteoporosis at the primary health-care level. Technical report. WHO Collaborating Centre, University of Sheffield, UK. Available at http://www.shef.ac.uk/FRAX/index.htm. Accessed 25 March 2020

  2. Kanis JA, Johnell O, Oden A, Johansson H, McCloskey EV (2008b) FRAX™ and the assessment of fracture probability in men and women from the UK. Osteoporos Int 19:385–397

    PubMed  PubMed Central  CAS  Google Scholar 

  3. Kanis JA, Odén A, McCloskey EV, Johansson H, Wahl D, Cyrus Cooper C, on behalf of the IOF Working Group on Epidemiology and Quality of Life (2012) A systematic review of hip fracture incidence and probability of fracture worldwide. Osteoporos Int 23:2239–2256

    PubMed  PubMed Central  CAS  Google Scholar 

  4. Kanis JA, Johansson H, Oden A, Cooper C, McCloskey EV, the Epidemiology and Quality of Life Working Group of IOF (2014) Worldwide uptake of FRAX. Arch Osteoporos 9:166. https://doi.org/10.1007/s11657-013-0166-8

    Article  PubMed  CAS  Google Scholar 

  5. National Institute for Health and Care Excellence (2012) CG146: osteoporosis: fragility fracture risk. Short clinical guideline- evidence and recommendation. National Clinical Guideline Centre, London

    Google Scholar 

  6. National Institute for Health and Care Excellence (2017) TA 464: bisphosphonates for treating osteoporosis. Technology appraisal guidance 464. National Institute for Health and Care Excellence, London nice.org.uk/guidance/ta464. Accessed 25 March 2020

  7. Kanis JA, Cooper C, Rizzoli R, Reginster J-Y, Scientific Advisory Board of the European Society for Clinical and Economic Aspects of Osteoporosis (ESCEO) and the Committees of Scientific Advisors and National Societies of the International Osteoporosis Foundation (IOF) (2019) European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 30:3–44

    CAS  PubMed  Google Scholar 

  8. Committee for Medicinal Products for Human Use (CHMP) (2006) Guideline on the evaluation of medicinal products in the treatment of primary osteoporosis. CHMP, London

    Google Scholar 

  9. Klotzbuecher CM, Ross PD, Landsman PB, Abbott TA 3rd, Berger M (2000) Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis. J Bone Miner Res 15:721–739

    PubMed  CAS  Google Scholar 

  10. Haentjens P, Johnell O, Kanis JA, Bouillon R, Cooper C, Lamraski G, Vanderschuren D, Kauffman J-M, Boonen S (2004) Gender-related differences in short and long-term absolute risk of hip fracture after Colles’ or spine fracture: Colles’ fracture as an early and sensitive marker of skeletal fragility in men. J Bone Miner Res 19:1933–1944

    PubMed  Google Scholar 

  11. Johnell O, Kanis JA, Oden A, Sernbo I, Redlund-Johnell I, Pettersen C, De Laet C, Jonsson B (2004) Fracture risk following an osteoporotic fracture. Osteoporos Int 15:175–179

    PubMed  CAS  Google Scholar 

  12. Kanis JA, Johnell O, De Laet C, Johansson H, Oden A, Delmas P, Eisman J, Fujiwara S, Garnero P, Kroger H, McCloskey EV, Mellstrom D, Melton LJ III, Pols H, Reeve J, Silman A, Tenenhouse A (2004) A meta-analysis of previous fracture and subsequent fracture risk. Bone 35:375–382

    PubMed  CAS  Google Scholar 

  13. Hansen L, Petersen KD, Eriksen SA, Langdahl BL, Eiken PA, Brixen K, Abrahamsen B, Jensen JE, Harslof T, Vestergaard P (2015) Subsequent fracture rates in a nationwide population-based cohort study with a 10-year perspective. Osteoporos Int 26:513–519

    PubMed  CAS  Google Scholar 

  14. Johnell O, Oden A, Caulin F, Kanis JA (2001) Acute and long-term increase in fracture risk after hospitalization for vertebral fracture. Osteoporos Int 12:207–214

    PubMed  CAS  Google Scholar 

  15. Giangregorio LM, Leslie WD (2010) Manitoba bone density program. Time since prior fracture is a risk modifier for 10-year osteoporotic fractures. J Bone Miner Res 25:1400–1405

    PubMed  Google Scholar 

  16. Dretakis KE, Dretakis EK, Papakitsou EF, Psarakis S, Steriopoulos K (1998) Possible predisposing factors for the second hip fracture. Calcif Tissue Int 62:366–369

    PubMed  CAS  Google Scholar 

  17. Nymark T, Lauritsen JM, Ovesen O, Röck ND, Jeune B (2006) Short time-frame from first to second hip fracture in the Funen County Hip Fracture Study. Osteoporos Int 17(9):1353–1357

    PubMed  CAS  Google Scholar 

  18. Lindsay R, Silverman SL, Cooper C, Hanley DA, Barton I, Broy SB, Licata A, Benhamou L, Geusens P, Flowers K, Stracke H, Seeman E (2001) Risk of new vertebral fracture in the year following a fracture. JAMA 285:320–323

    PubMed  CAS  Google Scholar 

  19. Ryg J, Rejnmark L, Overgaard S, Brixen K, Vestergaard P (2009) Hip fracture patients at risk of second hip fracture: a nationwide population-based cohort study of 169,145 cases during 1977-2001. J Bone Miner Res 24:1299–1307

    PubMed  Google Scholar 

  20. van Geel TACM, van Helden S, Geusens PP, Winkens B, Dinant G-J (2016) Clinical subsequent fractures cluster in time after first fractures. Ann Rheum Dis 68:99–102

    Google Scholar 

  21. Johansson H, Siggeirsdóttir K, Harvey NC, Odén A, Gudnason V, McCloskey E, Sigurdsson G, Kanis JA (2017) Imminent risk of fracture after fracture. Osteoporos Int 28:775–780

    PubMed  CAS  Google Scholar 

  22. Kanis JA, Harvey NC, McCloskey E, Bruyère O, Veronese N, Lorentzon M, Cooper C, Rizzoli R, Adib G, Al-Daghri N, Campusano C, Chandran M, Dawson-Hughes B, Javaid K, Jiwa F, Johansson H, Lee JK, Liu E, Messina D, Mkinsi O, Pinto D, Prieto-Alhambra D, Saag K, Xia W, Zakraoui L, Reginster J-Y (2020) Algorithm for the management of patients at low/middle/high risk of osteoporotic fracture: a global perspective. Osteoporos Int 31:1–12

    PubMed  CAS  Google Scholar 

  23. Bjornsson G, Bjornsson OJ, Davidsson D et al (1982) Report abc XXIV. Health survey in the Reykjavik Area. – Women. Stages I-III, 1968–1969, 1971–1972 and 1976-1978. Participants, invitation, response etc. The Icelandic Heart Association, Reykjavík

  24. Bjornsson OJ, Davidsson. D., Olafsson H et al (1979) Report XVIII. Health Survey in the Reykjavik Area. — Men. Stages I–III, 1967–1968, 1970–1971 and 1974–1975. Participants, invitation, response etc. The Icelandic Heart Association, Reykjavík

  25. Kanis JA, Oden A, Johnell O, Jonsson B, de Laet C, Dawson A (2001) The burden of osteoporotic fractures: a method for setting intervention thresholds. Osteoporos Int 12:417–427

    PubMed  CAS  Google Scholar 

  26. Siggeirsdottir K, Aspelund T, Sigurdsson G, Mogensen B, Chang M, Jonsdottir B, Eiriksdottir G, Launer LJ, Harris TB, Jonsson BY, Gudnason V (2007) Inaccuracy in self-report of fractures may underestimate association with health outcomes when compared with medical record based fracture registry. Eur J Epidemiol 22:631–639

    PubMed  Google Scholar 

  27. Breslow NE, Day NE (1987) Statistical methods in cancer research, vol 2. IARC scientific publications, no 32, Lyon, pp 131–135

    Google Scholar 

  28. Albertsson-Wikland K, Martensson A, Savendahl L, Niklasson A, Bang P, Dahlgren J, Gustafsson J, Kriström B, Norgren S, Pehrsson NG, Odén A (2016) Mortality is not increased in recombinant human growth hormone-treated patients when adjusting for birth characteristics. J Clin Endocrinol Metab 101:2149–2159

    PubMed  CAS  Google Scholar 

  29. Kanis JA, Johnell O, Oden A, Sernbo I, Redlund-Johnell I, Dawson A, de Laet C, Jonsson B (2000) Long-term risk of osteoporotic fractures in Malmo. Osteoporisis Int 11:669–674

    CAS  Google Scholar 

  30. Kanis JA, Johnell O, De Laet C, Jonsson B, Oden A, Oglesby A (2002) International variations in hip fracture probabilities: implications for risk assessment. J Bone Mineral Res 17:1237–1244

    Google Scholar 

  31. United Nations (2019) Department of Economic and Social Affairs. World Population Prospects 2019 https://populationunorg/wpp/Download/Standard/Population/ accessed 15 Feb 2020

  32. Johansson H, Kanis JA, Ode’n A, Johnell O, McCloskey E (2009) BMD, clinical risk factors and their combination for hip fracture prevention. Osteoporos Int 20:1675–1682

    PubMed  CAS  Google Scholar 

  33. Kanis JA, Oden A, Johnell O, Johansson H, De Laet C, Brown J, Burckhardt P, Cooper C, Christiansen C, Cummings S, Eisman JA, Fujiwara S, Gluer C, Goltzman D, Hans D, Krieg MA, La Croix A, McCloskey E, Mellstrom D, Melton LJ 3rd, Pols H, Reeve J, Sanders K, Schott AM, Silman A, Torgerson D, van Staa T, Watts NB, Yoshimura N (2007) The use of clinical risk factors enhances the performance of BMD in the prediction of hip and osteoporotic fractures in men and women. Osteoporos Int 18:1033–1046

    PubMed  CAS  Google Scholar 

  34. Sekikawa A, Steingrimsdottir L, Ueshima H, Shin C, Curb JD, Evans RW, Hauksdottir AM, Kadota A, Choo J, Masaki K, Thorsson B, Launer LJ, Garcia ME, Maegawa H, Willcox BJ, Eiriksdottir G, Fujiyoshi A, Miura K, Harris TB, Kuller LH, Gudnason V (2012) Serum levels of marine-derived n-3 fatty acids in Icelanders, Japanese, Koreans, and Americans--a descriptive epidemiologic study. Prostaglandins Leukot Essent Fatty Acids 87:11–16

    PubMed  PubMed Central  CAS  Google Scholar 

  35. Kanis JA, Johansson H, Odén A, McCloskey EV (2012b) The distribution of FRAX® based probabilities in women from Japan. J Bone Miner Metab 30:700–705

    PubMed  Google Scholar 

  36. Dawson-Hughes B, Looker AC, Tosteson ANA, Johansson H, Kanis JA, Melton LJ III (2010) The potential impact of new National Osteoporosis Foundation guidance on treatment patterns. Osteoporos Int 21:41–52

    PubMed  CAS  Google Scholar 

  37. Johansson H, Kanis JA, Oden A, Compston J, McCloskey E (2012) A comparison of case-finding strategies in the UK for the management of hip fractures. Osteoporos Int 23:907–915

    PubMed  CAS  Google Scholar 

  38. Thordardottir M, Lindqvist EK, Lund SH et al (2018) Dietary intake is associated with risk of multiple myeloma and its precursor disease. PLoS One 13(11):e0206047. https://doi.org/10.1371/journal.pone.0206047

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Kanis JA, Oden A, Johnell O, De Laet C, Jonsson B, Oglesby AK (2003) The components of excess mortality after hip fracture. Bone 32:468–473

    PubMed  CAS  Google Scholar 

  40. Kanis JA, Oden A, Johnell O, De Laet C, Jonsson B (2004) Excess mortality after hospitalisation for vertebral fractures. Osteoporos Int 15:108–112

    PubMed  Google Scholar 

  41. Johnell O, Kanis JA, Oden A, Sernbo I, Redlund-Johnell I, Pettersen C, De Laet C, Jonsson B (2004) Mortality after osteoporotic fractures. Osteoporos Int 15:38–42

    PubMed  CAS  Google Scholar 

  42. Kanis JA, Harvey NC, Cooper C, Johansson H, Odén A, McCloskey EV (2016) A systematic review of intervention thresholds based on FRAX. Arch Osteoporos 11(1):25

    PubMed  PubMed Central  Google Scholar 

  43. Chakhtoura M, Baddoura R , El-Hajj Fuleihan G (2013) Lebanese FRAX-based osteoporosis guidelines. http://www.osteos.org.lb/admin/uploads/Full%20document.pdf accessed 19 Oct 2015

  44. Siris ES, Adler R, Bilezikian J, Bolognese M, Dawson-Hughes B, Favus MJ, Harris ST, Jan de Beur SM, Khosla S, Lane NE, Lindsay R, Nana AD, Orwoll ES, Saag K, Silverman S, Watts NB (2014) The clinical diagnosis of osteoporosis: a position statement from the National Bone Health Alliance Working Group. Osteoporos Int 25:1439–1443

    PubMed  PubMed Central  CAS  Google Scholar 

  45. Cosman F, de Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S, Lindsay R (2014) Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int 25:2359–2381

    PubMed  PubMed Central  CAS  Google Scholar 

  46. Papaioannou A, Morin S, Cheung AM, Atkinson S, Brown JP, Feldman S, Hanley DA, Hodsman A, Jamal SA, Kaiser SM, Kvern B, Siminoski K, Leslie WD, Scientific Advisory Council of Osteoporosis Canada (2010) 2010 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary. CMAJ 182:1864–1873

    PubMed  PubMed Central  Google Scholar 

  47. Scottish Intercollegiate Guidelines Network (SIGN) (2015) Management of osteoporosis and the prevention of fragility fractures. Edinburgh: SIGN; 2015 (SIGN publication no 142)[March 2015] Available from URL: http://wwwsignacuk accessed 11 May 2015

  48. Agency for care effectiveness (2018) Osteoporosis – identification and management in primary care. Available at http://wwwace-htagovsg/our-guidance/osteoporosis-identification-and-management-in-primary-carehtml Accessed 22 Dec 2019

  49. Cosman F, Nieves JW, Dempster DW (2017) Treatment sequence matters: anabolic and antiresorptive therapy for osteoporosis. J Bone Miner Res 32:198–202

    PubMed  CAS  Google Scholar 

  50. Saag KG, Petersen J, Brandi ML, Karaplis AC, Lorentzon M, Thomas T, Maddox J, Fan M, Meisner PD, Grauer A (2017) Romosozumab or alendronate for fracture prevention in women with osteoporosis. N Engl J Med 377:1417–1427

    PubMed  CAS  Google Scholar 

  51. Kendler DL, Marin F, Zerbini CAF, Russo LA, Greenspan SL, Zikan V, Bagur A, Malouf-Sierra J, Lakatos P, Fahrleitner-Pammer A, Lespessailles E, Minisola S, Body JJ, Geusens P, Möricke R, López-Romero P (2018) Effects of teriparatide and risedronate on new fractures in post-menopausal women with severe osteoporosis (VERO): a multicentre, double-blind, double-dummy, randomised controlled trial. Lancet 391:230–240

    PubMed  CAS  Google Scholar 

  52. Parsons CM, Harvey N, Shepstone L, Kanis JA, Lenaghan E, Clarke S, Fordham R, Gittoes N, Harvey I, Holland R, Redmond NM, Howe A, Marshall T, Peters TJ, Torgerson D, O'Neill TW, McCloskey E, Cooper C, SCOOP Trial Group (2020) Systematic screening using FRAX leads to increased use of, and adherence to, anti-osteoporosis medications: the Uk SCOOP Trial. Osteoporosis Int 2018 31:67–75

    CAS  Google Scholar 

Download references

Acknowledgements

We thank the participants in the Reykjavik Study for their valuable contribution. We are particularly grateful to the Committee of Scientific Advisors and the Committee of National Societies of the International Osteoporosis Foundation for their review, constructive comments and endorsement of this position paper.

Author information

Authors and Affiliations

  1. Mary McKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia

    J. A. Kanis, H. Johansson, M. Lorentzon, E. Liu & L. Vandenput

  2. Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Beech Hill Road, Sheffield, S10 2RX, UK

    J. A. Kanis, H. Johansson & E. V. McCloskey

  3. MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK

    N. C. Harvey

  4. NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK

    N. C. Harvey

  5. Icelandic Heart Association Research Institute, Kopavogur, Iceland

    V. Gudnason, G. Sigurdsson & K. Siggeirsdottir

  6. University of Iceland, Reykjavik, Iceland

    V. Gudnason

  7. Geriatric Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden

    M. Lorentzon

  8. Department of Internal Medicine and Clinical Nutrition, Institute of Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

    L. Vandenput

  9. Mellanby Centre for bone research, Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK

    E. V. McCloskey

Authors
  1. J. A. Kanis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. Johansson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N. C. Harvey
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. V. Gudnason
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G. Sigurdsson
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. K. Siggeirsdottir
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M. Lorentzon
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. E. Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. L. Vandenput
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. E. V. McCloskey
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. A. Kanis.

Ethics declarations

The study was approved by the National Bioethics Committee and the Data Protection Authority in Iceland. All participants gave informed written consent.

Conflicts of interest

V Gudnason, G Sigurdsson, K Siggeirsdottir, E Liu, L Vandenput and H Johansson have no competing interests to declare.

N. Harvey has received consultancy, lecture fees and honoraria from Alliance for Better Bone Health, AMGEN, MSD, Eli Lilly, Servier, Shire, UCB, Kyowa Kirin, Consilient Healthcare, Radius Health and Internis Pharma.

EV McCloskey has received consultancy/lecture fees/grant funding/honoraria from AgNovos, Amgen, AstraZeneca, Consilient Healthcare, Fresenius Kabi, Gilead, GSK, Hologic, Internis, Lilly, Merck, Novartis, Pfizer, Radius Health, Redx Oncology, Roche, SanofiAventis, Servier, Synexus, UCB, Viiv, Warner Chilcott, I3 Innovus and Unilever.

JA Kanis reports grants from Amgen, Eli Lilly and Radius Health and consulting fees from Theramex. JAK is the architect of FRAX® but has no financial interest.

M Lorentzon has received lecture fees from Amgen, Lilly, Meda, Renapharma, and UCB Pharma and consulting fees from Amgen, Radius Health, UCB Pharma, Renapharma and Consilient Health, all outside the presented work.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Appendix

Appendix

Table 4 Ten-year probability of a major osteoporotic fracture and hip fracture (%) in men and women with a prior fragility fracture (any site irrespective of its recency), probabilities for a recent clinical vertebral fracture (within 2 years) and the ratio between 10-year probabilities by age
Full size table
Table 5 Ten-year probability of a major osteoporotic fracture and hip fracture (%) in men and women with a prior fragility fracture (any site irrespective of its recency), probabilities for a recent clinical hip fracture (within 2 years) and the ratio between 10-year probabilities by age
Full size table
Table 6 Ten-year probability of a major osteoporotic fracture and hip fracture (%) in men and women with a prior fragility fracture (any site irrespective of its recency), probabilities for a recent clinical humeral fracture (within 2 years) and the ratio between 10-year probabilities by age
Full size table
Table 7 Ten-year probability of a major osteoporotic fracture and hip fracture (%) in men and women with a prior fragility fracture (any site irrespective of its recency), probabilities for a recent clinical forearm fracture (within 2 years) and the ratio between 10-year probabilities by age
Full size table

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kanis, J.A., Johansson, H., Harvey, N.C. et al. Adjusting conventional FRAX estimates of fracture probability according to the recency of sentinel fractures. Osteoporos Int 31, 1817–1828 (2020). https://doi.org/10.1007/s00198-020-05517-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-020-05517-7

Keywords

Search

Navigation