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Benzodiazepines and the Risk of Falling Leading to Femur Fractures: Dosage More Important Than Elimination Half-life

Benzodiazepines and the Risk of Falling Leading to Femur Fractures: Dosage More Important Than... Abstract Background: In the past decade, the use of benzodiazepines has been identified as a major independent risk factor for accidental falls. Objective: To study the role of dosing, timing, elimination half-life, and type of benzodiazepine in relation to the occurrence of accidental falls leading to hospitalization for femur fractures. Methods: A 1:3 age-, sex-, and pharmacy-matched case-control study was performed using data from a Dutch record linkage system (PHARMO) (N=300 000). Cases included 493 patients (55 years and older), newly admitted to the hospital for a femur fracture resulting from an accidental fall (between 1986 and 1992). Relative risk estimates were calculated using conditional logistic regression analyses to control for the potential confounding effects of concomitant drug use and presence of a wide range of underlying diseases. Results: Falls were significantly associated with current use of benzodiazepines (odds ratio, 1.6; 95% confidence interval, 1.2 to 2.1) and in particular with short half-life benzodiazepines (odds ratio, 1.5; 95% confidence interval, 1.1 to 2.0), sudden dose increases (odds ratio, 3.4; 95% confidence interval, 1.0 to 11.5),and concomitant use of several benzodiazepines (odds ratio, 2.5; 95% confidence interval, 1.3 to 4.9). A strong dose-response relationship (P<.0001) and dose-response relations among users of either short or long half-life benzodiazepines suggests that these increased risks are explained primarily by dose. Conclusions: Benzodiazepines are a major, independent risk factor for falls leading to femur fractures, and the increased risk is probably explained by prescribing too-high doses to the elderly.(Arch Intern Med. 1995;155:1801-1807) References 1. Ray WA. Psychotropic drugs and injuries among the elderly: a review. J Clin Psychopharmacol . 1992;12:386-396. 2. Ray WA, Griffin MR, Schaffner W, Baugh DK, Melton LJ. Psychotropic drug use and the risk of hip fracture. N Engl J Med . 1987;316:363-369.Crossref 3. Ray WA, Griffin MR, Downey W. Benzodiazepines of long and short elimination half-life and the risk of hip fracture. JAMA . 1989;262:3303-3307.Crossref 4. Cumming RG, Klineberg RJ. Psychotropics, thiazide diuretics and hip fractures in the elderly. Med J Aust . 1993;158:414-417. 5. Lichtenstein MJ, Griffin MR, Cornell JE, Malcolm E, Ray W. Risk factors for hip fractures occurring in the hospital. Am J Epidemiol . 1994;140:830-838. 6. Cumming RG, Miller JP, Kelsey JL, et al. Medications and multiple falls in elderly people: the St Louis OASIS Study. Age Ageing . 1991;20:455-461.Crossref 7. Sorock GS, Shimkin EE. Benzodiazepine sedatives and the risk of falling in a community-dwelling elderly cohort. Arch Intern Med . 1988;148:2441-2444.Crossref 8. Sobel KG, McCart GM. Drug use and accidental falls in an intermediate care facility. Drug Intell Clin Pharmacy . 1983;17:539-542. 9. Granek E, Baker SP, Abbey H, et al. Medications and diagnoses in relation to falls in a long-term care facility. J Am Geriatr Soc . 1987;35:503-511. 10. Malmivaara A, Heliovaara M, Knekt P, Reunanen A, Aromaa A. Risk factors for injurious falls leading to hospitalization or death in a cohort of 19,500 adults. Am J Epidemiol . 1993;138:384-394. 11. Ryynänen O-P, Kivelä S-L, Honkanen R, Laippala P, Saano V. Medications and chronic diseases as risk factors for falling injuries in the elderly. Scand J Soc Med . 1993;4:264-271. 12. Joseph KS. The evolution of clinical practice and time trends in drug effects. J Clin Epidemiol . 1994;47:539-538.Crossref 13. Herings RMC. PHARMO: A Record Linkage System for Postmarketing Surveillance of Prescription Drugs in the Netherlands . Utrecht, the Netherlands: Dept of Pharmacoepidemiology, Utrecht University; 1993. Dissertation. 14. Howe GR, Lindsay J. A generalized iterative record linkage computer system for use in medical follow-up studies. Comp Biomed Res . 1981;14:327-340.Crossref 15. Gill LE, Baldwin JA. Methods and technology of record linkage: some practical considerations. In: Baldwin JA, Acheson ED, Graham WJ, eds. Textbook of Medical Record Linkage . New York, NY: Oxford University Press; 1987;39-55. 16. Anatomical Therapeutic Classification (ATC) Index: Including Defined Daily Doses (DDD) for Plain Substances . Oslo, Norway: World Health Organization; 1992. 17. Kuy van der A, ed. Farmacotherapeutisch Kompas . Amstelveen, the Netherlands: Centrale Medische Commissie van de Ziekenfondsraad; 1992. 18. Ray WA, Griffin MR, Malcolm E. Cyclic antidepressants and the risk of hip fracture. Arch Intern Med . 1991;151:754-756.Crossref 19. Ray WA, Fought RL, Decker MD. Psychoactive drugs and the risk of injurious motor vehicle crashes in the elderly drivers. Am J Epidemiol . 1992;136:873-883.Crossref 20. Shorr RI, Griffin MR, Daugherty JR, Ray WA. Opioid analgesics and the risk of hip fracture in the elderly: codeine and propoxyphene. J Gerontol . 1992;47: M111-M115.Crossref 21. Buchner DN, Larson EB. Falls and fractures in patients with Alzheimer-type dementia. JAMA . 1987;257:1492-1495.Crossref 22. Hansiota P, Broste SK. The effect of diabetes mellitus on the risk of automobile accidents. N Engl J Med . 1991;324:22-26.Crossref 23. Kiel DP, Felson DT, Anderson JJ, Wilson PWF, Moskowitz MA. Hip fracture and the use of estrogens in postmenopausal women. N Engl J Med . 1987; 317:1169-1174.Crossref 24. Krumholz A, Fisher RS, Lesser RP, Hauser A. Driving and epilepsy. JAMA . 1991;265:622-626.Crossref 25. McMurdo MET, Gaskell A. Dark adaptation and falls in the elderly. Gerontology . 1991;37:221-224.Crossref 26. Sambrook P, Birmingham J, Kelly P, et al. Prevention of corticoid osteoporosis: a comparison of calcium, calcitrol and calcitonin. N Engl J Med . 1993; 328:1747-1752.Crossref 27. Deyo RA, Cherkin DC, Ciol MA. Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol . 1992;45:613-619.Crossref 28. Von Korff M, Wagner EH, Saunders K. A chronic disease score from automated pharmacy data. J Clin Epidemiol . 1992;45:197-203.Crossref 29. Tinetti ME, Speechley MS, Ginter SF. Risk factors for falls among elderly persons living in the community. N Engl J Med . 1988;319:1701-1707.Crossref 30. EGRET . Seattle, Wash: Statistic and Epidemiology Research Corp; 1993. 31. O'Loughlin JL, Robitaille Y, Boivin J-F, Suissa S. Incidence of and risk factors for falls and injurious falls among the community-dwelling elderly. Am J Epidemiol . 1993;137:342-354. 32. Nelson DE, Sattin RW, Langlois JA, DeVito CA, Stevens JA. Alcohol as a risk factor for fall injury events among elderly persons living in the community. JAm Geriatr Soc . 1992;40:658-661. 33. van Steveninck AL, Schoemaker HC, den Hartigh J, Pieters MSM, Breimer DD, Cohen AF. Effects of intravenous temazepam, II: a study on the long-term reproducibility of pharmacokinetics, pharmacodynamics, and concentration-effect parameters. Clin Pharmacol Ther . 1994;55:546-555.Crossref 34. Kahn HA, Sempos CT. Statistical Methods in Epidemiology . New York, NY: Oxford University Press; 1989. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

Benzodiazepines and the Risk of Falling Leading to Femur Fractures: Dosage More Important Than Elimination Half-life

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Publisher
American Medical Association
Copyright
Copyright © 1995 American Medical Association. All Rights Reserved.
ISSN
0003-9926
eISSN
1538-3679
DOI
10.1001/archinte.1995.00430160149015
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Abstract

Abstract Background: In the past decade, the use of benzodiazepines has been identified as a major independent risk factor for accidental falls. Objective: To study the role of dosing, timing, elimination half-life, and type of benzodiazepine in relation to the occurrence of accidental falls leading to hospitalization for femur fractures. Methods: A 1:3 age-, sex-, and pharmacy-matched case-control study was performed using data from a Dutch record linkage system (PHARMO) (N=300 000). Cases included 493 patients (55 years and older), newly admitted to the hospital for a femur fracture resulting from an accidental fall (between 1986 and 1992). Relative risk estimates were calculated using conditional logistic regression analyses to control for the potential confounding effects of concomitant drug use and presence of a wide range of underlying diseases. Results: Falls were significantly associated with current use of benzodiazepines (odds ratio, 1.6; 95% confidence interval, 1.2 to 2.1) and in particular with short half-life benzodiazepines (odds ratio, 1.5; 95% confidence interval, 1.1 to 2.0), sudden dose increases (odds ratio, 3.4; 95% confidence interval, 1.0 to 11.5),and concomitant use of several benzodiazepines (odds ratio, 2.5; 95% confidence interval, 1.3 to 4.9). A strong dose-response relationship (P<.0001) and dose-response relations among users of either short or long half-life benzodiazepines suggests that these increased risks are explained primarily by dose. Conclusions: Benzodiazepines are a major, independent risk factor for falls leading to femur fractures, and the increased risk is probably explained by prescribing too-high doses to the elderly.(Arch Intern Med. 1995;155:1801-1807) References 1. Ray WA. Psychotropic drugs and injuries among the elderly: a review. J Clin Psychopharmacol . 1992;12:386-396. 2. Ray WA, Griffin MR, Schaffner W, Baugh DK, Melton LJ. Psychotropic drug use and the risk of hip fracture. N Engl J Med . 1987;316:363-369.Crossref 3. Ray WA, Griffin MR, Downey W. Benzodiazepines of long and short elimination half-life and the risk of hip fracture. JAMA . 1989;262:3303-3307.Crossref 4. Cumming RG, Klineberg RJ. Psychotropics, thiazide diuretics and hip fractures in the elderly. Med J Aust . 1993;158:414-417. 5. Lichtenstein MJ, Griffin MR, Cornell JE, Malcolm E, Ray W. Risk factors for hip fractures occurring in the hospital. Am J Epidemiol . 1994;140:830-838. 6. Cumming RG, Miller JP, Kelsey JL, et al. Medications and multiple falls in elderly people: the St Louis OASIS Study. Age Ageing . 1991;20:455-461.Crossref 7. Sorock GS, Shimkin EE. Benzodiazepine sedatives and the risk of falling in a community-dwelling elderly cohort. Arch Intern Med . 1988;148:2441-2444.Crossref 8. Sobel KG, McCart GM. Drug use and accidental falls in an intermediate care facility. Drug Intell Clin Pharmacy . 1983;17:539-542. 9. Granek E, Baker SP, Abbey H, et al. Medications and diagnoses in relation to falls in a long-term care facility. J Am Geriatr Soc . 1987;35:503-511. 10. Malmivaara A, Heliovaara M, Knekt P, Reunanen A, Aromaa A. Risk factors for injurious falls leading to hospitalization or death in a cohort of 19,500 adults. Am J Epidemiol . 1993;138:384-394. 11. Ryynänen O-P, Kivelä S-L, Honkanen R, Laippala P, Saano V. Medications and chronic diseases as risk factors for falling injuries in the elderly. Scand J Soc Med . 1993;4:264-271. 12. Joseph KS. The evolution of clinical practice and time trends in drug effects. J Clin Epidemiol . 1994;47:539-538.Crossref 13. Herings RMC. PHARMO: A Record Linkage System for Postmarketing Surveillance of Prescription Drugs in the Netherlands . Utrecht, the Netherlands: Dept of Pharmacoepidemiology, Utrecht University; 1993. Dissertation. 14. Howe GR, Lindsay J. A generalized iterative record linkage computer system for use in medical follow-up studies. Comp Biomed Res . 1981;14:327-340.Crossref 15. Gill LE, Baldwin JA. Methods and technology of record linkage: some practical considerations. In: Baldwin JA, Acheson ED, Graham WJ, eds. Textbook of Medical Record Linkage . New York, NY: Oxford University Press; 1987;39-55. 16. Anatomical Therapeutic Classification (ATC) Index: Including Defined Daily Doses (DDD) for Plain Substances . Oslo, Norway: World Health Organization; 1992. 17. Kuy van der A, ed. Farmacotherapeutisch Kompas . Amstelveen, the Netherlands: Centrale Medische Commissie van de Ziekenfondsraad; 1992. 18. Ray WA, Griffin MR, Malcolm E. Cyclic antidepressants and the risk of hip fracture. Arch Intern Med . 1991;151:754-756.Crossref 19. Ray WA, Fought RL, Decker MD. Psychoactive drugs and the risk of injurious motor vehicle crashes in the elderly drivers. Am J Epidemiol . 1992;136:873-883.Crossref 20. Shorr RI, Griffin MR, Daugherty JR, Ray WA. Opioid analgesics and the risk of hip fracture in the elderly: codeine and propoxyphene. J Gerontol . 1992;47: M111-M115.Crossref 21. Buchner DN, Larson EB. Falls and fractures in patients with Alzheimer-type dementia. JAMA . 1987;257:1492-1495.Crossref 22. Hansiota P, Broste SK. The effect of diabetes mellitus on the risk of automobile accidents. N Engl J Med . 1991;324:22-26.Crossref 23. Kiel DP, Felson DT, Anderson JJ, Wilson PWF, Moskowitz MA. Hip fracture and the use of estrogens in postmenopausal women. N Engl J Med . 1987; 317:1169-1174.Crossref 24. Krumholz A, Fisher RS, Lesser RP, Hauser A. Driving and epilepsy. JAMA . 1991;265:622-626.Crossref 25. McMurdo MET, Gaskell A. Dark adaptation and falls in the elderly. Gerontology . 1991;37:221-224.Crossref 26. Sambrook P, Birmingham J, Kelly P, et al. Prevention of corticoid osteoporosis: a comparison of calcium, calcitrol and calcitonin. N Engl J Med . 1993; 328:1747-1752.Crossref 27. Deyo RA, Cherkin DC, Ciol MA. Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol . 1992;45:613-619.Crossref 28. Von Korff M, Wagner EH, Saunders K. A chronic disease score from automated pharmacy data. J Clin Epidemiol . 1992;45:197-203.Crossref 29. Tinetti ME, Speechley MS, Ginter SF. Risk factors for falls among elderly persons living in the community. N Engl J Med . 1988;319:1701-1707.Crossref 30. EGRET . Seattle, Wash: Statistic and Epidemiology Research Corp; 1993. 31. O'Loughlin JL, Robitaille Y, Boivin J-F, Suissa S. Incidence of and risk factors for falls and injurious falls among the community-dwelling elderly. Am J Epidemiol . 1993;137:342-354. 32. Nelson DE, Sattin RW, Langlois JA, DeVito CA, Stevens JA. Alcohol as a risk factor for fall injury events among elderly persons living in the community. JAm Geriatr Soc . 1992;40:658-661. 33. van Steveninck AL, Schoemaker HC, den Hartigh J, Pieters MSM, Breimer DD, Cohen AF. Effects of intravenous temazepam, II: a study on the long-term reproducibility of pharmacokinetics, pharmacodynamics, and concentration-effect parameters. Clin Pharmacol Ther . 1994;55:546-555.Crossref 34. Kahn HA, Sempos CT. Statistical Methods in Epidemiology . New York, NY: Oxford University Press; 1989.

Journal

Archives of Internal Medicine – American Medical Association

Published: Sep 11, 1995

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