Lithium Use and Risk of Fracture: A Systematic Review and Meta-analysis of Observational Studies

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Osteoporosis International

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Summary 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. Introduction 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. Methods 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. Results 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. Conclusion 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


Medicine and Health Sciences



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