Bipolar disorder and its treatments may have very different implications for bone health, a retrospective cohort study found.
Among nearly 23,000 patients with bipolar disorder, the incidence rate of osteoporosis was 8.70 per 1,000 person-years compared with 7.90 per 1,000 person-years for an age- and sex-matched reference group (hazard rate ratio [HRR] 1.14, 95% CI 1.08-1.20), reported Søren Dinesen Østergaard, MD, PhD, of Aarhus University Hospital in Denmark, and colleagues in JAMA Psychiatry.
However, certain treatments for bipolar disorder appeared to not only offset this risk, but significantly reduce it. In a fully adjusted model, those with bipolar disorder who were on lithium -- 38.2% of patients -- saw a reduced risk for osteoporosis compared with those not on lithium (HRR 0.62, 95% CI 0.53-0.72).
"This [finding] resonates well with prior studies" that "suggested a potentially bone-protective effect of lithium, likely mediated by its activation of β-catenin via inhibition of glycogen synthase kinase-3β," Østergaard and team wrote.
But duration of treatment appeared to play a significant role in this benefit. Only patients on lithium who fell into the highest categories of exposure over time -- over 730 cumulative daily doses -- saw their risk for osteoporosis drop:
- >730 to 1,460 cumulative daily doses: HR 0.77 (95% CI 0.64-0.93)
- >1,460 cumulative daily doses: HR 0.76 (95% CI 0.58-0.99)
This wasn't the case for other bipolar disorder treatments though, including antipsychotics, valproate, and lamotrigine.
"[A]s new treatment modalities for osteoporosis are sorely needed, the potential bone protective effect of lithium should be subjected to further study," the researchers noted, adding that a future randomized clinical trial should look at the effects of lithium on bone healing for patients with long bone fractures.
Notably, the link between bipolar disorder and osteoporosis wasn't equitable between the sexes. Although the overall incidence of osteoporosis was lower in men than women, the association between bipolar disorder and osteoporosis was far higher for men:
- Male patients: HRR 1.42 (95% CI 1.26-1.60)
- Female patients: HRR 1.07 (95% CI 1.01-1.13)
The study's findings aren't exactly new, but simply add to the "growing body of evidence suggesting that bone health should be a priority in the clinical management of bipolar disorder," Østergaard and colleagues wrote. Previous studies have indicated an increased risk for fractures, low bone mineral density, and osteopenia among bipolar disorder patients.
"[G]uiding 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 added.
Data for the study came from a nationwide Danish register and included 22,912 patients with incident bipolar disorder diagnosed from 1996 to 2019 (median age 50.4, 56.6% women), who were paired with 114,560 age- and sex-matched reference individuals.
Over a median follow-up of 7.68 years, 1,585 patients with bipolar disorder and 8,146 reference individuals developed osteoporosis.
Osteoporosis was identified via hospital discharge diagnoses and prescribed medications rather than more quantitative measures of bone health, such as DXA scans, which may have led to an underreporting of osteoporosis diagnoses, Østergaard and colleagues acknowledged.
Disclosures
Østergaard reported support from the Novo Nordisk Foundation, the Lundbeck Foundation, the Danish Cancer Society, the Central Denmark Region Fund for Strengthening of Health Science, the Danish Agency for Digitisation Investment Fund for New Technologies, and the Independent Research Fund Denmark. Several co-authors also reported disclosures.
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