One of the side effects of using antidepressant medications of the SSRI class (selective serotonin reuptake inhibitors) may be an increased risk of bone loss and fractures. A study published September 5 in Nature Medicine shows that in mice, the SSRI fluoxetine (Prozac) affects bone formation in two ways that could lead to bone loss. (SSRI antidepressants are taken by millions of people, and are sold under many other brand names including Paxil, Zoloft, Celexa and others.)

The research team, led by Patricia Ducy, Ph.D., an associate professor of pathology and cell biology at New York’s Columbia University, also discovered that giving the mice a beta-blocker drug along with an SSRI antidepressant could prevent bone loss. Beta blockers are usually prescribed to treat high blood pressure. Scientific Council Member and a 2008 Distinguished Investigator grantee J. John Mann, M.D., was also on the research team.

In the first three weeks of treatment with fluoxetine, the drug prevented osteoclasts -- cells that break down bone tissue -- from developing and functioning properly. At first, this effect boosted bone mass in the mice. But six weeks into the treatment, fluoxetine triggered a secondary response, where altered serotonin signaling in the brain produced by the drug triggered an increase in signaling by epinephrine, acting as a neuromediator, or transmitter, of messages. This in turn led to increased bone resorption, thereby counteracting the initial anti-resorption effect produced by fluoxetine. Resorption is the natural process where bone material is broken down and its minerals are absorbed by the body.

When the mice received a low dose of the beta-blocker drug propanol along with fluoxetine, however, the beta-blocker decreased epinephrine signaling and as a result prevented bone loss.

The team is not able to say whether the mechanisms observed in the mice are the same as those operating in humans. If the mechanisms are the same in humans, the findings may suggest a new way to block bone loss side effects in patients taking SSRI antidepressants.

The researchers note that the dual effects on bone loss that they observe in this study are consistent with some clinical observations in human patients. They also point out that there may be some variation in how different SSRI drugs affect bone loss, which, they say, should be further studied.