Osteoporosis International

, Volume 30, Issue 6, pp 1167–1173 | Cite as

Metformin use and risk of fracture: a systematic review and meta-analysis of observational studies

  • A. Salari-Moghaddam
  • O. Sadeghi
  • A. H. Keshteli
  • B. Larijani
  • A. EsmaillzadehEmail author
Review Article



No study is available summarizing earlier publications on the association between metformin use and risk of fracture. This systematic review and meta-analysis were conducted to summarize earlier findings on the association between metformin use and risk of fracture.


We conducted a systematic search on all published articles up to October 2018 using online databases including PubMed/Medline, ISI Web of Science, and Scopus. Observational studies that considered metformin use as the exposure variable and bone fracture as the main outcome variable or as one of the outcome variables and participants included were 18 years and older were included in the systematic review. Publications in which hazard ratios (HRs), rate or risk ratios (RRs), or odds ratios (ORs) were reported as effect size were included in the meta-analysis.


Totally, three cohort studies, one cross-sectional study, one nested case-control study, and one case-control study were included in this systematic review and meta-analysis. When seven effect sizes from six studies were combined, a significant inverse association between metformin use and risk of fracture was observed (RR 0.82; 95% CI 0.72, 0.93). No significant between-study heterogeneity was found (I2 = 22.4%, Pheterogeneity = 0.25). In addition, no evidence of publication bias was seen using Egger’s test (P = 0.99).


We found that metformin use was inversely associated with the risk of fracture.


Fracture Metformin Meta-analysis Systematic review 



Advanced glycation end products


Bone mineral density


Confidence interval




Hazard ratio




Newcastle-Ottawa Scale


Odds ratio


Reactive oxygen species


Risk ratio


Standard error



The authors wish to thank Cheryl Nickurak RD, Edmonton, Canada, for her help in editing the final version of the manuscript.

Author’s contribution

ASM and OS contributed to the conception, design, search, statistical analyses, data interpretation, and manuscript drafting. AHK contributed to the manuscript drafting. BL contributed to the design, data interpretation, and manuscript drafting. AE contributed to the conception, design, statistical analyses, data interpretation, and manuscript drafting. AE supervised the study. All authors approved the final manuscript for submission.

Funding information

This study was financially supported by the Tehran University of Medical Sciences, Tehran, Iran.

Compliance with ethical standards

Conflicts of interest



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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2019

Authors and Affiliations

  • A. Salari-Moghaddam
    • 1
    • 2
  • O. Sadeghi
    • 1
  • A. H. Keshteli
    • 3
    • 4
  • B. Larijani
    • 5
  • A. Esmaillzadeh
    • 2
    • 6
    • 7
    Email author
  1. 1.Students’ Scientific Research CenterTehran University of Medical SciencesTehranIran
  2. 2.Department of Community Nutrition, School of Nutritional Sciences and DieteticsTehran University of Medical SciencesTehranIran
  3. 3.Department of MedicineUniversity of AlbertaEdmontonCanada
  4. 4.Integrative Functional Gastroenterology Research CenterIsfahan University of Medical SciencesIsfahanIran
  5. 5.Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences InstituteTehran University of Medical SciencesTehranIran
  6. 6.Obesity and Eating Habits Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences InstituteTehran University of Medical SciencesTehranIran
  7. 7.Department of Community Nutrition, School of Nutrition and Food ScienceIsfahan University of Medical SciencesIsfahanIran

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