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

  • Pharmacodynamics
  • Published:
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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.

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Data availability

The authors declare that the data supporting the findings of this study are available within the article (and its Supplementary Information files).

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Acknowledgments

We are grateful to UGC-SAP DRS-II, DST-FIST program of Department of Pharmacology, and the Jamia Hamdard Pharmaceutical Medicine Program in collaboration with Sun Pharma Ltd. for financial support.

Funding

The financial support was provided by Sun Pharmaceutical Industries Ltd. in the form of fellowship.

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Authors and Affiliations

  1. Pharmaceutical Medicine, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India

    Manoj Kumar & Divya Vohora

  2. Research Institute for Primary Care and Health Sciences, Keele University, Keele, Staffordshire, ST5 5BG, UK

    Ram Bajpai

  3. Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India

    Abdul Rahaman Shaik & Divya Vohora

  4. Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, Directorate General of Health Services, Government of India, New Delhi, 110002, India

    Swati Srivastava

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Contributions

MK and DV conceived the original idea. DV supervised the project. SS, MK, and ARS searched databases and performed the selection of the studies; MK and ARS completed the data extraction; MK and ARS performed the quality assessment of the included studies; MK, RB, ARS, and DV wrote the manuscript; RB analyzed and interpreted the data. All authors provided crucial feedback and helped to shape the investigation, analysis, and preparation of the manuscript.

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Correspondence to Divya Vohora.

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Kumar, M., Bajpai, R., Shaik, A.R. et al. Alliance between selective serotonin reuptake inhibitors and fracture risk: an updated systematic review and meta-analysis. Eur J Clin Pharmacol 76, 1373–1392 (2020). https://doi.org/10.1007/s00228-020-02893-1

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