Split by light: the antidepressant fluoxetine can cause bone loss Antonio Romero/SPL

Antidepressants may be bad for your bones. People who take some selective serotonin reuptake inhibitors (SSRI) have been found to have a higher risk of fractures, but it wasn’t clear whether this was due to the drug or their depression.

“It’s a puzzling question,” says Patricia Ducy at Columbia University, New York. But her team have now found that giving mice fluoxetine – the active ingredient in Prozac – for six weeks causes them to lose bone mass.

The team identified a two-stage process by measuring bones, blood and gene activity. During the first three weeks, bones grew stronger as the fluoxetine impaired osteoclasts, cells that usually deplete bone tissue. But by six weeks, the higher levels of serotonin prompted by the drug disrupted the ability of the hypothalamus region of the brain to promote bone growth.


“We see bone gain, but it’s not long-lasting, and is rapidly overwhelmed by the negative effects,” says Ducy.

Two-step process

She says this two-phase pattern is also seen in people. In the short term, those who take fluoxetine are less likely to break a bone, but the risk of bone depletion and fractures rises when they have been taking the drug for a year or more.

“This elegant work provides a mechanism for how a widely prescribed SSRI affects bone,” says René Rizzoli of Geneva University Hospital in Switzerland. Until now, it has been difficult to tell if depression itself may have been causing bone fractures through lifestyle changes such as smoking and drinking more, and eating a poorer diet.

Other SSRI drugs may not have the same effects. Ducy’s team found that citalopram didn’t have any positive or negative impact on bones.

Journal reference: Nature Medicine, DOI: 10.1038/nm.4166

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