Reduced Relative Risk of Fractures Among Users of Lithium

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.