"The findings were in line with our hypothesis," Dr. Ole Köhler-Forsberg of Aarhus University Hospital-Psychiatry in Denmark told Reuters Health by email. "It is more surprising that the entire correlation between bipolar disorder, lithium and osteoporosis has been understudied."
"As bipolar disorder and osteoporosis are rather frequent on the population level, and as individuals with bipolar disorder often suffer from comorbid somatic conditions, these findings are important," he said. "Lithium should be prioritized in patients with bipolar disorder based on the 70-year history of its efficacy in treating mood episodes."
As reported in JAMA Psychiatry, the retrospective cohort study included 22, 912 adults (median age, 50.4; 56.6%, women) from the Danish Psychiatric Central Research Register who received an initial diagnosis of bipolar disorder from 1996 to 2019, and 114,560 randomly selected age- and sex-matched reference individuals.
Among patients, 38.2% received lithium; 73.6%, an antipsychotic; 16.8%, valproate; and 33.1%, lamotrigine (not mutually exclusive).
The primary outcome was osteoporosis, identified via hospital diagnoses and prescribed medications.
Participants were followed for 1,213,695 person-years (median, 7.68 years).
The incidence of osteoporosis per 1,000 person-years was 8.70 among patients and 7.90 among reference individuals (hazard rate ratio, 1.14).
Those who received lithium had a decreased risk of osteoporosis (HRR, 0.62) compared with those who did not.
By contrast, treatment with antipsychotics, valproate, or lamotrigine was not associated with a decreased risk of osteoporosis.
The authors write, "These findings suggest that bone health should be a priority in the clinical management of bipolar disorder and that the potential bone-protective properties of lithium should be subjected to further study, both in the context of bipolar disorder and in osteoporosis."
Dr. Paul Rosenfeld, associate professor of psychiatry at the Icahn School of Medicine at Mount Sinai and Director of psychiatry education and training at Mount Sinai Morningside/West, commented on the study in an email to Reuters Health.
"The authors have made a compelling case for the increased risk of osteoporosis in bipolar disorder and the unique capacity of lithium - among bipolar medications - to reduce the risk of osteoporosis," he said.
The study is retrospective, he said, "but it still makes a powerful case for the findings. Also it relies only on hospital diagnoses of osteoporosis and records of prescribed medication to identify cases, rather than quantitative measures of osteoporosis such as bone density scans, but overall they have adjusted for many potential confounding variables and acknowledge the limitations."
"This study adds a further argument in favor of lithium for patients with bipolar disorder," he continued. "But there are already many compelling reasons to consider lithium for bipolar disorder," including its efficacy for episodes of mania and depression, reduction of suicide risk, and reducing the risk of dementia.
"That said," he added, "clinicians need to monitor for serious side effects such as lithium toxicity from an elevated blood level...and adverse kidney and thyroid effects that can develop over time."
SOURCE: https://bit.ly/3jcrrFY JAMA Psychiatry, online March 30, 2022.
By Marilynn Larkin
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