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Reduced Relative Risk of Fractures Among Users of Lithium

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Abstract

Lithium has been shown to inhibit bone resorption and to interact with Wnt signaling, potentially pointing to bone anabolic properties. We, therefore, studied the effects of lithium on fracture risk using a case–control study design. Cases were all subjects including children with any fracture sustained during the year 2000 (n = 124,655). For each case, three controls (n = 373,962) matched according to age and gender was randomly drawn from the background population. Adjustments were made for use of other psychotropic drugs (neuroleptics, antidepressants, and anxiolytics/sedatives), psychiatric disease (manic depressive states, schizophrenia, and other psychoses), and other confounders. The effect of dose was examined by stratifying for cumulated dose (DDD, defined daily dose). In the crude analysis, there was a decreasing relative risk of any fracture with increasing accumulated dose of lithium. After adjustment for psychotropic drug use, the risk of any fracture was decreased (odds ratio [OR] 0.74, 95% confidence interval [CI] 0.60–0.92 for 250–849 DDD, and OR 0.67, 95% CI 0.55–0.81 for ≥ 850 DDD of lithium). For Colles’ fractures and spine fractures, a significant decrease was seen with ≥ 850 DDD (OR 0.57, 95% CI 0.35–0.94 for Colles’ fracture and OR 0.32, 95% CI 0.11–0.95 for spine fractures). For hip fractures, a nonsignificant trend toward a decrease was seen; however, without a dose-response relationship. Adjustment for further confounders did not change the results. Lithium treatment was associated with a decreased risk of fractures potentially pointing at bone anabolic properties.

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Acknowledgments

Danmarks Statistik (Statistics Denmark) is acknowledged for its assistance, without which this project would not have been possible. Research Librarian Ms.Edith Clausen is acknowledged for invaluable help with the references. The Danish Medical Research Council granted financial support (Grant number 22-04-0495).

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  1. Department of Endocrinology and Metabolism C, Aarhus University Hospital, Aarhus Sygehus, Aarhus, Denmark

    P. Vestergaard, L. Rejnmark & L. Mosekilde

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  1. P. Vestergaard
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Correspondence to P. Vestergaard.

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Vestergaard, P., Rejnmark, L. & Mosekilde, L. Reduced Relative Risk of Fractures Among Users of Lithium. Calcif Tissue Int 77, 1–8 (2005). https://doi.org/10.1007/s00223-004-0258-y

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