Alendronate for Osteoporosis Associated With Depression and Anxiety

Researchers recently found the use of alendronate for treatment of osteoporosis was significantly associated with depression and anxiety when compared to other first-line osteoporosis treatments.

While there is an established association between osteoporosis and depression—both prior to and after diagnosis—an association between depressive symptoms and bisphosphonates has also been demonstrated. Bisphosphonates (alendronate, zoledronate, risedronate, and ibandronate) are among the most commonly prescribed first-line treatment for osteoporosis. Other first-line therapies include denosumab, a monoclonal antibody, and teriparatide, a synthetic parathyroid hormone analog.

Researchers used the FDA Adverse Event Reporting System (FAERS)/ Adverse Event Reporting System (AERS) reports to gather data. Additional data coming from World Health Organization (WHO)’s VigiAccess database was used to confirm associations observed in FAERS/AERS reports. The researchers included only FAERS/AERS reports of patients with exclusively osteoporosis indication, being treated with monotherapy. Of those selected, there were 7821 reports for patients on alendronate, 9367 on zoledronate, 1168 on risedronate, and 3727 on ibandronate. Researchers also collected reports of 2 first-line therapies that are not within the bisphosphonates class: denosumab (n = 15,812) and teriparatide (control cohort, n = 45,052). All cohorts were further separated by age (under 65 years or over 65 years).

Researchers found that, for patients aged 65 years or younger, there was a higher odds ratio of both depression and anxiety for alendronate (depression ROR 14.67, 95% CI [11.55–18.63], anxiety ROR 7.10, 95% CI [5.79–8.71]). Of the other monotherapies, only risedronate showed an increase in odds ratio, though this was only true of the depression outcome, and at a lower magnitude than that of alendronate. Zoledronate and denosumab had a statistically significant decrease of anxiety. For patients aged over 65 years, alendronate was the only treatment for which significantly elevated odds ratio of depression and anxiety (3.60 [2.82–4.59], 2.28 [1.84–2.84]) were reported, compared to the teriparatide control. There was a significant decrease of odds ratio of anxiety for the zoledronate, ibandronate, and denosumab cohorts in this age group compared to the control.

The study authors wrote, “alendronate had the strongest association with depression and anxiety among bisphosphonates.” This association was also supported by analysis of the VigiAccess/WHO database. Researchers stated that controlled trials are necessary to determine any clinical causality.

—Allison Casey

Reference:
Keshishi D, Makunts T, Abagyan R. Common osteoporosis drug associated with increased rates of depression and anxiety. Sci Rep. 2021; 11.DOI:10.1038/s41598-021-03214-x.