Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Fracture mortality: associations with epidemiology and osteoporosis treatment

Key Points

  • Hip and vertebral osteoporotic fractures are associated with considerable immediate and long-term increased risk of death

  • The fracture event itself is responsible for part of this increased mortality risk; however, other factors such as age, sex, comorbidities and poor prefracture health status are also involved

  • The majority of incident osteoporotic fractures are nonhip, nonvertebral fractures

  • Evidence of mortality risk in nonhip, nonvertebral fractures is lacking, but evidence of an increased mortality risk with some fractures, such as those in the pelvis and humerus, does exist

  • Medical treatment with bisphosphonates has been associated with a decreased risk of mortality in patients with osteoporotic fractures in some observational studies and in one randomized controlled trial

  • Decreased cardiovascular-related mortality could be one of the potential mechanisms for the decreased risk of mortality with bisphosphonate therapy; however, further studies are required to clarify this point

Abstract

The rates of incident osteoporotic fractures seem to be stabilizing; however, fragility fractures are still associated with considerable disability, costs and an increased risk of mortality, which is particularly the case for fractures of the hip and vertebra. Mortality is usually highest during the first year after fracture; however, a notably increased mortality risk might persist for several years after the event. In addition to its efficacy in the prevention of new and recurrent osteoporotic fractures, medical treatment has been associated with improved survival after osteoporotic fractures. Observational studies and randomized controlled clinical trials have reported increased survival in patients with a fracture who are treated with bisphosphonates. Rates of medical treatment in patients with osteoporosis remain low, and although the rationale for the putative increase in survival is unclear, this emerging evidence might help further justify the use of medical treatment after fracture. However, further work is needed before medical therapy for mortality prevention in patients with osteoporotic fractures is accepted.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Browner, W. S., Seeley, D. G., Vogt, T. M. & Cummings, S. R. Non-trauma mortality in elderly women with low bone mineral density. Study of Osteoporotic Fractures Research Group. Lancet 338, 355–358 (1991).

    CAS  PubMed  Google Scholar 

  2. Johansson, C., Black, D., Johnell, O., Oden, A. & Mellstrom, D. Bone mineral density is a predictor of survival. Calcif. Tissue Int. 63, 190–196 (1998).

    CAS  PubMed  Google Scholar 

  3. Kado, D. M., Browner, W. S., Blackwell, T., Gore, R. & Cummings, S. R. Rate of bone loss is associated with mortality in older women: a prospective study. J. Bone Miner. Res. 15, 1974–1980 (2000).

    CAS  PubMed  Google Scholar 

  4. Qu, X. et al. Bone mineral density and all-cause, cardiovascular and stroke mortality: a meta-analysis of prospective cohort studies. Int. J. Cardiol. 166, 385–393 (2013).

    PubMed  Google Scholar 

  5. Burge, R. et al. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005–2025. J. Bone Miner. Res. 22, 465–475 (2007).

    PubMed  Google Scholar 

  6. Abrahamsen, B., van Staa, T., Ariely, R., Olson, M. & Cooper, C. Excess mortality following hip fracture: a systematic epidemiological review. Osteoporos. Int. 20, 1633–1650 (2009).

    CAS  PubMed  Google Scholar 

  7. Huntjens, K. M. et al. Risk of subsequent fracture and mortality within 5 years after a non-vertebral fracture. Osteoporos. Int. 21, 2075–2082 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Johnell, O. et al. Mortality after osteoporotic fractures. Osteoporos. Int. 15, 38–42 (2004).

    CAS  PubMed  Google Scholar 

  9. Alegre-Lopez, J., Cordero-Guevara, J., Alonso-Valdivielso, J. L. & Fernandez-Melon, J. Factors associated with mortality and functional disability after hip fracture: an inception cohort study. Osteoporos. Int. 16, 729–736 (2005).

    PubMed  Google Scholar 

  10. Empana, J. P., Dargent-Molina, P. & Breart, G. Effect of hip fracture on mortality in elderly women: the EPIDOS prospective study. J. Am. Geriatr. Soc. 52, 685–690 (2004).

    PubMed  Google Scholar 

  11. LeBlanc, E. S. et al. Hip fracture and increased short-term but not long-term mortality in healthy older women. Arch. Intern. Med. 171, 1831–1837 (2011).

    PubMed  PubMed Central  Google Scholar 

  12. Cameron, I. D. et al. Hip fracture causes excess mortality owing to cardiovascular and infectious disease in institutionalized older people: a prospective 5-year study. J. Bone Miner. Res. 25, 866–872 (2010).

    PubMed  Google Scholar 

  13. Ioannidis, G. et al. Relation between fractures and mortality: results from the Canadian Multicentre Osteoporosis Study. CMAJ 181, 265–271 (2009).

    PubMed  PubMed Central  Google Scholar 

  14. Cauley, J. A., Thompson, D. E., Ensrud, K. C., Scott, J. C. & Black, D. Risk of mortality following clinical fractures. Osteoporos. Int. 11, 556–561 (2000).

    CAS  PubMed  Google Scholar 

  15. Center, J. R., Nguyen, T. V., Schneider, D., Sambrook, P. N. & Eisman, J. A. Mortality after all major types of osteoporotic fracture in men and women: an observational study. Lancet 353, 878–882 (1999).

    CAS  PubMed  Google Scholar 

  16. Jalava, T. et al. Association between vertebral fracture and increased mortality in osteoporotic patients. J. Bone Miner. Res. 18, 1254–1260 (2003).

    PubMed  Google Scholar 

  17. Kanis, J. A., Oden, A., Johnell, O., De Laet, C. & Jonsson, B. Excess mortality after hospitalisation for vertebral fracture. Osteoporos. Int. 15, 108–112 (2004).

    PubMed  Google Scholar 

  18. Naves, M. et al. The effect of vertebral fracture as a risk factor for osteoporotic fracture and mortality in a Spanish population. Osteoporos. Int. 14, 520–524 (2003).

    CAS  PubMed  Google Scholar 

  19. Bliuc, D. et al. Mortality risk associated with low-trauma osteoporotic fracture and subsequent fracture in men and women. JAMA 301, 513–521 (2009).

    CAS  PubMed  Google Scholar 

  20. Morin, S. et al. Mortality rates after incident non-traumatic fractures in older men and women. Osteoporos. Int. 22, 2439–2448 (2011).

    CAS  PubMed  Google Scholar 

  21. Cooper, C., Atkinson, E. J., Jacobsen, S. J., O'Fallon, W. M. & Melton, L. J. 3rd. Population-based study of survival after osteoporotic fractures. Am. J. Epidemiol. 137, 1001–1005 (1993).

    CAS  PubMed  Google Scholar 

  22. Browner, W. S., Pressman, A. R., Nevitt, M. C. & Cummings, S. R. Mortality following fractures in older women. The study of osteoporotic fractures. Arch. Intern. Med. 156, 1521–1525 (1996).

    CAS  PubMed  Google Scholar 

  23. Cummings, S. R. & Melton, L. J. Epidemiology and outcomes of osteoporotic fractures. Lancet 359, 1761–1767 (2002).

    PubMed  Google Scholar 

  24. Teng, G. G., Curtis, J. R. & Saag, K. G. Mortality and osteoporotic fractures: is the link causal, and is it modifiable? Clin. Exp. Rheumatol. 26, S125–S137 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Kanis, J. A. et al. The components of excess mortality after hip fracture. Bone 32, 468–473 (2003).

    CAS  PubMed  Google Scholar 

  26. Lyles, K. W. et al. Zoledronic acid and clinical fractures and mortality after hip fracture. N. Engl. J. Med. 357, 1799–1809 (2007).

    CAS  PubMed  Google Scholar 

  27. Center, J. R., Bliuc, D., Nguyen, N. D., Nguyen, T. V. & Eisman, J. A. Osteoporosis medication and reduced mortality risk in elderly women and men. J. Clin. Endocrinol. Metab. 96, 1006–1014 (2011).

    CAS  PubMed  Google Scholar 

  28. Beaupre, L. A. et al. Oral bisphosphonates are associated with reduced mortality after hip fracture. Osteoporos. Int. 22, 983–991 (2011).

    CAS  PubMed  Google Scholar 

  29. Cree, M. W., Juby, A. G. & Carriere, K. C. Mortality and morbidity associated with osteoporosis drug treatment following hip fracture. Osteoporos. Int. 14, 722–727 (2003).

    PubMed  Google Scholar 

  30. Kamel, H. K. Secondary prevention of hip fractures among the hospitalized elderly: are we doing enough? J. Clin. Rheumatol. 11, 68–71 (2005).

    PubMed  Google Scholar 

  31. Petrella, R. J. & Jones, T. J. Do patients receive recommended treatment of osteoporosis following hip fracture in primary care? BMC Fam. Pract. 7, 31 (2006).

    PubMed  PubMed Central  Google Scholar 

  32. Butler, M., Forte, M. L., Joglekar, S. B., Swiontkowski, M. F. & Kane, R. L. Evidence summary: systematic review of surgical treatments for geriatric hip fractures. J. Bone Joint Surg. Am. 93, 1104–1115 (2011).

    PubMed  Google Scholar 

  33. Della Rocca, G. J. & Crist, B. D. Hip fracture protocols: what have we changed? Orthop. Clin. North Am. 44, 163–182 (2013).

    PubMed  Google Scholar 

  34. Hu, F., Jiang, C., Shen, J., Tang, P. & Wang, Y. Preoperative predictors for mortality following hip fracture surgery: a systematic review and meta-analysis. Injury 43, 676–685 (2012).

    PubMed  Google Scholar 

  35. Miyamoto, R. G., Kaplan, K. M., Levine, B. R., Egol, K. A. & Zuckerman, J. D. Surgical management of hip fractures: an evidence-based review of the literature. I: femoral neck fractures. J. Am. Acad. Orthop. Surg. 16, 596–607 (2008).

    PubMed  Google Scholar 

  36. Moja, L. G. et al. Timing matters in hip fracture surgery: patients operated within 48 hours have better outcomes. A meta-analysis and meta-regression of over 190,000 patients. PLoS ONE 7, e46175 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Johnell, O. & Kanis, J. A. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos. Int. 17, 1726–1733 (2006).

    CAS  PubMed  Google Scholar 

  38. Rapp, K., Becker, C., Lamb, S. E., Icks, A. & Klenk, J. Hip fractures in institutionalized elderly people: incidence rates and excess mortality. J. Bone Miner. Res. 23, 1825–1831 (2008).

    PubMed  Google Scholar 

  39. Tosteson, A. N., Gottlieb, D. J., Radley, D. C., Fisher, E. S. & Melton, L. J. 3rd. Excess mortality following hip fracture: the role of underlying health status. Osteoporos. Int. 18, 1463–1472 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Wolinsky, F. D., Fitzgerald, J. F. & Stump, T. E. The effect of hip fracture on mortality, hospitalization, and functional status: a prospective study. Am. J. Public Health 87, 398–403 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Magaziner, J. et al. Excess mortality attributable to hip fracture in white women aged 70 years and older. Am. J. Public Health 87, 1630–1636 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Fisher, E. S. et al. Hip fracture incidence and mortality in New England. Epidemiology 2, 116–122 (1991).

    CAS  PubMed  Google Scholar 

  43. Tsuboi, M., Hasegawa, Y., Suzuki, S., Wingstrand, H. & Thorngren, K. G. Mortality and mobility after hip fracture in Japan: a ten-year follow-up. J. Bone Joint Surg. Br. 89, 461–466 (2007).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  45. Haentjens, P. et al. Meta-analysis: excess mortality after hip fracture among older women and men. Ann. Intern. Med. 152, 380–390 (2010).

    PubMed  PubMed Central  Google Scholar 

  46. Wehren, L. E. et al. Gender differences in mortality after hip fracture: the role of infection. J. Bone Miner. Res. 18, 2231–2237 (2003).

    PubMed  Google Scholar 

  47. Chiang, C. H. et al. Hip fracture and risk of acute myocardial infarction: a nationwide study. J. Bone Miner. Res. 28, 404–411 (2013).

    PubMed  Google Scholar 

  48. Brauer, C. A., Coca-Perraillon, M., Cutler, D. M. & Rosen, A. B. Incidence and mortality of hip fractures in the United States. JAMA 302, 1573–1579 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Bass, E., French, D. D., Bradham, D. D. & Rubenstein, L. Z. Risk-adjusted mortality rates of elderly veterans with hip fractures. Ann. Epidemiol. 17, 514–519 (2007).

    PubMed  Google Scholar 

  50. Holt, G., Smith, R., Duncan, K., Hutchison, J. D. & Gregori, A. Gender differences in epidemiology and outcome after hip fracture: evidence from the Scottish Hip Fracture Audit. J. Bone Joint Surg. Br. 90, 480–483 (2008).

    CAS  PubMed  Google Scholar 

  51. Mortimore, E. et al. Amount of social contact and hip fracture mortality. J. Am. Geriatr. Soc. 56, 1069–1074 (2008).

    PubMed  PubMed Central  Google Scholar 

  52. Farahmand, B. Y., Michaelsson, K., Ahlbom, A., Ljunghall, S. & Baron, J. A. Survival after hip fracture. Osteoporos. Int. 16, 1583–1590 (2005).

    PubMed  Google Scholar 

  53. Forsen, L., Sogaard, A. J., Meyer, H. E., Edna, T. & Kopjar, B. Survival after hip fracture: short- and long-term excess mortality according to age and gender. Osteoporos. Int. 10, 73–78 (1999).

    CAS  PubMed  Google Scholar 

  54. Hindmarsh, D. M., Hayen, A., Finch, C. F. & Close, J. C. Relative survival after hospitalisation for hip fracture in older people in New South Wales, Australia. Osteoporos. Int. 20, 221–229 (2009).

    CAS  PubMed  Google Scholar 

  55. Penrod, J. D. et al. The association of race, gender, and comorbidity with mortality and function after hip fracture. J. Gerontol. A Biol. Sci. Med. Sci. 63, 867–872 (2008).

    PubMed  Google Scholar 

  56. Jacobsen, S. J. et al. Race and sex differences in mortality following fracture of the hip. Am. J. Public Health 82, 1147–1150 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Hoenig, H., Rubenstein, L. & Kahn, K. Rehabilitation after hip fracture—equal opportunity for all? Arch. Phys. Med. Rehabil. 77, 58–63 (1996).

    CAS  PubMed  Google Scholar 

  58. Harada, N. D., Chun, A., Chiu, V. & Pakalniskis, A. Patterns of rehabilitation utilization after hip fracture in acute hospitals and skilled nursing facilities. Med. Care 38, 1119–1130 (2000).

    CAS  PubMed  Google Scholar 

  59. Paksima, N. et al. Predictors of mortality after hip fracture: a 10-year prospective study. Bull. NYU Hosp. Jt Dis. 66, 111–117 (2008).

    PubMed  Google Scholar 

  60. Nather, A., Seow, C. S., Iau, P. & Chan, A. Morbidity and mortality for elderly patients with fractured neck of femur treated by hemiarthroplasty. Injury 26, 187–190 (1995).

    CAS  PubMed  Google Scholar 

  61. Schroder, H. M. & Erlandsen, M. Age and sex as determinants of mortality after hip fracture: 3,895 patients followed for 2.5–18.5 years. J. Orthop. Trauma 7, 525–531 (1993).

    CAS  PubMed  Google Scholar 

  62. Poor, G., Atkinson, E. J., O'Fallon, W. M. & Melton, L. J. 3rd. Determinants of reduced survival following hip fractures in men. Clin. Orthop. Relat. Res. 319, 260–265 (1995).

    Google Scholar 

  63. Roche, J. J., Wenn, R. T., Sahota, O. & Moran, C. G. Effect of comorbidities and postoperative complications on mortality after hip fracture in elderly people: prospective observational cohort study. BMJ 331, 1374 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Hasegawa, Y., Suzuki, S. & Wingstrand, H. Risk of mortality following hip fracture in Japan. J. Orthop. Sci. 12, 113–117 (2007).

    PubMed  Google Scholar 

  65. Richmond, J., Aharonoff, G. B., Zuckerman, J. D. & Koval, K. J. Mortality risk after hip fracture. 2003. J. Orthop. Trauma 17 (8 Suppl.), S2–S5 (2003).

    PubMed  Google Scholar 

  66. Jiang, H. X. et al. Development and initial validation of a risk score for predicting in-hospital and 1-year mortality in patients with hip fractures. J. Bone Miner. Res. 20, 494–500 (2005).

    CAS  PubMed  Google Scholar 

  67. Pioli, G. et al. Predictors of mortality after hip fracture: results from 1-year follow-up. Aging Clin. Exp. Res. 18, 381–387 (2006).

    CAS  PubMed  Google Scholar 

  68. Pande, I. et al. Quality of life, morbidity, and mortality after low trauma hip fracture in men. Ann. Rheum. Dis. 65, 87–92 (2006).

    CAS  PubMed  Google Scholar 

  69. Kannegaard, P. N., van der Mark, S., Eiken, P. & Abrahamsen, B. Excess mortality in men compared with women following a hip fracture. National analysis of comedications, comorbidity and survival. Age Ageing 39, 203–209 (2010).

    PubMed  Google Scholar 

  70. Fox, K. M., Magaziner, J., Hebel, J. R., Kenzora, J. E. & Kashnei, T. M. Intertrochanteric versus femoral neck hip fractures: differential characteristics, treatment, and sequelae. J. Gerontol. A Biol. Sci. Med. Sci. 54, M635–M640 (1999).

    CAS  PubMed  Google Scholar 

  71. Haentjens, P. et al. Survival and functional outcome according to hip fracture type: a one-year prospective cohort study in elderly women with an intertrochanteric or femoral neck fracture. Bone 41, 958–964 (2007).

    CAS  PubMed  Google Scholar 

  72. Karagiannis, A. et al. Mortality rates of patients with a hip fracture in a southwestern district of Greece: ten-year follow-up with reference to the type of fracture. Calcif. Tissue Int. 78, 72–77 (2006).

    CAS  PubMed  Google Scholar 

  73. Leibson, C. L., Tosteson, A. N., Gabriel, S. E., Ransom, J. E. & Melton, L. J. Mortality, disability, and nursing home use for persons with and without hip fracture: a population-based study. J. Am. Geriatr. Soc. 50, 1644–1650 (2002).

    PubMed  Google Scholar 

  74. Melton, L. J. 3rd. The prevalence of osteoporosis. J. Bone Miner. Res. 12, 1769–1771 (1997).

    PubMed  Google Scholar 

  75. Cooper, C., Atkinson, E. J., O'Fallon, W. M. & Melton, L. J. 3rd. Incidence of clinically diagnosed vertebral fractures: a population-based study in Rochester, Minnesota, 1985–1989. J. Bone Miner. Res. 7, 221–227 (1992).

    CAS  PubMed  Google Scholar 

  76. Fink, H. A. et al. What proportion of incident radiographic vertebral deformities is clinically diagnosed and vice versa? J. Bone Miner. Res. 20, 1216–1222 (2005).

    PubMed  Google Scholar 

  77. Gehlbach, S. H. et al. Recognition of vertebral fracture in a clinical setting. Osteoporos. Int. 11, 577–582 (2000).

    CAS  PubMed  Google Scholar 

  78. Bouza, C., Lopez, T., Palma, M. & Amate, J. M. Hospitalised osteoporotic vertebral fractures in Spain: analysis of the national hospital discharge registry. Osteoporos. Int. 18, 649–657 (2007).

    CAS  PubMed  Google Scholar 

  79. Ensrud, K. E. et al. Prevalent vertebral deformities predict mortality and hospitalization in older women with low bone mass. Fracture Intervention Trial Research Group. J. Am. Geriatr. Soc. 48, 241–249 (2000).

    CAS  PubMed  Google Scholar 

  80. Hasserius, R., Karlsson, M. K., Jonsson, B., Redlund-Johnell, I. & Johnell, O. Long-term morbidity and mortality after a clinically diagnosed vertebral fracture in the elderly—a 12- and 22-year follow-up of 257 patients. Calcif. Tissue Int. 76, 235–242 (2005).

    CAS  PubMed  Google Scholar 

  81. Ismail, A. A. et al. Mortality associated with vertebral deformity in men and women: results from the European Prospective Osteoporosis Study (EPOS). Osteoporos. Int. 8, 291–297 (1998).

    CAS  PubMed  Google Scholar 

  82. Lee, A. Y. et al. Five-year outcome of individuals with hip fracture admitted to a Singapore hospital: quality of life and survival rates after treatment. J. Am. Geriatr. Soc. 60, 994–996 (2012).

    PubMed  Google Scholar 

  83. Lau, E., Ong, K., Kurtz, S., Schmier, J. & Edidin, A. Mortality following the diagnosis of a vertebral compression fracture in the Medicare population. J. Bone Joint Surg. Am. 90, 1479–1486 (2008).

    PubMed  Google Scholar 

  84. Pongchaiyakul, C. et al. Asymptomatic vertebral deformity as a major risk factor for subsequent fractures and mortality: a long-term prospective study. J. Bone Miner. Res. 20, 1349–1355 (2005).

    PubMed  Google Scholar 

  85. Kado, D. M. et al. Vertebral fractures and mortality in older women: a prospective study. Study of Osteoporotic Fractures Research Group. Arch. Intern. Med. 159, 1215–1220 (1999).

    CAS  PubMed  Google Scholar 

  86. Lee, Y. K. et al. Mortality after vertebral fracture in Korea: analysis of the National Claim Registry. Osteoporos. Int. 23, 1859–1865 (2012).

    PubMed  Google Scholar 

  87. Kado, D. M. et al. Incident vertebral fractures and mortality in older women: a prospective study. Osteoporos. Int. 14, 589–594 (2003).

    CAS  PubMed  Google Scholar 

  88. Trone, D. W., Kritz-Silverstein, D., von Muhlen, D. G., Wingard, D. L. & Barrett-Connor, E. Is radiographic vertebral fracture a risk factor for mortality? Am. J. Epidemiol. 166, 1191–1197 (2007).

    PubMed  Google Scholar 

  89. Melton, L. J. 3rd, Achenbach, S. J., Atkinson, E. J., Therneau, T. M. & Amin, S. Long-term mortality following fractures at different skeletal sites: a population-based cohort study. Osteoporos. Int. 24, 1689–1696 (2013).

    PubMed  Google Scholar 

  90. Bolland, M. J., Grey, A. B., Gamble, G. D. & Reid, I. R. Effect of osteoporosis treatment on mortality: a meta-analysis. J. Clin. Endocrinol. Metab. 95, 1174–1181 (2010).

    CAS  PubMed  Google Scholar 

  91. Black, D. M. et al. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet 348, 1535–1541 (1996).

    CAS  PubMed  Google Scholar 

  92. Cummings, S. R. et al. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. JAMA 280, 2077–2082 (1998).

    CAS  PubMed  Google Scholar 

  93. Harris, S. T. et al. 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 (1999).

    CAS  PubMed  Google Scholar 

  94. Reginster, J. et al. Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group. Osteoporos. Int. 11, 83–91 (2000).

    CAS  PubMed  Google Scholar 

  95. McClung, M. R. et al. Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group. N. Engl. J. Med. 344, 333–340 (2001).

    CAS  PubMed  Google Scholar 

  96. Meunier, P. J. et al. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N. Engl. J. Med. 350, 459–468 (2004).

    CAS  PubMed  Google Scholar 

  97. Reginster, J. Y. et al. Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) study. J. Clin. Endocrinol. Metab. 90, 2816–2822 (2005).

    CAS  PubMed  Google Scholar 

  98. Black, D. M. et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N. Engl. J. Med. 356, 1809–1822 (2007).

    CAS  PubMed  Google Scholar 

  99. Nurmi-Luthje, I. et al. Post-fracture prescribed calcium and vitamin D supplements alone or, in females, with concomitant anti-osteoporotic drugs is associated with lower mortality in elderly hip fracture patients: a prospective analysis. Drugs Aging 26, 409–421 (2009).

    CAS  PubMed  Google Scholar 

  100. Sambrook, P. N. et al. Oral bisphosphonates are associated with reduced mortality in frail older people: a prospective five-year study. Osteoporos. Int. 22, 2551–2556 (2011).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  102. Colon-Emeric, C. S. et al. Potential mediators of the mortality reduction with zoledronic acid after hip fracture. J. Bone Miner. Res. 25, 91–97 (2010).

    CAS  PubMed  Google Scholar 

  103. Beloosesky, Y. et al. Cytokines and C-reactive protein production in hip-fracture-operated elderly patients. J. Gerontol. A Biol. Sci. Med. Sci. 62, 420–426 (2007).

    PubMed  Google Scholar 

  104. Miller, R. R. et al. Association between interleukin-6 and lower extremity function after hip fracture—the role of muscle mass and strength. J. Am. Geriatr. Soc. 56, 1050–1056 (2008).

    PubMed  PubMed Central  Google Scholar 

  105. Svensen, C. H. Vascular endothelial growth factor (VEGF) in plasma increases after hip surgery. J. Clin. Anesth. 16, 435–439 (2004).

    CAS  PubMed  Google Scholar 

  106. Onuoha, G. N. & Alpar, E. K. Elevation of plasma CGRP and SP levels in orthopedic patients with fracture neck of femur. Neuropeptides 34, 116–120 (2000).

    CAS  PubMed  Google Scholar 

  107. Roelofs, A. J., Thompson, K., Ebetino, F. H., Rogers, M. J. & Coxon, F. P. Bisphosphonates: molecular mechanisms of action and effects on bone cells, monocytes and macrophages. Curr. Pharm. Des. 16, 2950–2960 (2010).

    CAS  PubMed  Google Scholar 

  108. Hewitt, R. E. et al. The bisphosphonate acute phase response: rapid and copious production of proinflammatory cytokines by peripheral blood gd T cells in response to aminobisphosphonates is inhibited by statins. Clin. Exp. Immunol. 139, 101–111 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Farhat, G. N. et al. Volumetric and areal bone mineral density measures are associated with cardiovascular disease in older men and women: the health, aging, and body composition study. Calcif. Tissue Int. 79, 102–111 (2006).

    CAS  PubMed  Google Scholar 

  110. Kalinowski, L., Dobrucki, L. W., Brovkovych, V. & Malinski, T. Increased nitric oxide bioavailability in endothelial cells contributes to the pleiotropic effect of cerivastatin. Circulation 105, 933–938 (2002).

    CAS  PubMed  Google Scholar 

  111. Tuominen, O. M. et al. Effects of bisphosphonates on prostaglandin E2 and thromboxane B2 production in human whole blood and monocytes stimulated by lipopolysaccharide and A23187. Methods Find. Exp. Clin. Pharmacol. 28, 361–367 (2006).

    CAS  PubMed  Google Scholar 

  112. Ugur Ural, A., Avcu, F. & Ozturk, K. Bisphosphonates may retrieve endothelial function in vascular diseases similar to statins' effects. Eur. J. Haematol. 81, 77–78 (2008).

    CAS  PubMed  Google Scholar 

  113. Kang, J. H., Keller, J. J. & Lin, H. C. Bisphosphonates reduced the risk of acute myocardial infarction: a 2-year follow-up study. Osteoporos. Int. 24, 271–277 (2013).

    CAS  PubMed  Google Scholar 

  114. Shao, W., Orlando, R. C. & Awayda, M. S. Bisphosphonates stimulate an endogenous nonselective cation channel in Xenopus oocytes: potential mechanism of action. Am. J. Physiol. Cell Physiol. 289, C248–C256 (2005).

    CAS  PubMed  Google Scholar 

  115. Dobrucali, A. et al. Physiological and morphological effects of alendronate on rabbit esophageal epithelium. Am. J. Physiol. Gastrointest. Liver Physiol. 283, G576–G586 (2002).

    CAS  PubMed  Google Scholar 

  116. Pittman, C. B. et al. Myocardial infarction risk among patients with fractures receiving bisphosphonates. Mayo Clin. Proc. 89, 43–51 (2014).

    CAS  PubMed  Google Scholar 

  117. Kang, H. Y. et al. Incidence and mortality of hip fracture among the elderly population in South Korea: a population-based study using the national health insurance claims data. BMC Public Health 10, 230 (2010).

    PubMed  PubMed Central  Google Scholar 

  118. Muraki, S., Yamamoto, S., Ishibashi, H. & Nakamura, K. Factors associated with mortality following hip fracture in Japan. J. Bone Miner. Metab. 24, 100–104 (2006).

    PubMed  Google Scholar 

  119. Edidin, A. A., Ong, K. L., Lau, E. & Kurtz, S. M. Mortality risk for operated and nonoperated vertebral fracture patients in the medicare population. J. Bone Miner. Res. 26, 1617–1626 (2011).

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

S.E.S researched data for the article, wrote the article and reviewed and edited the manuscript before submission. K.G.S. wrote the article and reviewed and edited the manuscript before submission.

Corresponding author

Correspondence to Kenneth G. Saag.

Ethics declarations

Competing interests

K.G.S. receives research support from Amgen and Merck. He also serves as a consultant for Amgen, Eli Lilly and Merck. S.E.S. declares no competing interests.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sattui, S., Saag, K. Fracture mortality: associations with epidemiology and osteoporosis treatment. Nat Rev Endocrinol 10, 592–602 (2014). https://doi.org/10.1038/nrendo.2014.125

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrendo.2014.125

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing