Are selective serotonin reuptake inhibitors associated with fractures?

Antidepressant use in North America is on the rise. From 2007 to 2011, antidepressants were the most commonly used medication class by Canadian women aged 25 to 79 years and among the top 5 classes of drugs used by men aged 25 to 64 years.1 Selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, paroxetine, sertraline) are one of the most widely used classes of antidepressants because of their efficacy, favourable side effect profile and broad indications for use.2 In the past decade, more attention has been paid to the adverse effects of medications on bone health. Glucocorticoids, aromatase inhibitors (e.g., anastrazole, letrozole, exemestane), thiazolidinediones or “glitazones” (e.g., pioglitazone) and proton pump inhibitors (e.g., pantoprazole, omeprazole), among others, are suspected contributors to fractures.3 There is evidence indicating that SSRIs may also be implicated.3 In patients aged 66 years and older, current exposure to SSRIs has been associated with hip fractures compared with no antidepressant exposure (adjusted odds ratio [aOR]; 2.4; 95% CI: 2.0-2.7).4 One-third of women and one-fifth of men in Canada will experience an osteoporotic fracture during their lifetime. In 2010, osteoporosis and fractures cost the Canadian health care system upwards of 2.3 billion dollars.5 Fractures can cause a loss of long-term mobility and increase the risk of institutionalization. A prospective observational cohort of older adults showed that 12 months after a hip fracture, only half of patients regained their prefracture mobility level and only one-third of those who were previously mobile without an aid regained full mobility.6 A Canadian cohort (2001-2006) revealed that 12 months after a hip fracture, 24% of adults aged 75 years and older who were previously living in the community required institutionalization.7 However, that risk was much lower in patients aged 60 to 74 years, in whom only 14% of men and 4% of women required a transfer to a long-term care institution.7 Fractures are also associated with mortality, with 28% of women and 37% of men who experience a hip fracture dying within a year.5 It is therefore increasingly important to quantify the association between SSRIs and bone health. This review will discuss the current evidence that explores their association with an increased fracture risk.