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Anxiolytics, sedatives, antidepressants, neuroleptics and the risk of fracture

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Abstract

Introduction: Our objective was to study the association between fracture risk and the use of anxiolytics and sedatives (benzodiazepines, etc.), neuroleptics and antidepressants. Subjects and 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 ≥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.

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Acknowledgements

Danmarks Statistik (Statistics Denmark) is acknowledged for the help without which this project would not have been possible. Research Librarian ms. Edith Clausen is acknowledged for invaluable help with the references.

The Danish Medical Research Council granted financial support (Grant number 22-04-0495).

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Authors and Affiliations

  1. Department of Endocrinology and Metabolism C, Aarhus University Hospital, Aarhus Sygehus, Tage Hansens Gade 2, 8000, Aarhus  C, Denmark

    P. Vestergaard, L. Rejnmark & L. Mosekilde

  2. The Osteoporosis Clinic, Aarhus Amtssygehus, Tage Hansens Gade 2, 8000, Aarhus C, Denmark

    P. Vestergaard

Authors
  1. P. Vestergaard
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  2. L. Rejnmark
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  3. L. Mosekilde
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Corresponding author

Correspondence to P. Vestergaard.

Appendix: Codes used

Appendix: Codes used

ATC codes

Anxiolytics and sedatives: N05BA01, N05BA02, N05BA04, N05BA06, N05BA08, N05BA09, N05BA12, N05BB01, N05BE01, N05CC01, N05CD02, N05CD03, N05CD05, N05CD06, N05CD08, N05CD09, N05CF01, N05CF02, N05CF03, N05CM02

Neuroleptics: N05AA01, N05AA02, N05AA04, N05AB02, N05AB03, N05AB04, N05AC01, N05AC02, N05AD01, N05AD03, N05AD05, N05AE05, N05AF01, N05AF03, N05AF05, N05AG02, N05AG03, N05AH02, N05AH03, N05AH04, N05AK01, N05AL01, N05AL05, N05AX08

Antidepressants: N06AA09, N06AA04, N06AA16, N06AA12, N06AA02, N06AA10, N06AA06, N06AA21, N06AX03, N06AX16, N06AX11, N06AB04, N06AB10, N06AB03, N06AB08, N06AB05, N06AB06, N06AX18, N06AF01, N06AG02

ICD8 and 10 codes for psychiatric disorders:

Manic depressive states: ICD8 codes 29609, 29619, 29629, 29639, 29689, 29699, IDC10 codes F300, F301, F302, F308, F309, F310–F319, F320–F329, F330–F339

Schizophrenia: ICD8 codes 29509, 29519, 29529, 29539, 29549, 29559, 29569, 29579, 29589, 29599, IDC10 codes F200–F209

Other psychoses: ICD8 codes 29209, 29219, 29229, 29239, 29299, 29309, 29319, 29329, 29339, 29349, 29359, 29399, 29409, 29419, 29429, 29430, 29438, 29439, 29449, 29489, 29499, 29709, 29719, 29799, 29809, 29819, 29829, 29839, 29889, 29899, 29900, 29901, 29902, 29903, 29904, 29905, 29909, IDC10 codes F220, F228, F229, F230–F233, F238, F239, F249, F250, F251, F252, F258, F259, F289, F299, F340, F341, F348, F349, F380, F381, F388, F399

Eating disorders: ICD8 codes 30658, 30659, IDC10 codes F502, F503, F504, F505, F508, F509

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Vestergaard, P., Rejnmark, L. & Mosekilde, L. Anxiolytics, sedatives, antidepressants, neuroleptics and the risk of fracture. Osteoporos Int 17, 807–816 (2006). https://doi.org/10.1007/s00198-005-0065-y

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