Anxiolytics, sedatives, antidepressants, neuroleptics and the risk of fracture.
BACKGROUND
Our objective was to study the association between fracture risk and the use of anxiolytics and sedatives (benzodiazepines, etc.), neuroleptics and antidepressants.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Vestergaard
P
P
Department of Endocrinology and Metabolism C, Aarhus University Hospital, Aarhus Sygehus, Tage Hansens Gade 2, 8000, Aarhus C, Denmark. p-vest@post4.tele.dk
Rejnmark
L
L
Mosekilde
L
L
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014151:Anti-Anxiety Agents / Q000009:adverse effects*; D000928:Antidepressive Agents / Q000009:adverse effects*; D014150:Antipsychotic Agents / Q000009:adverse effects*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003718:Denmark / Q000453:epidemiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D050723:Fractures, Bone / Q000139:chemically induced* / Q000453:epidemiology; D006753:Hospital Records; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects*; D007223:Infant; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012307:Risk Factors
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D006993:Hypnotics and Sedatives