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Published in: Osteoporosis International 9/2009

Open Access 01-09-2009 | Original Article

Antipsychotic use and the risk of hip/femur fracture: a population-based case–control study

Authors: S. Pouwels, T. P. van Staa, A. C. G. Egberts, H. G. M. Leufkens, C. Cooper, F. de Vries

Published in: Osteoporosis International | Issue 9/2009

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Abstract

Summary

This case–control study showed that current use of conventional antipsychotics, but not atypical antipsychotics, seems to be associated with an increased risk of a hip/femur fracture, possibly related to the pharmacological properties of conventional antipsychotics. Furthermore, no evidence for a dose effect was found.

Introduction

The aim of this study was to assess the risk of hip/femur fracture associated with antipsychotic use, with particular reference to any difference in risk with conventional versus atypical antipsychotics, dose, and pharmacological properties.

Methods

A case–control study was conducted using data from the PHARMO Record Linkage System among individuals aged 18 years and older between 1991 and 2002. Cases had a record of a hip or femur fracture, while controls had no evidence of ever having sustained any fracture.

Results

Most cases were elderly (77.6% aged ≥70 years). We found an increased risk for hip/femur fracture associated with the use of antipsychotic drugs. The risk for current users (ORadj 1.68 [1.43, 1.99]) was significantly greater than with past use (ORadj 1.33 [1.14, 1.56]; p = 0.036). Current use of conventional antipsychotics (ORadj 1.76 [1.48, 2.08]) but not atypical antipsychotics (ORadj 0.83 [0.42, 1.65]) was associated with an increased risk. We did not find evidence for a dose effect.

Conclusion

The use of conventional, but not atypical antipsychotics, seems to be associated with an increased risk of hip/femur fracture, possibly related to the pharmacological properties of conventional antipsychotics. However, the numbers of atypical antipsychotic users were small, and therefore this observation needs further attention in other study populations.
Literature
1.
go back to reference Rang HP et al (1999) Pharmacology, 4th edn. Churchill Livingstone, Edinburgh Rang HP et al (1999) Pharmacology, 4th edn. Churchill Livingstone, Edinburgh
2.
go back to reference Jeste DV, Dolder CR (2004) Treatment of non-schizophrenic disorders: focus on atypical antipsychotics. J Psychiatr Res 38(1):73–103PubMedCrossRef Jeste DV, Dolder CR (2004) Treatment of non-schizophrenic disorders: focus on atypical antipsychotics. J Psychiatr Res 38(1):73–103PubMedCrossRef
3.
go back to reference Neutel CI, Perry S, Maxwell C (2002) Medication use and risk of falls. Pharmacoepidemiol Drug Saf 11(2):97–104PubMedCrossRef Neutel CI, Perry S, Maxwell C (2002) Medication use and risk of falls. Pharmacoepidemiol Drug Saf 11(2):97–104PubMedCrossRef
4.
go back to reference Miyamoto S et al (2005) Treatments for schizophrenia: a critical review of pharmacology and mechanisms of action of antipsychotic drugs. Mol Psychiatry 10(1):79–104PubMedCrossRef Miyamoto S et al (2005) Treatments for schizophrenia: a critical review of pharmacology and mechanisms of action of antipsychotic drugs. Mol Psychiatry 10(1):79–104PubMedCrossRef
5.
go back to reference Melkersson KI, Hulting AL, Rane AJ (2001) Dose requirement and prolactin elevation of antipsychotics in male and female patients with schizophrenia or related psychoses. Br J Clin Pharmacol 51(4):317–324PubMedCrossRef Melkersson KI, Hulting AL, Rane AJ (2001) Dose requirement and prolactin elevation of antipsychotics in male and female patients with schizophrenia or related psychoses. Br J Clin Pharmacol 51(4):317–324PubMedCrossRef
6.
go back to reference Haddad PM, Wieck A (2004) Antipsychotic-induced hyperprolactinaemia: mechanisms, clinical features and management. Drugs 64(20):2291–314PubMedCrossRef Haddad PM, Wieck A (2004) Antipsychotic-induced hyperprolactinaemia: mechanisms, clinical features and management. Drugs 64(20):2291–314PubMedCrossRef
7.
go back to reference Van de Kar LD et al (2001) 5-HT2A receptors stimulate ACTH, corticosterone, oxytocin, renin, and prolactin release and activate hypothalamic CRF and oxytocin-expressing cells. J Neurosci 21(10):3572–3579PubMed Van de Kar LD et al (2001) 5-HT2A receptors stimulate ACTH, corticosterone, oxytocin, renin, and prolactin release and activate hypothalamic CRF and oxytocin-expressing cells. J Neurosci 21(10):3572–3579PubMed
8.
go back to reference Misra M, Papakostas GI, Klibanski A (2004) Effects of psychiatric disorders and psychotropic medications on prolactin and bone metabolism. J Clin Psychiatry 65(12):1607–1618 quiz 1590, 1760–1761PubMedCrossRef Misra M, Papakostas GI, Klibanski A (2004) Effects of psychiatric disorders and psychotropic medications on prolactin and bone metabolism. J Clin Psychiatry 65(12):1607–1618 quiz 1590, 1760–1761PubMedCrossRef
9.
go back to reference Meaney AM et al (2004) Effects of long-term prolactin-raising antipsychotic medication on bone mineral density in patients with schizophrenia. Br J Psychiatry 184:503–508PubMedCrossRef Meaney AM et al (2004) Effects of long-term prolactin-raising antipsychotic medication on bone mineral density in patients with schizophrenia. Br J Psychiatry 184:503–508PubMedCrossRef
10.
go back to reference O’Keane V, Meaney AM (2005) Antipsychotic drugs: a new risk factor for osteoporosis in young women with schizophrenia. J Clin Psychopharmacol 25(1):26–31PubMedCrossRef O’Keane V, Meaney AM (2005) Antipsychotic drugs: a new risk factor for osteoporosis in young women with schizophrenia. J Clin Psychopharmacol 25(1):26–31PubMedCrossRef
11.
go back to reference Diem SJ 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):1240–1245PubMedCrossRef Diem SJ 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):1240–1245PubMedCrossRef
12.
go back to reference Richards JB et al (2007) Effect of selective serotonin reuptake inhibitors on the risk of fracture. Arch Intern Med 167(2):188–194PubMedCrossRef Richards JB et al (2007) Effect of selective serotonin reuptake inhibitors on the risk of fracture. Arch Intern Med 167(2):188–194PubMedCrossRef
13.
go back to reference Howard L, Kirkwood G, Leese M (2007) Risk of hip fracture in patients with a history of schizophrenia. Br J Psychiatry 190:129–134PubMedCrossRef Howard L, Kirkwood G, Leese M (2007) Risk of hip fracture in patients with a history of schizophrenia. Br J Psychiatry 190:129–134PubMedCrossRef
14.
go back to reference Cumming RG, Klineberg RJ (1993) Psychotropics, thiazide diuretics and hip fractures in the elderly. Med J Aust 158(6):414–417PubMed Cumming RG, Klineberg RJ (1993) Psychotropics, thiazide diuretics and hip fractures in the elderly. Med J Aust 158(6):414–417PubMed
15.
go back to reference Liperoti R et al (2007) Conventional or atypical antipsychotics and the risk of femur fracture among elderly patients: results of a case–control study. J Clin Psychiatry 68(6):929–934PubMedCrossRef Liperoti R et al (2007) Conventional or atypical antipsychotics and the risk of femur fracture among elderly patients: results of a case–control study. J Clin Psychiatry 68(6):929–934PubMedCrossRef
16.
go back to reference Ray WA et al (1987) Psychotropic drug use and the risk of hip fracture. N Engl J Med 316(7):363–369PubMed Ray WA et al (1987) Psychotropic drug use and the risk of hip fracture. N Engl J Med 316(7):363–369PubMed
17.
go back to reference Vestergaard P, Rejnmark L, Mosekilde L (2006) Anxiolytics, sedatives, antidepressants, neuroleptics and the risk of fracture. Osteoporos Int 17(6):807–816PubMedCrossRef Vestergaard P, Rejnmark L, Mosekilde L (2006) Anxiolytics, sedatives, antidepressants, neuroleptics and the risk of fracture. Osteoporos Int 17(6):807–816PubMedCrossRef
18.
go back to reference Hugenholtz GW et al (2005) Risk of hip/femur fractures in patients using antipsychotics. Bone 37(6):864–870PubMedCrossRef Hugenholtz GW et al (2005) Risk of hip/femur fractures in patients using antipsychotics. Bone 37(6):864–870PubMedCrossRef
19.
go back to reference Sernbo I, Hansson A, Johnell O (1987) Drug consumption in patients with hip fractures compared with controls. Compr Gerontol [A] 1(3):93–96 Sernbo I, Hansson A, Johnell O (1987) Drug consumption in patients with hip fractures compared with controls. Compr Gerontol [A] 1(3):93–96
20.
go back to reference Buurma H et al (2008) Prevalence and determinants of pharmacy shopping behaviour. J Clin Pharm Ther 33(1):17–23PubMed Buurma H et al (2008) Prevalence and determinants of pharmacy shopping behaviour. J Clin Pharm Ther 33(1):17–23PubMed
21.
go back to reference Herings RM et al (1996) Current use of thiazide diuretics and prevention of femur fractures. J Clin Epidemiol 49(1):115–119PubMedCrossRef Herings RM et al (1996) Current use of thiazide diuretics and prevention of femur fractures. J Clin Epidemiol 49(1):115–119PubMedCrossRef
22.
go back to reference de Vries F et al (2007) Use of inhaled and oral glucocorticoids, severity of inflammatory disease and risk of hip/femur fracture: a population-based case–control study. J Intern Med 261(2):170–177PubMed de Vries F et al (2007) Use of inhaled and oral glucocorticoids, severity of inflammatory disease and risk of hip/femur fracture: a population-based case–control study. J Intern Med 261(2):170–177PubMed
23.
go back to reference de Vries F et al (2007) Use of beta-2 agonists and risk of hip/femur fracture: a population-based case–control study. Pharmacoepidemiol Drug Saf 16(6):612–619PubMedCrossRef de Vries F et al (2007) Use of beta-2 agonists and risk of hip/femur fracture: a population-based case–control study. Pharmacoepidemiol Drug Saf 16(6):612–619PubMedCrossRef
24.
go back to reference de Vries F et al (2007) Use of beta-blockers and the risk of hip/femur fracture in the United Kingdom and The Netherlands. Calcif Tissue Int 80(2):69–75PubMedCrossRef de Vries F et al (2007) Use of beta-blockers and the risk of hip/femur fracture in the United Kingdom and The Netherlands. Calcif Tissue Int 80(2):69–75PubMedCrossRef
25.
go back to reference WHO (2005) WHO Collaborating Centre for drug statistics methodology. The ATC/DDD system. World Health Organisation WHO (2005) WHO Collaborating Centre for drug statistics methodology. The ATC/DDD system. World Health Organisation
26.
go back to reference Becker D et al (2003) Risperidone, but not olanzapine, decreases bone mineral density in female premenopausal schizophrenia patients. J Clin Psychiatry 64(7):761–766PubMedCrossRef Becker D et al (2003) Risperidone, but not olanzapine, decreases bone mineral density in female premenopausal schizophrenia patients. J Clin Psychiatry 64(7):761–766PubMedCrossRef
27.
go back to reference Koda-Kimble MA, Young LY, Kradjan WA (2003) Applied therapeutics: the clinical use of drugs, 7th edn. . Lippincott, Williams & Wilkins, New York Koda-Kimble MA, Young LY, Kradjan WA (2003) Applied therapeutics: the clinical use of drugs, 7th edn. . Lippincott, Williams & Wilkins, New York
28.
go back to reference Speight TM, Holford NHG (1997) Avery’s drug treatment: A guide to the properties, choice, therapeutic use and economic value of drugs in disease management, 4th edn. Adis Press, Auckland Speight TM, Holford NHG (1997) Avery’s drug treatment: A guide to the properties, choice, therapeutic use and economic value of drugs in disease management, 4th edn. Adis Press, Auckland
29.
go back to reference AMAM (1996) American Medical Association. Division of Drugs and Toxicology. Drug Evaluations Annual, Chicago AMAM (1996) American Medical Association. Division of Drugs and Toxicology. Drug Evaluations Annual, Chicago
30.
go back to reference Hummer M et al (2005) Osteoporosis in patients with schizophrenia. Am J Psychiatry 162(1):162–167PubMedCrossRef Hummer M et al (2005) Osteoporosis in patients with schizophrenia. Am J Psychiatry 162(1):162–167PubMedCrossRef
31.
go back to reference Petty RG (1999) Prolactin and antipsychotic medications: mechanism of action. Schizophr Res 35(Suppl):S67–S73PubMedCrossRef Petty RG (1999) Prolactin and antipsychotic medications: mechanism of action. Schizophr Res 35(Suppl):S67–S73PubMedCrossRef
32.
go back to reference Warrel DA, Cox TM, Firth JD (2005) Oxford textbook of medicine, vol. 3. 4th edn. Oxford University Press, Oxford Warrel DA, Cox TM, Firth JD (2005) Oxford textbook of medicine, vol. 3. 4th edn. Oxford University Press, Oxford
33.
go back to reference Grisso JA, Capezuti E, Schwartz A (1996) Falls as risk factors for fractures. In: Marcus D, Kelsey J, Feldman D (eds) Osteoporosis. Academic, San Diego, pp 599–611 Grisso JA, Capezuti E, Schwartz A (1996) Falls as risk factors for fractures. In: Marcus D, Kelsey J, Feldman D (eds) Osteoporosis. Academic, San Diego, pp 599–611
34.
go back to reference Cummings SR et al (1995) Risk factors for hip fracture in white women. Study of osteoporotic fractures research group. N Engl J Med 332(12):767–773PubMedCrossRef Cummings SR et al (1995) Risk factors for hip fracture in white women. Study of osteoporotic fractures research group. N Engl J Med 332(12):767–773PubMedCrossRef
35.
go back to reference Owens DC (1999) A guide to the extrapyramidal side-effects of antipsychotic drugs. Cambridge University Press, Cambridge Owens DC (1999) A guide to the extrapyramidal side-effects of antipsychotic drugs. Cambridge University Press, Cambridge
36.
37.
go back to reference Cauley JA et al (2005) Factors associated with the lumbar spine and proximal femur bone mineral density in older men. Osteoporos Int 16(12):1525–1537PubMedCrossRef Cauley JA et al (2005) Factors associated with the lumbar spine and proximal femur bone mineral density in older men. Osteoporos Int 16(12):1525–1537PubMedCrossRef
38.
go back to reference Alanen HM et al (2006) Use of antipsychotic medications among elderly residents in long-term institutional care: a three-year follow-up. Int J Geriatr Psychiatry 21(3):288–295PubMedCrossRef Alanen HM et al (2006) Use of antipsychotic medications among elderly residents in long-term institutional care: a three-year follow-up. Int J Geriatr Psychiatry 21(3):288–295PubMedCrossRef
39.
go back to reference Jeste DV et al (2008) ACNP white paper: update on use of antipsychotic drugs in elderly persons with dementia. Neuropsychopharmacology 33(5):957–970PubMedCrossRef Jeste DV et al (2008) ACNP white paper: update on use of antipsychotic drugs in elderly persons with dementia. Neuropsychopharmacology 33(5):957–970PubMedCrossRef
40.
go back to reference Melton LJ III et al (1994) Fracture risk in patients with Alzheimer’s disease. J Am Geriatr Soc 42:614–619PubMed Melton LJ III et al (1994) Fracture risk in patients with Alzheimer’s disease. J Am Geriatr Soc 42:614–619PubMed
41.
go back to reference van Staa TP et al (2002) Utility of medical and drug history in fracture risk prediction among men and women. Bone 31:508–514PubMedCrossRef van Staa TP et al (2002) Utility of medical and drug history in fracture risk prediction among men and women. Bone 31:508–514PubMedCrossRef
42.
go back to reference Whooley MA et al (1999) Depression, falls, and risk of fracture in older women. Arch Intern Med 159(5):484–490PubMedCrossRef Whooley MA et al (1999) Depression, falls, and risk of fracture in older women. Arch Intern Med 159(5):484–490PubMedCrossRef
43.
go back to reference Bolton JM et al (2008) Fracture risk from psychotropic medications: a population-based analysis. J Clin Psychopharmacol 28(4):384–391PubMedCrossRef Bolton JM et al (2008) Fracture risk from psychotropic medications: a population-based analysis. J Clin Psychopharmacol 28(4):384–391PubMedCrossRef
Metadata
Title
Antipsychotic use and the risk of hip/femur fracture: a population-based case–control study
Authors
S. Pouwels
T. P. van Staa
A. C. G. Egberts
H. G. M. Leufkens
C. Cooper
F. de Vries
Publication date
01-09-2009
Publisher
Springer-Verlag
Published in
Osteoporosis International / Issue 9/2009
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-008-0826-5

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