Anxiolytics and sedatives and risk of fractures: effects of half-life.
To study the risk of fractures associated with anxiolytics, sedatives, and hypnotics, we conducted a case-control study. Cases were all subjects with any fracture during the year 2000 (n = 124,655). For each case, three controls (n = 373,962) matched on age and gender were randomly drawn from the background population. The exposure was use of any anxiolytic, sedative, or hypnotics. Adjustments were made for a number of potential confounders. Most anxiolytics, sedatives, and hypnotics were associated with a limited increase in the risk of fractures. There was a dose-response relationship, and drugs with a half-life longer than 24 h were associated with a trend toward a higher relative risk of fractures than drugs with a shorter half-life. Both current use (last use <1 year ago) and past use (last use more than one year ago) were associated with an increased risk of fractures. We conclude that anxiolytics, sedatives, and hypnotics are associated with a limited increase in the risk of fractures. For most drugs a dose-response relationship was present, and drugs with a half-life >24 h tended to be associated with a higher risk of fractures than drugs with a shorter half-life. This points to a dose-dependent risk of, for example, falls leading to fractures. However, the increased risk of fractures with past use may suggest an effect of the condition for which the drug was prescribed rather than the drug per se (confounding by indication).
Vestergaard
Peter
P
Department of Endocrinology and Metabolism C, Aarhus University Hospital, Aarhus University, Aarhus, Denmark. p-vest@post4.tele.dk
Rejnmark
Lars
L
Mosekilde
Leif
L
D000058:Accidental Falls / Q000706:statistics & numerical data*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015986:Confounding Factors, Epidemiologic; D003718:Denmark / Q000453:epidemiology; D004305:Dose-Response Relationship, Drug; D004363:Drug Utilization / Q000706:statistics & numerical data; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology*; D006207:Half-Life; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism / Q000493:pharmacokinetics; D008658:Inactivation, Metabolic; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D012042:Registries / Q000706:statistics & numerical data; D012307:Risk Factors; D013997:Time Factors
D014151:Anti-Anxiety Agents; D006993:Hypnotics and Sedatives