Advertisement

Osteoporosis International

, Volume 24, Issue 2, pp 671–680 | Cite as

Fractures in users of antidepressants and anxiolytics and sedatives: effects of age and dose

  • P. VestergaardEmail author
  • D. Prieto-Alhambra
  • M. K. Javaid
  • C. Cooper
Original Article

Abstract

Summary

Antidepressants have been associated with fractures. In a case–control study, increasing age was associated with more fractures in users of selective serotonin reuptake inhibitors and tricyclic antidepressants, whereas for anxiolytics and sedatives, more fractures were seen among the younger users. Depression per se did not seem associated with fractures.

Introduction

This study aims to study the effects of age and dose of selective serotonin reuptake inhibitors (SSRI), tricyclic antidepressants (TCA) and anxiolytics/sedatives on fracture risk.

Methods

The study was designed as a case–control study. From the Danish National Health Service, we identified 124,655 fracture cases and 373,962 age- and gender-matched controls. Crude odds ratios were estimated, and propensity score adjustment was used to minimise confounding by indication.

Results

A higher risk of fractures was associated with an increasing dose of anxiolytics and sedatives; the highest excess risk was present in the age stratum below 40 years of age (p < 0.01), and thereafter, the excess risk of fractures declined with age. For SSRI, a growing excess risk of fractures was seen with both increasing dose and age. Regarding TCA, no particular trend with age was present. However, an increasing risk of fractures was associated with increasing TCA dose in the age group above 60 years. Finally, for other antidepressants, no particular trend with age or dose was observed. In our data, a hospital diagnosis of depression or manic depression was associated with fewer fractures.

Conclusion

Caution should be shown upon prescription of SSRI to older subjects. A hospital diagnosis of depression or manic depression and thus potentially a more severe disease was not a risk factor for fractures.

Keywords

Antidepressant Fracture Selective serotonin reuptake inhibitors Tricyclic antidepressants 

Notes

Acknowledgments

Danmarks Statistik (Statistics Denmark) is acknowledged for the help, without which this project would not have been possible. This study was made possible through a grant by the A.P. Møller Foundation (Fonden til Lægevidenskabens Fremme) and the Danish Medical Research Council (grant number 22-04-0495). The sponsors had no role in obtaining, analysing and interpreting the data.

Conflicts of interest

None.

References

  1. 1.
    Wu Q, Bencaz AF, Hentz JG, Crowell MD (2012) Selective serotonin reuptake inhibitor treatment and risk of fractures: a meta-analysis of cohort and case-control studies. Osteoporos Int 23:365–375PubMedCrossRefGoogle Scholar
  2. 2.
    Ginzburg R, Rosero E (2009) Risk of fractures with selective serotonin-reuptake inhibitors or tricyclic antidepressants. Ann Pharmacother 43:98–103PubMedCrossRefGoogle Scholar
  3. 3.
    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 158:77–84PubMedCrossRefGoogle Scholar
  4. 4.
    Schwan S, Hallberg P (2009) SSRIs, bone mineral density, and risk of fractures—a review. Eur Neuropsychopharmacol 19:683–692PubMedCrossRefGoogle Scholar
  5. 5.
    Atteritano M, Lasco A, Mazzaferro S, Macrì I, Catalano A, Santangelo A, Bagnato G, Bagnato G, Frisina N (2011) Bone mineral density, quantitative ultrasound parameters and bone metabolism in postmenopausal women with depression. Intern Emerg Med. doi: 10.1007/s11739-011-0628-1
  6. 6.
    Frank L (2000) Epidemiology, When an entire country is a cohort. Science 287:2398–2399PubMedCrossRefGoogle Scholar
  7. 7.
    Andersen T, Madsen M, Jørgensen J, Mellemkjær L, Olsen J (1999) The Danish National Hospital Register. Dan Med Bull 46:263–268PubMedGoogle Scholar
  8. 8.
    Mosbech J, Jørgensen J, Madsen M, Rostgaard K, Thornberg K, Poulsen T (1995) The Danish National Patient Register: evaluation of data quality. Ugeskr Laeger 157:3741–3745PubMedGoogle Scholar
  9. 9.
    Vestergaard P, Mosekilde L (2002) Fracture risk in patients with celiac disease, Crohn's disease, and ulcerative colitis: a nationwide follow-up study in 16,416 patients in Denmark. Am J Epidemiol 156:1–10PubMedCrossRefGoogle Scholar
  10. 10.
    Wacholder S, McLaughlin J, Silverman D, Mandel J (1992) Selection of controls in case-control studies. I. Principles. Am J Epidemiol 135:1019–1028PubMedGoogle Scholar
  11. 11.
    Capella D (1993) Descriptive tools and analysis. In: Dukes MNG (ed) Drug utilization studies: methods and uses. World Health Organization, Copenhagen, pp 55–78Google Scholar
  12. 12.
    Nielsen G, Sørensen H, Zhou W, Steffensen F, Olsen J (1997) The pharmaco-epidemiologic prescription database of North Jutland. Int J Risk Saf Med 10:203–205Google Scholar
  13. 13.
    Munk-Jørgensen P, Mortensen P (1997) The Danish Psychiatric Central Register. Dan Med Bull 44:82–84PubMedGoogle Scholar
  14. 14.
    Austin PC (2008) The performance of different propensity-score methods for estimating relative risks. J Clin Epidemiol 61:537–545PubMedCrossRefGoogle Scholar
  15. 15.
    Oakes JM, Church TR (2007) Invited commentary: advancing propensity score methods in epidemiology. Am J Epidemiol 165:1119–1121, discussion 1122-1123PubMedCrossRefGoogle Scholar
  16. 16.
    Glynn RJ, Schneeweiss S, Stürmer T (2006) Indications for propensity scores and review of their use in pharmacoepidemiology. Basic Clin Pharmacol Toxicol 98:253–259PubMedCrossRefGoogle Scholar
  17. 17.
    Prieto-Alhambra D, Javaid MK, Judge A, Maskell J, Kiran A, de Vries F, Cooper C, Arden NK (2011) Fracture risk before and after total hip replacement in patients with osteoarthritis: potential benefits of bisphosphonate use. Arthritis Rheum 63:992–1001PubMedCrossRefGoogle Scholar
  18. 18.
    Prieto-Alhambra D, Javaid MK, Judge A, Maskell J, Kiran A, Cooper C, Arden NK (2011) Bisphosphonate use and risk of post-operative fracture among patients undergoing a total knee replacement for knee osteoarthritis: a propensity score analysis. Osteoporos Int 22:1555–1571PubMedCrossRefGoogle Scholar
  19. 19.
    Austin PC (2009) Some methods of propensity-score matching had superior performance to others: results of an empirical investigation and Monte Carlo simulations. Biom J 51:171–184PubMedCrossRefGoogle Scholar
  20. 20.
    Sogaard A, Joakimsen R, Tverdal A, Fonnebo V, Magnus J, Berntsen G (2005) Long-term mental distress, bone mineral density and non-vertebral fractures. The Tromsø Study. Osteoporosis Int 16:887–897CrossRefGoogle Scholar
  21. 21.
    Wong S, Lau E, Lynn H, Leung P, Woo J, Cummings S, Orwoll E (2005) Depression and bone mineral density: is there a relationship in elderly Asian men? Results from Mr. Os (Hong Kong). Osteoporosis Int 16:610–615CrossRefGoogle Scholar
  22. 22.
    Mussolino M, Jonas BS, Looker AC (2004) Depression and bone mineral density in young adults: results from NHANES III. Psychosom Med 66:533–537PubMedCrossRefGoogle Scholar
  23. 23.
    Verdel BM, Souverein PC, Egberts TCG, van Staa TP, Leufkens HGM, de Vries F (2010) Use of antidepressant drugs and risk of osteoporotic and non-osteoporotic fractures. Bone 47:604–609PubMedCrossRefGoogle Scholar
  24. 24.
    Vestergaard P, Rejnmark L, Mosekilde L (2008) Selective serotonin reuptake inhibitors and other antidepressants and risk of fracture. Calcif Tissue Int 82:92–101PubMedCrossRefGoogle Scholar
  25. 25.
    Diem SJ, Blackwell TL, Stone KL, Yaffe K, Haney EM, Bliziotes MM, Ensrud KE (2007) Use of antidepressants and rates of hip bone loss in older women: the study of osteoporotic fractures. Arch Intern Med 167:1240–1245PubMedCrossRefGoogle Scholar
  26. 26.
    Haney EM, Chan BK, Diem SJ, Ensrud KE, Cauley JA, Barrett-Connor E, Orwoll E, Bliziotes M, for the Osteoporotic Fractures in Men Study Group (2007) Association of low bone mineral density with selective serotonin reuptake inhibitor use by older men. Arch Intern Med 167:1246–1251CrossRefGoogle Scholar
  27. 27.
    Pollock B (1999) Adverse reactions of antidepressants in elderly patients. J Clin Psychiat 60(Suppl 20):4–8Google Scholar
  28. 28.
    Rodriguez DLT, Dreher J, Malevany I, Bagli M, Kolbinger M, Omran H, Luderitz B, Rao M (2001) Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients. Ther Drug Monit 23:435–440CrossRefGoogle Scholar
  29. 29.
    Christensen P, Thomsen H, Pedersen O, Gram L, Kragh-Sorensen P (1985) Orthostatic side effects of clomipramine and citalopram during treatment for depression. Psychopharmacol (Berl) 86:383–385CrossRefGoogle Scholar
  30. 30.
    Deandrea S, Lucenteforte E, Bravi F, Foschi R, La Vecchia C, Negri E (2010) Risk factors for falls in community-dwelling older people: a systematic review and meta-analysis. Epidemiology 21:658–668PubMedCrossRefGoogle Scholar
  31. 31.
    Tromp AM, Pluijm SM, Smit JH, Deeg DJ, Bouter LM, Lips P (2001) Fall-risk screening test: a prospective study on predictors for falls in community-dwelling elderly. J Clin Epidemiol 54:837–844PubMedCrossRefGoogle Scholar
  32. 32.
    World Health Organization (2003) Prevention and management of osteoporosis. WHO technical report series no 921. WHO, GenevaGoogle Scholar
  33. 33.
    Gagne JJ, Patrick AR, Mogun H, Solomon DH (2011) Antidepressants and fracture risk in older adults: a comparative safety analysis. Clin Pharmacol Ther 89:880–887PubMedCrossRefGoogle Scholar
  34. 34.
    Diem SJ, Blackwell TL, Stone KL, Cauley JA, Hillier TA, Haney EM, Ensrud KE (2011) Use of antidepressant medications and risk of fracture in older women. Calcif Tissue Int 88:476–484PubMedCrossRefGoogle Scholar
  35. 35.
    Vestergaard P, Rejnmark L, Mosekilde L (2008) Anxiolytics and sedatives and risk of fractures: effects of half-life. Calcif Tissue Int 82:34–43PubMedCrossRefGoogle Scholar
  36. 36.
    Aydin H, Mutlu N, Akbas NBG (2011) Treatment of a major depression episode suppresses markers of bone turnover in premenopausal women. J Psychiatr Res 45:1316–1320PubMedCrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2012

Authors and Affiliations

  • P. Vestergaard
    • 1
    Email author
  • D. Prieto-Alhambra
    • 2
    • 3
    • 4
  • M. K. Javaid
    • 4
  • C. Cooper
    • 4
    • 5
  1. 1.Department of Endocrinology and Internal Medicine (MEA)Aarhus University Hospital THGAarhus CDenmark
  2. 2.IDIAP Jordi Gol Primary Care Research InstituteUniversitat Autònoma de BarcelonaBarcelonaSpain
  3. 3.URFOA-IMIM and RETICEFParc de Salut Mar and Instituto de Salud Carlos IIIMadridSpain
  4. 4.Oxford NIHR Musculoskeletal BRU, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal SciencesUniversity of OxfordOxfordUK
  5. 5.MRC Lifecourse Epidemiology UnitUniversity of SouthamptonSouthamptonUK

Personalised recommendations