Benzodiazepines increase hip fracture risk

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The use of benzodiazepines and related drugs increases the risk of hip fracture by 43% in persons with Alzheimer’s disease, according to a new study from the University of Eastern Finland.

The hip fracture risk was investigated in community-dwelling Finns with Alzheimer’s disease.

In total, 21% of persons with Alzheimer’s disease initiated benzodiazepine and related drug use during the study. During benzodiazepine and related drug use, 2.5 hip fractures occurred per 100 person-years whereas without drug use, the incidence was 1.4 hip fractures per 100 person-years. The use of benzodiazepines and related drugs increased the hip fracture risk especially during the first six months of drug use. There was no difference within the drug group, as benzodiazepines increased the hip fracture risk as much as benzodiazepine-related drugs.

Additionally, long-term hospital stays exceeding four months after hip fracture were more common in persons with Alzheimer’s disease who used benzodiazepines and related drugs at the time of hip fracture than in persons who did not use such drugs.

Treatment guidelines in different countries recommend that behavioural and psychological symptoms of dementia should be treated with nonpharmacological options. Benzodiazepines and related drugs can be used in infrequent or short-term treatment of symptoms. The results of this study highlight the importance of the guidelines to avoid adverse events associated with benzodiazepine and related drug use.

The study was based on the MEDALZ (MEDication use and ALZheimer’s disease) cohort, including all Finnish persons diagnosed with Alzheimer’s disease between 2005 and 2011, amounting to 70,718 persons. This study involved 46,373 persons who had no history of hip fractures and who had not used benzodiazepines and related drugs during the year preceding the study. The follow-up time in the study was up to five years.


Objectives: To investigate the association between benzodiazepine and related drug (BZDR) use and hip fracture as well as postfracture mortality and duration of hospital stay in community-dwellers with and without Alzheimer disease (AD).
Design: Retrospective cohort study.
Setting: The register-based Medication Use and Alzheimer’s disease (MEDALZ) study, including all community-dwelling persons diagnosed with AD in Finland during 2005–2011 (n = 70,718) and their matched comparison persons without AD.
Participants: Persons without BZDR use during the year preceding the AD diagnosis or the corresponding matching date as well as persons without history of hip fracture were included in this study.
Measurements: We investigated the risk of hip fracture associated with BZDR use compared with nonuse separately in persons with and without AD. Further, we investigated the association between BZDR use during hip fracture and 1-year mortality as well as longer than a 4-month hospital stay after hip fracture. Associations were reported as hazard ratios and odds ratios with 95% confidence intervals (CI).
Results: BZDR use was associated with an increased risk of hip fracture in persons with and without AD (adjusted hazard ratio 1.4 [95% CI 1.2–1.7] and 1.6 [95% CI 1.3–1.9], respectively). BZDR use during hip fracture was associated with longer than 4-month postfracture hospital stay in persons with AD [adjusted odds ratio 1.9 (95% CI 1.3–2.8)] but not in comparison persons. One-year mortality was not associated with BZDR use during hip fracture.
Conclusions: Higher threshold in prescribing BZDRs for neuropsychiatric symptoms might decrease the hip fracture rate and affect the length of hospital stay in persons with AD.

Laura Saarelainen, Anna-Maija Tolppanen, Marjaana Koponen, Antti Tanskanen, Reijo Sund, Jari Tiihonen, Sirpa Hartikainen, Heidi Taipale

University of Eastern Finland material
Journal of the American Medical Doctors Association

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