Bone Fracture Risk Goes Up With Certain Antidepressants

SSRIs prescribed to treat menopausal symptoms of hot flashes and night sweats increased women's risk of bone fractures.

An interview with Caroline Messer, MD

A class of antidepressant drugs, known as selective serotonin reuptake inhibitors (SSRIs), that are prescribed to reduce the symptoms of menopause may increase the risk of a bone fracture, according to the result of a study in the journal Injury Prevention.1

“SSRIs appear to increase fracture risk among middle-aged [menopausal] women without psychiatric disorders, an effect sustained over time, suggesting that shorter duration of treatment may decrease fracture risk,” the authors wrote. “Future efforts should examine whether this association pertains at lower doses of SSRIs.”

Study Design

The study looked at women between the ages of 40 and 64, and included information from approximately  61 million patients in nearly 100 managed care plans in the United States. It found that the increased fracture risk appeared to last for a few years.

When compared with study participants who took drugs for indigestion, the fracture rate for those who took SSRIs was 76% higher 1 year after initiating treatment, 73% after 2 years, and 67% after 5 years of treatment.1

Some drugs typically taken for indigestion, such as proton pump inhibitors and H2 blockers, are known to cause bone loss, explained Caroline Messer, MD, an endocrinologist at Lenox Hill Hospital in New York City. The study was simply comparing SSRIs to those known contributors to bone loss, she told Practical Pain Management.

In their article, the researchers theorize that the higher fracture risk may be explained in part by “antidepressant-related modulation of bone homeostasis in favor of osteoclastic activity.” Osteoclasts are cells that break down the bony matrix, said Dr. Messer.

What this means is that the SSRIs may actually shift the balance of bone turnover, causing thinning, rather than strengthening, of bones. And this could result in “lower bone mineral density and higher risk of fractures,” write the authors.

There have been reports that other classes of antidepressants, the SNRIs (serotonin and norepinephrine reuptake inhibitors) and TCAs (tricyclic antidepressants), have similarly been linked to bone fractures, Dr. Messer said. But the current study did not compare these agents.

HRT vs SSRI for Hot Flashes

Hormone replacement therapy (HRT) remains the standard of care for night sweats, said Dr. Messer. One SSRI, paroxetine, was approved in 2014 by the US Food and Drug Administration “for the treatment of vasomotor menopausal symptoms—including hot flashes and night sweats—at about one-third of the dose used to treat most psychiatric disorders.2

Although paroxetine is currently the only SSRI FDA-approved for menopause, other SSRIs are prescribed as an alternative to HRT because they have been shown to be effective when given at the same doses used to treat depression, noted the authors.

However, the benefit of taking an SSRI rather than HRT for menopause symptoms is that there is less risk of blood clots, explained Dr. Messer. They work more slowly than HRT, however. “HRT kicks in nearly immediately, while SSRIs can take weeks.” The SSRIs are given in the same dose when prescribed for women with psychiatric disorders as when they are prescribed for women without psychiatric disorders, she noted.

Prevention Tips

For chronic pain patients and the elderly, “It’s important to keep in mind that medication side effects such as low blood pressure and sedation can increase the risk of a fall and maybe of a fracture,” she noted. “Lying in bed for extended periods of time can result in a loss of bone density.” 

 If you are taking an SSRI and are concerned about the risk of fractures, there are certain measures you can take to stay strong, Dr. Messer explained.

  • Make sure that you are getting adequate doses of vitamin D and calcium.
  • If you smoke, quit.
  • Schedule a baseline bone density test and follow up with your health care provider to determine if treatment is needed for osteoporosis.
  • At home, make sure there are no loose rugs or other objects on the floor that pose a tripping hazard.
  • Exercise! It helps strengthen your bones.

Further Study Needed

The research is interesting but further study is needed, said Dr. Messer. “The observed association does not prove causality. Prospective studies [ongoing, rather than review] are needed to definitively assess the relationship between fractures and SSRI use. From this one study, it is too early to draw the conclusion that taking an SSRI increases the risk of a fracture.”

Updated on: 02/03/16
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