Use of dopaminergic drugs and risk of hip or femur fracture: A population-based case-control study

Background: Dopaminergic drugs (DD) are often used in the treatment of Parkinson's Disease (PD). DD may increase bone mineral density, but the clinically more important risk of hip fractures is not clear. A substantial number of patients with PD suffers from depression and use antidepressants. Both have been previously identified as independent risk factors for hip fractures. Objectives: To study the effect of DD on the risk of hip/femur fractures. Methods: A casecontrol study in the Dutch PHARMO database (1991-2002) was conducted. Cases (n=6763) aged 18+ with a first hip or femur fracture during enrolment were matched to up to 4 control patients (n=26341) by year of birth, sex and region. Exposure to DD was measured before the index date and stratified to time since discontinuation, and to drug class of DD. We estimated the risk of hip fracture using conditional logistic regression analysis and adjusted for disease and drug history. Results: Current DD use (1-30 days before the index date) increased risk of hip/femur fractures compared to never use (adjusted [adj.] OR 1.86; 95%CI: 1.48-2.34), and vs. patients who had discontinued use of DD for > 3 months (adj. OR 2.31; 95% CI 1.32-4.02). There were no risk differences between the classes of DD. Concomitant current use of antidepressants and DD further increased the risk of hip/femur fractures (adj. OR 3.68; 95%CI: 2.19-6.18). It was also significantly increased compared to use of DD with no antidepressants (adj. OR 2.13; 95% CI 1.21-3.75). Conclusions: Current DD use is associated with a nearly two fold risk of hip/femur fractures. Concomitant use of antidepressants further increases the risk of hip/ femur fractures. Although the observed association may be confounded by the severity of PD, fracture risk assessment may be indicated among elderly patients using DD and antidepressants.