Antipsychotic Drugs and Risk of Hip Fracture in People Aged 60 and Older in Norway

Marit S. Bakken, MD, PhD; Jan Schjøtt, MD, PhD; Anders Engeland, MSc, PhD; Lars B. Engesæter, MD, PhD; Sabine Ruths, MD, PhD


J Am Geriatr Soc. 2016;64(6):1203-1209. 

In This Article


The study population comprised 906,422 people with a mean age of 72.8 ± 8.9 on January 1, 2005 (56% women). Mean follow-up was 5.2 ± 1.6 years; 218,775 people died (53% women), and 4,949 emigrated (44% women).

Eight percent of the study population was exposed to an antipsychotic drug during the study period; 66% were women (Table 2). For both sexes, drug use was most prevalent in individuals born from 1920 to 1924 and 1925 to 1929 (data not shown). Of users of antipsychotic drugs, 62% purchased more than one prescription (71% of those who experienced a hip fracture).

During the study period, 39,938 individuals (4.4%) experienced a primary hip fracture; 72% of hip fractures occurred among women. Mean age at the time of fracture was 83.

Most fractures in people exposed to antipsychotics occurred in those born from 1925 to 1934 (39%) and 1915 to 1924 (33%).

Table 1 shows that the associations between overall use of any antipsychotic drug and hip fracture were stable at the population level when SIRs were calculated for the number of days corresponding to 1.0, 0.5, or 0.25 DDDs. In women, the SIRs decreased with increasing estimated time of exposure. The opposite was true in men, but the differences between the sexes were small.

Table 3 compares the incidence of hip fracture during overall exposed person-time (number of days corresponding to the 0.5 DDDs prescribed) with the incidence of hip fracture during overall unexposed person-time. The risk of hip fracture was greater in people exposed to any antipsychotic drug (SIR = 2.1, 95% CI = 1.9–2.1). Generally, the observed excess risk was higher in exposed men (SIR = 2.3, 95% CI = 2.0–2.7) than in exposed women (SIR = 2.0, 95% CI = 1.8–2.2). The risk decreased with increasing age. There were too few hip fractures in people born before 1915 to yield representative results.

Subgroups of Antipsychotics

Greater risk of hip fracture was associated with exposure to any antipsychotic (SIR = 2.1, 95% confidence interval (CI) = 1.9–2.1), first-generation antipsychotics (SIR = 2.0, 95% CI = 1.8–2.2), second-generation antipsychotics (SIR = 2.2, 95% CI = 1.9–2.4), prolactin-sparing antipsychotics (clozapine, quetiapine, aripiprazole) (SIR = 2.4, 95% CI = 1.8–3.1) and prolactin-elevating antipsychotics (e.g., chlorpromazine, haloperidol, olanzapine, risperidone) (SIR = 2.0, 95% CI = 1.9–2.2). The percentage of hip fractures attributable to exposure to any antipsychotic drug at the population level was an estimated 0.9% (Table 3).

Recently Started Drug use

Subanalysis for recently started antipsychotic drug use revealed that 48 individuals fractured their hips during the first 14 days of exposure to any antipsychotic drug after a 360-day washout period (whole population: SIR = 1.8, 95% CI = 1.3–2.4; women: SIR = 1.7, 95% CI = 1.2–2.3; men: SIR = 2.2, 95% CI = 1.2–3.8). Within all subgroups, except for antipsychotics with low risk of increasing prolactin levels (n = 4 with nonsignificant results), the excess risk of hip fracture was higher in exposed men than in exposed women (not shown).