Alliance between selective serotonin reuptake inhibitors and fracture risk: an updated systematic review and meta-analysis

Eur J Clin Pharmacol. 2020 Oct;76(10):1373-1392. doi: 10.1007/s00228-020-02893-1. Epub 2020 Jun 16.

Abstract

Purpose: In the past few years, several fracture-related events have been reported with chronic use of selective serotonin reuptake inhibitors (SSRIs) throughout the globe. Hence, an updated systematic review and meta-analysis was necessary to ascertain the risk involved. The present work evaluated the association of SSRIs with the risk of fracture in adults.

Methods: We systematically searched PubMed, Cochrane library, and Google Scholar for observational studies on the same from inception to April 2019. Screening, data extraction, and risk of bias assessment were conducted independently by 2 authors.

Results: We assessed 69 studies out of which 37 (14 case-control, 23 cohorts) were included. Our results showed that SSRIs were significantly associated with an increased fracture risk (relative risk of 1.62, 95% CI 1.52-1.73; P < 0.000; I2 = 90.8%). The relative risk values for case-control and cohort studies were found to be 1.80 (95% CI 1.58-2.03; P < 0.000; I2 = 93.2%) and 1.51 (95% CI 1.39-1.64; P < 0.000; I2 = 88.0%) respectively. Subgroup analysis showed that association of risk of fracture persisted regardless of geographical location, study design, risk factors, defined daily dose, SSRI use duration, site of the fracture, period of study and after adjusting for depression, physical activity, gender, and age group. The sensitivity analysis data shows that the studies adjusted for bone mineral density and osteoporosis show lesser fracture risk.

Conclusion: Our findings suggests that SSRIs may be associated with an increased fracture risk; hence, bone health should be taken into consideration while prescribing this class of drugs.

Keywords: Antidepressants; Fracture risk; Meta-analysis; SSRI; Selective serotonin reuptake inhibitors; Systematic review.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Age Factors
  • Dose-Response Relationship, Drug
  • Fractures, Bone / chemically induced*
  • Fractures, Bone / epidemiology
  • Humans
  • Risk Factors
  • Selective Serotonin Reuptake Inhibitors / administration & dosage
  • Selective Serotonin Reuptake Inhibitors / adverse effects*
  • Sex Factors
  • Time Factors

Substances

  • Serotonin Uptake Inhibitors