Anxiolytics, sedatives, antidepressants, neuroleptics and the risk of fracture. Osteoporos Int

Department of Endocrinology and Metabolism C, Aarhus University Hospital, Aarhus Sygehus, Tage Hansens Gade 2, 8000, Aarhus C, Denmark.
Osteoporosis International (Impact Factor: 4.17). 05/2006; 17(6):807-16. DOI: 10.1007/s00198-005-0065-y
Source: PubMed


Our objective was to study the association between fracture risk and the use of anxiolytics and sedatives (benzodiazepines, etc.), neuroleptics and antidepressants.
This was a case control study. All cases consisted of subjects who had sustained a fracture during the year 2000 (n=124,655). For each case, three controls (n=373,962) matched for age and gender were randomly drawn from the background population. Exposure was defined as the use of neuroleptics, antidepressants and anxiolytics/sedatives, psychiatric disease (manic depressive states, schizophrenia, other psychoses), and other confounders. The effect of dose was examined as a defined daily dose per day (DDD/day). The values referred to are confounder-adjusted.
For anxiolytics and sedatives, there was a small increase in overall fracture risk (OR: around 1.1) even with limited doses (<0.1 DDD/day). No dose-response relationship was observed for anxiolytics and sedatives. For neuroleptics, a limited increase in overall fracture risk was observed (OR: around 1.2 from <0.05 DDD/day with no dose-response relationship). For antidepressants, a dose-response relationship was observed for fracture risk (OR: increasing from 1.15, 95% CI: 1.11-1.19 at <0.15 DDD/day to 1.40, 95% CI: 1.35-1.46 for >or=0.75 DDD/day). The risk of fracture was higher with selective serotonin re-uptake inhibitors than with tricyclic antidepressants.
Small increases in fracture risk were seen with the use of anxiolytics and sedatives and neuroleptics without a dose-response relationship. The increase may be linked to an increased risk of falls. For antidepressants, a dose-response relationship was found, with a higher fracture risk for selective serotonin re-uptake inhibitors.

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Available from: Peter Vestergaard, Oct 07, 2015
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    • "antipsychotics, and antidepressants increase fracture risk by reducing balance [7] [8] [24]. "
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    ABSTRACT: Introduction: In this study we evaluated fracture risk in patients with Charcot-Marie-Tooth (CMT) disease. Methods: We conducted a retrospective cohort study using the UK Clinical Practice Research Datalink (1987-2012). Each patient with CMT disease was matched with up to 6 patients without a history of CMT disease. The outcome measure was fractures. Results: The risk of non-osteoporotic fracture was statistically significantly increased [adjusted hazard ratio (AHR) 1.47, 95% confidence interval (CI) 1.01-2.14], whereas risk of any and osteoporotic fracture did not reach statistical significance compared with control patients [AHR 1.31 (95% CI 0.98-1.74) and AHR 1.10 (95% CI 0.69-1.74), respectively]. Conclusions: CMT patients have a 1.5-fold increased risk for non-osteoporotic fracture. Studies with larger numbers of CMT patients and with additional data on CMT subtype, bone mineral density, and functional status should be performed to confirm a true association between CMT and an increased risk of fracture.
    Muscle & Nerve 12/2014; 50(6). DOI:10.1002/mus.24240 · 2.28 Impact Factor
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    • "Many factors may influence the risk of falls and fractures, such as acute and chronic somatic and mental health conditions, sleep disturbances and physical activity at night, balance impairment, frailty, lifestyle and concomitant drug use [45]. Nevertheless, previous studies have shown the excess risk of hip fracture associated with anxiolytics and hypnotics to remain when adjusting for cognitive and functional status, BMI and smoking [46], and concomitant drug use [8]. Thus, we chose not to adjust for concomitant drug use, which would also have introduced further uncertainty (due to the lack of clinical information). "
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    ABSTRACT: Purpose Anxiolytics and hypnotics are widely used and may cause injurious falls. We aimed to examine associations between exposure to anxiolytics and hypnotics and the risk of hip fracture among all older people in Norway. Further, we wanted to examine associations between exposure to hypnotics and time of fracture. Methods A nationwide prospective cohort study of people in Norway born before 1945 (n = 906,422) was conducted. We obtained information on all prescriptions of anxiolytics and hypnotics dispensed in 2004–2010 (the Norwegian Prescription Database) and all primary hip fractures in 2005–2010 (the Norwegian Hip Fracture Registry). We compared the incidence rates of hip fracture during drug exposure and non-exposure by calculating the standardized incidence ratio (SIR). Results Altogether, 39,938 people (4.4 %) experienced a primary hip fracture. The risk of hip fracture was increased for people exposed to anxiolytics (SIR 1.4, 95 % confidence interval (CI) 1.4–1.5) and hypnotics (SIR 1.2, 95 % CI 1.1–1.2); the excess risk was highest regarding short-acting benzodiazepine anxiolytics (SIR 1.5, 95 % CI 1.4–1.6). Benzodiazepine-like hypnotics (z-hypnotics) were associated with higher excess risk of hip fracture at night (SIR 1.3, 95 % CI 1.2–1.4) than during the day (SIR 1.1, 95 % CI 1.1–1.2). Conclusions Older people had an increased risk of hip fracture during anxiolytic or hypnotic drug use, including short-acting benzodiazepine anxiolytics and z-hypnotics that were previously considered less harmful; cautious prescribing is therefore needed. People using z-hypnotics were at greatest excess risk at night; this association deserves further investigation.
    European Journal of Clinical Pharmacology 07/2014; 70(7). DOI:10.1007/s00228-014-1684-z · 2.97 Impact Factor
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    • "A number of studies have furthermore addressed the long-term effects of 0924-977X/$ -see front matter & 2013 Published by Elsevier B.V. antipsychotics in relation to risk of hip fracture and possible mechanisms behind the association (Howard et al., 2007; Hugenholtz et al., 2005; Pouwels et al., 2009; Vestergaard et al., 2006). A large UK based study found that schizophrenia and prolactin-increasing antipsychotics were associated with increased risk of hip fracture in univariate analyses but in light of a strong association with prolactin-increasing antipsychotics , the effect of schizophrenia did not remain significant (Howard et al., 2007). "
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    ABSTRACT: In a nationwide study using linkage of Danish hospital registers we examined predictors of hip fracture (ICD-10: S72) in 15,431 patients with schizophrenia (ICD-10: F20 or ICD-8: 295) and 3,807,597 population controls. Shorter education, disability pension, lifetime alcohol abuse, somatic co-morbidity, antipsychotics (IRR=1.19; 95% CI 1.15-1.24), antidepressant (IRR=1.18; 95% CI 1.16-1.20), anticholinergics (IRR=1.29; 95% CI 1.22-1.36), benzodiazepines (IRR=1.06; 95% CI 1.04-1.08) and corticosteroids (IRR=1.44; 95% CI 1.36-1.53) were significant predictors. In 556 persons with schizophrenia and hip fracture (matched to 1:3 to schizophrenia controls without hip fracture), antipsychotic polypharmacy predicted hip fracture. Analyses among antipsychotic monotherapy patients showed no differential effect of individual antipsychotics. A dose-response relationship of hip fracture and lifetime antipsychotics consumption was found (IRR=1.13 95% CI 1.07-1.19) and both prolactin-increasing and non-prolactin-increasing antipsychotics contributed to the effect. In conclusion, several factors, including complex psychopharmacological treatment, contribute in the prediction of hip fracture in large populations. Preventive strategies should focus attention to severely ill patients with high likelihood of a receiving complex psychopharmacologic treatment and high doses of antipsychotics.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 05/2013; 23(8). DOI:10.1016/j.euroneuro.2013.04.002 · 4.37 Impact Factor
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