Advertisement

Springer Nature is making Coronavirus research free. View research | View latest news | Sign up for updates

Impact of osteoporotic fracture type and subsequent fracture on mortality: the Tromsø Study

Abstract

Summary

Less is known about the impact of non-hip non-vertebral fractures (NHNV) on early death. This study demonstrated increased risk of dying following hip and NHNV fractures which was further increased by a subsequent fracture. This highlights the importance of early intervention to prevent both initial and subsequent fractures and improve survival.

Introduction

Osteoporotic fractures are a major health concern. Limited evidence exists on their impact on mortality in ageing populations. This study examined the contribution of initial fracture type and subsequent fracture on mortality in a Norwegian population that has one of the highest rates of fractures.

Methods

The Tromsø Study is a prospective population-based cohort in Norway. Women and men aged 50+ years were followed from 1994 to 2010. All incident hip and non-hip non-vertebral (NHNV) fractures were registered. NHNV fractures were classified as either proximal or distal. Information on self-reported co-morbidities, lifestyle factors, general health and education level was collected. Multivariable Cox models were used to quantify mortality risk with incident and subsequent fractures analysed as time-dependent variables.

Results

Of 5214 women and 4620 men, 1549 (30%) and 504 (11%) sustained a fracture, followed by 589 (38%) and 254 (51%) deaths over 10,523 and 2821 person-years, respectively. There were 403 (26%) subsequent fractures in women and 68 (13%) in men. Hip fracture was associated with a two-fold increase in mortality risk (HR 2.05, 95% CI 1.73–2.42 in women and 2.49, 95% CI 2.00–3.11 in men). Proximal NHNV fractures were associated with 49% and 81% increased mortality risk in women and men (HR 1.49, 95% CI 1.21–1.84 and 1.81, 95% CI 1.37–2.41), respectively. Distal NHNV fractures were not associated with mortality. Subsequent fracture was associated with 89% and 77% increased mortality risk in women and men (HR 1.89, 95% CI 1.52–2.35 and 1.77, 95% CI 1.16–2.71), respectively.

Conclusion

Hip, proximal NHNV and subsequent fractures were significantly associated with increased mortality risk in the elderly, highlighting the importance of early intervention.

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

Fig. 1
Fig. 2

References

  1. 1.

     The global burden of osteoporosis (2017) A fact sheet. International Osteoporosis Foundation

  2. 2.

    Center JR, Bliuc D, Nguyen TV, Eisman JA (2007) Risk of subsequent fracture after low-trauma fracture in men and women. Jama 297(4):387–394

  3. 3.

    Kanis JA, Johnell O, De Laet C, Johansson H, Oden A, Delmas P et al (2004) A meta-analysis of previous fracture and subsequent fracture risk. Bone 35(2):375–382

  4. 4.

    Gehlbach S, Saag KG, Adachi JD, Hooven FH, Flahive J, Boonen S et al (2012) Previous fractures at multiple sites increase the risk for subsequent fractures: the Global Longitudinal Study of Osteoporosis in Women. J Bone Miner Res 27(3):645–653

  5. 5.

    Ahmed LA, Center JR, Bjornerem A, Bluic D, Joakimsen RM, Jorgensen L et al (2013) Progressively increasing fracture risk with advancing age after initial incident fragility fracture: the Tromso study. J Bone Miner Res 28(10):2214–2221

  6. 6.

    Haentjens P, Magaziner J, Colon-Emeric CS, Vanderschueren D, Milisen K, Velkeniers B et al (2010) Meta-analysis: excess mortality after hip fracture among older women and men. Ann Intern Med 152(6):380–390

  7. 7.

    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

  8. 8.

    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

  9. 9.

    Cauley JA, Thompson DE, Ensrud KC, Scott JC, Black D (2000) Risk of mortality following clinical fractures. Osteoporos Int 11(7):556–561

  10. 10.

    Ioannidis G, Papaioannou A, Hopman WM, Akhtar-Danesh N, Anastassiades T, Pickard L et al (2009) Relation between fractures and mortality: results from the Canadian Multicentre Osteoporosis Study. CMAJ 181(5):265–271

  11. 11.

    Melton LJ 3rd, Achenbach SJ, Atkinson EJ, Therneau TM, Amin S (2013) Long-term mortality following fractures at different skeletal sites: a population-based cohort study. Osteoporos Int 24(5):1689–1696

  12. 12.

    Morin S, Lix LM, Azimaee M, Metge C, Caetano P, Leslie WD (2011) Mortality rates after incident non-traumatic fractures in older men and women. Osteoporos Int 22(9):2439–2448

  13. 13.

    Bliuc D, Nguyen TV, Eisman JA, Center JR (2014) The impact of nonhip nonvertebral fractures in elderly women and men. J Clin Endocrinol Metab 99(2):415–423

  14. 14.

    Huntjens KM, Kosar S, van Geel TA, Geusens PP, Willems P, Kessels A et al (2010) Risk of subsequent fracture and mortality within 5 years after a non-vertebral fracture. Osteoporos Int 21(12):2075–2082

  15. 15.

    Somersalo A, Paloneva J, Kautiainen H, Lonnroos E, Heinanen M, Kiviranta I (2015) Increased mortality after upper extremity fracture requiring inpatient care. Acta Orthop 86(5):533–557

  16. 16.

    Tran T, Bliuc D, van Geel T, Adachi JD, Berger C, van den Bergh J et al (2017) Population-wide impact of non-hip non-vertebral fractures on mortality. J Bone Miner Res 32(9):1802–1810

  17. 17.

    Chen W, Simpson JM, March LM, Blyth FM, Bliuc D, Tran T et al (2018) Comorbidities only account for a small proportion of excess mortality after fracture: a record linkage study of individual fracture types. J Bone Miner Res 33(5):795–802

  18. 18.

    Bliuc D, Nguyen ND, Nguyen TV, Eisman JA, Center JR (2013) Compound risk of high mortality following osteoporotic fracture and refracture in elderly women and men. J Bone Miner Res 28(11):2317–2324

  19. 19.

    Dhanwal DK, Cooper C, Dennison EM (2010) Geographic variation in osteoporotic hip fracture incidence: the growing importance of Asian influences in coming decades. J Osteoporos 2010:757102

  20. 20.

    Cooper C, Cole ZA, Holroyd CR, Earl SC, Harvey NC, Dennison EM et al (2011) Secular trends in the incidence of hip and other osteoporotic fractures. Osteoporos Int 22(5):1277–1288

  21. 21.

    Kanis JA, Johnell O, De Laet C, Jonsson B, Oden A, Ogelsby AK (2002) International variations in hip fracture probabilities: implications for risk assessment. J Bone Miner Res 17(7):1237–1244

  22. 22.

    Kanis JA, Odén A, McCloskey EV, Johansson H, Wahl DA, Cooper C et al (2012) A systematic review of hip fracture incidence and probability of fracture worldwide. Osteoporos Int 23(9):2239–2256

  23. 23.

    Duarte Sosa D, Vilaplana L, Guerri R, Nogues X, Wang-Fagerland M, Diez-Perez A et al (2015) Are the high hip fracture rates among Norwegian women explained by impaired bone material properties? J Bone Miner Res 30(10):1784–1789

  24. 24.

    Gronskag AB, Romundstad P, Forsmo S, Langhammer A, Schei B (2012) Excess mortality after hip fracture among elderly women in Norway. The HUNT study. Osteoporos Int 23(6):1807–1811

  25. 25.

    Diamantopoulos AP, Hoff M, Skoie IM, Hochberg M, Haugeberg G (2013) Short- and long-term mortality in males and females with fragility hip fracture in Norway. A population-based study. Clin Interv Aging 8:817–823

  26. 26.

    Omsland TK, Emaus N, Tell GS, Magnus JH, Ahmed LA, Holvik K et al (2014) Mortality following the first hip fracture in Norwegian women and men (1999–2008). A NOREPOS study. Bone 63:81–86

  27. 27.

    Jacobsen BK, Eggen AE, Mathiesen EB, Wilsgaard T, Njølstad I (2012) Cohort profile: the Tromsø Study. Int J Epidemiol 41(4):961–967

  28. 28.

    The Tromsø study: the Arctic University of Norway (2017) [Available from: https://en.uit.no/forskning/forskningsgrupper/gruppe?p_document_id=453582

  29. 29.

    Ahmed LA, Schirmer H, Bjornerem A, Emaus N, Jorgensen L, Stormer J et al (2009) The gender- and age-specific 10-year and lifetime absolute fracture risk in Tromso, Norway. Eur J Epidemiol 24(8):441–448

  30. 30.

    Joakimsen RM, Fonnebo V, Sogaard AJ, Tollan A, Stormer J, Magnus JH (2001) The Tromso study: registration of fractures, how good are self-reports, a computerized radiographic register and a discharge register? Osteoporos Int 12(12):1001–1005

  31. 31.

    Heller RF, Dobson AJ, Attia J, Page J (2002) Impact numbers: measures of risk factor impact on the whole population from case-control and cohort studies. J Epidemiol Community Health 56(8):606

  32. 32.

    Tran T, Bliuc D, Hansen L, Abrahamsen B, van den Bergh J, Eisman JA et al (2018) Persistence of excess mortality following individual nonhip fractures: a relative survival analysis. J Clin Endocrinol Metab 103(9):3205–3214

  33. 33.

    Johnell O, Kanis JA, Oden A, Sernbo I, Redlund-Johnell I, Petterson C et al (2004) Mortality after osteoporotic fractures. Osteoporos Int 15(1):38–42

  34. 34.

    Doll R, Peto R (1976) Mortality in relation to smoking: 20 years’ observations on male British doctors. Br Med J 2(6051):1525–1536

  35. 35.

    Vestergaard P, Rejnmark L, Mosekilde L (2007) Increased mortality in patients with a hip fracture-effect of pre-morbid conditions and post-fracture complications. Osteoporos Int 18(12):1583–1593

  36. 36.

    Tosteson AN, Gottlieb DJ, Radley DC, Fisher ES, Melton LJ 3rd. (2007) Excess mortality following hip fracture: the role of underlying health status. Osteoporos Int 18(11):1463–1472

  37. 37.

    Bass E, French DD, Bradham DD, Rubenstein LZ (2007) Risk-adjusted mortality rates of elderly veterans with hip fractures. Ann Epidemiol 17(7):514–519

  38. 38.

    Roche JJW, Wenn RT, Sahota O, Moran CG (2005) Effect of comorbidities and postoperative complications on mortality after hip fracture in elderly people: prospective observational cohort study. BMJ 331(7529):1374

  39. 39.

    Pioli G, Barone A, Giusti A, Oliveri M, Pizzonia M, Razzano M et al (2006) Predictors of mortality after hip fracture: results from 1-year follow-up. Aging Clin Exp Res 18(5):381–387

  40. 40.

    Paksima N, Koval KJ, Aharanoff G, Walsh M, Kubiak EN, Zuckerman JD et al (2008) Predictors of mortality after hip fracture: a 10-year prospective study. Bull NYU Hosp Jt Dis 66(2):111–117

  41. 41.

    MacLean C, Newberry S, Maglione M, McMahon M, Ranganath V, Suttorp M et al (2008) Systematic review: comparative effectiveness of treatments to prevent fractures in men and women with low bone density or osteoporosis. Ann Intern Med 148(3):197–213

  42. 42.

    Center JR, Bliuc D, Nguyen ND, Nguyen TV, Eisman JA (2011) Osteoporosis medication and reduced mortality risk in elderly women and men. J Clin Endocrinol Metab 96(4):1006–1014

  43. 43.

    Beaupre LA, Morrish DW, Hanley DA, Maksymowych WP, Bell NR, Juby AG et al (2011) Oral bisphosphonates are associated with reduced mortality after hip fracture. Osteoporos Int 22(3):983–991

  44. 44.

    Sambrook PN, Cameron ID, Chen JS, March LM, Simpson JM, Cumming RG et al (2011) Oral bisphosphonates are associated with reduced mortality in frail older people: a prospective five-year study. Osteoporos Int 22(9):2551–2556

  45. 45.

    Bondo L, Eiken P, Abrahamsen B (2013) Analysis of the association between bisphosphonate treatment survival in Danish hip fracture patients-a nationwide register-based open cohort study. Osteoporos Int 24(1):245–252

  46. 46.

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

  47. 47.

    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

  48. 48.

    Bliuc D, Tran T, van Geel T, Adachi JD, Berger C, van den Bergh J, et al (2019) Mortality risk reduction differs according to bisphosphonate class: a 15-year observational study. Osteoporos Int

  49. 49.

    Reid IR, Horne AM, Mihov B, Stewart A, Garratt E, Wong S et al (2018) Fracture prevention with zoledronate in older women with osteopenia. N Engl J Med 379(25):2407–2416

  50. 50.

    (2012) Osteoporosis costing all Australians: a new burden of disease analysis – 2012 to 2022. Osteoporosis Australia

  51. 51.

    Port L, Center J, Briffa NK, Nguyen T, Cumming R, Eisman J (2003) Osteoporotic fracture: missed opportunity for intervention. Osteoporos Int 14(9):780–784

  52. 52.

    Bliuc D, Ong CR, Eisman JA, Center JR (2005) Barriers to effective management of osteoporosis in moderate and minimal trauma fractures: a prospective study. Osteoporos Int 16(8):977–982

Download references

Acknowledgements

We are grateful to Professor Ragnar Joakimsen for his great contribution to The Tromsø Study.

Funding

The Tromsø Study was funded by the University of Tromsø and from contributions by the National Screening Services, the Research Council of Norway, Northern Norway Regional Health Authority, Norwegian Council on Cardiovascular Diseases and Norwegian Foundation for Health and Rehabilitation. This work was supported by the National Health Medical Research Council Australia (NHMRC project ID; DA 1114676, DB 1073430, TT 1070187 and JRC 1008219). Other funding bodies were the Bupa Health Foundation (formerly MBF Foundation) and the Mrs. Gibson and Ernst Heine Family Foundation.

Author information

Correspondence to D. Alarkawi.

Ethics declarations

Conflict of interest

DA, DB, TT, LAA, NE, ÅB, LJ and TC have no competing interests to declare. JRC has consulted for and/or given educational talks for Merck Sharp and Dohme, Amgen, Actavis and Sanofi-Aventis. JAE has consulted for and/or received research funding from Amgen, deCode, Merck Sharp and Dohme and Sanofi-Aventis.

Disclaimer

The study sponsors had no role in the study design; collection, analyses and interpretation of the data; the writing of this report; or the decision to submit this manuscript for publication.

Additional information

Publisher’s note

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

Electronic supplementary material

Supplementary Table S1.

Multivariable adjusted mortality risk following subsequent fracture by gender in fracture cohort – a paired comparison for each fracture type (DOCX 15 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Alarkawi, D., Bliuc, D., Tran, T. et al. Impact of osteoporotic fracture type and subsequent fracture on mortality: the Tromsø Study. Osteoporos Int 31, 119–130 (2020). https://doi.org/10.1007/s00198-019-05174-5

Download citation

Keywords

  • Non-hip non-vertebral fractures
  • Mortality
  • Tromsø Study
  • Subsequent fracture