Selective Serotonin Reuptake Inhibitor Use and Hip Fracture Risk Among Patients on Hemodialysis

Am J Kidney Dis. 2020 Mar;75(3):351-360. doi: 10.1053/j.ajkd.2019.07.015. Epub 2019 Oct 9.


Rationale & objective: Use of selective serotonin reuptake inhibitors (SSRIs) has been associated with hip fracture risk in the general population. This study examined this relationship among patients with kidney failure treated by hemodialysis, a unique high-risk subpopulation, within which the impact of SSRIs on hip fracture risk remains unexplored.

Study design: Case-control study.

Settings & participants: Eligible cases of hip fracture among maintenance hemodialysis patients between January 1, 2009, and September 30, 2015, were identified using the US Renal Data System. Each case was matched on index date with 10 eligible controls. To be eligible, study participants needed to have more than 1 year of Medicare Parts A and B coverage and more than 3 years of Part D coverage. For a separate examination of new short-term SSRI exposure, we selected cases and controls with more than 18 months of Part D coverage and no prior antidepressant use for 1 year.

Exposure: During the 3-year Part D coverage period, use of SSRIs characterized as any (≥1 prescription filled), low, moderate, and high use (<20%, 20%-<80%, and≥80% of days covered by filled prescriptions, respectively).

Outcome: We selected cases using International Classification of Diseases, Ninth Revision codes 820.xx and 821.xx. In addition to 1 of these codes tied to a hospitalization, we required a corresponding surgical procedural code within 7 days of diagnosis.

Analytic approach: Conditional logistic regression to estimate unadjusted and multivariable-adjusted ORs and 95% CIs.

Results: We identified 4,912 cases and 49,120 controls. SSRI use was associated with increased hip fracture risk (adjusted OR, 1.25; 95% CI, 1.17-1.35). Risk for fracture was estimated for any, low, moderate, and high SSRI use: adjusted conditional ORs were 1.25 (95% CI, 1.17-1.35), 1.20 (95% CI, 1.08-1.32), 1.31 (95% CI, 1.18-1.43), and 1.26 (95% CI, 1.12-1.41), respectively. The association between hip fracture events and SSRI use was also seen in the examination of new short-term use (adjusted OR, 1.43; 95% CI, 1.23-1.67).

Limitations: Biomarkers of mineral bone disorder were not captured and accounted for in this analysis.

Conclusions: We demonstrated an association between increased hip fracture risk and both long- and new short-term SSRI use. The stronger association with new short-term use may suggest an acute mechanism potentially related to falls.

Keywords: End-stage kidney disease (ESKD); USRDS; antidepressants; anxiety; case-control; depression; drug safety; end-stage renal disease (ESRD); hemodialysis; hip fracture; selective-serotonin reuptake inhibitor (SSRI).

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Depression / complications
  • Depression / drug therapy*
  • Female
  • Follow-Up Studies
  • Hip Fractures / epidemiology*
  • Hip Fractures / etiology
  • Humans
  • Incidence
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / therapy*
  • Male
  • Middle Aged
  • Prognosis
  • Renal Dialysis*
  • Retrospective Studies
  • Risk Assessment / methods*
  • Risk Factors
  • Selective Serotonin Reuptake Inhibitors / adverse effects*
  • United States / epidemiology


  • Serotonin Uptake Inhibitors