Lithium Reduces Osteoporosis

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A study in JAMA Psychiatry reveals another potential benefit of lithium treatment. Bipolar patients in general have a significantly higher rate of osteoporosis than the general population, for reasons that are not clear, but could have to do with treatment with antipsychotic medications, a higher rate of alcohol use and a higher rate of tobacco consumption. Thus it is noteworthy that this study shows that lithium protects against osteoporosis.

In fact, lithium is the only treatment with a clear, dose dependent, protective effect.

Association Between the Cumulative Dose of Lithium, Antipsychotics, Valproate, and Lamotrigine Treatment of Bipolar Disorder and the Risk of OsteoporosisThe cumulative dose was calculated based on the period from the index date through the 5 years following. Patients were then followed up from the date 5 years after the index date until osteoporosis, death, or January 1, 2019, whichever came first. The incidence rates of osteoporosis were compared between patients who received treatment (corresponding to the cumulative doses outlined in the figure) and patients who did not, stratified by cumulative dose. The hazard rate ratios (HRR) were adjusted for age, sex, Charlson Comorbidity Index, use of systemic corticosteroids, use of sedative medication, and any eating disorder diagnosis. The P values for the log-rank tests of dose-response associations were as follows: lithium, P < .001; antipsychotics, P = .13; valproate, P = .13; and lamotrigine, P = .30. DDD indicates defined daily dose; HR, hazard ratio.

The authors note that there is evidence to suggest that lithium’s effects are mediated by the stimulation of bone formation through activation of β-catenin via inhibition of glycogen synthase kinase-3β. This effect has led to an ongoing study of lithium as a potential treatment designed to improve the outcomes of bone fractures (see Nam, et al below).

There are a number of other studies derived from the same large database of all the individuals ever treated for a psychiatric disorder since 1970 in Denmark.


Köhler-Forsberg O, Rohde C, Nierenberg AA, Østergaard SD. Association of Lithium Treatment With the Risk of Osteoporosis in Patients With Bipolar Disorder. JAMA Psychiatry. Published online March 30, 2022. doi:10.1001/jamapsychiatry.2022.0337
Nam  D, Balasuberamaniam  P, Milner  K,  et al.  Lithium for Fracture Treatment (LiFT): a double-blind randomised control trial protocol.   BMJ Open. 2020;10(1):e031545. doi:10.1136/bmjopen-2019-031545

Mors O, Perto GP, Mortensen PB. The Danish Psychiatric Central Research Register. Scandinavian Journal of Public Health. 2011;39(7_suppl):54-57. doi:10.1177/1403494810395825