Adherence to treatment with selective serotonin reuptake inhibitors and the risk for fractures and bone loss: a population-based cohort study

CNS Drugs. 2012 Jun 1;26(6):537-47. doi: 10.2165/11633300-000000000-00000.


Background: Selective serotonin reuptake inhibitors (SSRIs) are suspected of increasing the risk of bone loss and osteoporotic fractures.

Objective: The aim of this study was to investigate the association between adherence to SSRI treatment and the risk of bone loss-related events.

Methods: The data used in this retrospective cohort study are part of the ongoing medical documentation routinely collected in a large health maintenance organization in Israel. Specifically, we used the information collected between January 2004 and April 2010. The study cohort included 10 621 women who were new users of SSRIs. Bone loss-related events were defined as fractures or initiation of bisphosphonate treatment. Adherence level was assessed by calculating the proportion of days covered (PDC) with an SSRI from the date of first dispensed SSRI (index date) to the end of follow-up and was categorized as low (PDC ≤20%), intermediate (PDC 21-79%) and high (PDC ≥80%). To validate the study model, we conducted a similar analysis on patients using antiepileptic drugs, which are known to be positively associated with an increased risk of osteoporotic fractures.

Results: Higher adherence to SSRI treatment was significantly associated with an increased risk of bone loss-related events in a dose-response manner. The adjusted hazard ratio for bone loss-related events adjusted for age, physician visits and body mass index in patients who were covered with an SSRI for 21-79% of the time and 80% or more of the time was 1.15 (95% CI 0.97, 1.37) and 1.40 (95% CI 1.14, 1.73) compared with patients who were covered for less than 21% of the follow-up period.

Conclusion: Exposure to SSRI treatment is associated with an increased risk of bone loss-related events. Further studies are required to determine the causality of the association and its relevance to the clinical use of SSRIs.

MeSH terms

  • Adult
  • Anticonvulsants / adverse effects
  • Bone Demineralization, Pathologic / chemically induced
  • Bone Demineralization, Pathologic / epidemiology*
  • Cohort Studies
  • Diphosphonates / therapeutic use
  • Dose-Response Relationship, Drug
  • Female
  • Fractures, Bone / chemically induced
  • Fractures, Bone / epidemiology*
  • Humans
  • Israel / epidemiology
  • Medication Adherence / statistics & numerical data*
  • Middle Aged
  • Risk Factors
  • Selective Serotonin Reuptake Inhibitors / adverse effects*
  • Selective Serotonin Reuptake Inhibitors / therapeutic use


  • Anticonvulsants
  • Diphosphonates
  • Serotonin Uptake Inhibitors