Osteoporosis International

, Volume 30, Issue 2, pp 257–266 | Cite as

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

  • B. Liu
  • Q. WuEmail author
  • S. Zhang
  • A. Del Rosario
Original Article



This systematic review and meta-analysis summarized the results from nine eligible observational studies. Lithium use was significantly associated with a decrease risk of fractures.


The association between lithium use and risk of fracture is uncertain. To date, there have been no meta-analyses that have studied the association between the two. We conducted a systematic review and meta-analysis to examine the effect of lithium medication on the risk of fracture.


A comprehensive literature search was performed in PubMed, Embase, and MEDLINE to include eligible observational studies. Three reviewers conducted the literature search, study selection, study appraisal, and data abstraction independently. Random effects models were used to obtain the overall estimate for meta-analysis. Cochran’s Q and Higgins’ I2 were used to assess heterogeneity. A funnel plot and Egger’s regression test were employed to assess publication bias.


Of the 3819 studies that were identified by our search strategy, eight were eligible for the systematic review, while seven of them qualified for the meta-analysis. In studies that reported risk ratio (RR) of fracture as an outcome (five studies [n = 1,134,722]), lithium use was associated with a 20% decrease in risk of fracture (RR = 0.80; 95% CI, 0.73–0.87; p < 0.01). A decreased risk of fracture associated with lithium was also observed in studies that adjusted for previous fractures (RR = 0.81; 95% CI, 0.73–0.89; p < 0.01). The decreased risk of fracture associated with lithium use remained consistent in all the analyses with different inclusion criteria. Neither significant heterogeneity nor significant publication bias was observed.


The present systematic review and meta-analysis demonstrated that lithium use was associated with a significant decreased risk of fracture.


Bone fracture Lithium Meta-analysis Osteoporosis Systematic review 



Bone mineral density


Confidence interval


Hazard ratio


Meta-analysis of Observational Studies in Epidemiology


Preferred Reporting Items for Systematic Review and Meta-analyses


Odds ratio


Risk ratio or relative risk


Research Electronic Data Capture



We thank X Goodman for her advice on the literature search strategy.

Sources of funding

The project was supported by the Fund of Knowledge from the University of Nevada, Las Vegas.

Compliance with ethical standards

Role of sponsors 

In the data collection, management, analysis, and interpretation and in the preparation, review, approval, and study design of the manuscript, funding sponsors were not involved.

Conflicts of interest


Supplementary material

198_2018_4745_MOESM1_ESM.docx (58 kb)
Supplemental Table 1 (DOCX 57.7 kb)
198_2018_4745_MOESM2_ESM.docx (44 kb)
Supplemental Table 2 (DOCX 43.6 kb)


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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2018

Authors and Affiliations

  1. 1.Nevada Institute of Personalized Medicine, Department of Environmental & Occupational Health, School of Community Health SciencesUniversity of Nevada, Las VegasLas VegasUSA
  2. 2.Department of Mathematical SciencesUniversity of Nevada, Las VegasLas VegasUSA
  3. 3.Department of Environmental & Occupational Health, School of Community Health SciencesUniversity of Nevada, Las VegasLas VegasUSA

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