Skip to main content
Log in

Excess risk of hip fractures attributable to the use of antidepressants in five European countries and the USA

  • Original Article
  • Published:
Osteoporosis International Aims and scope Submit manuscript



The association between antidepressant use and hip fracture remains unclear. We conducted a systematic review to estimate Population Attributable Risks (PAR) for France, Germany, Italy, Spain, UK, and the USA. We report a heterogeneous prevalence of antidepressant use and related PARs, both lowest for Italy and highest for the USA.


Antidepressant use has been associated with an increased hip fracture risk in observational studies. However, the potential contribution of antidepressant consumption on the population rate of hip fractures has not been described. Our aim was to estimate the impact of the use of different classes of antidepressants on the rate of hip fracture at a population-level in France, Germany, Italy, Spain, the UK, and the USA.


We conducted a systematic literature review to estimate the pooled relative risk (RR) of hip fracture according to use of antidepressants. Prevalence rates of antidepressant use (Pe) in 2009 were calculated for each country using the The Intercontinental Medical Statistics database and three public databases from Denmark, the Netherlands, and Norway. Both the RR and Pe were used to calculate PAR of hip fractures associated with antidepressant use.


The literature review showed an increased risk of hip fractures in antidepressant users (RR, 1.7; 95 % confidence interval (CI), 1.5–2.0). Rates of antidepressant use showed considerable differences between countries, ranging from 4.4 % (Italy) to 11.2 % (USA) in the year 2009. The estimated PAR of antidepressants on hip fracture rates were 3.0 % (95 % CI, 2.0–4.1; Italy), 3.1 % (95 % CI, 2.1–4.3; Germany), 3.8 % (95 % CI, 2.6–5.3; France), 4.8 % (95 % CI, 3.3–6.5; Spain), 4.9 % (95 % CI, 3.4–6.8; UK), and 7.2 % (95 % CI, 5.0–9.9; USA). PARs differed for different types of antidepressants, with highest attributable risks for selective serotonin reuptake inhibitors.


These findings suggest that the potential contribution of antidepressant use to the population rate of hip fractures in the five large EU countries and the USA varies between 3 and 7 %.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others


  1. Gullberg B, Johnell O, Kanis JA (1997) World-wide projections for hip fracture. Osteoporos Int 7(5):407–413

    Article  CAS  PubMed  Google Scholar 

  2. van Staa TP, Dennison EM, Leufkens HG, Cooper C (2001) Epidemiology of fractures in England and Wales. Bone 29(6):517–522

    Article  PubMed  Google Scholar 

  3. Pagès-Castellà A, Carbonell-Abella C, Avilés FF, Alzamora M, Baena-Díez JM, Laguna DM, Nogués X, Díez-Pérez A, Prieto-Alhambra D (2012) Burden of osteoporotic fractures in primary health care in Catalonia (Spain): a population-based study. BMC Musculoskelet Disord 13:79

    Article  PubMed Central  PubMed  Google Scholar 

  4. Haentjens P, Lamraski G, Boonen S (2005) Costs and consequences of hip fracture occurrence in old age: an economic perspective. Disabil Rehabil 27(18–19):1129–1141

    Article  CAS  PubMed  Google Scholar 

  5. Braithwaite RS, Col NF, Wong JB (2003) Estimating hip fracture morbidity, mortality and costs. J Am Geriatr Soc 51(3):364–370

    Article  PubMed  Google Scholar 

  6. Lefauveau P, Fardellone P (2004) Extraskeletal risk factors for fractures of the proximal femur. Joint Bone Spine 71(1):14–17

    Article  PubMed  Google Scholar 

  7. Pharmacovigilance Working Party (PhVWP) (2010) Summary Assessment Report of the PhVWP March 2010 Antidepressants—risk of bone fractures. Accessed September

  8. Warden SJ, Robling AG, Sanders MS, Bliziotes MM, Turner CH (2005) Inhibition of the serotonin (5-hydroxytryptamine) transporter reduces bone accrual during growth. Endocrinology 146(2):685–693

    Article  CAS  PubMed  Google Scholar 

  9. Woolcott JC, Richardson KJ, Wiens MO, Patel B, Marin J, Khan KM et al (2009) Meta-analysis of the impact of 9 medication classes on falls in elderly persons. Arch Intern Med 169(21):1952–1960

    Article  PubMed  Google Scholar 

  10. Verdel BM, Souverein PC, Egberts TC, van Staa TP, Leufkens HG, de Vries F (2010) Use of antidepressant drugs and risk of osteoporotic and non-osteoporotic fractures. Bone 47(3):604–609

    Article  CAS  PubMed  Google Scholar 

  11. IMS Health Retail & Hospital Audits Synopsis (2010) 22nd July 2

  12. IMS MIDAS International Data Overview (2005) Basel, 26 October: 37–38

  13. IMI PROTECT Study (2011) Accessed January

  14. Coughlin SS, Benichou J, Weed DL (1994) Attributable risk estimation in case–control studies. Epidemiol Rev 16:51–64

    CAS  PubMed  Google Scholar 

  15. The Register of Medicinal of Product Statistics of the Danish Medicines Agency: Statistics on medicinal products, 2005–2009. Accessed November 2010

  16. The Dutch Drug Information System of the Health Care Insurance Board. Accessed November 2010

  17. Norwegian Institute of Public Health. Norwegian Prescription Database. Accessed November 2010

  18. U.S. Census Bureau, Housing and Household Economic Statistics Division. Last revised: September 21, 2009. Accessed on October 2010

  19. European Commission, Eurostat.>. Accessed October 2010

  20. World Health Organization (editor) (2003) Introduction to drug utilization research. Oslo, Norway

  21. Macera CA, Powell KE (2001) Population attributtable risk: implications of physical activity dose. Med Sci Sports Exerc 33(6 Suppl):S635–S639, discussion 640–1

    Article  CAS  PubMed  Google Scholar 

  22. Guo Z, Wills P, Viitanen M, Fastbom J, Winblad B (1998) Cognitive impairment, drug use, and the risk of hip fracture in persons over 75 years old: a community-based prospective study. Am J Epidemiol 148(9):887–892

    Article  CAS  PubMed  Google Scholar 

  23. Jacqmin-Gadda H, Fourrier A, Commenges D, Dartigues JF (1998) Risk factors for fractures in the elderly. Epidemiology 9(4):417–423

    Article  CAS  PubMed  Google Scholar 

  24. Ensrud KE, Blackwell T, Mangione CM, Bowman PJ, Bauer DC, Schwartz A et al (2003) Central nervous system active medications and risk for fractures in older women. Arch Intern Med 163(8):949–957

    Article  PubMed  Google Scholar 

  25. Spangler L, Scholes D, Brunner RL, Robbins J, Reed SD, Newton KM et al (2008) Depressive symptoms, bone loss, and fractures in postmenopausal women. J Gen Intern Med 23(5):567–574

    Article  PubMed Central  PubMed  Google Scholar 

  26. Ray WA, Griffin MR, Schaffner W, Baugh DK, Melton LJ 3rd (1987) Psychotropic drug use and the risk of hip fracture. N Engl J Med 316(7):363–369

    Article  CAS  PubMed  Google Scholar 

  27. Liu B, Anderson G, Mittmann N, To T, Axcell T, Shear N (1998) Use of selective serotonin-reuptake inhibitors or tricyclic antidepressants and risk of hip fractures in elderly people. Lancet 351(9112):1303–1307

    Article  CAS  PubMed  Google Scholar 

  28. van den Brand MW, Samson MM, Pouwels S, van Staa TP, Thio B, Cooper C et al (2009) Use of anti-depressants and the risk of fracture of the hip or femur. Osteoporos Int 20(10):1705–1713

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Wang PS, Bohn RL, Glynn RJ, Mogun H, Avorn J (2001) Zolpidem use and hip fractures in older people. J Am Geriatr Soc 49(12):1685–1690

    Article  CAS  PubMed  Google Scholar 

  30. Ray WA, Griffin MR, Malcolm E (1991) Cyclic antidepressants and the risk of hip fracture. Arch Intern Med 151(4):754–756

    Article  CAS  PubMed  Google Scholar 

  31. Hubbard R, Farrington P, Smith C, Smeeth L, Tattersfield A (2003) Exposure to tricyclic and selective serotonin reuptake inhibitor antidepressants and the risk of hip fracture. Am J Epidemiol 158(1):77–84

    Article  PubMed  Google Scholar 

  32. Vestergaard P, Rejnmark L, Mosekilde L (2006) Anxiolytics, sedatives, antidepressants, neuroleptics and the risk of fracture. Osteoporos Int 17(6):807–816

    Article  CAS  PubMed  Google Scholar 

  33. Abrahamsen B, Brixen K (2009) Mapping the prescriptiome to fractures in men—a national analysis of prescription history and fracture risk. Osteoporos Int 20(4):585–597

    Article  CAS  PubMed  Google Scholar 

  34. Bauer M, Monz BU, Montejo AL, Quail D, Dantchev N, Demyttenaere K et al (2008) Prescribing patterns of antidepressants in Europe: results from the Factors Influencing Depression Endpoints Research (FINDER) study. Eur Psychiatry 23(1):66–73

    Article  PubMed  Google Scholar 

  35. Takkouche B, Montes-Martinez A, Gill SS, Etminan M (2007) Psychotropic medications and the risk of fracture: a meta-analysis. Drug Saf 30(2):171–184

    Article  PubMed  Google Scholar 

  36. Haney EM, Warden SJ (2008) Skeletal effects of serotonin (5-hydroxytryptamine) transporter inhibition: evidence from clinical studies. J Musculoskelet Neuronal Interact 8(2):133–145

    CAS  PubMed  Google Scholar 

  37. Battaglino R, Fu J, Spate U, Ersoy U, Joe M, Sedaghat L et al (2004) Serotonin regulates osteoclast differentiation through its transporter. J Bone Miner Res 19(9):1420–1431

    Article  CAS  PubMed  Google Scholar 

  38. Diem SJ, Blackwell TL, Stone KL, Yaffe K, Haney EM, Bliziotes MM et al (2007) Use of antidepressants and rates of hip bone loss in older women: the study of osteoporotic fractures. Arch Intern Med 167(12):1240–1245

    Article  PubMed  Google Scholar 

  39. Richards JB, Papaioannou A, Adachi JD, Joseph L, Whitson HE, Prior JC et al (2007) Effect of selective serotonin reuptake inhibitors on the risk of fracture. Arch Intern Med 167(2):188–194

    Article  CAS  PubMed  Google Scholar 

  40. Haney EM, Chan BK, Diem SJ, Ensrud KE, Cauley JA, Barrett-Connor E et al (2007) Association of low bone mineral density with selective serotonin reuptake inhibitor use by older men. Arch Intern Med 167(12):1246–1251

    Article  PubMed  Google Scholar 

  41. Hernandez JF, Mantel-Teeuwisse AK, van Thiel GJ, Belitser SV, Warmerdam J, de Valk V, Raaijmakers JA, Pieters T (2012) A 10-year analysis of the effects of media coverage of regulatory warnings on antidepressant use in the Netherlands and UK. PLoS One 7(9):e45515

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Pratt LA, Brody DJ, Gu Q (2011) Antidepressant use in persons aged 12 and over: United States, 2005–2008. NCHS Data Brief 76:1–8

    PubMed  Google Scholar 

  43. Schneeweiss S, Wang PS (2004) Association between SSRI use and hip fractures and the effect of residual confounding bias in claims database studies. J Clin Psychopharmacol 24(6):632–638

    Article  PubMed  Google Scholar 

Download references

Conflicts of interest

OK has received unrestricted funding for pharmacoepidemiological research from the private-public funded Top Institute Pharma ( DPA has received partial support from unrestricted research grants by AMGEN SA and BIOIBERICA S.A. The authors PK, JG, NJR, and HP were all employees of Roche at the time of conduct of this research. Roche does not produce antidepressant drugs, which are the subject of this publication. JG is currently an employee of Abbott Healthcare Products B.V. in the Netherlands. She conducted this work as part of an internship at Roche when she was a student at Utrecht University.

The research leading to these results was conducted as part of the PROTECT consortium (Pharmacoepidemiological Research on Outcomes of Therapeutics by a European ConsorTium; which is a public-private partnership coordinated by the European Medicines Agency.

The PROTECT project has received support from the Innovative Medicine Initiative Joint Undertaking ( under Grant Agreement no 115004, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution.

In the context of the IMI Joint Undertaking (IMI JU), the Department of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, also received a direct financial contribution from Pfizer. The views expressed are those of the authors only and not of their respective institution or company.

Author information

Authors and Affiliations


Corresponding author

Correspondence to F. de Vries.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Prieto-Alhambra, D., Petri, H., Goldenberg, J.S.B. et al. Excess risk of hip fractures attributable to the use of antidepressants in five European countries and the USA. Osteoporos Int 25, 847–855 (2014).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: