Lithium and the risk of fractures in patients with bipolar disorder: A population-based cohort study.

Lithium is considered to be the most effective mood stabilizer for bipolar disorder. Evolving evidence suggested lithium can also regulate bone metabolism which may reduce the risk of fractures. While there are concerns about fractures for antipsychotics and mood stabilizing antiepileptics, very little is known about the overall risk of fractures associated with specific treatments. This study aimed to compare the risk of fractures in patients with bipolar disorder prescribed lithium, antipsychotics or mood stabilizing antiepileptics (valproate, lamotrigine, carbamazepine). Among 40,697 patients with bipolar disorder from 1993 to 2019 identified from a primary care electronic health record database in the UK, 13,385 were new users of mood stabilizing agents (lithium:2339; non-lithium: 11,046). Lithium was associated with a lower risk of fractures compared with non-lithium treatments (HR 0.66, 95 % CI 0.44-0.98). The results were similar when comparing lithium with prolactin raising and sparing antipsychotics, and individual antiepileptics. Lithium use may lower fracture risk, a benefit that is particularly relevant for patients with serious mental illness who are more prone to falls due to their behaviors. Our findings could help inform better treatment decisions for bipolar disorder, and lithium's potential to prevent fractures should be considered for patients at high risk of fractures.
Competing Interests: Declaration of competing interest Esther W. Chan has received grants from Research Grants Council (RGC, Hong Kong), Research Fund Secretariat of the Food and Health Bureau, National Natural Science Fund of China, Bayer, Bristol-Myers Squibb, Pfizer, Janssen, Novartis, Amgen, AstraZeneca, Takeda, the RGA Reinsurance Company, Narcotics Division of the Security Bureau of the Hong Kong Special Administrative Region, the National Health and Medical Research Council Australia; consulting fees from AstraZeneca, Pfizer and Novartis; and honorarium from the Hospital Authority Hong Kong, outside the submitted work. Joseph F. Hayes has received consultancy fees from Wellcome Trust and juli Health. Kenneth K.C. Man received the CW Maplethorpe Fellowship, grants from the National Institute for Health Research (United Kingdom), the European Union Horizon 2020 Framework, Innovation and Technology Commission of the Hong Kong Special Administration Region Government, and Hong Kong Research Grant Council and personal fees from IQVIA Holdings, Inc., unrelated to this work. Ian C.K.Wong received research grants from Amgen, Janssen, GSK, Novartis, Pfizer, Bayer and Bristol-Myers Squibb and Takeda, Institute for Health Research in England, European Commission, National Health and Medical Research Council in Australia, The European Union's Seventh Framework Programme for research, technological development, Research Grants Council Hong Kong and Health and Medical Research Fund Hong Kong; consulting fee from IQVIA and WHO; payment for expert testimony for Appeal Court in Hong Kong; serves on advisory committees for Member of Pharmacy and Poisons Board; Member of the Expert Committee on Clinical Events Assessment Following COVID-19 Immunization; Member of the Advisory Panel on COVID-19 Vaccines of the Hong Kong Government; is the non-executive director of Jacobson Medical in Hong Kong; is the Founder and Director of Therakind Limited (UK), Advance Data Analytics for Medical Science (ADAMS) Limited (HK), Asia Medicine Regulatory Affairs (AMERA) Services Limited and OCUS Innovation Limited (HK, Ireland and UK). Ching-Lung Cheung received research grants and the honorarium from Amgen, research grant support from HMRF, and the honorarium from Abbott. Wallis C.Y. Lau reports grant from Diabetes UK, AIR@InnoHK administered by Innovation and Technology Commission, outside the submitted work. Vanessa W.S. Ng, Miriam T.Y. Leung, and David P.J. Osborn declare no conflict of interest.
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