NEW ORLEANS –
“Our findings emphasize that bone health should be a priority in the clinical management of bipolar disorder, and that the potential bone-protective effects of lithium should be subjected to further study – both in the context of osteoporosis and bipolar disorder,” said Soren D. Ostergaard, MD, PhD, the study’s first author and a professor in the psychosis research unit, Aarhus (Denmark) University Hospital – Psychiatry.
courtesy Aarhus University
Dr. Soren D. Ostergaard
For the retrospective cohort study, presented at the annual meeting of the American Psychiatric Association, and also published recently in JAMA Psychiatry, the authors reviewed data on 22,912 patients treated for bipolar disorder in Denmark between 1996 and 2019, and compared each patient with 5 age- and sex-matched controls, amounting to 114,560 individuals in the general population.
Of the patients with bipolar disorder, 38.2% were treated with lithium, while 73.6% received an antipsychotic drug; 16.8% received valproate and 33.1% received lamotrigine.
With a median follow-up of 7.7 years, the incidence of osteoporosis per 1,000 person-years was 8.70 among patients with bipolar disorder, compared with an incidence of 7.84 among controls, (hazard rate ratio, 1.15).
The association of bipolar disorder with osteoporosis was notably more pronounced among males (HRR, 1.42) compared with females (HRR, 1.07).
Notably, those with bipolar disorder treated with lithium showed a significantly reduced risk of osteoporosis compared with patients not receiving lithium (HRR, 0.62), after adjustment for factors including age, sex, Charlson Comorbidity Index, use of systemic corticosteroids, use of sedative medication, and eating disorder diagnosis. No similar reductions in osteoporosis risk were observed among those treated with antipsychotics, valproate or lamotrigine.
Of note, the reduced risk of osteoporosis with lithium appeared after about year 2 of treatment (HR, 0.77) and remained steady at more than 4 years (HR, 0.76). A higher cumulative lithium dose was meanwhile associated with a greater decrease in the risk of osteoporosis (P < .001).
Results confirm prior research
The results are consistent with previous smaller studies indicating that people with bipolar disorders shown an increased risk of low bone density, osteopenia, and even fracture.
The higher risk of osteoporosis in bipolar disorder may be explained by lifestyle factors, Dr. Ostergaard noted in an interview.
“It could be the depressive and manic phases in bipolar disorder, but generally speaking, both phases can lead to an unhealthy lifestyle and that’s likely what drives the association between bipolar disorder and osteoporosis,” he said. “Increases in behaviors such as smoking and alcohol consumption may be factors as well. Similar findings are seen with depression.”
While more needs to be understood, Dr. Ostergaard speculated that higher rates of such behaviors in men with bipolar disorder may explain the higher osteoporosis risk observed in men.
In general, however, the increased risk underscores the importance of raising awareness of bone health among patients with bipolar disorder, the authors concluded.
“Specifically, guiding patients toward a lifestyle supporting bone health (no smoking, reduced alcohol consumption, healthy diet, and exercising) and monitoring bone density via dual-energy x-ray absorptiometry scans among those with additional risk factors seems warranted,” they wrote.
The implications of the lithium findings are trickier to determine, Dr. Ostergaard said.
“The evidence for lithium in bipolar disorder are well established, and our findings don’t really add to that,” he said. “The main thing is it suggests there might be some advantages of lithium that we’re not really aware of.”