Nancy A. Melville

October 07, 2013

BALTIMORE — In a new study in postmenopausal women, the use of selective serotonin-receptor inhibitors (SSRIs) was associated with a higher risk of fracture than use of glucocorticoids, which are well-known for their link to fractures.

SSRI fracture risk also exceeded that of proton-pump inhibitors (PPIs), also known to be associated with this side effect, said lead author Jonathan Adachi, MD, FRCPC, a professor in the McMaster University department of medicine, Hamilton, Ontario, who reported the findings here at the American Society for Bone and Mineral Research (ASBMR) 2013 Annual Meeting. This is believed to be the first study of its kind to compare the fracture risk of the 3 drug classes, he noted.

"We do a lot to prevent glucocorticoid fractures, but this study showed that SSRIs seem to have as great an association with fractures as glucocorticoids and in fact have a slightly greater effect," Dr. Adachi told Medscape Medical News. "This is important because we have a lot of guidelines advising us on what to do about glucocorticoid-induced osteoporosis, but we don't have any on SSRI-induced osteoporosis."

SSRI Fracture Risk Not New but Magnitude of Effect Is

SSRIs have been linked with fracture risk in the past, and recent research suggested the drug class also increases the risk for falls in dementia patients.

Dr. Adachi and colleagues assessed participants in the observational GLOW study who were using 1 of the 3 drug classes — SSRIs, glucocorticoids (GCs), and PPIs — all of which have been associated with fractures, and they then compared patterns of self-reported fractures across 5 years with those of women in the study not using any of these drug classes.

The GLOW study includes women aged 55 and older from 615 primary-care practices in 10 countries who all had similar baseline characteristics in terms of body mass index, age, and use of tobacco or alcohol.

Among the participants, 9347 subjects were never treated with SSRIs, glucocorticoids, PPIs, estrogen, or antiosteoporosis medication; 2715 were treated with PPIs; 5304 were on glucocorticoids; and 1149 were on SSRIs at some point between the study's baseline and year 2.

The glucocorticoid group had higher levels of Crohn's disease, while anxiety was highest in the SSRI group, and the PPI group had the lowest general health, as well as the highest previous fracture rate.

At 5 years, following multivariate adjustment, SSRIs were the only therapy that showed a significantly increased risk in overall fractures (P < .0001), clinical spine fractures (P = .022), and nonhip/nonvertebral fractures (P < .0001).

Use of glucocorticoids was associated with an increase in spine fractures (P = .02), and PPIs showed an association with nonhip/nonvertebral fractures, but the increase was not statistically significant.

Adherence, Fall Differences, Could Be Limitations

"It was surprising to see that PPIs didn't seem to have any statistically significant effect on fracture rate," Dr. Adachi said. "It may be that we didn't follow the [patients] long enough."

He noted that one explanation for the findings could be the extent of adherence to the various drug classes.

"One might argue that patients on SSRIs tend to stay more adherent and stay on their medication longer. Glucocorticoid users may start low, while PPI users may be the ones who take the medications when they feel they need them, and if they don't feel they need them, they don't take them."

"We don't know whether women were truly adherent to the medication or if the therapy was interrupted. Nor do we have any real perspective on dosage," he acknowledged, noting that both factors were important study limitations.

Dr. Adachi also noted that the study also wasn't powered to determine whether any particular drug within the classes was associated with a higher fracture risk than another.

Moderator of the session, Suzanne Jan De Beur, MD, an associate professor of medicine at Johns Hopkins University School of Medicine, Baltimore, Maryland, noted that there were other potential confounders, too.

"I think an important limitation was that there was a difference in falls, with more people falling in the baseline SSRI group than the other 2 groups, and that group wound up having the highest rate of fractures," she commented.

The rate of 2 or more falls in the past 12 months was highest among the SSRI users, at 19%, compared with 15% in the glucocorticoid group and 14% in the PPI group. This raises the question of whether there is something about SSRIs that are making people fall, she said, or "are they on other different drugs that are making them fall?"

And there are likely multiple people who are on 2 or more of the agents examined, she added, noting "this study didn't tease that out — it's entirely unlikely that all of those people were only on a single agent."

Dr. Adachi said the potential effect of taking the drugs together needs to be probed in future, although "the preliminary results suggest that in taking multiple drugs, the risk is greater than taking just one," he concluded.

Dr. Adachi disclosed relationships with Warner Chilcott and Sanofi. Dr. De Beur has reported no financial relationships.

American Society for Bone and Mineral Research 2013 Annual Meeting. Abstract 1049, presented October 6, 2013.

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